Cariprazine, a potent dopamine D3-preferring D3/D2 receptor partial agonist, has demonstrated benefits on negative symptoms among patients with schizophrenia. Secondary endpoint and post-hoc analyses have also suggested a benefit of cariprazine on quality of life (QoL) and attention.

Data for this post-hoc analysis were pooled from two 6-week, placebo-controlled phase 3 trials evaluating cariprazine among patients with acute exacerbations of schizophrenia. One study included an aripiprazole active-control arm for assay sensitivity.Two populations were analyzed: pooled intention-to-treat (ITT) population (N = 1043), and the pooled subgroup with predominant negative symptoms (PNS, n = 215), as defined by the Positive and Negative Syndrome Scale (PANSS) subscale and item cut-off criteria at baseline. Analyses of interest were: Schizophrenia Quality of Life Scale Revision 4 (SQLS-R4) total score; Cognitive Drug Research (CDR) power of attention (PoA), and continuity of attention (CoA).

Among study completers, cariprazine and aripiprazole were associated with significant SQLS-R4 improvements in the ITT and PNS populations. Differences in CDR-PoA scores were significant for cariprazine vs. placebo in the ITT and PNS populations, but not for aripiprazole in the ITT or PNS analyses. Differences in CDR-CoA scores were significant for cariprazine vs. placebo in the ITT and PNS analyses; and was significant for aripiprazole vs. placebo in the PNS analysis, but not in the ITT analysis.

This post-hoc analysis suggests that cariprazine may be associated with beneficial effects on measures of attention and QoL among patients with schizophrenia, and these effects could be more pronounced among individuals with PNS.

Cognitive deficits play an important role in Bipolar Disorder (BPD). The Cognitive Problems and Strategies Assessment (CPSA) is a measure that evaluates the patient's perception of cognitive difficulties, and the spontaneous use of compensatory strategies and could thus have potential utility for clinical practice in patients with BPD. Our aim was to determine the validity and reliability of the Cognitive Problems and Strategies Assessment (CPSA) in Bipolar Disorder (BPD). Ninety-three BPD outpatients and 90 controls completed the Assessment of Problems with Thinking and Memory (APTM) questionnaire and the Assessment of Memory and Thinking Strategies (AMTS) questionnaire which constitute the CPSA, the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA), as a measure of convergent validity, and general sociodemographic data. Cronbach's alpha coefficient, Spearman's correlation coefficient and independent sample t tests were used for Internal consistency, Convergent validity and Discriminant validity. The APTM had a Cronbach's alpha coefficient of 0.93 and the AMTS 0.90. The COBRA score and the APTM were significantly correlated. BPD patients exhibited higher scores on the APTM and lower scores on the AMTS than controls. The present instrument enriches the clinician's repertoire for rapid and inexpensive cognitive evaluation in BPD.

This study aimed to analyse the differences in creative thinking dispositions between patients with bipolar disorder (BD) and healthy controls (HCs) and to examine the potential role of cognitive flexibility (CF) and theory of mind (ToM) as mediators of this relationship.

Fifty patients diagnosed with BD in remission and fifty HCs participated in the study. The participants completed the Wisconsin Card Sorting Test (WCST), the Reading the Mind in the Eyes Test (RMET), the Dokuz Eylul Theory of Mind Index (DEToMI) and the Marmara Creative Thinking Dispositions Scale (MCTDS).

There was no significant difference between the groups in terms of creative thinking dispositions, t(98)=-0.99, p =.323. However, patients performed worse in several areas, such as the number of perseverative errors (PEs) t(98) = 4.84, p <.001, number of completed categories (z=-4.38, p <.001), DEToMI total score t(98)=-3.51, p <.001, and RMET score t(98)=-2.77, p <.007, than HCs. In the patient group, correlations were found between innovation search and irony scores (r (48) = 0.44, p =.001) and between innovation search and the DEToMI total score (r [(48) = 0.44, p =.002). In the HC group, associations were found between PEs and innovation search, r (48)=-0.33, p =.019; PEs and inquisitive, r (48)=-0.29, p =.044; SOFB and inquisitive, r (48) = - 0.30, p =.034; doubt and irony, r (48) = 0.29, p =.043; and the RMET score and courage, r (48)=-0.31, p =.027. In the HC group, 44% of the MCTDS score was explained by the model variables at a statistically significant level.

Not all factors affecting creative thinking dispositions and cognitive functions were examined.

The relationship between creativity and BD varies depending on the research approach; however, consistent with the current literature, our study found no significant differences in creative thinking dispositions between the groups. While CF and ToM predicted creative thinking in healthy individuals, they do not predict these dispositions in BD patients. Therefore, focusing on other cognitive factors related to creativity in individuals with BD may help clarify this issue. Our study contributes to the limited literature by investigating the effects of CF and ToM on creative thinking dispositions in BD patients.

Max Reger was an organist, university teacher and composer whose life, illnesses, death and dying are not or hardly known to many.

Which illnesses determined Reger's life and did his lifestyle and illnesses influence his compositional work? Could his early death have been avoided? From today's point of view, could modern intensive care medicine have helped him?

A detailed analysis of Reger's diseases was performed using scientific databases (medline, pubmed). All published articles were evaluated and examined in detail.

Max Reger was born in Brand in 1873 and received early lessons in violin, piano and organ playing. From 1890 he studied at the conservatory in Sondershausen, later at the conservatory in Wiesbaden. In 1901 he moved to Munich, and in 1907 to Leipzig, where he became university director and professor at the conservatory. Four years later he took over the court chapel in Meiningen, but ended this activity again in 1914. A year later he moved to Jena and wrote his late works in the "Jenaish style". Reger suffered from many illnesses, especially bipolar disorder with manic and depressive phases. He had metabolic syndrome with arterial hypertension, was overweight and smoked incredibly heavily. Overeating ("binge eating" syndrome) and polydipsia were other prominent findings. Reger's life was characterized by alcohol abuse, often aggravated by professional and/or human crises. In 1916 Reger died suddenly and unexpectedly in Leipzig of cardiovascular failure.

