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Ding X, Chen Y, Aierken A, Chen Y, Li Y. Association between social cognition, depressive symptoms and resilience among elderly people. J Affect Disord 2025; 380:584-590. [PMID: 40180041 DOI: 10.1016/j.jad.2025.03.174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 03/28/2025] [Accepted: 03/29/2025] [Indexed: 04/05/2025]
Abstract
BACKGROUND Depression is a serious mental and psychological problem among elderly people. This study aimed to explore the association between social cognition, depressive symptoms and resilience among elderly people living in communities. METHODS A cross-sectional study was conducted in China from January 2022 to August 2024. A total of 1958 participants aged 60 years or older were selected using a complex multistage sampling design from 39 locations. Data were collected through face-to-face interviews. Social cognition was measured using six items from the Blessed Dementia Rating Scale and the short form Chinese Geriatric Depression Scale was used to measure depressive symptoms. Logistic regression models were used to assess the association between social cognition and depressive symptoms. RESULTS Univariate analysis results showed that the prevalence of depressive symptoms were high in group with low levels of social cognition function and in group with low levels of general cognition function. Logistic regression analysis results showed that depressive symptoms were negatively associated with social cognition and general cognition levels adjusted for covariates, and the odds ratios were 0.29 and 0.46 (P < 0.001), respectively. LIMITATIONS This was a cross-sectional study and conducted a post-hoc analysis that could not determine the causal association between social cognition and increased prevalence of depressive symptoms. CONCLUSION Social cognition function was more strongly associated with depressive symptoms compared with general cognition function among elderly people. These results suggest that the prevalence of depressive symptoms may be directly or indirectly decreased by improving the social cognition level among elderly people.
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Affiliation(s)
- XiWen Ding
- Department of Social Medicine, School of Public Health, Zhejiang University, Hangzhou, China
| | - Yin Chen
- Department of Social Medicine, School of Public Health, Zhejiang University, Hangzhou, China
| | - Ayizuhere Aierken
- Department of Social Medicine, School of Public Health, Zhejiang University, Hangzhou, China
| | - YiLin Chen
- Department of Social Medicine, School of Public Health, Zhejiang University, Hangzhou, China
| | - Ying Li
- Department of Social Medicine, School of Public Health, Zhejiang University, Hangzhou, China; School of medicine, Zhejiang University, Hangzhou, China.
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2
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Ou A, Wu GWY, Kassel MT, Mackin RS, Rampersaud R, Reus VI, Mellon SH, Wolkowitz OM. Cognitive function in physically healthy, unmedicated individuals with major depression: Relationship with depressive symptoms and antidepressant response. J Affect Disord 2025; 378:191-200. [PMID: 40032138 DOI: 10.1016/j.jad.2025.02.115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Revised: 01/31/2025] [Accepted: 02/27/2025] [Indexed: 03/05/2025]
Abstract
We studied cognitive dysfunction in Major Depressive Disorder (MDD) in a sample of healthy, unmedicated individuals without comorbidities. Additionally, we studied the association of cognitive function with response to selective serotonin reuptake inhibitors (SSRIs). Our sample consisted of 113 adult MDD participants and 88 matched healthy controls (HC). Sixty-nine of the MDD participants completed 8 weeks of SSRI treatment. All participants completed a cognitive battery assessing processing speed, executive function, and learning and memory at baseline. This was repeated at week 8 for MDD participants. MDD "Responders" were defined as having ≥50 % improvement on the Hamilton Depression Rating Scale score at week 8 compared to baseline. At baseline, MDD participants performed significantly worse than HC participants on the Symbol Digit Modalities Test (SDMT) (p < .001), Stroop color naming (p = .005) and color-word naming (p = .047), and Brief Visuospatial Memory Test-Revised (BVMT) total recall (p = .02), delayed recall (p < .001), and percent retention (p = .01). MDD participants improved significantly on 6 of the cognitive assessments over 8 weeks. However, there were no significant baseline differences between Responders and Non-responders. SSRI Response was associated with improvement only in the HVLT total recall (p = .02). Our results suggest: 1) a differentiated pattern of cognitive dysfunction exists in healthy, unmedicated MDD compared to HCs; 2) baseline cognition does not delineate an SSRI-responsive/-nonresponsive subgroup, and 3) SSRI response is not associated with broad cognitive improvement after 8 weeks when compared to Non-responders, emphasizing unmet therapeutic challenges.
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Affiliation(s)
- Anna Ou
- Weill Institute for Neurosciences and Department of Psychiatry and Behavioral Sciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA; University of California San Diego (UCSD) School of Medicine, La Jolla, CA, USA
| | - Gwyneth W Y Wu
- Weill Institute for Neurosciences and Department of Psychiatry and Behavioral Sciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA.
| | - Michelle T Kassel
- Weill Institute for Neurosciences and Department of Psychiatry and Behavioral Sciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA; San Francisco Veterans Affairs Health Care System, San Francisco, CA, USA
| | - R Scott Mackin
- Weill Institute for Neurosciences and Department of Psychiatry and Behavioral Sciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA; San Francisco Veterans Affairs Health Care System, San Francisco, CA, USA
| | - Ryan Rampersaud
- Weill Institute for Neurosciences and Department of Psychiatry and Behavioral Sciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA
| | - Victor I Reus
- Weill Institute for Neurosciences and Department of Psychiatry and Behavioral Sciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA
| | - Synthia H Mellon
- Department of OB-GYN and Reproductive Sciences, UCSF School of Medicine, San Francisco, CA, USA
| | - Owen M Wolkowitz
- Weill Institute for Neurosciences and Department of Psychiatry and Behavioral Sciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA
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Cao X. Sleep Time and Depression Symptoms as Predictors of Cognitive Development Among Adolescents: A Cross-Lagged Study From China. Psychol Rep 2025; 128:1566-1587. [PMID: 37164938 DOI: 10.1177/00332941231175833] [Citation(s) in RCA: 17] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/12/2023]
Abstract
Sleep time and depression symptoms are important factors affecting cognitive development in adolescents. Based on the China Education Panel Survey (CEPS) database, this study used a two-wave cross-lagged model to examine the bidirectional relationship between sleep time, depression symptoms, and cognitive development. Descriptive statistics showed that Chinese adolescents' cognitive development increased significantly from 7th to 8th grade in junior high school, but unfortunately, their depression level and average sleep time per night demonstrated a slightly deteriorating trend. Correlation analysis showed that there was a relatively stable negative correlation between cognitive development, sleep time, and depression symptoms. Moreover, the cross-lagged model revealed that there was a bidirectional relationship between cognitive development and sleep time, a bidirectional relationship between depression symptoms and sleep time, and a unidirectional relationship between depression symptoms and cognitive development. Male adolescents in the subgroup were consistent with the total sample. Among female adolescents, only cognitive development and sleep time have a bidirectional relationship, while depression symptoms and cognitive development, and depression symptoms and sleep time have a unidirectional relationship. Therefore, it is of significance to take targeted action to promote cognitive development and healthy growth in adolescents worldwide.
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Affiliation(s)
- Xiaojie Cao
- Graduate School of Education, Peking University, Beijing, China
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4
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Olivier N, Harvey BH, Gobec S, Shahid M, Košak U, Žakelj S, Brink CB. A novel butyrylcholinesterase inhibitor induces antidepressant, pro-cognitive, and anti-anhedonic effects in Flinders Sensitive Line rats: The role of the ghrelin-dopamine cascade. Biomed Pharmacother 2025; 187:118093. [PMID: 40318448 DOI: 10.1016/j.biopha.2025.118093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2025] [Revised: 04/04/2025] [Accepted: 04/24/2025] [Indexed: 05/07/2025] Open
Abstract
BACKGROUND AND PURPOSE Major depressive disorder (MDD) is often treatment resistant, particularly in addressing anhedonia and cognitive deficits. Novel pharmacological strategies are needed. While butyrylcholinesterase, ghrelin, and dopamine (DA) have been well studied in the context of stress and MDD, their interaction remains unclear. EXPERIMENTAL APPROACH The dose-dependent antidepressant effects of a novel butyrylcholinesterase inhibitor (BChEI) were evaluated in the Flinders Sensitive Line (FSL) rat model of MDD. Behavioural assessments included the forced swim test (despair), sucrose preference test (reward-related), and novel object recognition test (cognition). Brain-derived neurotrophic factor (BDNF), acetylcholine (ACh), and brain monoamines were analysed, as well as serum growth hormone and acyl- and desacyl-ghrelin. To confirm the role of ghrelin, pharmacological exploration was undertaken using the ghrelin receptor antagonist, D-Lys-3-GHRP-6. KEY RESULTS FSL rats had significantly lower ghrelin ratios, BDNF, ACh, DA and growth hormone levels. In FSL rats, both BChEI and escitalopram significantly reduced despair. BChEI significantly outperformed escitalopram in enhancing reward-related and cognitive behaviours. Biochemically, BChEI treatment significantly increased ghrelin ratios and brain DA levels without altering brain 5-HT, ACh or BDNF. D-Lys-3-GHRP-6 significantly reversed the antidepressant-like, rewarding, and pro-cognitive effects of BChEI, accompanied by significant reductions in BDNF and DA. CONCLUSIONS AND IMPLICATIONS FSL rats display impaired ghrelin, DA, serotonin, growth hormone, and BDNF signalling, akin to MDD. BChEI exerts antidepressant-like effects across despair, reward, and cognitive domains, most likely via the BChE-ghrelin-DA cascade. Reversal of these effects by ghrelin antagonism underscores the critical role of ghrelin, specifically via growth hormone secretagogue receptor-ghrelin interaction. These findings suggest a potentially novel multimodal neurobiological target for the treatment of MDD.
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Affiliation(s)
- Nadia Olivier
- Centre of Excellence for Pharmaceutical Sciences, School of Pharmacy (Pharmacology), Faculty of Health Sciences, North-West University, Potchefstroom 2520, South Africa
| | - Brian H Harvey
- Centre of Excellence for Pharmaceutical Sciences, School of Pharmacy (Pharmacology), Faculty of Health Sciences, North-West University, Potchefstroom 2520, South Africa; South African Medical Research Council Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town 7505, South Africa; The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong 3220, Australia.
| | - Stanislav Gobec
- Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, Ljubljana 1000, Slovenia
| | | | - Urban Košak
- Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, Ljubljana 1000, Slovenia
| | - Simon Žakelj
- Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, Ljubljana 1000, Slovenia
| | - Christiaan B Brink
- Centre of Excellence for Pharmaceutical Sciences, School of Pharmacy (Pharmacology), Faculty of Health Sciences, North-West University, Potchefstroom 2520, South Africa
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Philippi CL, Bruss J, Brandauer C, Trapp NT, Tranel D, Boes AD. Reduced mind-wandering and fewer depressive symptoms associated with damage to the medial prefrontal cortex and default mode network. Neuropsychologia 2025; 214:109168. [PMID: 40350145 DOI: 10.1016/j.neuropsychologia.2025.109168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 05/07/2025] [Accepted: 05/08/2025] [Indexed: 05/14/2025]
Abstract
Depressive disorders have been consistently associated with elevated levels of mind-wandering and self-focused negative rumination. Separate tracks of research have implicated brain structures within the default mode network (DMN) in both mind-wandering and depression. In this study, we hypothesized that diminished mind-wandering and fewer depressive symptoms would co-occur in individuals with damage to the DMN. To test this hypothesis, we used a k-means clustering algorithm to identify a target group of patients with reduced mind-wandering and fewer depressive symptoms relative to brain-damaged comparison subjects (n = 37 of 68; ps < .001). The anatomical localization of lesions for this target group was predominantly within the medial prefrontal cortex (mPFC). Structural and functional lesion network mapping results revealed that lesions of the target group had significantly greater connectivity with DMN and limbic regions. Taken together, these results suggest that brain injury affecting the mPFC and DMN is associated with both reduced mind-wandering and fewer depressive symptoms. Further investigation of neuroanatomical substrates that mediate a causal relationship between mind-wandering and mood may facilitate the identification of new therapeutic targets for neuromodulation in patients with disorders characterized by maladaptive mind-wandering, such as rumination.
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Affiliation(s)
- Carissa L Philippi
- Department of Psychological Sciences, University of Missouri-St. Louis, 1 University Blvd., St. Louis, Missouri, 63121, USA.
| | - Joel Bruss
- Department of Neurology, University of Iowa, 200 Hawkins Drive, Iowa City, Iowa, 52242, Iowa City, IA, USA; Department of Pediatrics, University of Iowa, 200 Hawkins Drive, Iowa City, Iowa, 52242, Iowa City, IA, USA; Department of Psychiatry, University of Iowa, 200 Hawkins Drive Iowa City, Iowa, 52242, Iowa City, IA, USA
| | - Carrie Brandauer
- Department of Neurology, University of Iowa, 200 Hawkins Drive, Iowa City, Iowa, 52242, Iowa City, IA, USA
| | - Nicholas T Trapp
- Department of Psychiatry, University of Iowa, 200 Hawkins Drive Iowa City, Iowa, 52242, Iowa City, IA, USA
| | - Daniel Tranel
- Department of Neurology, University of Iowa, 200 Hawkins Drive, Iowa City, Iowa, 52242, Iowa City, IA, USA
| | - Aaron D Boes
- Department of Neurology, University of Iowa, 200 Hawkins Drive, Iowa City, Iowa, 52242, Iowa City, IA, USA; Department of Pediatrics, University of Iowa, 200 Hawkins Drive, Iowa City, Iowa, 52242, Iowa City, IA, USA; Department of Psychiatry, University of Iowa, 200 Hawkins Drive Iowa City, Iowa, 52242, Iowa City, IA, USA.
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6
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Li S, Jia J, Xu B, Wang X. Effects of chronic exercise on different central features of depression in adults with depression: A systematic review and meta-analysis of random controlled trials. PSYCHOLOGY OF SPORT AND EXERCISE 2025; 78:102824. [PMID: 39923828 DOI: 10.1016/j.psychsport.2025.102824] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Revised: 12/19/2024] [Accepted: 01/14/2025] [Indexed: 02/11/2025]
Abstract
BACKGROUND Exercise is considered an effective treatment for improving central symptoms of depression. However, the antidepressant effects of exercise on specific central features in adults with depression and the optimal exercise prescription remain unclear. The present review aimed to explore the impact of exercise on emotion regulation (ER) and executive function (EF) among adults living with depression as well as the moderating effects of exercise prescription characteristics. METHODS Two Chinese databases and two English databases were systematically searched from January 1, 2000 to October 30, 2023 to identify relevant randomized controlled trials (RCTs). Based on the results of heterogeneity analyses, the random effects model was used for the meta-analysis of rumination (260 participants in 5 studies), inhibition (578 participants in 7 studies) and updating (832 participants in 9 studies), whereas the fixed effects model was used for the meta-analysis for shifting (802 participants in 8 studies). RESULTS Exercise improved rumination (standardized mean difference [SMD] = -0.59, p = 0.02); however, these benefits were observed only for moderate-intensity aerobic exercise in one or two 31-60 min sessions per week for 5-8 weeks. The results indicated significant post-exercise improvement in shifting (SMD = -0.22, p = 0.002) but not inhibition (SMD = -0.21, p = 0.18) or updating (SMD = 0.15, p = 0.14). Moreover, substantial improvements in shifting were observed only from high-intensity aerobic exercise in three or four 31-60 min sessions per week for more than 8 weeks. CONCLUSIONS Exercise improved ER (i.e., rumination) and EF (i.e., shifting) in adults with depression. It is important to consider symptoms when prescribing exercise to adults with depression. However, given the limited number of included RCTs, these findings are preliminary and tentative.
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Affiliation(s)
- Shuhua Li
- School of Psychology, Shanghai University of Sport, Shanghai, 200438, China
| | - Jiafeng Jia
- School of Psychology, Shanghai University of Sport, Shanghai, 200438, China
| | - Bingrui Xu
- School of Psychology, Shanghai University of Sport, Shanghai, 200438, China
| | - Xiaochun Wang
- School of Psychology, Shanghai University of Sport, Shanghai, 200438, China.
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Santopetro NJ, Thompson B, Albanese B, Brush CJ, Schmidt NB. Depression Remission Over Six Months Characterized by Elevated Target-Locked P300 ERP Component: Prospective Evidence Employing an Affective Visual Oddball Task. Psychophysiology 2025; 62:e70067. [PMID: 40345151 DOI: 10.1111/psyp.70067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 03/06/2025] [Accepted: 04/23/2025] [Indexed: 05/11/2025]
Abstract
Depression is a mental health disorder characterized by dysfunction in cognitive and motivational neural systems. Event-related potential (ERP) research has explored these issues and has found that depression is associated with a reduced P300 ERP component, which likely reflects deficits in processes related to attentional allocation, decision-making, and context updating. However, most of the extant research has employed cross-sectional designs, limiting insight into the temporal precedence between the P300 and depression. Prospective investigations of the P300 and depression association are scarce and would provide further insight into the etiopathology of depression. The present study sought to examine the relationship between baseline P300 amplitude, elicited from an affective visual oddball paradigm, and depression remission after 6 months in a sample of adults (n = 48) suffering from current depressive disorders. Findings indicated that a larger P300 amplitude to target stimuli at baseline was associated with depression remission at the six-month follow-up visit, while no differences were observed for P300 components elicited by the distractor or standard stimuli. The present findings suggest that a reduced P300 amplitude to imperative stimuli may indicate a trait-like neural vulnerability of cognitive and motivational deficits contributing to a greater risk of relapse and a more chronic course of depression. Trial Registration: NCT01941862.