Reger was an outstanding personality who left behind an extensive oeuvre. Among the highlights of Max Reger's oeuvre are his chorale fantasies such as on "Ein' feste Burg ist unser Gott" (op. 27) or also the "Fantasia and Fugue on B A C H" (op. 46), but other compositions such as the Mozart Variations (op. 132) and the Clarinet Quintet (op. 146) are also world-famous. His lifestyle certainly favored coronary heart disease, the consequences of which caused Reger's sudden, unexpected and much too early death. Today's modern intensive care medicine could probably have prolonged his life.

Cognitive impairment is common in bipolar disorder (BD), especially in older age (≥50 years). Underlying causes of BD-related cognitive impairment are not fully elucidated. This study investigates the association between physical multimorbidity and subjective and objective cognitive performance in patients with older age bipolar disorder (OABD).

Cross-sectional design.

Dutch Older Bipolars (DOBi) dynamic cohort.

170 outpatients with BD aged ≥ 50 years.

Chronic physical diseases were assessed in a structured interview. Objective cognitive performance was measured with neuropsychological tests, subjective cognitive performance with the Cognitive Failures Questionnaire (CFQ). Linear regression analyses were performed between multimorbidity, defined as two or more affected physical disease domains, and 1) objective cognitive performance, 2) subjective cognitive functioning, and 3) four cognitive domain scores (attention, learning and memory, verbal fluency, executive functioning). Analyses were hierarchically adjusted for demographic, lifestyle, and psychiatric characteristics.

Multimorbidity was significantly associated with a lower composite cognitive score (B=-0.205, p = 0.040), but after full adjustment statistical significance disappeared (B=-0.044, p = 0.633). Controlled for demographics only, multimorbidity was not significantly associated with higher CFQ (B=6.009, p = 0.053). Multimorbidity was associated with worse executive functioning (B=-0.279, p = 0.018), but statistical significance disappeared after full adjustment (B=-0.085, p = 0.469).

In OABD physical multimorbidity is not independently associated with poorer cognitive performance and subjective functioning. Rather, shared risk factors, such as demographics, psychiatric characteristics, and lifestyle factors might lead to both the presence of physical diseases and worse cognitive performance in OABD.

We aimed to determine the relationship between altered brain imaging characteristics, cognitive function and profiles of gene expression of bipolar disorder (BD).

Functional magnetic resonance imaging (fMRI) was presented in three groups of BD participants (depressed, manic and euthymic) and healthy controls. Regional Homogeneity (ReHo) and region of interest based functional analysis combining with neuroimaging-transcription association analysis were utilized to investigate abnormalities and their correlation with clinical symptoms.

Our data showed that all three groups of BD patients exhibited significantly altered ReHo values whilst the bilateral precuneus/posterior cingulate cortex (PCC) and lateral occipital cortex exhibited significant increase in BD. Functional connectivity (FC) revealed distinct characteristics of the precuneus/PCC-based default mode network. ReHo values in the Precuneus/middle cingulate cortex displayed significantly negative correlations with cognition and YMRS scores. Gene enrichment analysis also revealed that ReHo values were spatially correlated with pathways including chromatin organization and innate immune response.

Altered ReHo values in specific brain regions may be associated with different clinical stages and increased FC in brain may potentially function as BD imaging biomarkers. The heterogeneity of gene expression was associated with altered brain imaging properties in BD, contributing to distinguishing different stages of BD from healthy individuals.

Major depressive disorder (MDD) and bipolar depression (BD-D) are both intricate, enduring, and profound psychiatric conditions characterized primarily by depressive episodes and cognitive dysfunction. However, distinguishing the characteristics and influencing factors of cognitive impairment in unipolar and BD-D is crucial for identification and intervention.

To compare neurocognitive characteristics and investigate associations between cognitive function and clinical features in unipolar and BD-D.

The THINC-integrated tool (THINC-it) as a cognitive assessment tool was applied to 295 individuals: 75 patients with depressive disorders (MDD), 120 individuals with BD-D, and 100 healthy controls. The Hamilton Depression Scale-17 (HAMD), Hamilton Anxiety Scale-14 (HAMA), and Pittsburgh Sleep Quality Index (PSQI) were employed to assess depression, anxiety, and sleep. Neurocognitive function characteristics and the relationships between cognitive impairment and general clinical attributes were analyzed.

There were no statistically significant differences in the overall THINC-it with each objective subscale. However, the subjective subscale (Perceived Deficits Questionnaire for Depression-5-item) showed significant differences between MDD and BD-D (P < 0.001). Linear regression analyses were explored to determine associations. Age, years of education, age at onset, and HAMD were significantly co-associated with the overall THINC-it and each subscale in both MDD and BD-D (P < 0.05). Furthermore, years of education showed a positive correlation with objective cognitive impairment (e.g., Codebreaker, Trails) (P < 0.05). There was a notable difference in that the number of depressive episodes, disease duration, hospitalizations, HAMA, and PSQI were significantly associated with the overall THINC-it with each subscale between MDD and BD-D (P < 0.05).

Although both unipolar and BD-D showed similar objective cognitive impairments, there was a significant difference in subjective cognitive impairment. Our findings suggest that factors like age, years of education, age at onset, and depression severity might not be significantly difference in the influence of cognitive impairment. Furthermore, we found that education was a protective factor for cognitive impairment in both unipolar and BD-D. Our analysis revealed that distinct factors including disease duration, number of depressive episodes, hospitalizations, anxiety levels, and sleep quality influenced cognitive impairment between unipolar and BD-D. Therefore, it was important to investigate the specific characteristics of cognitive impairment and influencing factors to identify differentiating unipolar and BD-D.

Bipolar depression is commonly accompanied by cognitive impairments. Transcranial direct current stimulation (tDCS) is emerging as a novel non-invasive treatment for bipolar depression. Given the portability and safety of tDCS, we developed a home-based protocol with real-time supervision. Our aim was to assess the cognitive effects of a course of tDCS treatment in bipolar depression. 44 participants (31 women, mean age 47.27 years, SD 12.89) with bipolar depression of at least a moderate severity received 21 sessions of home-based tDCS over 6 weeks in an open-label design. The stimulation protocol involved 2 mA in a bilateral frontal montage (F3 anode, F4 cathode) for 30 min per session. Cognitive assessments were conducted at baseline and after the course of treatment: Rey Auditory Verbal Learning Test (RAVLT) to assess verbal learning and memory and Symbol Digit Modalities Test (SDMT) to assess psychomotor processing speed and visuospatial attention. 93.18% (n = 41) completed RAVLT and 59.09% of participants (n = 26) completed SDMT. A significant improvement was observed in RAVLT verbal learning score post-treatment (p = 0.002), which was not maintained following adjustment for improvement in depressive symptoms. In summary, a course of home-based tDCS in bipolar depression was associated with an improvement in verbal learning, which appeared to be related to improvement in depressive symptoms. These findings suggest potential benefits of tDCS for addressing cognitive impairments in bipolar depression, which can be investigated further in a sham-controlled design.

Mitochondria, often known as the cell's powerhouses, are primarily responsible for generating energy through aerobic oxidative phosphorylation. However, their functions extend far beyond just energy production. Mitochondria play crucial roles in maintaining calcium balance, regulating apoptosis (programmed cell death), supporting cellular signaling, influencing cell metabolism, and synthesizing reactive oxygen species (ROS). Recent research has highlighted a strong link between bipolar disorder (BD) and mitochondrial dysfunction. Mitochondrial dysfunction contributes to oxidative stress, particularly through the generation of ROS, which are implicated in the pathophysiology of BD. Oxidative stress arises when there is an imbalance between the production of ROS and the cell's ability to neutralize them. In neurons, excessive ROS can damage various cellular components, including proteins in neuronal membranes and intracellular enzymes. Such damage may interfere with neurotransmitter reuptake and the function of critical enzymes, potentially affecting brain regions involved in mood regulation and emotional control, which are key aspects of BD. In this review, we will explore how various types of mitochondrial dysfunction contribute to the production of ROS. These include disruptions in energy metabolism, impaired ROS management, and defects in mitochondrial quality control mechanisms such as mitophagy (the process by which damaged mitochondria are selectively degraded). We will also examine how abnormalities in calcium signaling, which is crucial for synaptic plasticity, can lead to mitochondrial dysfunction. Additionally, we will discuss the specific mitochondrial dysfunctions observed in BD, highlighting how these defects may contribute to the disorder's pathophysiology. Finally, we will identify potential therapeutic targets to improve mitochondrial function, which could pave the way for new treatments to manage or mitigate symptoms of BD.

Long-acting injectable antipsychotics (LAIs) are not routinely offered to patients living with bipolar disorder type I (BP-I), despite widespread evidence that supports their benefits over oral antipsychotics, particularly in early disease.

A round-table meeting of psychiatrists convened to discuss barriers and opportunities and provide consensus recommendations around the early use of LAIs for BP-I.

LAIs are rarely prescribed to treat BP-I unless a patient has severe symptoms, sub-optimal adherence to oral antipsychotics, or has experienced multiple relapses. Beyond country-specific accessibility issues (e.g., healthcare infrastructure and availability/approval status), primary barriers to the effective use of LAIs were identified as attitudinal and knowledge/experience-based. Direct discussions between healthcare providers and patients about treatment preferences may not occur due to a preconceived notion that patients prefer oral antipsychotics. Moreover, as LAIs have historically been limited to the treatment of schizophrenia and the most severe cases of BP-I, healthcare providers might be unaware of the benefits LAIs provide in the overall management of BP-I. Improved treatment adherence associated with LAIs compared to oral antipsychotics may support improved outcomes for patients (e.g., reduced relapse and hospitalization). Involvement of all stakeholders (healthcare providers, patients, and their supporters) participating in the patient journey is critical in early and shared decision-making processes. Clinical and database studies could potentially bridge knowledge gaps to facilitate acceptance of LAIs.

This review discusses the benefits of LAIs in the management of BP-I and identifies barriers to use, while providing expert consensus recommendations for potential solutions to support informed treatment decision-making.

Lithium has long been used as a cornerstone mood stabilizer in the treatment of bipolar disorder (BD). However, reliable biomarkers that can predict which patients will respond better to lithium are still lacking. This study aims to evaluate the potential of NR1D1 gene SNP; rs2071427 and actigraphic measurements in predicting lithium response. Thirty-one patients diagnosed with BD at Selçuk University Faculty of Medicine and who were euthymic for at least 8 weeks were included in the study. Sleep-wake cycles and circadian rhythms of the participants were monitored by actigraph for approximately 1 week. For genetic analyses, the SNP rs2071427 variant of the NR1D1 gene was evaluated. A significant proportion of patients with homozygous (AA/GG) genotypes responded well to lithium, whereas some patients with heterozygous (AG) genotypes did not respond to lithium. Actigraphic data showed that there were marked variations in the sleep patterns of BD patients. The Morningness-Eveningness Questionnaire scale did not adequately discriminate the morning chronotype. Seasonal Pattern Assessment Questionnaire results showed that most patients had a seasonal pattern, but this was insufficient to predict response to lithium. This study once again demonstrates the need for new biomarkers to predict lithium response. The findings are an important step in the personalization of BD treatment and may improve treatment efficacy and minimize side effects by tailoring the treatment process to the individual characteristics of patients. Future studies should support these findings with larger sample groups and studies on different genetic markers.

The resting-state functional connectivity (FC) patterns of the fronto-parietal network (FPN) and language network (LN) underlying bipolar disorder (BD) are obscure. This study aimed to uncover abnormal FC patterns of FPN and LN underlying BD and their evolution following treatment.

Imaging data at rest state and clinical variables were acquired from 82 patients with BD (with 43 finishing the follow-up) and 88 healthy controls (HCs). Seed-based FC analysis was performed, and correlations between FCs and clinical variables were investigated with whole-brain multiple regression analyses. Furthermore, a neuroimaging-transcription spatial association analysis was conducted.

At baseline, BD patients presented elevated FPN-LN and FPN-prefrontal gyrus FCs, and hyperconnectivity between the LN and bilateral thalamus, right angular gyrus (AG), and right cerebellum. Following 3 months of treatment intervention, there were decreased FCs between the FPN and left superior temporal gyrus (STG), left superior frontal gyrus (SFG), left insula, and bilateral middle temporal gyrus (MTG) (part of LN). Neuroimaging transcription analysis discovered genes correlated with FC alterations in BD.

Aberrant FC patterns of FPN and LN might be involved in the neural pathogenetic and therapeutic mechanisms of BD. We also provided potential genetic pathways underlying these functional impairments in BD.