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Affiliation(s)
| | - Brittney Thompson
- Department of Psychology, Florida State University, Tallahassee, Florida, USA
| | - Brian Albanese
- Department of Psychological and Brain Sciences, Texas A&M University, College Station, Texas, USA
| | - C J Brush
- Department of Movement Sciences, University of Idaho, Moscow, Idaho, USA
| | - Norman B Schmidt
- Department of Psychology, Florida State University, Tallahassee, Florida, USA
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Qin Q, Liu X, Wang B, Wang X, Liang S, Chen C, Li M, Han C, Zhao X. Association between Electroencephalographic microstates abnormalities and cognitive dysfunction in drug-naive MDD. Brain Res 2025; 1860:149660. [PMID: 40294714 DOI: 10.1016/j.brainres.2025.149660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Revised: 04/15/2025] [Accepted: 04/23/2025] [Indexed: 04/30/2025]
Abstract
OBJECTIVES This study aims to investigate the link between Electroencephalography (EEG) microstate anomalies and cognitive impairments in individuals with drug-naive Major depressive disorder (MDD). METHODS We recruited 29 patients with drug-naive MDD and 30 healthy controls. The Hamilton Depression Rating Scale (HDRS-17) measured symptom severity, the MATRICS Consensus Cognitive Battery (MCCB) assessed neurocognitive function, and resting-state EEG data were collected using 64 scalp electrodes. Analysis of EEG microstates was conducted via the Microstate Analysis plugin for EEGLAB. RESULTS MDD group had lower scores in six neurocognitive MCCB domains. For EEG microstates, four similar ones (A - D) were found in both groups. Notably, microstate C duration was lower in MDD group (t = 4.549, P < 0.001), microstate D occurrence (t = 2.258, P = 0.028) and proportion (t = 3.733, P < 0.001) were lower in MDD group. There were significant differences in all 4 microstate transition probabilities between groups. For example, A - B, B - A etc. transitions were higher in MDD, while A - C, A - D etc. were lower.The proportion of microstate D was found positively correlated with Speed of processing (SOP) score (r = 0.499, df = 26, P = 0.007) and Working memory (WM) score (r = 0.451, df = 26, P = 0.016). The Occurrence of microstate D was found positively correlated with SOP score (r = 0.383, df = 26, P = 0.044) and WM score (r = 0.389, df = 26, P = 0.041). CONCLUSIONS MDD patients show alterations in sub-second brain dynamics, characterized by a decreased proportion and occurrence of microstate D and shorter duration of microstate C, and significant shifts in microstate transition probabilities. These changes correlate with cognitive deficits across several domains, including processing speed and working memory.
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Affiliation(s)
- Qin Qin
- National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, PR China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, PR China
| | - Xinyu Liu
- Department of Clinical Psychology, Shandong Provincial Hospital affiliated to Shandong First Medical University, Shandong, PR China
| | - Bin Wang
- National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, PR China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, PR China
| | - Xin Wang
- Key Laboratory of Complex System Control Theory and Application, Tianjin University of Technology, Tianjin 300384, PR China
| | - Sixiang Liang
- National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, PR China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, PR China
| | - Chao Chen
- Key Laboratory of Complex System Control Theory and Application, Tianjin University of Technology, Tianjin 300384, PR China
| | - Meijia Li
- Faculty of Psychology and Center for Neuroscience, Vrije Universiteit Brussel, 1050 Brussels, Belgium
| | - Chuanliang Han
- School of Biomedical Sciences and The Gerald Choa Neuroscience Institute, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
| | - Xixi Zhao
- National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, PR China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, PR China.
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9
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Delcourte S, Bouloufa A, Rovera R, Brunet E, Le HD, Williams AE, Panda S, Azmani R, Raineteau O, Dkhissi-Benyahya O, Haddjeri N. Lateral habenula astroglia modulate the potentiating antidepressant-like effects of bright light stimulation in intractable depression. Front Pharmacol 2025; 16:1592909. [PMID: 40337515 PMCID: PMC12055791 DOI: 10.3389/fphar.2025.1592909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2025] [Accepted: 04/07/2025] [Indexed: 05/09/2025] Open
Abstract
Background Beside image vision, light plays a pivotal role in regulating diverse non-visual functions, including affective behaviors. Recently, bright light stimulation (BLS) was revealed to be beneficial for treating non-seasonal depression, although its mechanism of action is not fully understood. Methods We developed a novel mouse model of refractory depression, induced through social isolation and chronic despair during the active (dark) phase of the animal, and we have tested if antidepressant treatments, including BLS, could protect against anxio-depressive-like behavior. Results We report that anxiety- and depressive-like behaviors are resistant to BLS as well as to both conventional and new antidepressants, including ketamine. Remarkably, we unveil that BLS potentiates the effect of antidepressants, and this beneficial effect is mediated via rod retinal photoreceptors. Furthermore, we demonstrate that both chemogenetic activation of lateral habenula (LHb) astroglia and serotonin (5-HT) depletion prevent the potentiating effect of BLS on chronic despair. Conclusion These results reveal, for the first time, that BLS enhances the efficacy of antidepressants through an unexpectedly circuit involving rods, LHb astroglia and 5-HT.
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Affiliation(s)
- Sarah Delcourte
- Univ Lyon, Université Claude Bernard Lyon 1, Inserm U1208, Stem Cell and Brain Research Institute, Bron, France
| | - Amel Bouloufa
- Univ Lyon, Université Claude Bernard Lyon 1, Inserm U1208, Stem Cell and Brain Research Institute, Bron, France
| | - Renaud Rovera
- Univ Lyon, Université Claude Bernard Lyon 1, Inserm U1208, Stem Cell and Brain Research Institute, Bron, France
| | - Elie Brunet
- Univ Lyon, Université Claude Bernard Lyon 1, Inserm U1208, Stem Cell and Brain Research Institute, Bron, France
| | - Hiep D. Le
- Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, United States
| | - April E. Williams
- Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, United States
| | - Satchidananda Panda
- Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, United States
| | - Rihab Azmani
- Univ Lyon, Université Claude Bernard Lyon 1, Inserm U1208, Stem Cell and Brain Research Institute, Bron, France
| | - Olivier Raineteau
- Univ Lyon, Université Claude Bernard Lyon 1, Inserm U1208, Stem Cell and Brain Research Institute, Bron, France
| | - Ouria Dkhissi-Benyahya
- Univ Lyon, Université Claude Bernard Lyon 1, Inserm U1208, Stem Cell and Brain Research Institute, Bron, France
| | - Nasser Haddjeri
- Univ Lyon, Université Claude Bernard Lyon 1, Inserm U1208, Stem Cell and Brain Research Institute, Bron, France
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10
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Ren FF, Chen FT, Zhou WS, Tian MY, Li RH, Wang DS, Liang WM, Yang Y, Chang YK. Effects of exercise training on cognition in adults with depression: A systematic review and three-level meta-analysis. Int J Nurs Stud 2025; 168:105083. [PMID: 40288074 DOI: 10.1016/j.ijnurstu.2025.105083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 02/13/2025] [Accepted: 04/07/2025] [Indexed: 04/29/2025]
Abstract
BACKGROUND Cognitive impairment is a central feature of depression. Exercise training has enormous potential as a nonpharmacological intervention to improve cognition in depressed individuals. OBJECTIVE This review aimed to evaluate and update the effect of exercise training on overall cognition and its subdomains, as well as whether moderators influence the effect of exercise training on cognition in depressed adults. DESIGN Systematic review and three-level meta-analysis of randomized controlled trials. METHODS We systematically searched Embase, Ovid MEDLINE, Web of Science, PubMed, and Scopus from their inception to February 14, 2024, and updated the search results on December 5, 2024. Randomized controlled trials investigating how exercise training affected cognition in depressed adults were included. The meta-analysis was performed using a random-effects model in R. We used the Physiotherapy Evidence Database scale to evaluate the study's quality. RESULTS Twenty-two studies were included. Exercise training showed statistically significant improvements in overall cognition [g = 0.21; 95 % confidence interval (CI) = 0.12, 0.30] and cognitive subdomains of processing speed (g = 0.20; 95 % CI = 0.04, 0.36), attention (g = 0.21; 95 % CI = 0.06, 0.35), memory (g = 0.24; 95 % CI = 0.11, 0.38), and executive function (g = 0.21; 95 % CI = 0.09, 0.33) compared with comparison groups in depressed adults. The greater cognitive benefits were observed when participants exercised twice a week (g = 0.30; 95 % CI = 0.03, 0.56), at a low intensity (g = 0.26; 95 % CI = 0.08, 0.43), spent more than 60 min per session (g = 0.24; 95 % CI = 0.05, 0.44), 150 min or more per week (g = 0.27; 95 % CI = 0.09, 0.45), had a program duration more than 10 weeks (g = 0.25; 95 % CI = 0.12, 0.39), and engaged in mind-body exercise (g = 0.26; 95 % CI = 0.08, 0.43). The clinical setting, sample size, and comparison group for memory moderated the effects of exercise training on cognition. CONCLUSIONS Exercise training is an effective nonpharmacological intervention that enhances overall cognition and subdomains of processing speed, attention, memory, and executive function compared with comparison groups in depressed adults. This study only included English-language articles, which may have caused a language bias, and Egger's test revealed a possibility of publication bias. REGISTRATION NUMBER CRD42023457900 (PROSPERO). TWEETABLE ABSTRACT Exercise training is an effective nonpharmacological intervention for adults with depression to improve overall cognition and cognitive subdomains of processing speed, attention, memory, and executive function compared with comparison groups.
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Affiliation(s)
- Fei-Fei Ren
- Department of Physical Education, Beijing Language and Culture University, Beijing 100083, China
| | - Feng-Tzu Chen
- Department of Kinesiology, National Tsing Hua University, Hsinchu 30014, Taiwan
| | - Wen-Sheng Zhou
- Department of Physical Education, Jiangsu Second Normal University, Jiangsu 211222, China
| | - Meng-Yi Tian
- China Wushu School, Beijing Sport University, Beijing 100084, China
| | - Ruei-Hong Li
- Department of Physical Education and Sport Sciences, National Taiwan Normal University, Taipei 106209, Taiwan
| | - Dong-Shi Wang
- Faculty of Sports Science, Ningbo University, Ningbo 315211, China
| | - Wen-Ming Liang
- Physical Education Institute of Jimei University, Jimei University, Xiamen 361021, China
| | - Yong Yang
- Laboratory of Kinesiology and Rehabilitation, School of Physical Education and Sport, Chaohu University, Anhui 238000, China
| | - Yu-Kai Chang
- Department of Physical Education and Sport Sciences, National Taiwan Normal University, Taipei 106209, Taiwan; Social Emotional Education and Development Center, National Taiwan Normal University, Taipei 106209, Taiwan.
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11
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Akhtar A, Shafiq S, Parveen S, Nwofe E, Windle K. Exploring the Impact of Cognitive Dysfunction During Recurrent Depression in a Sample of Mid-to-Older Age British South Asians: A Qualitative Study. J Psychiatr Ment Health Nurs 2025; 32:332-341. [PMID: 39314128 PMCID: PMC11891430 DOI: 10.1111/jpm.13113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 08/20/2024] [Accepted: 09/05/2024] [Indexed: 09/25/2024]
Abstract
INTRODUCTION Depression is a major public health issue, increasing the risk of comorbidities. Some people with depression experience cognitive dysfunction, which can persist even after symptomatic recovery. British South Asians are at greater risk of developing depression and are less likely to seek treatment. It is important to understand their experience of subjective cognitive dysfunction in depression and how best to support them. AIMS This study explored subjective experience of cognitive dysfunction during recurrent depression, in a sample of 12 British South Asians aged between 45 and 60 years. METHODS We conducted semi-structured interviews to explore cognitive dysfunction during recurrent depression. We analysed the data using thematic analysis. RESULTS Difficulties in attention and concentration resulted in lower quality of social relationships, including not feeling present and social isolation. Learning new information was difficult, thus impacting productivity. Participants found it difficult to engage in enjoyable activities that promoted brain health. The emotional, physical and spiritual impact negatively impacted on quality of life. DISCUSSION Cognitive strategies used in therapies could improve brain health and functional recovery in people living with depression. IMPLICATIONS Mental health nurses play a pivotal role in providing culturally appropriate information and strategies for managing cognitive dysfunction in recurrent depression.
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Affiliation(s)
- Amirah Akhtar
- Centre for Applied Dementia StudiesUniversity of BradfordBradfordUK
| | - Shabana Shafiq
- Centre for Applied Dementia StudiesUniversity of BradfordBradfordUK
| | - Sahdia Parveen
- Centre for Applied Dementia StudiesUniversity of BradfordBradfordUK
| | - Emmanuel Nwofe
- Centre for Applied Dementia StudiesUniversity of BradfordBradfordUK
| | - Karen Windle
- Centre for Applied Dementia StudiesUniversity of BradfordBradfordUK
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12
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Krasner H, Ong CV, Hewitt P, Vida TA. From Stress to Synapse: The Neuronal Atrophy Pathway to Mood Dysregulation. Int J Mol Sci 2025; 26:3219. [PMID: 40244068 PMCID: PMC11989442 DOI: 10.3390/ijms26073219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 03/02/2025] [Accepted: 03/29/2025] [Indexed: 04/18/2025] Open
Abstract
Mood disorders, including major depressive disorder and bipolar disorder, are among the most prevalent mental health conditions globally, yet their underlying mechanisms remain incompletely understood. This review critically examines the neuronal atrophy hypothesis, which posits that chronic stress and associated neurobiological changes lead to structural and functional deficits in critical brain regions, contributing to mood disorder pathogenesis. Key mechanisms explored include dysregulation of neurotrophic factors such as brain-derived neurotrophic factor (BDNF), elevated glucocorticoids from stress responses, neuroinflammation mediated by cytokines, and mitochondrial dysfunction disrupting neuronal energy metabolism. These processes collectively impair synaptic plasticity, exacerbate structural atrophy, and perpetuate mood dysregulation. Emerging evidence from neuroimaging, genetic, and epigenetic studies underscores the complexity of these interactions and highlights the role of environmental factors such as early-life stress and urbanization. Furthermore, therapeutic strategies targeting neuroplasticity, including novel pharmacological agents, lifestyle interventions, and anti-inflammatory treatments, are discussed as promising avenues for improving patient outcomes. Advancing our understanding of the neuronal atrophy hypothesis could lead to more effective, sustainable interventions for managing mood disorders and mitigating their global health burden.
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Affiliation(s)
| | | | | | - Thomas A. Vida
- Kirk Kerkorian School of Medicine, University of Nevada, Las Vegas, 625 Shadow Lane, Las Vegas, NV 89106, USA; (H.K.); (C.V.O.); (P.H.)
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13
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Zhu X, Chen X, Wu Y, Feng L, Chen X. Longitudinal trajectories of subjective cognitive complaints in patients with major depressive disorder and similar objective cognitive trajectories. BMC Psychiatry 2025; 25:287. [PMID: 40140756 PMCID: PMC11938668 DOI: 10.1186/s12888-025-06538-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 01/26/2025] [Indexed: 03/28/2025] Open
Abstract
BACKGROUND We examined the factors influencing various subtypes of subjective cognitive change in patients who shared similar objective cognitive trajectories within 6 months. METHOD We used data from an observational, prospective, cohort study, including 598 patients with major depressive disorder (MDD) in latent class mixed models based on the digit symbol substitution test performance. Participants were stratified into four distinct objective cognitive layers: "low cognitive performance," "lower-middle cognitive performance," "upper-middle cognitive performance," and "high cognitive performance." Within each of the four layers, the trajectories of subjective cognitive complaints were identified. Multinomial regression was employed, with cognitive complaint trajectories as the outcome, and depressive symptoms, clinical features, and other covariates as predictors. RESULTS The factors influencing the subjective trajectories varied among the different objective layers. Patients with comorbid anxiety disorders or functional syndromes had more prominent self-reported cognitive symptoms and a slower rate of improvement. Younger age and lower education level were also influential factors for delayed remission of subjective cognitive function. Disease severity and antidepressant type did not contribute to dedifferentiating subjective cognitive trajectory subtypes within different subjective cognitive trajectories. CONCLUSION Despite similar objective cognitive trajectories, subjective perceptions of these cognitive changes are heterogeneous. These findings deepen our understanding of the multifaceted nature of cognitive change in individuals with MDD and underscore the importance of considering a range of factors when interpreting and treating cognitive impairment at an early stage.
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Affiliation(s)
- Xuequan Zhu
- Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Capital Medical University, Beijing, China
| | - Xiongying Chen
- Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Capital Medical University, Beijing, China
| | - Yuanzhen Wu
- Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Capital Medical University, Beijing, China
| | - Lei Feng
- Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Capital Medical University, Beijing, China
| | - Xu Chen
- Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Capital Medical University, Beijing, China.
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14
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Xu CC, Zhao WX, Sheng Y, Yun YJ, Ma T, Fan N, Song JQ, Wang J, Zhang Q. Serum homocysteine showed potential association with cognition and abnormal gut microbiome in major depressive disorder. World J Psychiatry 2025; 15:102567. [PMID: 40109991 PMCID: PMC11886347 DOI: 10.5498/wjp.v15.i3.102567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 12/18/2024] [Accepted: 01/06/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND Cognitive impairment is one of the common clinical manifestations of depression, causing negative distress to patients. Elevated homocysteine (Hcy) concentrations and gut microbiome dysfunction may be observed in patients with depression. AIM To investigate the relationship between Hcy, microbiome, and cognition in depressive patients. METHODS We recruited 67 patients with major depressive disorder (MDD) (MDD group) and 94 healthy controls (HCs) individuals (HCs group). Serum Hcy levels were determined using the enzyme circulation method. 16s rRNA sequencing was used to classify and identify the fecal bacteria. 17 Hamilton depression rating scale and MATRICS consensus cognitive battery were used to evaluate mood states and cognition in patients with MDD. Correlation analysis was performed to explore the correlation between fecal flora, Hcy, and depressive cognitive function. RESULTS Elevated serum levels of Hcy were seen in patients with MDD compared to healthy individuals. Patients with MDD indicated significant decreases in cognitive scores (P < 0.001) in six modules: Speed of processing, working memory, visual learning, reasoning and problem-solving, social cognition, and total scores. Hcy levels showed a negative correlation with processing speed, social cognition, and total MDD scores (P < 0.05). Hcy was also significantly negatively correlated with Alistipes, Ruminococcae, Tenericides, and Porphyromonas (P < 0.05). CONCLUSION Our results highlight that Hcy was correlated with cognition and gut microbiome in MDD. This interaction may be related to the physiological and pathological mechanisms underlying cognitive deficits in depression.
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Affiliation(s)
- Chen-Chen Xu
- Department of Psychiatry, The Affiliated Wuxi Mental Health Center of Nanjing Medical University, Wuxi 214151, Jiangsu Province, China
| | - Wen-Xuan Zhao
- Department of Psychiatry, Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing 100096, China
| | - Yu Sheng
- Department of Psychiatry, Chinese People’s Liberation Army Unit 94710, Wuxi 214141, Jiangsu Province, China
| | - Ya-Jun Yun
- Department of Psychiatry, Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing 100096, China
| | - Ting Ma
- Department of Psychiatry, Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing 100096, China
| | - Ning Fan
- Department of Psychiatry, Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing 100096, China
| | - Jia-Qi Song
- Department of Psychiatry, Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing 100096, China
| | - Jun Wang
- Department of Psychiatry, The Affiliated Wuxi Mental Health Center of Nanjing Medical University, Wuxi 214151, Jiangsu Province, China
- Department of Psychiatry, The Affiliated Mental Health Center of Jiangnan University, Wuxi 214151, Jiangsu Province, China
| | - Qi Zhang
- Department of Psychiatry, The Affiliated Wuxi Mental Health Center of Nanjing Medical University, Wuxi 214151, Jiangsu Province, China
- Department of Psychiatry, The Affiliated Mental Health Center of Jiangnan University, Wuxi 214151, Jiangsu Province, China
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15
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Martin JL, Strawbridge RJ, Christmas D, Fleming M, Kelly S, Varveris D, Martin D. Electroconvulsive Therapy: A Scotland-Wide Naturalistic Study of 4826 Treatment Episodes. BIOLOGICAL PSYCHIATRY GLOBAL OPEN SCIENCE 2025; 5:100434. [PMID: 39926701 PMCID: PMC11804586 DOI: 10.1016/j.bpsgos.2024.100434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Revised: 12/03/2024] [Accepted: 12/07/2024] [Indexed: 02/11/2025] Open
Abstract
Background Electroconvulsive therapy (ECT) is an effective treatment option for several psychiatric disorders, including treatment-resistant depression, but there are concerns about potential adverse effects, particularly on cognition. This study describes ECT response and side effects in the Scottish ECT Audit Network. Methods Data collected from 4826 treatment episodes includes pre-ECT and post-ECT illness severity scores (Clinical Global Impression-Severity [CGI-S] and Montgomery-Åsberg Depression Rating Scale [MADRS]), diagnosis, age, sex, consent status, treatment year, treatment frequency, dose, and reported side effects. Descriptive statistics were used to assess the response to ECT by diagnosis, and logistic regression was used to investigate which factors influenced ECT response and side-effect occurrence. Results CGI-S scale scores were reduced after ECT in all diagnoses. For patients with depression or bipolar depression, MADRS scores were also reduced after ECT. The most common side effect was headaches (29%). Increased age and increased CGI-S scores were significantly associated (multiple-testing corrected p < .05) with better treatment response and more cognitive side effects. Conclusions In a large observational outcome study of ECT, ECT appears to be effective (measured by reduction in CGI-S or MADRS scores) across a range of psychiatric diagnoses. Furthermore, increased age and increased illness severity scores at entry were the variables most significantly associated with treatment response and cognitive side effects.
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Affiliation(s)
- Julie Langan Martin
- School of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom
| | - Rona J. Strawbridge
- School of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom
- Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden
| | - David Christmas
- National Health Service Tayside, Ninewells Hospital, Dundee, United Kingdom
| | - Michael Fleming
- School of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom
| | - Stephen Kelly
- National Health Service Greater Glasgow and Clyde, Glasgow, United Kingdom
| | - Daphne Varveris
- National Health Service Greater Glasgow and Clyde, Glasgow, United Kingdom
| | - Daniel Martin
- National Health Service Forth Valley, Stirling, United Kingdom
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16
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Ross-Adelman M, Aalbers G, Matcham F, Simblett S, Leightley D, Siddi S, Haro JM, Oetzmann C, Narayan VA, Hotopf M, Myin-Germeys I, de Jonge P, Lamers F, Penninx BWJH. The Association Between Cognitive Functioning and Depression Severity: A Multiwave Longitudinal Remote Assessment Study. Depress Anxiety 2025; 2025:1509978. [PMID: 40225736 PMCID: PMC11918956 DOI: 10.1155/da/1509978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Accepted: 01/28/2025] [Indexed: 04/15/2025] Open
Abstract
Cognitive difficulties are prevalent in depression and are linked to various negative life outcomes such as psychosocial impairment, absenteeism, lower chance of recovery or remission, and overall poor quality of life. Thus, assessing cognitive functioning over time is key to expanding our understanding of depression. Recent methodological advances and the ubiquity of smartphones enable remote assessment of cognitive functioning through smartphone-based tasks and surveys. However, the association of smartphone-based assessments of cognitive functioning to depression severity remains underexplored. Using a dedicated mobile application for assessing cognitive functioning (THINC-it), we investigate within- and between-person associations between performance-based (attention, working memory, processing speed, attention switching) and self-report measures of cognitive functioning with depression severity in 475 participants from the RADAR-MDD (Remote Assessment of Disease and Relapse-Major Depressive Disorder) cohort study (t = 2036 observations over an average of 14 months of follow-up). At the between-person level, we found stronger negative associations between the self-reported cognitive functioning measure and depression severity (β = -0.649, p < 0.001) than between the performance-based measures and depression severity (βs = -0.220 to -0.349, p s < 0.001). At the within-person level, we found negative associations between depression severity and the self-reported measure (β = -0.223, p < 0.001), processing speed (β = -0.026, p=0.032) and attention (β = -0.037, p=0.003). These findings suggest that although THINC-it could adequately and remotely detect poorer cognitive performance in people with higher depressive symptoms, it was not capable of tracking within-person change over time. Nonetheless, repeatedly measuring self-reports of cognitive functioning showed more potential in tracking within-person changes in depression severity, underscoring their relevance for patient monitoring.
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Affiliation(s)
- Marcos Ross-Adelman
- Department of Psychiatry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Amsterdam Public Health, Mental Health Program, Amsterdam, The Netherlands
| | - George Aalbers
- Department of Psychiatry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Amsterdam Public Health, Mental Health Program, Amsterdam, The Netherlands
| | - Faith Matcham
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
- School of Psychology, University of Sussex, Falmer, UK
| | - Sara Simblett
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Daniel Leightley
- School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Sara Siddi
- Parc Sanitari Sant Joan de Déu, Institut de Recerca San Joan de Déu (IRSJD), Sant Boi de Llobregat, Barcelona, Spain
- Centro de Investigación Biomédica en Red en Salud Mental (CIBERSAM), Madrid, Spain
| | - Josep M. Haro
- Parc Sanitari Sant Joan de Déu, Institut de Recerca San Joan de Déu (IRSJD), Sant Boi de Llobregat, Barcelona, Spain
- Centro de Investigación Biomédica en Red en Salud Mental (CIBERSAM), Madrid, Spain
| | - Carolin Oetzmann
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Vaibhav A. Narayan
- Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK
| | - Matthew Hotopf
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
- South London and Maudsley NHS Foundation Trust, London, UK
| | - Inez Myin-Germeys
- Department of Neurosciences, Center of Contextual Psychiatry, KU Leuven, Leuven, Belgium
| | - Peter de Jonge
- Department of Developmental Psychology, University of Groningen, Groningen, The Netherlands
| | - Femke Lamers
- Department of Psychiatry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Amsterdam Public Health, Mental Health Program, Amsterdam, The Netherlands
| | - Brenda W. J. H. Penninx
- Department of Psychiatry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Amsterdam Public Health, Mental Health Program, Amsterdam, The Netherlands
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17
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Liu J, Li K, Li S, Liu S, Wang C, Huang S, Tu Y, Wang B, Zhang P, Luo Y, Sun G, Chen T. A new method for identifying and evaluating depressive disorders in young people based on cognitive neurocomputing: an exploratory study. Front Comput Neurosci 2025; 19:1555416. [PMID: 40070399 PMCID: PMC11893619 DOI: 10.3389/fncom.2025.1555416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2025] [Accepted: 02/12/2025] [Indexed: 03/14/2025] Open
Abstract
Background Depressive disorders are one of the most common mental disorders among young people. However, there is still a lack of objective means to identify and evaluate young people with depressive disorders quickly. Cognitive impairment is one of the core characteristics of depressive disorders, which is of great value in the identification and evaluation of young people with depressive disorders. Methods This study proposes a new method for identifying and evaluating depressive disorders in young people based on cognitive neurocomputing. The method evaluates cognitive impairments such as reduced attention, executive dysfunction, and slowed information processing speed that may exist in the youth depressive disorder population through an independently designed digital evaluation paradigm. It also mines digital biomarkers that can effectively identify these cognitive impairments. A total of 50 young patients with depressive disorders and 47 healthy controls were included in this study to validate the method's identification and evaluation capability. Results The differences analysis results showed that the digital biomarkers of cognitive function on attention, executive function, and information processing speed extracted in this study were significantly different between young depressive disorder patients and healthy controls. Through stepwise regression analysis, four digital biomarkers of cognitive function were finally screened. The area under the curve for them to jointly distinguish patients with depressive disorders from healthy controls was 0.927. Conclusion This new method rapidly characterizes and quantifies cognitive impairment in young people with depressive disorders. It provides a new way for organizations, such as schools, to quickly identify and evaluate the population of young people with depressive disorders based on human-computer interaction.
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Affiliation(s)
- Jiakang Liu
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, China
| | - Kai Li
- School of Information Engineering, Hangzhou Medical College, Hangzhou, China
- Zhejiang Engineering Research Center for Brain Cognition and Brain Diseases Digital Medical Instruments, Hangzhou Medical College, Hangzhou, China
| | - Shuwu Li
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, China
| | - Shangjun Liu
- Department of Medical Psychology, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Chen Wang
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, China
| | - Shouqiang Huang
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yuting Tu
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, China
| | - Bo Wang
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, China
| | - Pengpeng Zhang
- School of Information Engineering, Hangzhou Medical College, Hangzhou, China
| | - Yuntian Luo
- School of Information Engineering, Hangzhou Medical College, Hangzhou, China
| | - Guanqun Sun
- School of Information Engineering, Hangzhou Medical College, Hangzhou, China
| | - Tong Chen
- Department of Neurology, Second Medical Center of Chinese PLA General Hospital, Beijing, China
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18
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Humes EC, Iosifescu DV, Siqueira JO, Fraguas R. Association of performance in medical residency selection with a psychiatric diagnosis, and depressive and anxiety symptoms. MEDICAL TEACHER 2025; 47:353-361. [PMID: 38608667 DOI: 10.1080/0142159x.2024.2337248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Accepted: 03/27/2024] [Indexed: 04/14/2024]
Abstract
OBJECTIVE Few studies have focused on medical students and residents' mental health impact on medical residency selection (MRS) performance. The authors evaluated the association of performance in MRS with depressive and anxiety symptoms and with a reported psychiatric diagnosis (rPD). METHODS The authors enrolled candidates after the second round of MRS examinations at a Brazilian Medical School. Performance was assessed by final grade. Depressive and anxiety symptoms were assessed by the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) and the State-Trait Anxiety Inventory (STAI). The authors performed mediation analysis and multiple linear regression analysis to investigate the impact of rPD, state and trait anxiety, and depressive symptom severity on performance. RESULTS 515 of the 643 MRS candidates (80.1%) participated in the study. Higher age, attending a preparatory course for MRS, rPD, and the number of MRS applications that year were associated with poorer performance. In mediation analysis, trait anxiety was associated with a direct effect on performance and an indirect effect mediated by rPD. CONCLUSION The data suggest that psychiatric diagnosis is associated with poorer performance on MRS, regardless of current symptoms of anxiety and depression. Additionally, increased levels of trait anxiety may negatively impact performance, directly and indirectly.
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Affiliation(s)
- Eduardo C Humes
- Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | | | - Jose O Siqueira
- Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Renerio Fraguas
- Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
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19
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Zuidersma M, de Vries YA, Bogers ICHM, Rhebergen D, Oude Voshaar RC. Six-year course over time and predictors of suicidal ideation in depressed older patients. J Affect Disord 2025; 370:90-99. [PMID: 39481688 DOI: 10.1016/j.jad.2024.10.097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 09/30/2024] [Accepted: 10/20/2024] [Indexed: 11/02/2024]
Abstract
BACKGROUND It is important to know predictors of long-term course over time of suicidal thoughts and ideation in depressed older persons. METHODS In this study, 378 depressed older persons were interviewed at baseline, and after 2 and 6 years to evaluate the presence of depressive disorder. The Inventory of Depressive Symptomatology (IDS) was administered every 6 months for 6 years. Latent Class Growth Analysis was performed on the IDS item on suicidal ideation to identify subgroups with different trajectories. RESULTS Five subgroups with suicidal ideation trajectories were identified: 1) severe, transient (10.9 %), 2) severe, persisting (8.0 %), 3) mild, but increasing (14.9 %), 4) moderate, persisting (35.6 %), and 5) no thoughts (30.6 %). Mixed model analysis showed that trajectories were related to 6-year course of depressive symptoms. Yet, suicidal ideation or thoughts of loss of meaning of life were still present in 22.7 % and 17.4 % of those who remitted after 2 and 6 years. Independent of baseline depressive symptom severity, loneliness, childhood trauma, history of suicidal ideation or attempt, openness to experience, earlier age of depression onset, anxiety symptom severity and worse mastery predicted worse trajectories. LIMITATIONS 47 % dropped out at 6-years follow-up, we did not distinguish between thoughts of death and suicide, we did not assess death by suicide. CONCLUSIONS Although trajectories of suicidal ideation and thoughts of loss of meaning of life were strongly related to the course of depression severity, they also appear after remission. Clinicians should be vigilant for suicidal ideation or death wish, even after remission of depression.
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Affiliation(s)
- Marij Zuidersma
- University of Groningen, University Medical Centre Groningen, Department of Psychiatry, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), 9700 RB Groningen, the Netherlands.
| | - Ymkje Anna de Vries
- Department of Child and Adolescent Psychiatry, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands
| | - Ista C H M Bogers
- University of Groningen, University Medical Centre Groningen, Department of Psychiatry, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), 9700 RB Groningen, the Netherlands
| | - Didi Rhebergen
- GGZ Centraal Mental Health Care, Amersfoort, the Netherlands; Amsterdam Public Health Research Institute, Mental Health Program, Amsterdam, the Netherlands; Department of Psychiatry, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Richard C Oude Voshaar
- University of Groningen, University Medical Centre Groningen, Department of Psychiatry, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), 9700 RB Groningen, the Netherlands
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20
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Santopetro NJ, Luby JL, Barch DM, Luking KR, Hennefield L, Gilbert KE, Whalen DJ, Hajcak G. Association Between Early Childhood P300 Deficits and Risk for Preadolescence Depressive Disorder Mediated by Responsiveness to PCIT-ED Treatment. Res Child Adolesc Psychopathol 2025:10.1007/s10802-025-01293-2. [PMID: 39862380 DOI: 10.1007/s10802-025-01293-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/14/2025] [Indexed: 01/27/2025]
Abstract
Preschool-onset major depressive disorder (PO-MDD) is an impairing pediatric mental health disorder that impacts children as young as three years old. There is limited work dedicated to uncovering neural measures of this early childhood disorder which could be leveraged to further understand both treatment responsiveness and future depression risk. Event-related potentials (ERPs) such as the P300 have been employed extensively in adult populations to examine depression-related deficits in cognitive and motivational systems. Few studies examine the prospective relationships between depression and P300, especially in young children. Moreover, limited research examines the relationship between P300 with psychotherapy treatment responsiveness in youths. The current study sought to examine the prospective relationships between pre-intervention P300 (i.e., choice-locked) elicited from the doors task in depressed preschool children (i.e., PO-MDD; ages 3-to-6) with reductions in depressive symptoms after completing an 18-week long dyadic psychotherapy intervention (n = 59). We also explored relations to risk for depression assessed at a follow-up visit during preadolescence (ages 8-to-12; n = 82). Those with PO-MDD exhibiting reduced choice (doors)-locked P300 demonstrated worse treatment response to psychotherapy and were more likely to meet criteria for depression during preadolescence. Moreover, the relationship between pre-intervention P300 and later preadolescence depression was significantly mediated by response to treatment. These findings suggest that deficits in brain systems linked to the choice-locked P300 component (i.e., cognitive and motivational) might be indicative of non-responsiveness to early dyadic psychotherapeutic intervention efforts for depression which impacts risk for recurrent patterns of depression in youths.