Increasing evidences suggests that depression is a heterogeneous clinical syndrome. Cognitive deficits in depression are associated with poor psychosocial functioning and worse response to conventional antidepressants. However, a consistent profile of neurocognitive abnormalities in depression remains unclear.

We used data-driven parsing of cognitive performance to reveal subgroups present across depressed individuals and then investigate the change pattern of cognitive subgroups across the course in follow-up.

We assessed cognition in 163 patients with depression using The Chinese Brief Cognitive Test(C-BCT) and the scores were compared with those of 196 healthy controls (HCs). 58 patients were reassessed after 8 weeks. We used K-means cluster analysis to identify cognitive subgroups, and compared clinical variables among these subgroups. A linear mixed-effects model, incorporating time and group (with interaction term: time × group) as fixed effects, was used to assess cognitive changes over time. Stepwise logistic regression analysis was conducted to identify risk factors associated with these subgroups.

Two distinct neurocognitive subgroups were identified: (1) a cognitive-impaired subgroup with global impairment across all domains assessed by the C-BCT, and (2) a cognitive-preserved subgroup, exhibited intact cognitive function, with performance well within the healthy range. The cognitive-impaired subgroup presented with more severe baseline symptoms, including depressed mood, guilt, suicidality, and poorer work performance. Significant group × time interactions were observed in the Trail Making Test Part A (TMT-A) and Continuous Performance Test (CPT), but not in Symbol Coding or Digit Span tests. Despite partial improvement in TMT-A and CPT tests, the cognitive-impaired subgroup's scores remained lower than those of the cognitive-preserved subgroup across all tests at the study endpoint. Multiple regression analysis indicated that longer illness duration, lower educational levels, and antipsychotic medication use may be risk factors for cognitive impairment.

This study identifies distinguishable cognitive subgroups in acute depression, thereby confirming the presence of cognitive heterogeneity. The cognitive-impaired subgroup exhibits distinct symptoms and persistent cognitive deficits even after treatment. Screening for cognitive dysfunction may facilitate more targeted interventions.

https://www.chictr.org, identifier ChiCTR2400092796.

Given the influence of cognitive abilities on life outcomes, there is inherent value in identifying genes involved in controlling learning and memory. Further, cognitive dysfunction is a core feature of many neuropsychiatric disorders. Here, we use a combinatory in silico approach to identify human gene targets that will have an especially high likelihood of individually and directly impacting cognition. This broad and unbiased screen led to the specific identification of ARHGEF11, which encodes PDZ-RhoGEF. PDZ-RhoGEF is a largely RhoA-specific activator that is highly enriched in dendritic spines, and recent work identified hyperexpression of PDZ-RhoGEF in the prefrontal cortex of bipolar disorder subjects, a disease characterized by an early emergence and persistence of broad scope cognitive dysfunction. Here, we characterize the effects of PDZ-RhoGEF on synaptic and behavioral phenotypes, and we identify molecular and biochemical mechanisms that control PDZ-RhoGEF's expression, synaptic spatial localization, and enzymatic activity. Importantly, our identified direct regulators of PDZ-RhoGEF (miR-132 and DISC1) have themselves been repeatedly implicated in controlling cognitive phenotypes in humans, including those caused by several neuropsychiatric disorders. Taken together, our findings indicate that PDZ-RhoGEF is a key convergence point among multiple synaptic and cognition-relevant signaling cascades with potential translational significance.

Patients with bipolar disorder (BD) frequently exhibit cognitive impairments. However, the association between childhood trauma as a risk factor for BD and cognitive deficits remains ambiguous.

To investigate the relationship between childhood trauma and cognitive function among patients with BD.

The study included 90 patients with BD and 94 healthy controls (HC). Childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ), and cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The relationships between childhood trauma and cognitive function.

In BD group, childhood abuse and neglect were more prevalent than in HC group. Mood stabilizer use was positively associated with language abilities, while antipsychotic use negatively impacted attention. Emotional abuse predicted impaired immediate memory, with the number of episodes and valproate dosage negatively correlating with total RBANS scores, whereas education and mood stabilizer use showed positive correlations.

The incidence of childhood trauma was higher among BD than HC, and different types of childhood trauma had varying effects on different aspects of cognition. These studies will deepen the understanding of the complexity of BD and support the development of more effective treatment methods.

Bipolar disorder (BD) is a severe mental illness characterized by significant mood swings. Effective drug treatment modalities are crucial for managing BD.

To analyze the current status and future trends of global research on BD drug treatment over the last decade.

The Web of Science Core Collection database spanning from 2015 to 2024 was utilized to retrieve literature related to BD drug treatment. A total of 2624 articles were extracted. Data visualization and analysis were conducted using CiteSpace, VOSviewer, Pajek, Scimago Graphica, and R-studio bibliometrix to identify research hotspots, key contributors, and future trends.

The United States, China, and the United Kingdom have made the most significant contributions to research on BD drug treatment and formed notable research collaboration networks. The University of Pittsburgh, Massachusetts General Hospital, and the University of Michigan have been identified as the major research institutions in this field. The Journal of Affective Disorders is the most influential journal. A keyword analysis revealed research hotspots related to clinical symptoms, drug efficacy, and genetic mechanisms. A citation analysis identified the management guidelines published by Yatham et al in 2018 as the most cited paper.

This study provides a detailed overview of the field of BD drug treatment, highlighting key contributors, research hotspots, and future directions. The study findings can be employed as a reference for future research and policymaking, which may enable further development and optimization of BD pharmacotherapy.

Executive dysfunction and dysregulated inflammation are found in patients with different psychiatric disorders. However, whether there are different associations between inflammatory markers and executive performance in patients with different psychiatric diagnoses is unknown. Our study aims were (1) to compare peripheral cytokine expression and executive function in patients with bipolar disorder (BD), substance use disorder (SUD), and schizophrenia (SCZ), and in healthy controls (HC) and (2) to explore the potential association between inflammatory cytokines and executive function in different patient groups and HC. Participants with BD (n = 816), SUD (opioid use disorder and/or methamphetamine use disorder, n = 518), SCZ (n = 146), and HC (n = 186) were recruited. Plasma cytokine levels [tumor necrosis factor (TNF)-α, interleukin (IL)-8 (only measured in 8 SCZ patients), transforming growth factor (TGF)-β1 (not measured in SCZ patients)], C-reactive protein (CRP), brain-derived neurotrophic factor (BDNF) levels, and executive function [Wisconsin Card Sorting Test (WCST) and Continuous Performance Test (CPT)] were assessed. We found that all patient groups had worse executive performance and higher inflammatory cytokine levels than the HC group. SCZ patients had the worst executive performance, while SUD patients had the highest inflammatory cytokine levels. Increased plasma IL-8, CRP, and TNF-α levels were specifically associated with worse executive function in BD, SUD, and SCZ patients (P = 0.009, 0.04, and 0.03, respectively). We concluded that dysregulated inflammation might be a transdiagnostic feature among different psychiatric disorders and associated with executive dysfunction. Further studies to investigate the causal relationship and mechanisms between inflammation and executive dysfunction may be needed.