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Affiliation(s)
| | - Joan L Luby
- Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, MO, USA
| | - Deanna M Barch
- Department of Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO, USA
| | | | - Laura Hennefield
- Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, MO, USA
| | - Kirsten E Gilbert
- Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, MO, USA
| | - Diana J Whalen
- Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, MO, USA
| | - Greg Hajcak
- School of Education and Counseling Psychology, Santa Clara University, Santa Clara, CA, USA
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21
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Danon M, Poupon D, Courtet P, Gorwood P. Clustering and drivers of symptoms observed at week six after antidepressant treatment in depressed outpatients. Eur Psychiatry 2025; 67:e85. [PMID: 39819366 PMCID: PMC11795446 DOI: 10.1192/j.eurpsy.2024.1801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 11/05/2024] [Accepted: 11/09/2024] [Indexed: 01/19/2025] Open
Abstract
BACKGROUND Depressive symptoms remaining after antidepressant treatment increase the risk of relapse and recurrence. We aimed to analyze the distribution and main drivers of remaining symptoms in patients with a major depressive episode. METHODS Two independent samples of 8,229 and 5,926 patients from two large naturalistic studies were retrospectively analyzed. DSM-IV criteria for major depressive episodes were assessed during two face-to-face visits with clinicians: before the prescription of a new antidepressant, and after 6 weeks of treatment. The Hospital Anxiety and Depression Scale (HADS) was used to assess baseline severity of anxiety and depression. RESULTS In both samples, two clusters of remaining symptoms were observed. The first cluster encompassed symptoms related to a negative emotional and cognitive bias and was specifically driven by the baseline severity of depression. The second cluster encompassed neurovegetative symptoms and was specifically driven by the baseline severity of anxiety. CONCLUSIONS The baseline anxiety-depressive balance of patients could be considered to adapt the treatment, focusing on emotional and cognitive symptoms with patients with high baseline severity of depression, and neurovegetative symptoms with patients with high baseline anxiety severity.
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Affiliation(s)
- Michel Danon
- Clinique des Maladies Mentales et de l’Encéphale, GHU Paris Psychiatrie et Neurosciences, Paris, France
- Université Paris Cité, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Paris, France
| | - Daphnée Poupon
- Clinique des Maladies Mentales et de l’Encéphale, GHU Paris Psychiatrie et Neurosciences, Paris, France
| | - Philippe Courtet
- Department of Emergency Psychiatry and Post-Acute Care, CHUMontpellier, France
- IGF, Hôpital La Colombière, University of Montpellier, Montpellier, France
| | - Philip Gorwood
- Clinique des Maladies Mentales et de l’Encéphale, GHU Paris Psychiatrie et Neurosciences, Paris, France
- Université Paris Cité, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Paris, France
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22
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Żółkowska B, Lee CS, Denfeld QE, Jędrzejczyk M, Diakowska D, Lisiak M, Wleklik M, Czapla M, Uchmanowicz I. Clinical and Psychological Factors Associated with Frailty in Patients with Heart Failure. J Clin Med 2024; 13:7345. [PMID: 39685803 DOI: 10.3390/jcm13237345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2024] [Revised: 11/26/2024] [Accepted: 11/27/2024] [Indexed: 12/18/2024] Open
Abstract
Background/Objectives: Heart failure (HF) is a significant public health issue with high morbidity and mortality rates. This study aims to investigate the interrelationships between frailty, cognitive impairment, and depression in older adults with HF, specifically focusing on how the physical and neuropsychiatric dimensions of frailty contribute to cognitive decline. Methods: This study included 250 patients aged 60 years or older, diagnosed with HF and hospitalized for acute decompensated HF. The patients were assessed using standardized protocols for frailty, cognitive function, and depression. The frailty was evaluated using Fried's phenotype criteria, cognitive function with MMSE and MoCA, and depression and anxiety with HADS and PHQ-9. Statistical analyses included univariable and multivariable linear regression to identify the predictors of frailty. Results: Of the 250 patients, 151 (60.4%) were identified as frail. The frail patients were older (mean age 73.58 ± 6.80 years) compared to the non-frail patients (mean age 70.39 ± 6.16 years, p = 0.0002). Significant differences were observed in the NYHA class, length of the hospital stay, and prevalence of diabetes mellitus. The frail patients had worse cognitive (MMSE: 27.39 ± 2.12 vs. 28.13 ± 1.72, p = 0.004; MoCA: 24.68 ± 3.65 vs. 25.64 ± 3.98, p = 0.050) and psychological outcomes (higher prevalence of marked depression based on HADS categories: 8.61% vs. 1.01%, p = 0.021; and PHQ-9 categories: severe depression: 2.65% vs. 1.01%, p < 0.001). Conclusions: Age, C-reactive protein (CRP) levels, and anxiety were identified as independent predictors of frailty in the patients with heart failure. Depression, cognitive dysfunction, and the length of the hospital stay showed significant differences between the frail and non-frail patients in the group comparisons but were not independent predictors.
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Affiliation(s)
- Bernadetta Żółkowska
- Student Research Club of Heart Diseases, Faculty of Medicine, Wroclaw Medical University, 51-618 Wroclaw, Poland
| | - Christopher S Lee
- Boston College William F. Connell School of Nursing, Chestnut Hill, MA 02467, USA
| | - Quin E Denfeld
- School of Nursing, Oregon Health & Science University, Portland, OR 97239, USA
| | - Maria Jędrzejczyk
- Department of Nursing, Faculty of Nursing and Midwifery, Wroclaw Medical University, 51-618 Wroclaw, Poland
| | - Dorota Diakowska
- Department of Midwifery, Faculty of Nursing and Midwifery, Wroclaw Medical University, 51-618 Wroclaw, Poland
| | - Magdalena Lisiak
- Department of Nursing, Faculty of Nursing and Midwifery, Wroclaw Medical University, 51-618 Wroclaw, Poland
- Institute of Heart Diseases, University Hospital, 50-556 Wroclaw, Poland
| | - Marta Wleklik
- Department of Nursing, Faculty of Nursing and Midwifery, Wroclaw Medical University, 51-618 Wroclaw, Poland
| | - Michał Czapla
- Institute of Heart Diseases, University Hospital, 50-556 Wroclaw, Poland
- Department of Emergency Medical Service, Faculty of Nursing and Midwifery, Wroclaw Medical University, 51-618 Wroclaw, Poland
- Group of Research in Care (GRUPAC), Faculty of Health Science, University of La Rioja, 26006 Logroño, Spain
| | - Izabella Uchmanowicz
- Department of Nursing, Faculty of Nursing and Midwifery, Wroclaw Medical University, 51-618 Wroclaw, Poland
- Centre for Cardiovascular Health, Edinburgh Napier University, Sighthill Campus, Edinburgh EH11 4DN, UK
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23
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Scala M, Fabbri C, Fusar-Poli P, Di Lorenzo G, Ferrara M, Amerio A, Fusar-Poli L, Pichiecchio A, Asteggiano C, Menchetti M, De Ronchi D, Fanelli G, Serretti A. The revival of psilocybin between scientific excitement, evidence of efficacy, and real-world challenges. CNS Spectr 2024; 29:570-584. [PMID: 39655426 DOI: 10.1017/s1092852924002268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/20/2025]
Abstract
The revival of psilocybin in psychopharmacological research heralds a potential paradigm shift for treating mood and anxiety disorders, and other psychiatric conditions beyond the psychotic spectrum. This critical review evaluates current evidence on psilocybin's efficacy, juxtaposing potential benefits with the practical aspects of psychedelic-assisted psychotherapy (PAP) and the methodological constraints of existing research.An electronic literature search was conducted using PubMed/MEDLINE, selecting studies published up to December 2023 that explored the clinical use of psilocybin in mood and anxiety disorders, obsessive-compulsive disorder, post-traumatic stress disorder, and substance use disorder. Despite promising preliminary results suggesting psilocybin's efficacy in alleviating depression and anxiety, as well as obsessions, compulsions, and addictive behaviors, significant evidence gaps persist. These include evaluating the efficacy of psilocybin compared to standard antidepressants or anxiolytic molecules and identifying patient subpopulations that might benefit most from PAP. Concerns about psilocybin's safety, long-term efficacy, and optimal dosage remain unclear due to previous trials' limitations. Real-world implementation faces challenges, including infrastructural requirements, personnel training, and unresolved legal and ethical issues. This paper argues for further research to substantiate the evidence base, emphasizing the need for larger studies that overcome current methodological limitations and explore psilocybin's full therapeutic potential. While psilocybin holds promise for psychiatry, its successful translation from research to clinical practice demands more robust evidence on efficacy, safety, and methodological rigor. In addition, other factors, such as cultural stigma and legal/ethical issues, need to be successfully addressed to facilitate psilocybin's implementation in healthcare systems.
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Affiliation(s)
- Mauro Scala
- Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy
- Health Research Institute Hospital 12 de Octubre (imas12), Madrid, Spain
| | - Chiara Fabbri
- Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy
| | - Paolo Fusar-Poli
- Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, King's College London, London, United Kingdom
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
- OASIS Service, South London and Maudsley NHS Foundation Trust, London, United Kingdom
- Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilian-University, Munich, Germany
| | - Giorgio Di Lorenzo
- Department of Systems Medicine, Tor Vergata University of Rome, Rome, Italy
- IRCCS Fondazione Santa Lucia, Rome, Italy
| | - Maria Ferrara
- Institute of Psychiatry, Department of Neuroscience and Rehabilitation, University of Ferrara, Ferrara, Italy
| | - Andrea Amerio
- Health Research Institute Hospital 12 de Octubre (imas12), Madrid, Spain
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Laura Fusar-Poli
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
| | - Anna Pichiecchio
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
- Advanced Imaging and Artificial Intelligence Center, Department of Neuroradiology, IRCCS Mondino Foundation, Pavia, Italy
| | - Carlo Asteggiano
- Advanced Imaging and Artificial Intelligence Center, Department of Neuroradiology, IRCCS Mondino Foundation, Pavia, Italy
| | - Marco Menchetti
- Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy
| | - Diana De Ronchi
- Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy
| | - Giuseppe Fanelli
- Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy
- Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands
| | - Alessandro Serretti
- Department of Medicine and Surgery, Kore University of Enna, Italy
- Oasi Research Institute-IRCCS, Troina, Italy
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24
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Myasoedova E, Sattui SE, Lee J, O'Brien JT, Makris UE. Cognitive impairment in individuals with rheumatic diseases: the role of systemic inflammation, immunomodulatory medications, and comorbidities. THE LANCET. RHEUMATOLOGY 2024; 6:e871-e880. [PMID: 39542002 PMCID: PMC11827066 DOI: 10.1016/s2665-9913(24)00190-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 05/07/2024] [Accepted: 06/26/2024] [Indexed: 11/17/2024]
Abstract
Inflammation is an important risk factor, a potential therapeutic target for cognitive decline and dementia, and an inherent feature of autoimmune and immune-mediated rheumatic diseases. The risk of cognitive impairment and dementia is increased in individuals with immune-mediated rheumatic diseases, particularly in those with cardiovascular risk factors and cardiovascular disease. Immunomodulatory medications have been associated with a reduced risk of dementia, but whether this effect is mediated through their anti-inflammatory immunomodulating properties or other mechanisms, such as cardiovascular risk reduction, is unclear. A better understanding of the role of chronic inflammation as a modifiable risk factor for cognitive performance in rheumatic diseases will help inform opportunities for the management of cognitive impairment in people with rheumatic diseases and other chronic inflammatory diseases. In this Series paper, we discuss the epidemiology, risk factors, and current evidence on the role of immunomodulatory medications in cognitive impairment and dementia in people with rheumatic diseases.
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Affiliation(s)
- Elena Myasoedova
- Division of Rheumatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA; Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
| | - Sebastian E Sattui
- Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Jiha Lee
- Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - John T O'Brien
- Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge, UK; Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK
| | - Una E Makris
- Division of Rheumatic Diseases, Department of Medicine, UT Southwestern Medical Center, Dallas, TX, USA; Rheumatology Section, Veterans Affairs North Texas Health Care System, Dallas, TX, USA
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25
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Buehring B, van Onna M, Myasoedova E, Lee J, Makris UE. Understanding the multiple dimensions of ageing: 5Ms for the rheumatologist. THE LANCET. RHEUMATOLOGY 2024; 6:e892-e902. [PMID: 39542005 PMCID: PMC11831986 DOI: 10.1016/s2665-9913(24)00230-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 07/10/2024] [Accepted: 07/24/2024] [Indexed: 11/17/2024]
Abstract
The global population is ageing and the rheumatology workforce should be prepared to take care of the inevitable complexities of ageing patients. We can learn from our colleagues and experts in geriatrics about how best to manage multimorbidity, polypharmacy, geriatric syndromes, and shifting priorities of older patients in the context of delivering care for rheumatic diseases. One approach to learning and adopting key ageing constructs within rheumatology practice is to incorporate the established Geriatric 5Ms-principles fundamental to caring for older adults. In this Series paper we discuss the 5Ms in the context of rheumatology practice (1) multicomplexity: assessing and managing multimorbidity and challenging biopsychosocial situations, (2) medications: ensuring that medications do not interfere with the other Ms, (3) mind: managing neurocognitive disorders and comorbid mental health conditions, (4) mobility: ensuring older adults can move independently and safely, and (5) what matters most: aligning care with an older adult's specific goals.
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Affiliation(s)
- Bjoern Buehring
- Bergisches Rheuma-Zentrum, Krankenhaus St Josef, Wuppertal, Germany; Rheumazentrum Ruhrgebiet, Ruhr-University Bochum, Bochum, Germany
| | - Marloes van Onna
- Department of Medicine, Division of Rheumatology, Maastricht University Medical Center, Maastricht, Netherlands; School for Public Health and Primary Care, Maastricht University, Maastricht, Netherlands
| | - Elena Myasoedova
- Division of Rheumatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA; Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| | - Jiha Lee
- Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Una E Makris
- Division of Rheumatic Diseases, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA; Division of Rheumatology, Dallas Veterans Affairs Medical Center, Veterans Affairs North Texas Health Care System, Dallas, TX, USA.
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26
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Chen Q, Zhao W, Zhang Q, Li S, Zhao J, Chen W, Xia M, Liu Y. Association of Life's Essential 8 With Incident Cardiovascular Disease Among Individuals With Depression: A Prospective Study. Can J Cardiol 2024; 40:2640-2648. [PMID: 39216657 DOI: 10.1016/j.cjca.2024.08.280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 08/14/2024] [Accepted: 08/25/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND Depression is an increasing illness worldwide that severely diminishes the quality of life. In this study we sought to elucidate the association of the American Heart Association's Life's Essential 8 (LE8) metrics with the incidence of cardiovascular disease (CVD) among depression participants and further quantify the related theoretical reduction of long-term CVD burden. METHODS We included 20,832 participants with depression from the UK Biobank. LE8, including diet quality, physical activity, nicotine exposure, sleep duration, body mass index, lipids, glucose, and blood pressure, was calculated at baseline and categorized into low, medium, and high levels. Hazard ratios (HRs) and 95% confidence interval (CI) for major cardiovascular events (MACE) were calculated using Cox models. We further quantified the population-attributable fraction (PAF) for CVD. RESULTS During a median follow-up of 12.0 years, 658 MACE were recorded. After multi-variable adjustment, compared with participants with low LE8, people with high LE8 had a decreased risk of MACE (HR, 0.32; 95% CI, 0.22-0.47), non-fatal MACE (HR, 0.39, 0.26-0.61), myocardial infarction (HR, 0.23, 0.12-0.44), and ischemic stroke (HR, 0.52, 0.27-0.99). Overall 50.7% (95% CI, 34.5%-66.9%) of MACE and 48.0% (95% CI, 29.5%-66.4%) of nonfatal MACE were attributable to the low and medium adherence to LE8 at the 5-year follow-up, respectively. Suboptimal control of blood pressure ranked as the top contributor to all types of CVD in individuals with depression. CONCLUSIONS Optimal adherence to LE8 was associated with lower burden of CVD in those with depression. Adopting a comprehensive lifestyle intervention might help further reduce CVD burden in those with mental disorders.
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Affiliation(s)
- Qian Chen
- Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangdong, China
| | - Wanying Zhao
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, and Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangdong, China
| | - Qi Zhang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, and Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangdong, China
| | - Siqi Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, and Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangdong, China
| | - Jiaqi Zhao
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, and Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangdong, China
| | - Wanlan Chen
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, and Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangdong, China
| | - Min Xia
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, and Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangdong, China
| | - Yan Liu
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, and Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangdong, China.