This study investigated impulsivity and working memory among CD inpatients across treatment and compared to controls.

Patients (N = 56, Mage = 38.2, SD = 11.7, 17F) and healthy controls (N = 50, Mage = 31.9, SD = 10.0, 25F) completed a battery of self-report questionnaires and behavioural tasks assessing working memory and impulsivity (response inhibition, delay discounting, reflection, decision-making). Patients were assessed within 2 weeks of admission (baseline) and at 6 months (follow-up). Controls completed a single session at baseline. Patient demographics, diagnostic status, and treatment outcome (discharge with or without medical advice) were retrieved from medical records.

Group differences in demographics were probed for inclusion as covariates. At baseline, patients had greater self-reported impulsivity on the UPPS-P (negative and positive urgency) and BIS (motor and non-planning), and greater delay discounting than controls. Among patients, there was no association between treatment adherence and working memory, self-report, or behavioural impulsivity, and no change in behavioural impulsivity was observed from baseline to follow-up.

This is the first study to assess impulsivity and working memory in the context of CD treatment. Patients exhibited greater impulsivity on choice-based and various self-report measures. The absence of treatment-related changes in impulsivity and working memory outcomes suggests that conventional treatments may be neglecting to target potentially key areas of functioning. Further research is needed to examine how treatment affects impulsivity and related functions in individuals with CD, and their impact on clinical outcomes.

Bipolar depression is commonly accompanied by cognitive impairments. Transcranial direct current stimulation (tDCS) is emerging as a novel non-invasive treatment for bipolar depression. Given the portability and safety of tDCS, we developed a home-based protocol with real-time supervision. Our aim was to assess the cognitive effects of tDCS in bipolar disorder. 44 participants (31 women, mean age 47.27 ± 12.89 years) experiencing a moderate to severe depressive episode received 21 sessions of home-based tDCS over 6 weeks. The stimulation protocol involved 2 mA in a bilateral frontal montage (F3 anode, F4 cathode) for 30 minutes per session. The cognitive assessments were conducted at baseline and after the course of treatment. Rey Auditory Verbal Learning Test (RAVLT) was used to assess verbal learning and memory and the Symbol Digit Modalities Test (SDMT) to assess psychomotor processing speed and visuospatial attention. 93.18% (n=41) completed RAVLT and 59.09% of participants (n=26) completed SDMT. A significant improvement was observed in the RAVLT short-term verbal memory score post-treatment (p = 0.002). Improvements were observed in RAVLT verbal learning, RAVLT post-interference recall, and SDMT, which were not statistically significant. In summary, cognitive performance showed an improvement in bipolar depression following treatment with home-based tDCS, suggesting it can be an effective intervention for cognitive deficits in bipolar depression and positively impact cognitive function.

Treatable mental disorders, such as psychotic, major depressive disorder (MDD), and bipolar disorder (BD), contribute to a substantial portion of suicide risk, often accompanied by neurocognitive deficits. We report the association between cognitive function and suicidal ideation/suicide attempts (SI/SA) in individuals with schizoaffective disorder, BD, and MDD.

A systematic search was conducted on PubMed, Ovid and Scopus databases for primary studies published from inception to April 2024. Eligible articles that reported on the effect size of association between cognition and SI/SA were pooled using a random effects model.

A total of 41 studies were included for analysis. There was a negative association between executive functioning and SI/SA in schizoaffective disorder (SA: Corr = -0·78, 95 % CI [-1·00, 0·98]; SI: Corr = -0·06, 95 % CI [-0·85, 0·82]) and MDD (SA: Corr = -0·227, 95 % CI [-0·419, -0·017]; SI: Corr = -0·14, 95 % CI [-0·33, 0·06]). Results were mixed for BD, with a significant positive association between SA and global executive functioning (Corr = 0·08, 95 % CI [0·01, 0·15]) and negative association with emotion inhibition. Mixed results were observed for processing speed, attention, and learning and memory, transdiagnostically.

There is heterogeneity across sample compositions and cognitive measures. We did not have detailed information on individuals with respect to demographics and comorbidities.

We observed a transdiagnostic association between measures of cognitive functions and aspects of suicidality. The interplay of cognitive disturbances, particularly in reward-based functioning, may underlie suicidality in individuals with mental disorders. Disturbances in impulse control, planning, and working memory may contribute to self-injurious behavior and suicide.

Frailty, cognitive decline, and depression are common syndromes among the elderly and are closely interconnected. However, it is still unclear whether the impact of frailty on depression depends on the role of cognitive decline.

We conducted the Mendelian randomization (MR) analysis based on the instrumental variables (IVs) from the genome-wide association study (GWAS) databases, and we also performed a cross-sectional study consisting of 1362 older adults aged ≥65 for validation.

The results of the multivariable MR analysis showed that frailty significantly increased the risk of depression, even after controlling for the influence of cognitive performance. Conversely, after controlling for frailty, the effect of cognitive performance on depression risk was noticeably reduced. In the cross-sectional study, frailty mediated 24.04 % of the relationship between cognition and depression, and cognition mediated 7.63 % of the relationship between frailty and depression.

We provide evidence that frailty could increase depression risk independently of cognitive decline. Further research with a larger sample size is necessary.

Individuals with bipolar disorder (BD) often struggle with emotional regulation and social interactions, partly due to difficulties in accurately recognizing facial emotions.