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27
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Flinkenflügel K, Meinert S, Hirtsiefer C, Grotegerd D, Gruber M, Goltermann J, Winter NR, Stein F, Brosch K, Leehr EJ, Böhnlein J, Dohm K, Bauer J, Redlich R, Hahn T, Repple J, Opel N, Nitsch R, Jamalabadi H, Straube B, Alexander N, Jansen A, Nenadić I, van den Heuvel MP, Kircher T, Dannlowski U. Associations between white matter microstructure and cognitive decline in major depressive disorder versus controls in Germany: a prospective case-control cohort study. Lancet Psychiatry 2024; 11:899-909. [PMID: 39419563 DOI: 10.1016/s2215-0366(24)00291-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 08/18/2024] [Accepted: 09/04/2024] [Indexed: 10/19/2024]
Abstract
BACKGROUND Cognitive deficits are a key source of disability in individuals with major depressive disorder (MDD) and worsen with disease progression. Despite their clinical relevance, the underlying mechanisms of cognitive deficits remain poorly elucidated, hampering effective treatment strategies. Emerging evidence suggests that alterations in white matter microstructure might contribute to cognitive dysfunction in MDD. We aimed to investigate the complex association between changes in white matter integrity, cognitive decline, and disease course in MDD in a comprehensive longitudinal dataset. METHODS In the naturalistic, observational, prospective, case-control Marburg-Münster Affective Disorders Cohort Study, individuals aged 18-65 years and of Caucasian ancestry were recruited from local psychiatric hospitals in Münster and Marburg, Germany, and newspaper advertisements. Individuals diagnosed with MDD and individuals without any history of psychiatric disorder (ie, healthy controls) were included in this subsample analysis. Participants had diffusion-weighted imaging, a battery of neuropsychological tests, and detailed clinical data collected at baseline and at 2 years of follow-up. We used linear mixed-effect models to compare changes in cognitive performance and white matter integrity between participants with MDD and healthy controls. Diffusion-weighted imaging analyses were conducted using tract-based spatial statistics. To correct for multiple comparisons, threshold free cluster enhancement (TFCE) was used to correct α-values at the family-wise error rate (FWE; ptfce-FWE). Effect sizes were estimated by conditional, partial R2 values (sr2) following the Nakagawa and Schielzeth method to quantify explained variance. The association between changes in cognitive performance and changes in white matter integrity was analysed. Finally, we examined whether the depressive disease course between assessments predicted cognitive performance at follow-up and whether white matter integrity mediated this association. People with lived experience were not involved in the research and writing process. FINDINGS 881 participants were selected for our study, of whom 418 (47%) had MDD (mean age 36·8 years [SD 13·4], 274 [66%] were female, and 144 [34%] were male) and 463 (53%) were healthy controls (mean age 35·6 years [13·5], 295 [64%] were female, and 168 [36%] were male). Baseline assessments were done between Sept 11, 2014, and June 3, 2019, and after a mean follow-up of 2·20 years (SD 0·19), follow-up assessments were done between Oct 6, 2016, and May 31, 2021. Participants with MDD had lower cognitive performance than did healthy controls (p<0·0001, sr2=0·056), regardless of timepoint. Analyses of diffusion-weighted imaging indicated a significant diagnosis × time interaction with a steeper decline in white matter integrity of the superior longitudinal fasciculus over time in participants with MDD than in healthy controls (ptfce-FWE=0·026, sr2=0·002). Furthermore, cognitive decline was robustly associated with the decline in white matter integrity over time across both groups (ptfce-FWE<0·0001, sr2=0·004). In participants with MDD, changes in white matter integrity (p=0·0040, β=0·071) and adverse depressive disease course (p=0·0022, β=-0·073) independently predicted lower cognitive performance at follow-up. INTERPRETATION Alterations of white matter integrity occurred over time to a greater extent in participants with MDD than in healthy controls, and decline in white matter integrity was associated with a decline in cognitive performance across groups. Our findings emphasise the crucial role of white matter microstructure and disease progression in depression-related cognitive dysfunction, making both priority targets for future treatment development. FUNDING German Research Foundation (DFG).
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Affiliation(s)
- Kira Flinkenflügel
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
| | - Susanne Meinert
- Institute for Translational Psychiatry, University of Münster, Münster, Germany; Institute for Translational Neuroscience, University of Münster, Münster, Germany.
| | | | - Dominik Grotegerd
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
| | - Marius Gruber
- Institute for Translational Psychiatry, University of Münster, Münster, Germany; Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe University, Frankfurt, Germany
| | - Janik Goltermann
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
| | - Nils R Winter
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
| | - Frederike Stein
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
| | - Katharina Brosch
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany; Institute of Behavioral Science, Feinstein Institutes for Medical Research, Manhasset, NY, USA
| | - Elisabeth J Leehr
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
| | - Joscha Böhnlein
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
| | - Katharina Dohm
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
| | - Jochen Bauer
- Department of Radiology, University of Münster, Münster, Germany
| | - Ronny Redlich
- Institute for Translational Psychiatry, University of Münster, Münster, Germany; Department of Psychology, University of Halle, Halle, Germany; German Center for Mental Health (DZPG), Halle-Jena-Magdeburg, Germany
| | - Tim Hahn
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
| | - Jonathan Repple
- Institute for Translational Psychiatry, University of Münster, Münster, Germany; Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe University, Frankfurt, Germany
| | - Nils Opel
- Institute for Translational Psychiatry, University of Münster, Münster, Germany; German Center for Mental Health (DZPG), Halle-Jena-Magdeburg, Germany; Department of Psychiatry, Jena University Hospital/Friedrich-Schiller-University Jena, Jena, Germany
| | - Robert Nitsch
- Institute for Translational Neuroscience, University of Münster, Münster, Germany
| | - Hamidreza Jamalabadi
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany; Center for Mind, Brain and Behavior, University of Marburg, Marburg, Germany
| | - Benjamin Straube
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany; Center for Mind, Brain and Behavior, University of Marburg, Marburg, Germany
| | - Nina Alexander
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany; Center for Mind, Brain and Behavior, University of Marburg, Marburg, Germany
| | - Andreas Jansen
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany; Center for Mind, Brain and Behavior, University of Marburg, Marburg, Germany; Core-Facility Brainimaging, Faculty of Medicine, University of Marburg, Marburg, Germany
| | - Igor Nenadić
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany; Center for Mind, Brain and Behavior, University of Marburg, Marburg, Germany
| | - Martijn P van den Heuvel
- Connectome Laboratory, Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, Netherlands; Department of Child Psychiatry, Amsterdam University Medical Center, Amsterdam Neuroscience, Amsterdam, Netherlands
| | - Tilo Kircher
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany; Center for Mind, Brain and Behavior, University of Marburg, Marburg, Germany
| | - Udo Dannlowski
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
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Myklebost SB, Heltne A, Hammar Å, Nordgreen T. Efficacy of an internet-delivered cognitive enhancement intervention for subjective residual cognitive deficits in remitted major depressive disorder: A randomized crossover trial. J Affect Disord 2024; 364:87-95. [PMID: 39142571 DOI: 10.1016/j.jad.2024.08.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 06/28/2024] [Accepted: 08/11/2024] [Indexed: 08/16/2024]
Abstract
BACKGROUND Cognitive deficits such as difficulties with attention, memory, and executive functions are frequently reported during remission from depression and relates to adverse functioning in daily life and risk of relapse. There is therefore a need for interventions targeting cognitive deficits after depression. However, few randomized controlled trials have investigated the efficacy of interventions targeting subjective residual cognitive deficits in adults remitted from depression. METHODS This randomized crossover trial aimed to investigate the efficacy of an internet-delivered cognitive enhancement intervention on subjective residual cognitive deficits. Forty-four formerly depressed adults (89 % female;mean age = 39 years) were included. Twenty-three participants received the intervention, and 21 participants were assigned to a waitlist control group. The waitlist control group received the intervention after seven weeks. Analyses of follow-up assessment after six months were conducted for the combined sample. RESULTS Significant differences were found between the intervention and waitlist control group in subjective cognitive functioning (d = 1.83) and rumination (d = 1.65). There was a difference in symptoms of depression between the groups (d = 1.22), whereas symptoms of depression increased in the waitlist control, but not in the intervention group. Fewer participants in the waitlist control group (43 %), compared to the intervention group (78 %) showed reliable improvement in self-reported cognitive deficits after receiving the intervention. LIMITATIONS Findings should be interpreted with caution due to the small sample, and lack of an active control group. CONCLUSIONS Internet-delivered cognitive enhancement interventions may improve subjective cognitive deficits. Waiting time to receive cognitive enhancement interventions may worsen symptoms and treatment response.
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Affiliation(s)
- Sunniva Brurok Myklebost
- Division of Psychiatry, Haukeland University Hospital, Bergen, Norway; Department of Biological and Medical Psychology, Faculty of Psychology, University of Bergen, Norway.
| | - Aleksander Heltne
- Division of Psychiatry, Haukeland University Hospital, Bergen, Norway
| | - Åsa Hammar
- Department of Biological and Medical Psychology, Faculty of Psychology, University of Bergen, Norway; Department of Clinical Sciences Lund, Psychiatry, Faculty of Medicine, Lund University, Lund, Sweden; Office for Psychiatry and Habilitation, Psychiatry Research Skåne, Region Skåne, Sweden
| | - Tine Nordgreen
- Division of Psychiatry, Haukeland University Hospital, Bergen, Norway; Department of Global Public Health and Primary Care, Faculty of Medicine, University of Bergen, Norway
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Wang M, Chen WT, Wang HT, Liu BS, Ju YM, Dong QL, Lu XW, Sun JR, Zhang L, Guo H, Zhao FT, Li WH, Zhang L, Li ZX, Liao M, Zhang Y, Liu J, Li LJ. Sleep disturbances and psychomotor retardation in the prediction of cognitive impairments in patients with major depressive disorder. World J Psychiatry 2024; 14:1474-1483. [DOI: 10.5498/wjp.v14.i10.1474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 08/26/2024] [Accepted: 09/25/2024] [Indexed: 10/17/2024] Open
Abstract
BACKGROUND Symptoms of depression and comorbid anxiety are known risk factors for cognitive impairment in major depressive disorder (MDD). Understanding their relationships is crucial for developing targeted interventions to mitigate cognitive impairments in MDD patients. We expect that the severity of sleep disturbances and other depressive symptoms will be positively correlated with the degree of cognitive impairments. We also hypothesize that anxiety symptoms, especially psychic anxiety, is a key factor in predicting cognitive performance in MDD patients and may indirectly contribute to cognitive impairment by affecting sleep disturbances and other potential factors.
AIM To determine which dimension of the depressive and anxiety symptoms predicts cognitive impairment during a depressive episode.
METHODS A comprehensive neurocognitive test battery assessed executive function, attention, processing speed, and memory in 162 medication-free MDD patients and 142 matched healthy controls. The 24-item Hamilton Depression Rating Scale was used to assess depressive symptoms, and the 14-item Hamilton Anxiety Scale was used to assess anxiety symptoms. Linear regression analyses and mediation analyses were conducted to evaluate the impact of depressive and anxiety symptoms, as well as their interactions, on cognitive impairments.
RESULTS Among the depressive symptoms, sleep disturbances were associated with poorer executive function (P = 0.004), lower processing speed (P = 0.047), and memory impairments (P < 0.001), and psychomotor retardation (PR) was associated with lower processing speed in patients with MDD (P = 0.019). Notably, PR was found to mediate the impact of sleep disturbances on the processing speed. Regarding anxiety symptoms, psychic anxiety, rather than somatic anxiety, was associated with cognitive impairments in all aspects. Sleep disturbances mediated the effect of psychic anxiety on executive function [β = -0.013, BC CI (-0.027, -0.001)] and memory [β = -0.149, BC CI (-0.237, -0.063)], while PR mediated its effect on processing speed (β = -0.023, BC CI (-0.045, -0.004)].
CONCLUSION Sleep disturbances may be a key predictor of poorer executive function, lower processing speed, and memory loss, while PR is crucial for lower processing speed during a depressive episode. Psychic anxiety contributes to all aspects of cognitive impairments, mediated by sleep disturbances and PR.
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Affiliation(s)
- Mi Wang
- Department of Mental Health Center, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
- National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Wen-Tao Chen
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Hao-Ting Wang
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Bang-Shan Liu
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Yu-Meng Ju
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Qiang-Li Dong
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Xiao-Wen Lu
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Jin-Rong Sun
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Liang Zhang
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Hua Guo
- Department of Psychiatry, Zhumadian Psychiatric Hospital, Zhumadian 463000, Henan Province, China
| | - Fu-Tao Zhao
- Department of Psychiatry, Zhumadian Psychiatric Hospital, Zhumadian 463000, Henan Province, China
| | - Wei-Hui Li
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Li Zhang
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Ze-Xuan Li
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Mei Liao
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Yan Zhang
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Jin Liu
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Ling-Jiang Li
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
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Flinkenflügel K, Gruber M, Meinert S, Thiel K, Winter A, Goltermann J, Usemann P, Brosch K, Stein F, Thomas-Odenthal F, Wroblewski A, Pfarr JK, David FS, Beins EC, Grotegerd D, Hahn T, Leehr EJ, Dohm K, Bauer J, Forstner AJ, Nöthen MM, Jamalabadi H, Straube B, Alexander N, Jansen A, Witt SH, Rietschel M, Nenadić I, van den Heuvel MP, Kircher T, Repple J, Dannlowski U. The interplay between polygenic score for tumor necrosis factor-α, brain structural connectivity, and processing speed in major depression. Mol Psychiatry 2024; 29:3151-3159. [PMID: 38693319 PMCID: PMC11449800 DOI: 10.1038/s41380-024-02577-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 04/15/2024] [Accepted: 04/19/2024] [Indexed: 05/03/2024]
Abstract
Reduced processing speed is a core deficit in major depressive disorder (MDD) and has been linked to altered structural brain network connectivity. Ample evidence highlights the involvement of genetic-immunological processes in MDD and specific depressive symptoms. Here, we extended these findings by examining associations between polygenic scores for tumor necrosis factor-α blood levels (TNF-α PGS), structural brain connectivity, and processing speed in a large sample of MDD patients. Processing speed performance of n = 284 acutely depressed, n = 177 partially and n = 198 fully remitted patients, and n = 743 healthy controls (HC) was estimated based on five neuropsychological tests. Network-based statistic was used to identify a brain network associated with processing speed. We employed general linear models to examine the association between TNF-α PGS and processing speed. We investigated whether network connectivity mediates the association between TNF-α PGS and processing speed. We identified a structural network positively associated with processing speed in the whole sample. We observed a significant negative association between TNF-α PGS and processing speed in acutely depressed patients, whereas no association was found in remitted patients and HC. The mediation analysis revealed that brain connectivity partially mediated the association between TNF-α PGS and processing speed in acute MDD. The present study provides evidence that TNF-α PGS is associated with decreased processing speed exclusively in patients with acute depression. This association was partially mediated by structural brain connectivity. Using multimodal data, the current findings advance our understanding of cognitive dysfunction in MDD and highlight the involvement of genetic-immunological processes in its pathomechanisms.
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Grants
- WI 3439/3-1, WI 3439/3-2 Deutsche Forschungsgemeinschaft (German Research Foundation)
- RI 908/11-1, RI 908/11-2 Deutsche Forschungsgemeinschaft (German Research Foundation)
- JA 1890/7-1, JA 1890/7-2 Deutsche Forschungsgemeinschaft (German Research Foundation)
- EP-C-16-015 EPA
- DA1151/5-1, DA1151/5-2, DA1151/11‑1 DA1151/6-1 Deutsche Forschungsgemeinschaft (German Research Foundation)
- NO 246/10-1, NO 246/10-2 Deutsche Forschungsgemeinschaft (German Research Foundation)
- HA7070/2-2, HA7070/3, HA7070/4 Deutsche Forschungsgemeinschaft (German Research Foundation)
- STR 1146/18-1 Deutsche Forschungsgemeinschaft (German Research Foundation)
- ERC-COG 101001062, VIDI-452-16-015 Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)
- KI 588/14-1, KI 588/14-2, KI 588/22-1 Deutsche Forschungsgemeinschaft (German Research Foundation)
- Interdisziplinäres Zentrum für Klinische Forschung, medizinische Fakultät, Münster (Dan3/012/17)
- Innovative medizinische Forschung Münster (IMF): RE111604, RE111722, RE 221707
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Affiliation(s)
- Kira Flinkenflügel
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
| | - Marius Gruber
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
- Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe University, Frankfurt, Germany
| | - Susanne Meinert
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
- Institute for Translational Neuroscience, University of Münster, Münster, Germany
| | - Katharina Thiel
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
| | - Alexandra Winter
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
| | - Janik Goltermann
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
| | - Paula Usemann
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
- Center for Mind, Brain and Behavior (CMBB), University of Marburg, Marburg, Germany
| | - Katharina Brosch
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
- Center for Mind, Brain and Behavior (CMBB), University of Marburg, Marburg, Germany
| | - Frederike Stein
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
- Center for Mind, Brain and Behavior (CMBB), University of Marburg, Marburg, Germany
| | - Florian Thomas-Odenthal
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
- Center for Mind, Brain and Behavior (CMBB), University of Marburg, Marburg, Germany
| | - Adrian Wroblewski
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
- Center for Mind, Brain and Behavior (CMBB), University of Marburg, Marburg, Germany
| | - Julia-Katharina Pfarr
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
- Center for Mind, Brain and Behavior (CMBB), University of Marburg, Marburg, Germany
| | - Friederike S David
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany
| | - Eva C Beins
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany
| | - Dominik Grotegerd
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
| | - Tim Hahn
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
| | - Elisabeth J Leehr
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
| | - Katharina Dohm
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
| | - Jochen Bauer
- Department of Radiology, University of Münster, Münster, Germany
| | - Andreas J Forstner
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany
- Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, Jülich, Germany
- Center for Human Genetics, University of Marburg, Marburg, Germany
| | - Markus M Nöthen
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany
| | - Hamidreza Jamalabadi
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
- Center for Mind, Brain and Behavior (CMBB), University of Marburg, Marburg, Germany
| | - Benjamin Straube
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
- Center for Mind, Brain and Behavior (CMBB), University of Marburg, Marburg, Germany
| | - Nina Alexander
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
- Center for Mind, Brain and Behavior (CMBB), University of Marburg, Marburg, Germany
| | - Andreas Jansen
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
- Center for Mind, Brain and Behavior (CMBB), University of Marburg, Marburg, Germany
- Core-Facility Brainimaging, Faculty of Medicine, University of Marburg, Marburg, Germany
| | - Stephanie H Witt
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany
| | - Marcella Rietschel
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany
| | - Igor Nenadić
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
- Center for Mind, Brain and Behavior (CMBB), University of Marburg, Marburg, Germany
| | - Martijn P van den Heuvel
- Connectome Lab, Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands
- Department of Child Psychiatry, Amsterdam University Medical Center, Amsterdam Neuroscience, Amsterdam, The Netherlands
| | - Tilo Kircher
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
- Center for Mind, Brain and Behavior (CMBB), University of Marburg, Marburg, Germany
| | - Jonathan Repple
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
- Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe University, Frankfurt, Germany
| | - Udo Dannlowski
- Institute for Translational Psychiatry, University of Münster, Münster, Germany.