From September 2021 to February 2023, 69 BD individuals-comprising 23 with bipolar manic/hypomanic episode (BME), 23 with bipolar depressive episode (BDE), 23 with bipolar euthymic (EUT)-and 23 healthy controls (HCs) were enrolled. Diagnosis adhered to DSM-IV criteria using M.I.N.I 5.0, alongside assessments via Hamilton Depression Scale 17 and Young Manic Rating Scale. Recognition tasks involving 84 facial expression images across six categories. The Wilcoxon rank-sum test compares two groups, while the Kruskal-Wallis test compares multiple groups with subsequent adjusted pairwise comparisons.

The overall correct recognition rate of facial expressions in the BD group (79 %) was significantly lower than that of the HC group (83 %) (P=0.004). Primary differences were noted in neutral (93 % vs. 100 %, P=0.012) and fear (79 % vs. 86 %, P=0.023) expressions. Within the BD group, correct recognition rates were 71 % for BME, 80 % for BDE, and 80 % for EUT, all lower than in the HC group. Significant differences in correct recognition rates of neutral, fear, and joy expressions were observed among the four groups (P<0.05), with the BME group exhibiting the lowest rate. Misidentification of facial expressions was more frequent in the BD group compared to the HC group, particularly among negative expressions.

Patients with BD demonstrate lower correct recognition and higher misidentification rates of facial expressions, with those experiencing manic episodes showing impaired recognition of neutral, joy, and fear expressions.

Increasing evidence has indicated a connection between bipolar disorder (BD) and arteriosclerosis (AS), yet the specific molecular mechanisms remain unclear. This study aims to investigate the hub genes and molecular pathways for BD with AS.

BD-related dataset GSE12649 were downloaded from the Gene Expression Omnibus database and differentially expressed genes (DEGs) and key module genes derived from Limma and weighted gene co-expression network analyses (WGCNA) were identified. AS-related genes were sourced from the DisGeNET database, and the overlapping genes between DEGs and AS-related genes were characterized as differentially expressed arteriosclerosis-related genes (DE-ASRGs). The functional enrichment analysis, protein-protein interaction (PPI) network and three machine learning algorithms were performed to explore the hub genes, which were validated with two external validation sets. Additionally, immune infiltration was performed in BD.

Overall, 67 DE-ASRGs were found to be overlapping between the DEGs and AS-related genes. Functional enrichment analysis highlighted the cancer pathways between BD and AS. We identified seven candidate hub genes (CTSD, IRF3, NPEPPS, ST6GAL1, HIF1A, SOX9 and CX3CR1). Eventually, two hub genes (CX3CR1 and ST6GAL1) were identified as BD and AS co-biomarkers by using machine learning algorithms. Immune infiltration had revealed the disorder of immunocytes.

This study identified the hub genes CX3CR1 and ST6GAL1 in BD and AS, providing new insights for further research on the bioinformatic mechanisms of BD with AS and contributing to the diagnosis and prevention of AS in psychiatric clinical practice.

Dementia, depression, and cardiovascular disease are major public health concerns for older adults, requiring early intervention. This study investigates whether a virtual reality cognitive remediation program (VR-CR) can improve cognitive function and depressive symptoms in older adults, and determines the necessary sample size for future studies. Integrated VR and CR interventions have shown promising outcomes in older adults with neurodegenerative and mental health disorders.

This secondary analysis of a randomized controlled trial involves adults aged 58-75 years with bipolar disorder, excluding those with acute episodes, epilepsy, or severe eye diseases. The experimental group received standard treatment plus VR-CR, while the control group received only standard treatment.

No baseline differences were found between the experimental and control groups. No significant improvement was observed in the overall cognitive function test (p = 0.897) or in depressive symptoms (p = 0.322). A phase III efficacy study requires a sample size of 28 participants (alpha = 0.05, beta = 0.20).

VR-CR can potentially treat depressive symptoms in adults and older adults, but the results support conducting phase III studies to further investigate these outcomes. However, the improvement in cognitive performance in the elderly is less pronounced than in younger individuals.

Cognitive functioning heterogeneity is a well-recognized phenomenon in individuals diagnosed with mood disorders. Cognitive Reserve (CR) has been linked to multiple positive outcomes, including cognitive performance in these patients. This systematic review and meta-analysis aim to provide a comprehensive analysis of the relationship between CR and cognitive functioning in individuals with mood disorders, including bipolar disorder and depressive disorders. Following PRISMA guidelines, a systematic review and meta-analysis was conducted of original research exploring the relationship between CR and cognitive performance in adult individuals with mood disorders. The literature search was conducted on PubMed, Scopus, and Web of Science, from 2002 to September 2023, and the Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of studies. Overall, 17 studies met the inclusion criteria for the systematic review and 11 for the meta-analysis. Both qualitative and quantitative findings suggested a positive relationship between CR measures and cognitive domains. CR emerges as a possible protective factor for cognitive functioning in adult individuals with mood disorders, potentially helping to mitigate the cognitive impairments associated with the disorder. These findings underscore the importance of the fact that promoting and enhancing CR could help in the cognitive prognosis of this population.

The serotonin type 7 (5-HT7) receptor is one of 14 5-HT receptors. It has received attention for its possible role in mood disorders and cognition. The 5-HT7 receptor antagonist, JNJ-18038683, has been reported to be effective in rodent models of depression and REM sleep. Also, 5-HT7 receptor blockade has been postulated to be a key component of cognitive enhancement in a number of drugs. Bipolar disorder (BD) usually endures cognitive impairment (CI); however, no treatment for CI in BD has been approved. This study aimed to evaluate the efficacy of JNJ-18038683 to improve the CI of BD compared to a placebo.

We conducted a placebo-controlled, 8-week trial of JNJ-18038683 in BD patients. Each patient's data were analyzed and reassessed blindly with a comprehensive neuropsychological battery, depression and hypomania ratings, and overall social and work function measures.

Of 60 patients, 38 (63%) were female, 43 (72%) had BD type 1, and most patients were Caucasian and married. The overall time effect for the combined group shows statistically significant improvement from baseline to week 8 for most of the neurocognitive battery measures. This indicates a significant improvement in psychopathology and cognition during the study time in both JNJ-18038683 and placebo groups, but no difference between groups.

This study showed no efficacy for the improvement of CIBD or mood symptoms with JNJ-18038683 compared to the placebo.

Our aims were to assess cognitive impairment in bipolar patients in remission compared with healthy controls, and to study its connection to clinical and therapeutic factors.

This was a case-control study of patients with bipolar disorder (BD) in remission and matched healthy controls. It was carried out at the Hédi Chaker University Hospital in Sfax, Tunisia. The Screen for Cognitive Impairment in Psychiatry (SCIP) scale was used to assess cognitive function in patients and controls. This scale comprises subtests for verbal learning with immediate (VLT-I) and delayed (VLT-D) recall, working memory (WMT), verbal fluency (VFT) and information processing speed (PST).

We recruited 61 patients and 40 controls. Compared with controls, patients had significantly lower scores on the overall SCIP scale and on all SCIP subtests (p < 0.001 throughout) with moderate to high effects. In multivariate analysis, the presence of psychotic characteristics correlated with lower scores on the overall SCIP (p = 0.001), VLT-I (p = 0.001) and VLT-D (p = 0.007), WMT (p = 0.002) and PST (p = 0.008). Bipolar II correlated with lower LTV-I scores (p = 0.023). Age of onset and duration of the disorder were negatively correlated with PST scores (p < 10-3 and p = 0.007, respectively). Predominantly manic polarity correlated with lower VFT scores (p = 0.007).

Our study showed that bipolar patients in remission presented significantly more marked cognitive impairments, affecting various cognitive domains, than the controls. These cognitive impairments appear to be linked to clinical and therapeutic factors that are themselves considered to be factors of poor prognosis in BD.

Bipolar disorder is a chronic disorder characterized by fluctuations in mood state and energy and recurrent episodes of mania/hypomania and depression. Bipolar disorder may be regarded as a neuro-progressive disorder in which repeated mood episodes may lead to cognitive decline and dementia development. In the current review, we employed genome-wide association studies to comprehensively investigate the genetic variants associated with bipolar disorder and dementia. Thirty-nine published manuscripts were identified: 20 on bipolar disorder and 19 on dementia. The results showed that the genes CACNA1C, GABBR2, SCN2A, CTSH, MSRA, and SH3PXD2A were overlapping between patients with bipolar disorder and dementia. In conclusion, the genes CACNA1C, GABBR2, SCN2A, CTSH, MSRA, and SH3PXD2A may be associated with the neuro-progression of bipolar disorder to dementia. Further genetic studies are needed to comprehensively clarify the role of genes in cognitive decline and the development of dementia in patients with bipolar disorder.

Background: Cognitive impairment is a relevant problem in psychiatry and can be well assessed with a cross-diagnostic test such as the Screen for Cognitive Impairment in Psychiatry (SCIP). The aim of our pilot study is to assess cognitive impairment in acute psychiatric inpatients diagnosed with psychotic disorders, bipolar disorder and depression using the German version of the SCIP (SCIP-G). We also investigate whether cognitive dysfunction improves over the course of the inpatient treatment, where patients are offered a combination of pharmacological treatment and cognitive remediation. Methods: A total of 143 adult inpatients were included in the study. Cognitive testing was performed using two different forms of the SCIP-G. All patients received state-of-the-art pharmacotherapy and cognitive remediation using the COGPACK® software package version 6.06. Results: Based on the ICD-10 Criteria for Research, 54 patients were given an F2 diagnosis (schizophrenia and schizotypal and delusional disorders). Thirty-nine patients met the criteria for bipolar disorder (F30 and F31) and fifty for depression (F32 and F33). At baseline, a significant difference was observed between the SCIP total scores of the F2 and F32/33 patients (p < 0.001) and between the F2 and F30/31 groups (p = 0.022). At the second measurement time point, the SCIP total score showed significant improvement in all three groups (p < 0.001), and there was no statistically significant interaction between SCIP total score and diagnostic groups (p = 0.860). Conclusions: Cognitive dysfunction is present in psychiatric disorders and can be easily assessed during an inpatient hospital stay. In our sample, patients with a psychotic disorder were more cognitively impaired at baseline than patients with an affective disorder. Inpatient treatment, consisting of pharmacotherapy and cognitive remediation, improved cognitive deficits. Patients with psychotic disorders, bipolar disorder and depression showed similar improvements in cognitive performance.

The understanding of the immunological mechanisms underlying bipolar disorder (BD) has enhanced in recent years due to the extensive use of high-density genetic markers for genotyping and advancements in genome-wide association studies (GWAS). However, studies on the relationship between immune cells and the risk of BD remain limited, necessitating further investigation.

Bidirectional two-sample Mendelian Randomization (MR) analysis was employed to investigate the causal association between immune cell morphologies and bipolar disorder. Immune cell traits were collected from a research cohort in Sardinia, whereas the GWAS summary statistics for BD were obtained from the Psychiatric Genomics Consortium. Sensitivity analyses were conducted, and the combination of MR-Egger and MR-Presso was used to assess horizontal pleiotropy. Cochran's Q test was employed to evaluate heterogeneity, and the results were adjusted for false discovery rate (FDR).

The study identified six immune cell phenotypes significantly associated with BD incidence (P< 0.01). These phenotypes include IgD- CD27- %lymphocyte, CD33br HLA DR+ CD14- AC, CD8 on CD28+ CD45RA+ CD8br, CD33br HLA DR+ AC, CD14 on CD14+ CD16+ monocyte, and HVEM on CD45RA- CD4+. After adjusting the FDR to 0.2, two immune cell phenotypes remained statistically significant: IgD-CD27-% lymphocyte (OR=1.099, 95% CI: 1.051-1.149, P = 3.51E-05, FDR=0.026) and CD33br HLA DR+ CD14-AC (OR=0.981, 95% CI: 0.971-0.991, P = 2.17E-04, FDR=0.079). In the reverse MR analysis, BD significantly impacted the phenotypes of four monocytes (P< 0.01), including CD64 on CD14+ CD16+ monocyte, CD64 on monocyte, CX3CR1 on CD14- CD16-, CD64 on CD14+ CD16- monocyte. However, after applying the FDR correction (FDR < 0.2), no statistically significant results were observed.

This MR investigation reveals associations between immune cell phenotypes, bipolar disorder, and genetics, providing novel perspectives on prospective therapeutic targets for bipolar disorder.