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Wang P, Wang WW, Liu YQ, Li WQ, Hu JX, Su YA, Li JT, Li N, Si TM. The dose-response relationship of vortioxetine on major depressive disorder: an umbrella review. Psychiatry Res 2024; 340:116118. [PMID: 39121757 DOI: 10.1016/j.psychres.2024.116118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 07/25/2024] [Accepted: 07/30/2024] [Indexed: 08/12/2024]
Abstract
Vortioxetine is a novel multimodal antidepressant, but its precise efficacy and dose-response relationship for treating different symptoms in major depressive disorder (MDD) is still unclear. This umbrella review aims to assess the effectiveness, tolerability, and dose-response relationship of vortioxetine across a comprehensive range of clinical features in adults with MDD, including cognition, depression, anxiety, quality of life, and side effects. We meticulously searched eight electronic databases and included systematic reviews (SRs) and meta-analyses (MAs) of vortioxetine. The methodological quality of each included SR was independently assessed using the AMSTAR2 tool. To evaluate the credibility of the evidence, we utilized the GRADE framework and the Ioannidis criteria. In total, 35 SRs with 278 MAs met the inclusion criteria and based on these studies we performed 56 MAs of interest. While vortioxetine has been consistently shown to have positive effects on various domains, the evidence regarding cognitive performance and depression symptoms is notably robust compared to placebo, despite of relatively overall low quality of evidence. Finally, a dose-response relationship was observed across all categories within the treatment range of 5-20 mg/d and a dosage of vortioxetine 20 mg/d is recommended for adult MDD patients to achieve full functional recovery.
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Affiliation(s)
- Ping Wang
- Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China; Department of Neurology and Psychiatry, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
| | - Wei-Wei Wang
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing 100088, China; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, China; Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing 100191, China
| | - Yi-Qi Liu
- Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China
| | - Wen-Qiang Li
- Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing 100191, China; Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
| | - Jian-Xin Hu
- Institute of Medical Technology, Peking University Health Science Center, Beijing 100191, China
| | - Yun-Ai Su
- Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China
| | - Ji-Tao Li
- Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China.
| | - Nan Li
- Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing 100191, China; Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China.
| | - Tian-Mei Si
- Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China.
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32
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Liu L, Hu Y, Shan Q, Li P, Ma T, Wang Y. VGLUT2 may improve cognitive function in depressed rats by protecting prefrontal cortex neurons. Front Behav Neurosci 2024; 18:1453161. [PMID: 39301432 PMCID: PMC11410701 DOI: 10.3389/fnbeh.2024.1453161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 08/28/2024] [Indexed: 09/22/2024] Open
Abstract
Objective Depression may be accompanied by cognitive impairment, but its pathogenesis remains unclear. This study aims to investigate the protective effects of fluoxetine on behavioral performance and prefrontal cortex neuronal damage in rats with depression-associated cognitive impairment, based on the observation of VGLUT2 protein expression. Methods Forty-five SPF-grade male SD rats were randomly divided into three groups (n = 15): normal control group (CON), depression group (DD), and fluoxetine group (DD + F). The CON group was reared normally, while the DD and DD + F groups underwent chronic unpredictable mild stress (CUMS) combined with social isolation to induce a depression-related cognitive dysfunction model. After modeling, the DD + F group was treated with fluoxetine (10 mg/kg, ig) for 14 days. Behavioral tests were performed to assess changes in mood, cognition, learning, and social abilities. Histopathological observations were made to examine pathological changes, neuronal apoptosis, ultrastructure, and dendritic spine density in the prefrontal cortex. The concentration, relative expression level, and mRNA expression of VGLUT2 protein were also measured. Finally, a correlation analysis was performed between the relative expression level and mRNA expression of VGLUT2 protein and the pathological changes in neurons. Results Compared to the CON group, the DD group exhibited decreased body weight, anhedonia, increased behavioral despair, reduced locomotor activity and spontaneous exploratory behavior, impaired spatial learning and memory, and decreased social interaction and social cognitive ability. Pathological damage was observed in the prefrontal cortex, with neuronal apoptosis, ultrastructural damage, and reduced neuroplasticity. The concentration, relative expression, and mRNA expression levels of VGLUT2 protein were decreased. Following fluoxetine intervention, the above behavioral phenotypes improved; pathological damage showed varying degrees of recovery; and the concentration, relative expression, and mRNA expression levels of VGLUT2 protein increased. Finally, there was a significant correlation between VGLUT2 protein expression and pathological changes in the prefrontal cortex. Conclusion After 28 days of CUMS combined with isolation rearing, rats exhibited impairments in mood, cognition, learning, and social abilities, with neuronal damage and decreased VGLUT2 protein levels in the prefrontal cortex. Following fluoxetine intervention, VGLUT2 protein expression increased, neuronal repair in the prefrontal cortex occurred, depressive-like behavior improved, and cognitive learning and social abilities were restored.
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Affiliation(s)
- Longfei Liu
- College of Clinical Medicine, Guizhou Medical University, Guiyang, China
- Department of Psychiatry, Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Yongxue Hu
- Department of Psychiatry, Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Qing Shan
- College of Clinical Medicine, Guizhou Medical University, Guiyang, China
- Department of Psychiatry, Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Peifan Li
- Department of Psychiatry, Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Tianpei Ma
- College of Clinical Medicine, Guizhou Medical University, Guiyang, China
- Department of Psychiatry, Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Yiming Wang
- College of Clinical Medicine, Guizhou Medical University, Guiyang, China
- Department of Psychiatry, Affiliated Hospital of Guizhou Medical University, Guiyang, China
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Liu M, Wang L, Zhang Y, Dong H, Wang C, Chen Y, Qian Q, Zhang N, Wang S, Zhao G, Zhang Z, Lei M, Wang S, Zhao Q, Liu F. Investigating the shared genetic architecture between depression and subcortical volumes. Nat Commun 2024; 15:7647. [PMID: 39223129 PMCID: PMC11368965 DOI: 10.1038/s41467-024-52121-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Accepted: 08/27/2024] [Indexed: 09/04/2024] Open
Abstract
Depression, a widespread and highly heritable mental health condition, profoundly affects millions of individuals worldwide. Neuroimaging studies have consistently revealed volumetric abnormalities in subcortical structures associated with depression. However, the genetic underpinnings shared between depression and subcortical volumes remain inadequately understood. Here, we investigate the extent of polygenic overlap using the bivariate causal mixture model (MiXeR), leveraging summary statistics from the largest genome-wide association studies for depression (N = 674,452) and 14 subcortical volumetric phenotypes (N = 33,224). Additionally, we identify shared genomic loci through conditional/conjunctional FDR analyses. MiXeR shows that subcortical volumetric traits share a substantial proportion of genetic variants with depression, with 44 distinct shared loci identified by subsequent conjunctional FDR analysis. These shared loci are predominantly located in intronic regions (58.7%) and non-coding RNA intronic regions (25.4%). The 269 protein-coding genes mapped by these shared loci exhibit specific developmental trajectories, with the expression level of 55 genes linked to both depression and subcortical volumes, and 30 genes linked to cognitive abilities and behavioral symptoms. These findings highlight a shared genetic architecture between depression and subcortical volumetric phenotypes, enriching our understanding of the neurobiological underpinnings of depression.
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Affiliation(s)
- Mengge Liu
- Department of Radiology and Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin, China
| | - Lu Wang
- Department of Geriatrics and Tianjin Geriatrics Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Yujie Zhang
- Department of Radiology and Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin, China
| | - Haoyang Dong
- Department of Radiology and Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin, China
| | - Caihong Wang
- Department of Radiology and Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin, China
- Department of Magnetic Resonance Imaging, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yayuan Chen
- Department of Radiology and Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin, China
| | - Qian Qian
- Department of Radiology and Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin, China
| | - Nannan Zhang
- Department of Radiology and Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin, China
| | - Shaoying Wang
- Department of Radiology and Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin, China
| | - Guoshu Zhao
- Department of Radiology and Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin, China
| | - Zhihui Zhang
- Department of Radiology and Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin, China
| | - Minghuan Lei
- Department of Radiology and Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin, China
| | - Sijia Wang
- Department of Radiology and Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin, China.
| | - Qiyu Zhao
- Department of Radiology and Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin, China.
| | - Feng Liu
- Department of Radiology and Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin, China.
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Wu Y, Zhang H, Shen Q, Jiang X, Yuan X, Li M, Chen M, Zhou J, Cui J. Exploring the neurocognitive correlates of suicidal ideation in major depressive disorder: The role of frontoparietal and default mode networks. J Psychiatr Res 2024; 177:211-218. [PMID: 39032275 DOI: 10.1016/j.jpsychires.2024.07.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 06/20/2024] [Accepted: 07/09/2024] [Indexed: 07/23/2024]
Abstract
Suicidal ideation (SI) is a common symptom of major depressive disorder (MDD), often accompanied by cognitive alterations and emotional dysregulation. However, it is unclear whether cognitive dysfunction in patients with MDD is related to the presence or absence of SI and impaired connectivity within or between large-scale neurocognitive networks. Previous studies have shown that the frontoparietal network (FPN) and default mode network (DMN) are critical for cognitive control and emotional regulation. Participants were 51 MDD patients with suicidal ideation (MDDSI), 52 MDD patients without suicidal ideation (MDDNSI), and 55 healthy controls (HC). Using areas located within FPN and DMN networks as regions of interest (ROIs), we compared the cognitive performance of the three groups and the strength of the resting state functional connections (RSFC) within and between the FPN and DMN networks. Additionally, we examined the correlation between the strength of FC within the FPN and cognitive function in the SI group. Furthermore, network-based statistics (NBS) were used to correct for the strength of FPN and DMN functional connections. The study identified significant cognitive deficits in MDD patients. Reduced strength of FC was observed within the FPN and DMN networks in the SI group compared to the NSI group. In the SI group, the strength of FC within the FPN network was positively correlated with attention/vigilance. These insights underscore the critical roles of the FPN and DMN in the suicidal ideation, shedding light on the cognitively relevant neurobiological characteristics of MDDSI, providing new insights into the neural mechanisms of MDDSI. URL: https://www.chictr.org.cn/bin/project/edit?pid=131537. Registration number: ChiCTR2100049646.
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Affiliation(s)
- Yang Wu
- Department of Psychiatry, Jining Medical University, Jining, 272000, China
| | - Hongyong Zhang
- Medical Imaging Department, Shandong Daizhuang Hospital, Jining, 272000, China
| | - Qinge Shen
- Department of Psychiatry, Jining Medical University, Jining, 272000, China
| | - Xianfei Jiang
- Department of Psychiatry, Shandong Daizhuang Hospital, Jining, 272000, China
| | - Xiaochi Yuan
- Department of Equipment, Shandong Daizhuang Hospital, Jining, 272000, China
| | - Meng Li
- Precision Medicine Laboratory, Shandong Daizhuang Hospital, Jining, 272000, China
| | - Min Chen
- Department of Psychiatry, Shandong Daizhuang Hospital, Jining, 272000, China
| | - Jingjing Zhou
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital & the Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, 100088, China
| | - Jian Cui
- Department of Psychiatry, Shandong Daizhuang Hospital, Jining, 272000, China; Precision Medicine Laboratory, Shandong Daizhuang Hospital, Jining, 272000, China.
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Rakesh C, Sharma R, Singh C. Cognitive Dysfunction in Unipolar Depression. Indian J Psychol Med 2024:02537176241259683. [PMID: 39564278 PMCID: PMC11572421 DOI: 10.1177/02537176241259683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2024] Open
Abstract
Background Cognitive dysfunctions play a critical role in the psychopathology of depression. They regulate various psychosocial and functional outcomes and affect workplace functionality, productivity, and relapses. An objective evaluation of affected cognitive domains is germane in understanding the relapses and functional recovery in depression. Thus, to know cognitive dysfunctions beyond affective biases, this study was conducted to compare the cognitive functions of drug-naïve patients with unipolar depression with healthy matched controls. Methods Fifty patients diagnosed with unipolar depression as per the International Classification of Diseases, tenth revision: Diagnostic Criteria for Research (Depressive Episode and Recurrent Depressive Disorder) and 50 healthy controls were enrolled on an outpatient basis from January 2022 to June 2023. Cases were regrouped as mild, moderate, and severe based on Beck's Depression Inventory (BDI-II). A battery of tests assessed the cognitive functions: Wisconsin Card Sorting Test, Trail Making Test, Visual Retention subtests of PGI Battery of Brain Dysfunction, Digit Span, and Verbal Memory. The Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire was used for a subjective assessment of cognitive functioning. Results The sociodemographic characteristics of cases and controls did not differ significantly. However, within-group and between-group analyses revealed significantly lower performance of cases compared to controls. Cognitive impairment was positively correlated with BDI-II scores. Conclusion Depression is associated with dysfunction in the domains of planning, attention, sustained attention, and visual and verbal memory. This dysfunction is independent of cognitive and affective bias and may exist even after clinical remission.
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Affiliation(s)
- Rakesh C
- Sree Uthradom Thirunal Academy of Medical Sciences, Vencod, Kerala, India
| | - Rachit Sharma
- Dept., of Psychiatry, 155 Base Hospital, Tezpur, Assam, India
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36
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Carney RM, Freedland KE, Rich MW. Treating Depression to Improve Survival in Coronary Heart Disease: What Have We Learned? J Am Coll Cardiol 2024; 84:482-489. [PMID: 39048281 DOI: 10.1016/j.jacc.2024.05.038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 05/07/2024] [Accepted: 05/08/2024] [Indexed: 07/27/2024]
Abstract
Major depressive disorder is a well-established risk factor for cardiac events in patients with coronary heart disease, but clinical trials have produced little evidence that treating depression reliably improves cardiac event-free survival in these patients. In this review, we offer evidence that certain symptoms that commonly remain after otherwise successful treatment of depression-insomnia, fatigue, and anhedonia-independently predict cardiac events. This may help to explain the failure of previous depression treatment trials to improve cardiac event-free survival even when other symptoms of depression improve. We thus propose that adverse cardiovascular effects that have long been attributed to syndromal depression may be instead caused by persistent fatigue, insomnia, and anhedonia, regardless of whether other symptoms of depression are present. We also identify interventions for these symptoms and call for more research to evaluate their effectiveness in depressed patients with coronary heart disease.
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Affiliation(s)
- Robert M Carney
- Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri, USA.
| | - Kenneth E Freedland
- Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri, USA
| | - Michael W Rich
- Department of Medicine, Washington University School of Medicine, St Louis, Missouri, USA
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37
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Di Nicola M, Adair M, Rieckmann A, Christensen M C. Effectiveness of vortioxetine in elderly patients with major depressive disorder in real-world clinical practice: Results from the RELIEVE study. J Psychopharmacol 2024; 38:615-623. [PMID: 39077889 PMCID: PMC11290038 DOI: 10.1177/02698811241260996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/31/2024]
Abstract
BACKGROUND Data demonstrating the real-world, long-term effectiveness of vortioxetine in elderly patients with major depressive disorder (MDD) are clinically useful to confirm findings from randomized trials. METHODS RELIEVE was a multinational, 24-week, observational, prospective study in outpatients with MDD initiating vortioxetine treatment in routine care settings (NCT03555136). Here, we report data from a subgroup of 130 patients aged ⩾ 65 years. The primary study outcome was changed from baseline in patient functioning assessed using the Sheehan Disability Scale (SDS). Other clinical outcomes included depression severity (Patient Health Questionnaire-9 [PHQ-9] and Clinical Global Impressions-Severity [CGI-S]), cognitive performance (Digit Symbol Substitution Test [DSST]) and symptoms (Perceived Deficits Questionnaire - Depression-5 item [PDQ-D-5]), and health-related quality of life (HRQoL) (EuroQoL 5 Dimensions 5 Levels [EQ-5D-5L]). RESULTS Clinically meaningful and statistically significant improvements in patient functioning, depressive symptoms, cognitive function, and HRQoL were observed at week 24. Least squares mean SDS, PHQ-9, CGI-S, PDQ-D-5, DSST, and EQ-5D-5L scores improved from baseline by 6.5, 5.7, 1.2, 3.2, 4.4, and 0.11 points, respectively (p < 0.01 for all). Adverse events were observed in 23.1% of patients. CONCLUSIONS Consistent with previous clinical studies of vortioxetine, this study supports the effectiveness and safety of vortioxetine in treating elderly patients with MDD in a real-world setting over a 6-month period. Patients showed clinically relevant and sustained improvements in psychosocial functioning, depressive symptoms, and cognitive function after receiving vortioxetine, which was generally well tolerated. Main study limitations include the open-label study design and lack of a placebo or comparator group.
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Affiliation(s)
- M Di Nicola
- Department of Psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Department of Neuroscience, Section of Psychiatry, Università Cattolica del Sacro Cuore, Rome, Italy
| | - M Adair
- H. Lundbeck A/S, Valby, Denmark
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38
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Liu T, Wang YH, Ng ZLY, Zhang W, Wong SMY, Wong GHY, Lum TYS. Comparison of networks of loneliness, depressive symptoms, and anxiety symptoms in at-risk community-dwelling older adults before and during COVID-19. Sci Rep 2024; 14:14737. [PMID: 38926445 PMCID: PMC11208589 DOI: 10.1038/s41598-024-65533-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 06/20/2024] [Indexed: 06/28/2024] Open
Abstract
Network analysis provides an innovative approach to examining symptom-to-symptom interactions in mental health, and adverse external conditions may change the network structures. This study compared the networks of common risk factors and mental health problems (loneliness, depressive symptoms, and anxiety symptoms) in community-dwelling older people before and during COVID-19. Older adults (aged ≥ 60) at risk for depression were recruited through non-governmental organizations. Loneliness, depressive symptoms and anxiety symptoms were measured using the three-item Loneliness Scale (UCLA-3), nine-item Patient Health Questionnaire (PHQ-9), and seven-item Generalized Anxiety Disorder Scale (GAD-7), respectively. Data from 2549 (before) and 3506 (during COVID-19) respondents were included using propensity score matching. Being restless (GAD-7-item5) was most central, indicated by Expected Influence, in both pre and during COVID-19 networks despite low severity (mean score). The network during COVID-19 had higher global strength and edge variability than the pre-pandemic network, suggesting easier symptom spread and potentially more complex symptom presentation. In addition, feeling isolated from others (UCLA-3-item3) had stronger connections with feeling worthless/guilty (PHQ-9-item6) and anticipatory anxiety (GAD-7-item7) during COVID-19 than before. These findings may enhance our knowledge of the symptom structure of common mental health problems and the impacts of the pandemic. Targeting central symptoms may offer novel preventive strategies for older people.
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Affiliation(s)
- Tianyin Liu
- Department of Applied Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China.
| | - Yun-Han Wang
- Department of Social Work and Social Administration, The University of Hong Kong, Hong Kong, China
| | - Zuna Loong Yee Ng
- Department of Social Work and Social Administration, The University of Hong Kong, Hong Kong, China
| | - Wen Zhang
- School of Nursing and Health Studies, Hong Kong Metropolitan University, Hong Kong, China
| | - Stephanie Ming Yin Wong
- Department of Social Work and Social Administration, The University of Hong Kong, Hong Kong, China
| | - Gloria Hoi-Yan Wong
- Department of Social Work and Social Administration, The University of Hong Kong, Hong Kong, China
| | - Terry Yat-Sang Lum
- Department of Social Work and Social Administration, The University of Hong Kong, Hong Kong, China
- Sau Po Centre on Ageing, The University of Hong Kong, Hong Kong, China
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39
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Stolfi F, Abreu H, Sinella R, Nembrini S, Centonze S, Landra V, Brasso C, Cappellano G, Rocca P, Chiocchetti A. Omics approaches open new horizons in major depressive disorder: from biomarkers to precision medicine. Front Psychiatry 2024; 15:1422939. [PMID: 38938457 PMCID: PMC11210496 DOI: 10.3389/fpsyt.2024.1422939] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Accepted: 05/28/2024] [Indexed: 06/29/2024] Open
Abstract
Major depressive disorder (MDD) is a recurrent episodic mood disorder that represents the third leading cause of disability worldwide. In MDD, several factors can simultaneously contribute to its development, which complicates its diagnosis. According to practical guidelines, antidepressants are the first-line treatment for moderate to severe major depressive episodes. Traditional treatment strategies often follow a one-size-fits-all approach, resulting in suboptimal outcomes for many patients who fail to experience a response or recovery and develop the so-called "therapy-resistant depression". The high biological and clinical inter-variability within patients and the lack of robust biomarkers hinder the finding of specific therapeutic targets, contributing to the high treatment failure rates. In this frame, precision medicine, a paradigm that tailors medical interventions to individual characteristics, would help allocate the most adequate and effective treatment for each patient while minimizing its side effects. In particular, multi-omic studies may unveil the intricate interplays between genetic predispositions and exposure to environmental factors through the study of epigenomics, transcriptomics, proteomics, metabolomics, gut microbiomics, and immunomics. The integration of the flow of multi-omic information into molecular pathways may produce better outcomes than the current psychopharmacological approach, which targets singular molecular factors mainly related to the monoamine systems, disregarding the complex network of our organism. The concept of system biomedicine involves the integration and analysis of enormous datasets generated with different technologies, creating a "patient fingerprint", which defines the underlying biological mechanisms of every patient. This review, centered on precision medicine, explores the integration of multi-omic approaches as clinical tools for prediction in MDD at a single-patient level. It investigates how combining the existing technologies used for diagnostic, stratification, prognostic, and treatment-response biomarkers discovery with artificial intelligence can improve the assessment and treatment of MDD.
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Affiliation(s)
- Fabiola Stolfi
- Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, Italy
- Center for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, Italy
| | - Hugo Abreu
- Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, Italy
- Center for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, Italy
| | - Riccardo Sinella
- Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, Italy
- Center for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, Italy
| | - Sara Nembrini
- Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, Italy
- Center for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, Italy
| | - Sara Centonze
- Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, Italy
- Center for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, Italy
| | - Virginia Landra
- Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Turin, Italy
| | - Claudio Brasso
- Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Turin, Italy
| | - Giuseppe Cappellano
- Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, Italy
- Center for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, Italy
| | - Paola Rocca
- Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Turin, Italy
| | - Annalisa Chiocchetti
- Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, Italy
- Center for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, Italy
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40
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Jian YL, Jia S, Shi S, Shi Z, Zhao Y. A nomogram to predict the risk of cognitive impairment in patients with depressive disorder. Res Nurs Health 2024; 47:302-311. [PMID: 38149849 DOI: 10.1002/nur.22364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 12/03/2023] [Accepted: 12/13/2023] [Indexed: 12/28/2023]
Abstract
This study was to describe the cognitive function status in patients with depressive disorder and to construct a nomogram model to predict the risk factors of cognitive impairment in these patients. From October 2019 to February 2021, a total of 141 patients with depressive disorder completed the survey in two hospitals. The Montreal cognitive assessment (MoCA) was used with a cutoff score of 26 to differentiate cognitive impairment. Univariable and multivariable logistic regression analyses were conducted to identify independent risk factors. A nomogram was then constructed based on the results of the multivariable logistic regression analysis. The patients had an average MoCA score of 23.99 ± 3.02. The multivariable logistic regression analysis revealed that age (OR: 1.096, 95% CI: 1.042-1.153, p < 0.001), education (OR: 0.065, 95% CI: 0.016-0.263, p < 0.001), depression severity (OR: 1.878, 95% CI: 1.021-3.456, p = 0.043), and sleep quality (OR: 2.454, 95% CI: 1.400-4.301, p = 0.002) were independent risk factors for cognitive impairment in patients with depressive disorder. The area under receiver operating characteristic (ROC) curves was 0.868 (95% CI: 0.807-0.929), indicating good discriminability of the model. The calibration curve of the model and the Hosmer-Lemeshow test (p = 0.571) demonstrated a well-fitted model with high calibration. Age, education, depression severity, and sleep quality were found to be significant predictors of cognitive function. A nomogram model was developed to predict cognitive impairment in patients with depressive disorder, providing a solid foundation for clinical interventions.
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Affiliation(s)
| | - Shoumei Jia
- School of Nursing, Fudan University, Shanghai, China
| | - Shenxun Shi
- Department of Psychiatry, Fudan University Huashan Hospital, Shanghai, China
| | | | - Ying Zhao
- School of Nursing, Fudan University, Shanghai, China
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41
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Ayyash S, Davis AD, Alders GL, MacQueen G, Strother SC, Hassel S, Zamyadi M, Arnott SR, Harris JK, Lam RW, Milev R, Müller DJ, Kennedy SH, Rotzinger S, Frey BN, Minuzzi L, Hall GB. Assessing remission in major depressive disorder using a functional-structural data fusion pipeline: A CAN-BIND-1 study. IBRO Neurosci Rep 2024; 16:135-146. [PMID: 38293679 PMCID: PMC10826332 DOI: 10.1016/j.ibneur.2023.12.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Accepted: 12/30/2023] [Indexed: 02/01/2024] Open
Abstract
Neural network-level changes underlying symptom remission in major depressive disorder (MDD) are often studied from a single perspective. Multimodal approaches to assess neuropsychiatric disorders are evolving, as they offer richer information about brain networks. A FATCAT-awFC pipeline was developed to integrate a computationally intense data fusion method with a toolbox, to produce a faster and more intuitive pipeline for combining functional connectivity with structural connectivity (denoted as anatomically weighted functional connectivity (awFC)). Ninety-three participants from the Canadian Biomarker Integration Network for Depression study (CAN-BIND-1) were included. Patients with MDD were treated with 8 weeks of escitalopram and adjunctive aripiprazole for another 8 weeks. Between-group connectivity (SC, FC, awFC) comparisons contrasted remitters (REM) with non-remitters (NREM) at baseline and 8 weeks. Additionally, a longitudinal study analysis was performed to compare connectivity changes across time for REM, from baseline to week-8. Association between cognitive variables and connectivity were also assessed. REM were distinguished from NREM by lower awFC within the default mode, frontoparietal, and ventral attention networks. Compared to REM at baseline, REM at week-8 revealed increased awFC within the dorsal attention network and decreased awFC within the frontoparietal network. A medium effect size was observed for most results. AwFC in the frontoparietal network was associated with neurocognitive index and cognitive flexibility for the NREM group at week-8. In conclusion, the FATCAT-awFC pipeline has the benefit of providing insight on the 'full picture' of connectivity changes for REMs and NREMs while making for an easy intuitive approach.
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Affiliation(s)
- Sondos Ayyash
- School of Biomedical Engineering, McMaster University, Hamilton, Ontario, Canada
- Department of Psychology, Neuroscience & Behaviour, McMaster University, Hamilton, Ontario, Canada
| | - Andrew D Davis
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada
- Rotman Research Institute, Baycrest, Toronto, Ontario, Canada
| | - Gésine L Alders
- Neuroscience Graduate Program, McMaster University, Hamilton, Ontario, Canada
| | - Glenda MacQueen
- Hotchkiss Brain Institute and Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Stephen C Strother
- Rotman Research Institute, Baycrest, Toronto, Ontario, Canada
- Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
- Department of Medical Biophysics, University of Toronto, Ontario, Canada
| | - Stefanie Hassel
- Hotchkiss Brain Institute and Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Mojdeh Zamyadi
- Rotman Research Institute, Baycrest, Toronto, Ontario, Canada
| | | | - Jacqueline K Harris
- Department of Computer Science, University of Alberta, Edmonton, Alberta, Canada
| | - Raymond W Lam
- Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada
| | - Roumen Milev
- Departments of Psychiatry and Psychology, Queen's University, Providence Care Hospital, Kingston, Ontario, Canada
| | - Daniel J Müller
- Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
- Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
| | - Sidney H Kennedy
- Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
- Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
- Centre for Mental Health, University Health Network, Toronto, Ontario, Canada
- Krembil Research Institute, University Health Network, Toronto, Ontario, Canada
- Centre for Depression and Suicide Studies, and Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada
| | - Susan Rotzinger
- Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
- Krembil Research Institute, University Health Network, Toronto, Ontario, Canada
- Centre for Depression and Suicide Studies, and Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada
| | - Benicio N Frey
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada
- Neuroscience Graduate Program, McMaster University, Hamilton, Ontario, Canada
- Mood Disorders Treatment and Research Centre and Women's Health Concerns Clinic, St. Joseph's Healthcare, Hamilton, Ontario, Canada
| | - Luciano Minuzzi
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada
- Neuroscience Graduate Program, McMaster University, Hamilton, Ontario, Canada
- Mood Disorders Treatment and Research Centre and Women's Health Concerns Clinic, St. Joseph's Healthcare, Hamilton, Ontario, Canada
| | - Geoffrey B Hall
- School of Biomedical Engineering, McMaster University, Hamilton, Ontario, Canada
- Department of Psychology, Neuroscience & Behaviour, McMaster University, Hamilton, Ontario, Canada
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada
- Neuroscience Graduate Program, McMaster University, Hamilton, Ontario, Canada
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Haniff ZR, Bocharova M, Mantingh T, Rucker JJ, Velayudhan L, Taylor DM, Young AH, Aarsland D, Vernon AC, Thuret S. Psilocybin for dementia prevention? The potential role of psilocybin to alter mechanisms associated with major depression and neurodegenerative diseases. Pharmacol Ther 2024; 258:108641. [PMID: 38583670 PMCID: PMC11847495 DOI: 10.1016/j.pharmthera.2024.108641] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 03/28/2024] [Accepted: 04/02/2024] [Indexed: 04/09/2024]
Abstract
Major depression is an established risk factor for subsequent dementia, and depression in late life may also represent a prodromal state of dementia. Considering current challenges in the clinical development of disease modifying therapies for dementia, the focus of research is shifting towards prevention and modification of risk factors to alter the neurodegenerative disease trajectory. Understanding mechanistic commonalities underlying affective symptoms and cognitive decline may reveal biomarkers to aid early identification of those at risk of progressing to dementia during the preclinical phase of disease, thus allowing for timely intervention. Adult hippocampal neurogenesis (AHN) is a phenomenon that describes the birth of new neurons in the dentate gyrus throughout life and it is associated with spatial learning, memory and mood regulation. Microglia are innate immune system macrophages in the central nervous system that carefully regulate AHN via multiple mechanisms. Disruption in AHN is associated with both dementia and major depression and microgliosis is a hallmark of several neurodegenerative diseases. Emerging evidence suggests that psychedelics promote neuroplasticity, including neurogenesis, and may also be immunomodulatory. In this context, psilocybin, a serotonergic agonist with rapid-acting antidepressant properties has the potential to ameliorate intersecting pathophysiological processes relevant for both major depression and neurodegenerative diseases. In this narrative review, we focus on the evidence base for the effects of psilocybin on adult hippocampal neurogenesis and microglial form and function; which may suggest that psilocybin has the potential to modulate multiple mechanisms of action, and may have implications in altering the progression from major depression to dementia in those at risk.
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Affiliation(s)
- Zarah R Haniff
- Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom.
| | - Mariia Bocharova
- Department of Old Age Psychiatry, Division of Academic Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom
| | - Tim Mantingh
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom
| | - James J Rucker
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom; South London and Maudsley NHS Foundation Trust, Maudsley Hospital, Denmark Hill, London, United Kingdom
| | - Latha Velayudhan
- Department of Old Age Psychiatry, Division of Academic Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom
| | - David M Taylor
- South London and Maudsley NHS Foundation Trust, Maudsley Hospital, Denmark Hill, London, United Kingdom
| | - Allan H Young
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom; South London and Maudsley NHS Foundation Trust, Bethlem Royal Hospital, Monks Orchard Road, Beckenham, Kent, United Kingdom
| | - Dag Aarsland
- Department of Old Age Psychiatry, Division of Academic Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom; Wolfson Centre for Age Related Diseases, Division of Neuroscience of the Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom; Stavanger University Hospital, Stavanger, Norway
| | - Anthony C Vernon
- Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom; MRC Centre for Neurodevelopmental Disorders, King's College London, United Kingdom.
| | - Sandrine Thuret
- Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom.
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Zhou T, Zhao J, Ma Y, He L, Ren Z, Yang K, Tang J, Liu J, Luo J, Zhang H. Association of cognitive impairment with the interaction between chronic kidney disease and depression: findings from NHANES 2011-2014. BMC Psychiatry 2024; 24:312. [PMID: 38658863 PMCID: PMC11044494 DOI: 10.1186/s12888-024-05769-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Accepted: 04/16/2024] [Indexed: 04/26/2024] Open
Abstract
BACKGROUND Cognitive impairment (CoI), chronic kidney disease (CKD), and depression are prevalent among older adults and are interrelated, imposing a significant disease burden. This study evaluates the association of CKD and depression with CoI and explores their potential interactions. METHOD Data for this study were sourced from the 2011-2014 National Health and Nutritional Examination Survey (NHANES). Multiple binary logistic regression models assessed the relationship between CKD, depression, and CoI while controlling for confounders. The interactions were measured using the relative excess risk of interaction (RERI), the attributable proportion of interaction (AP), and the synergy index (S). RESULTS A total of 2,666 participants (weighted n = 49,251,515) were included in the study, of which 700 (16.00%) had CoI. After adjusting for confounding factors, the risk of CoI was higher in patients with CKD compared to non-CKD participants (odds ratio [OR] = 1.49, 95% confidence interval [CI]:1.12-1.99). The risk of CoI was significantly increased in patients with depression compared to those without (OR = 2.29, 95% CI: 1.73-3.03). Furthermore, there was a significant additive interaction between CKD and depression in terms of the increased risk of CoI (adjusted RERI = 2.01, [95% CI: 0.31-3.71], adjusted AP = 0.50 [95% CI: 0.25-0.75], adjusted S = 2.97 [95% CI: 1.27-6.92]). CONCLUSION CKD and depression synergistically affect CoI, particularly when moderate-to-severe depression co-occurs with CKD. Clinicians should be mindful of the combined impact on patients with CoI. Further research is needed to elucidate the underlying mechanisms and assess the effects specific to different CKD stages.
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Affiliation(s)
- Tong Zhou
- Department of Nephrology, Affiliated Hospital of North Sichuan Medical College, 1 Maoyuan Road, Nanchong city, Sichuan Province, 637000, China
| | - Jiayu Zhao
- Department of physician, Nanchong Psychosomatic Hospital, Nanchong, China
| | - Yimei Ma
- Department of Nephrology, Affiliated Hospital of North Sichuan Medical College, 1 Maoyuan Road, Nanchong city, Sichuan Province, 637000, China
| | - Linqian He
- Department of Nephrology, Affiliated Hospital of North Sichuan Medical College, 1 Maoyuan Road, Nanchong city, Sichuan Province, 637000, China
| | - Zhouting Ren
- Department of Nephrology, Affiliated Hospital of North Sichuan Medical College, 1 Maoyuan Road, Nanchong city, Sichuan Province, 637000, China
| | - Kun Yang
- Department of Nephrology, Affiliated Hospital of North Sichuan Medical College, 1 Maoyuan Road, Nanchong city, Sichuan Province, 637000, China
| | - Jincheng Tang
- Department of Nephrology, Affiliated Hospital of North Sichuan Medical College, 1 Maoyuan Road, Nanchong city, Sichuan Province, 637000, China
| | - Jiali Liu
- Department of Clinical Medicine, North Sichuan Medical University, Nanchong, China
| | - Jiaming Luo
- Mental Health Center, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
- School of Psychiatry, North Sichuan Medical College, Nanchong, China
| | - Heping Zhang
- Department of Nephrology, Affiliated Hospital of North Sichuan Medical College, 1 Maoyuan Road, Nanchong city, Sichuan Province, 637000, China.
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Soto NN, Gaspar P, Bacci A. Not Just a Mood Disorder─Is Depression a Neurodevelopmental, Cognitive Disorder? Focus on Prefronto-Thalamic Circuits. ACS Chem Neurosci 2024; 15:1611-1618. [PMID: 38580316 PMCID: PMC11027097 DOI: 10.1021/acschemneuro.3c00828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 02/26/2024] [Accepted: 02/27/2024] [Indexed: 04/07/2024] Open
Abstract
Depression is one of the most burdensome psychiatric disorders, affecting hundreds of millions of people worldwide. The disease is characterized not only by severe emotional and affective impairments, but also by disturbed vegetative and cognitive functions. Although many candidate mechanisms have been proposed to cause the disease, the pathophysiology of cognitive impairments in depression remains unclear. In this article, we aim to assess the link between cognitive alterations in depression and possible developmental changes in neuronal circuit wiring during critical periods of susceptibility. We review the existing literature and propose a role of serotonin signaling during development in shaping the functional states of prefrontal neuronal circuits and prefronto-thalamic loops. We discuss how early life insults affecting the serotonergic system could be important in the alterations of these local and long-range circuits, thus favoring the emergence of neurodevelopmental disorders, such as depression.
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Affiliation(s)
- Nina Nitzan Soto
- ICM−Paris
Brain Institute, CNRS, INSERM, Sorbonne
Université, 47 Boulevard de l’Hopital, 75013 Paris, France
| | - Patricia Gaspar
- ICM−Paris
Brain Institute, CNRS, INSERM, Sorbonne
Université, 47 Boulevard de l’Hopital, 75013 Paris, France
| | - Alberto Bacci
- ICM−Paris
Brain Institute, CNRS, INSERM, Sorbonne
Université, 47 Boulevard de l’Hopital, 75013 Paris, France
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45
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Chen CYA, Chiu CC, Huang CY, Cheng YC, Huang MC, Kuo PH, Chen WY. Cluster analysis dissecting cognitive deficits in older adults with major depressive disorder and the association with neurofilament light chain. BMC Geriatr 2024; 24:344. [PMID: 38627748 PMCID: PMC11020442 DOI: 10.1186/s12877-024-04960-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 04/09/2024] [Indexed: 04/19/2024] Open
Abstract
BACKGROUND Cognitive impairment is a growing problem with increasing burden in global aging. Older adults with major depressive disorder (MDD) have higher risk of dementia. Neurofilament light chain (NfL) has been proven as a potential biomarker in neurodegenerative disease, including dementia. We aimed to investigate the association between cognitive deficits and NfL levels in older adults with MDD. METHODS In this cross-sectional study, we enrolled 39 MDD patients and 15 individuals with mild neurocognitive disorder or major neurocognitive disorder, Alzheimer's type, as controls, from a tertiary psychiatric hospital. Both groups were over age 65 and with matched Mini-Mental State Examination (MMSE) score. Demographic data, clinical variables, and plasma NfL levels were obtained. We used cluster analysis according to their cognitive profile and estimated the correlation between plasma NfL levels and each cognitive domain. RESULTS In the MDD group, participants had higher rate of family psychiatry history and current alcohol use habit compared with controls. Control group of neurocognitive disorders showed significantly lower score in total MMSE and higher plasma NfL levels. Part of the MDD patients presented cognitive deficits clustered with that of neurocognitive disorders (cluster A). In cluster A, the total MMSE score (r=-0.58277, p=0.0287) and the comprehension domain (r=-0.71717, p=0.0039) were negatively correlated to NfL levels after adjusting for age, while the associations had not been observed in the other cluster. CONCLUSIONS We noted the negative correlation between NfL levels and cognition in MDD patients clustered with neurodegenerative disorder, Alzheimer's type. NfL could be a promising candidate as a biomarker to predict subtype of patients in MDD to develop cognitive decline. Further longitudinal studies and within MDD cluster analysis are required to validate our findings for clinical implications.
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Affiliation(s)
- Cynthia Yi-An Chen
- Department of Psychiatry, Wan-Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Chih-Chiang Chiu
- Department of Psychiatry, Taipei City Psychiatric Center, Songde branch, Taipei City Hospital, Taipei, Taiwan
- Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Cho-Yin Huang
- Department of Psychiatry, Taipei City Psychiatric Center, Songde branch, Taipei City Hospital, Taipei, Taiwan
| | - Ying-Chih Cheng
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
- Department of Psychiatry, China Medical University Hsinchu Hospital, China Medical University, Hsinchu, Taiwan
| | - Ming-Chyi Huang
- Department of Psychiatry, Taipei City Psychiatric Center, Songde branch, Taipei City Hospital, Taipei, Taiwan
- Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Po-Hsiu Kuo
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
- Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Wen-Yin Chen
- Department of Psychiatry, Taipei City Psychiatric Center, Songde branch, Taipei City Hospital, Taipei, Taiwan.
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan.
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Bauer JF, Gerczuk M, Schindler-Gmelch L, Amiriparian S, Ebert DD, Krajewski J, Schuller B, Berking M. Validation of Machine Learning-Based Assessment of Major Depressive Disorder from Paralinguistic Speech Characteristics in Routine Care. Depress Anxiety 2024; 2024:9667377. [PMID: 40226679 PMCID: PMC11919192 DOI: 10.1155/2024/9667377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 03/14/2024] [Accepted: 03/22/2024] [Indexed: 04/15/2025] Open
Abstract
New developments in machine learning-based analysis of speech can be hypothesized to facilitate the long-term monitoring of major depressive disorder (MDD) during and after treatment. To test this hypothesis, we collected 550 speech samples from telephone-based clinical interviews with 267 individuals in routine care. With this data, we trained and evaluated a machine learning system to identify the absence/presence of a MDD diagnosis (as assessed with the Structured Clinical Interview for DSM-IV) from paralinguistic speech characteristics. Our system classified diagnostic status of MDD with an accuracy of 66% (sensitivity: 70%, specificity: 62%). Permutation tests indicated that the machine learning system classified MDD significantly better than chance. However, deriving diagnoses from cut-off scores of common depression scales was superior to the machine learning system with an accuracy of 73% for the Hamilton Rating Scale for Depression (HRSD), 74% for the Quick Inventory of Depressive Symptomatology-Clinician version (QIDS-C), and 73% for the depression module of the Patient Health Questionnaire (PHQ-9). Moreover, training a machine learning system that incorporated both speech analysis and depression scales resulted in accuracies between 73 and 76%. Thus, while findings of the present study demonstrate that automated speech analysis shows the potential of identifying patterns of depressed speech, it does not substantially improve the validity of classifications from common depression scales. In conclusion, speech analysis may not yet be able to replace common depression scales in clinical practice, since it cannot yet provide the necessary accuracy in depression detection. This trial is registered with DRKS00023670.
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Affiliation(s)
- Jonathan F. Bauer
- Department for Clinical Psychology and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91052 Erlangen, Germany
| | - Maurice Gerczuk
- Chair of Embedded Intelligence for Health Care & Wellbeing, University of Augsburg, 86159 Augsburg, Germany
| | - Lena Schindler-Gmelch
- Department for Clinical Psychology and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91052 Erlangen, Germany
| | - Shahin Amiriparian
- Chair of Embedded Intelligence for Health Care & Wellbeing, University of Augsburg, 86159 Augsburg, Germany
| | - David Daniel Ebert
- Department for Sport and Health Sciences, Technical University Munich, 80992 Munich, Germany
| | - Jarek Krajewski
- Rhenish University of Applied Science Cologne, 50676 Cologne, Germany
| | - Björn Schuller
- Chair of Embedded Intelligence for Health Care & Wellbeing, University of Augsburg, 86159 Augsburg, Germany
- Group on Language, Audio, & Music, Imperial College London, London SW7 2AZ, UK
| | - Matthias Berking
- Department for Clinical Psychology and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91052 Erlangen, Germany
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Finley JCA, Cladek A, Gonzalez C, Brook M. Perceived cognitive impairment is related to internalizing psychopathology but unrelated to objective cognitive performance among nongeriatric adults presenting for outpatient neuropsychological evaluation. Clin Neuropsychol 2024; 38:644-667. [PMID: 37518890 DOI: 10.1080/13854046.2023.2241190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 07/20/2023] [Indexed: 08/01/2023]
Abstract
Objective: This study investigated the relationship between perceived cognitive impairment, objective cognitive performance, and intrapersonal variables thought to influence ratings of perceived cognitive impairment. Method: Study sample comprised 194 nongeriatric adults who were seen in a general outpatient neuropsychology clinic for a variety of referral questions. The cognition subscale score from the WHO Disability Assessment Schedule served as the measure of perceived cognitive impairment. Objective cognitive performance was indexed via a composite score derived from a comprehensive neuropsychological battery. Internalizing psychopathology was indexed via a composite score derived from anxiety and depression measures. Medical and neuropsychiatric comorbidities were indexed by the number of different ICD diagnostic categories documented in medical records. Demographics included age, sex, race, and years of education. Results: Objective cognitive performance was unrelated to subjective concerns, explaining <1% of the variance in perceived cognitive impairment ratings. Conversely, internalizing psychopathology was significantly predictive, explaining nearly one-third of the variance in perceived cognitive impairment ratings, even after accounting for test performance, demographics, and number of comorbidities. Internalizing psychopathology was also highly associated with a greater discrepancy between scores on perceived and objective cognitive measures among participants with greater cognitive concerns. Clinically significant somatic symptoms uniquely contributed to the explained variance in perceived cognitive impairment (by ∼13%) when analyzed in a model with internalizing symptoms. Conclusions: These findings suggest that perceived cognitive impairment may be more indicative of the extent of internalizing psychopathology and somatic concerns than cognitive ability.
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Affiliation(s)
- John-Christopher A Finley
- Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Andrea Cladek
- Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA
| | | | - Michael Brook
- Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
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Liu X, Read SJ. Development of a multivariate prediction model for antidepressant resistant depression using reward-related predictors. Front Psychiatry 2024; 15:1349576. [PMID: 38590792 PMCID: PMC10999634 DOI: 10.3389/fpsyt.2024.1349576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Accepted: 03/11/2024] [Indexed: 04/10/2024] Open
Abstract
Introduction Individuals with depression who do not respond to two or more courses of serotonergic antidepressants tend to have greater deficits in reward processing and greater internalizing symptoms, yet there is no validated self-report method to determine the likelihood of treatment resistance based on these symptom dimensions. Methods This online case-control study leverages machine learning techniques to identify differences in self-reported anhedonia and internalizing symptom profiles of antidepressant non-responders compared to responders and healthy controls, as an initial proof-of-concept for relating these indicators to medication responsiveness. Random forest classifiers were used to identify a subset from a set of 24 reward predictors that distinguished among serotonergic medication resistant, non-resistant, and non-depressed individuals recruited online (N = 393). Feature selection was implemented to refine model prediction and improve interpretability. Results Accuracies for full predictor models ranged from .54 to .71, while feature selected models retained 3-5 predictors and generated accuracies of .42 to .70. Several models performed significantly above chance. Sensitivity for non-responders was greatest after feature selection when compared to only responders, reaching .82 with 3 predictors. The predictors retained from feature selection were then explored using factor analysis at the item level and cluster analysis of the full data to determine empirically driven data structures. Discussion Non-responders displayed 3 distinct symptom profiles along internalizing dimensions of anxiety, anhedonia, motivation, and cognitive function. Results should be replicated in a prospective cohort sample for predictive validity; however, this study demonstrates validity for using a limited anhedonia and internalizing self-report instrument for distinguishing between antidepressant resistant and responsive depression profiles.
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Affiliation(s)
- Xiao Liu
- Department of Psychology, University of Southern California, Los Angeles, CA, United States
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Zeng Y, Lao J, Wu Z, Lin G, Wang Q, Yang M, Zhang S, Xu D, Zhang M, Liang S, Liu Q, Yao K, Li J, Ning Y, Zhong X. Altered resting-state brain oscillation and the associated cognitive impairments in late-life depression with different depressive severity: An EEG power spectrum and functional connectivity study. J Affect Disord 2024; 348:124-134. [PMID: 37918574 DOI: 10.1016/j.jad.2023.10.157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Revised: 10/29/2023] [Accepted: 10/30/2023] [Indexed: 11/04/2023]
Abstract
OBJECTIVE Cognitive impairments are prevalent in late-life depression (LLD). However, it remains unclear whether there are concurrent brain oscillation alterations in resting condition across varying level of depression severity. This cross-sectional study aims to investigate the characteristics of altered resting-state oscillations, including power spectrum and functional connectivity, and their association with the cognitive impairments in LLD with different depression severity. METHODS A total of 65 patients with LLD and 40 elder participants without depression were recruited. Global cognition and subtle cognitive domains were evaluated. A five-minute resting-state electroencephalography (EEG) was conducted under eyes-closed conditions. Measurements included the ln-transformed absolute power for power spectrum analysis and the weighted phase lag index (wPLI) for functional connectivity analysis. RESULTS Attentional and executive dysfunction were exhibited in Moderate-Severe LLD group. Enhanced posterior upper gamma power was observed in both LLD groups. Additionally, enhanced parietal and fronto-parietal/occipital theta connectivity were observed in Moderate-Severe LLD group, which were associated with the attentional impairment. LIMITATIONS Limitations include a small sample size, concomitant medication use, and a relatively higher proportion of females. CONCLUSIONS Current study observed aberrant brain activity patterns in LLD across different levels of depression severity, which were linked to cognitive impairments. The altered posterior brain oscillations may be trait marker of LLD. Moreover, cognitive impairments and associated connectivity alterations were exhibited in moderate-severe group, which may be a state-like marker of moderate-to severe LLD. The study deepens understanding of cognitive impairments with the associated oscillation changes, carrying implications for neuromodulation targets in LLD.
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Affiliation(s)
- Yijie Zeng
- Geriatric Neuroscience Center, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China
| | - Jingyi Lao
- Geriatric Neuroscience Center, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China
| | - Zhangying Wu
- Geriatric Neuroscience Center, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China
| | - Gaohong Lin
- Geriatric Neuroscience Center, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China
| | - Qiang Wang
- Geriatric Neuroscience Center, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China
| | - Mingfeng Yang
- Geriatric Neuroscience Center, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China
| | - Si Zhang
- Geriatric Neuroscience Center, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China
| | - Danyan Xu
- Geriatric Neuroscience Center, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China
| | - Min Zhang
- Geriatric Neuroscience Center, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China
| | - Shuang Liang
- Geriatric Neuroscience Center, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China
| | - Qin Liu
- Geriatric Neuroscience Center, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China
| | - Kexin Yao
- Geriatric Neuroscience Center, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China
| | - Jiafu Li
- Geriatric Neuroscience Center, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China
| | - Yuping Ning
- Geriatric Neuroscience Center, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China; The First School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China; Key Laboratory of Neurogenetics and channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou.
| | - Xiaomei Zhong
- Geriatric Neuroscience Center, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China; Key Laboratory of Neurogenetics and channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou.
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50
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Zhou J, Zhou J, Feng Z, Feng L, Xiao L, Chen X, Yang J, Feng Y, Wang G. Identifying the core residual symptom in patients with major depressive disorder using network analysis and illustrating its association with prognosis: A study based on the national cohorts in China. Gen Hosp Psychiatry 2024; 87:68-76. [PMID: 38325144 DOI: 10.1016/j.genhosppsych.2024.01.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 01/29/2024] [Accepted: 01/30/2024] [Indexed: 02/09/2024]
Abstract
OBJECTIVE To identify the core residual symptom of MDD and assess its relationship with patients' long-term outcomes. METHOD All patients were administered antidepressants during the acute phase and treated continuously. The 521 patients remitted at month 6 of a multicenter prospective project were included. Remission was defined as a Quick Inventory of Depressive Symptoms-Self-Report total score of ≤5. Functional impairments were measured with the Sheehan Disability Scale, quality of life with the Quality of Life Enjoyment and Satisfaction Questionnaire - short form, and family burden with the Family Burden Scale of Disease. Visits were scheduled at baseline, weeks 2, 8, 12, and month 6. RESULTS Difficulty with concentration/decision making was the core residual symptom of MDD, determined with the centrality measure of network analysis. It was positively associated with functional impairments and family burden (r = 0.35, P < 0.01 and r = 0.31, P < 0.01, respectively) and negatively associated with life satisfaction (r = -0.29, P < 0.01). The exhibition of this residual symptom was associated with a family history of psychiatric disorders (OR = 2.610 [1.242-5.485]). CONCLUSIONS The core residual symptom of MDD, difficulty with concentration/decision making, is associated with poorer social functioning, heavier family burden, and lower life satisfaction. Early detection and intervention of this symptom may be beneficial. CLINICAL TRIALS REGISTRATION NUMBER (Chinese Clinical Trials.gov identifier) ChiCTR-OOC-17012566 and ChiCTR-INR-17012574.
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Affiliation(s)
- Jingjing Zhou
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Jia Zhou
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Zizhao Feng
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Lei Feng
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Le Xiao
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Xu Chen
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Jian Yang
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Yuan Feng
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China.
| | - Gang Wang
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China.
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