Estrogen is a group of hormones that collaborate with the nervous system to impact the overall well-being of all genders. It influences many processes, including those occurring in the central nervous system, affecting learning and memory, and playing roles in neurodegenerative diseases and mental disorders. The hormone's action is mediated by specific receptors. Significant roles of classical estrogen receptors, ERα and ERβ, in various diseases were known since many years, but after identifying a structurally and locationally distinct receptor, the G protein-coupled estrogen receptor (GPER), its role in human physiology and pathophysiology was investigated. This review compiles GPER-related information, highlighting its impact on homeostasis and diseases, while putting special attention on functions and dysfunctions of this receptor in neurobiology and biobehavioral processes. Understanding the receptor modulation possibilities is essential for therapy, as disruptions in receptors can lead to diseases or disorders, irrespective of correct estrogen levels. We conclude that studies on the GPER receptor have the potential to develop therapies that regulate estrogen and positively impact human health.

Based on recent genome-wide association studies, it is theorized that altered regulation of autophagy contributes to the pathophysiology of schizophrenia and bipolar disorder. As activity of autophagy-regulatory pathways is controlled by discrete phosphorylation sites on the relevant proteins, phospho-protein profiling is one of the few approaches available for enabling a quantitative assessment of autophagic activity in the brain. Despite this, a comprehensive phospho-protein assessment in the brains of schizophrenia and bipolar disorder subjects is currently lacking. Using this direction, our broad screening identifies an increase in AMP-activated protein kinase (AMPK)-mediated phospho-activation of the pro-autophagy protein beclin-1 solely in the prefrontal cortex of female, but not male, schizophrenia subjects. Using a reverse translational approach, we surprisingly find that this increase in beclin-1 activity facilitates synapse formation and enhances cognition. These findings are interpreted in the context of human studies demonstrating that female schizophrenia subjects have a lower susceptibility to cognitive dysfunction than males.

Patients with bipolar disorder (BD) and major depressive disorder (MDD) experience psychological distress associated with daily events that do not meet the threshold for traumatic experiences, referred to as event-related psychological distress (ERPD). Recently, we developed an assessment tool for ERPD, the ERPD-24. This tool considers four factors of ERPD: feelings of revenge, rumination, self-denial, and mental paralysis. We conducted a cross-sectional study between March 2021 and October 2022 to identify the differences and clinical features of ERPD among patients with MDD and BD and healthy subjects who did not experience traumatic events. Specifically, we assessed ERPD using the ERPD-24 and anxiety-related symptoms with the State-Trait Anxiety Inventory, Liebowitz Social Anxiety Scale, and anxious-depressive attack. Regarding the ERPD-24 scores among the groups, as the data did not rigorously follow the test of normality, the Kruskal-Wallis test was used to compare the differences among the groups, followed by the Dunn-Bonferroni adjusted post-hoc test. Non-remitted MDD patients and BD patients, regardless of remission/non-remission, presented more severe ERPD than healthy subjects. This study also demonstrated the relationships between all anxiety-related symptoms, including social phobia and anxious-depressive attack and ERPD, in both BD and MDD patients and in healthy subjects. In conclusion, patients with non-remitted MDD and with BD regardless of remission/non-remission experience severe ERPD related to anxiety-related symptoms.

Bipolar disorder (BD) has been related to various cognitive dysfunctions as well as to a high prevalence of metabolic syndrome (MS), which seems to influence the cognitive performance of patients with BD. Therefore, different hypotheses have been generated to try to explain the pathophysiological relationship between cognitive deficit in BD and MS. The objective was to review the current literature regarding the possible pathophysiological explanation of the relationship between BD and MS and its effect on cognitive performance of patients with BD.

A bibliographic search was carried out using MEDLINE, ClinicalKey, EMBASE, Literatura Latino-Americana y del Caribe en Ciencias de la Salud [Latin American and Caribbean Literature in Health Sciences] (LILACS), APA PsycNet, Scopus and Scielo databases, and the Pan-American Medical Electronic Library; using the following search terms: "bipolar disorder"[MeSH Terms] OR "bipolar disorder"[All Fields] OR "mood disorders"[All Fields] AND "cognitive deficit"[MeSH Terms] OR "cognitive deficit"[All Fields] OR "cognitive dysfunction"[All Fields] OR "cognitive impairment"[All Fields] OR "cognitive decline"[All Fields] AND "metabolic syndrome" [MeSH Terms] OR "metabolic abnormalities"[All Fields] OR "metabolic effects"[All Fields] OR "obesity" [All Fields] OR "abdominal obesity" [All Fields] OR "overweight" [All Fields] OR "diabetes" [All Fields] OR "hypertension" [All Fields] AND "antipsychotics" [MeSH Terms] OR "antipsychotics"[All Fields] AND "antidepressants" [MeSH Terms] OR "antidepressants"[All Fields] AND "mood stabilizers" [MeSH Terms] OR "mood stabilizers"[All Fields]. Filters: free full text, full text, from 2001 to 2022. A total of 80 articles in Spanish and English, of any type of design, were selected. Selection and reading were carried out by all the authors.

The various pathophysiological hypotheses proposed, inflammatory, endocrine, drug, environmental and social, suggest that a series of changes at the macro and microcellular level are correlated in patients with BD and MS with a negative effect on cognition of patients both globally and in specific domains, mainly executive function, memory, attention, and perceptual motor skills. Research processes should be continued to explore the various hypotheses that support the relationship between BD, MS and cognition.

Introduction: Rehabilitative interventions employing technology play a crucial role in bipolar disorder (BD) treatment. The study aims to appraise the virtual reality (VR)-based cognitive remediation (CR) and the interpersonal rhythm approaches to treatment outcomes of BD across different age groups. Methods: Post-hoc analysis of a 12-week randomizedcontrolled cross-over feasibility trial involving people with mood disorders (BD, DSM-IV) aged 18-75 years old: thirty-nine exposed to the experimental VR-based CR vs 25 waiting list controls. People with BD relapse, epilepsy or severe eye diseases (due to the potential VR risks exposure) were excluded. Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) was used to measure the outcome. Results: Cases and controls did not statistically significantly differ in age and sex distributions. Personal rhythm scores improved over the study follow-up in the experimental vs the control group (APC = 8.7%; F = 111.9; p < 0.0001), both in young (18-45 years) (APC = 5.5%; F = 70.46; p < 0.0001) and, to a lesser extent, older (>46 years) adults (APC = 10.5%; F = 12.110; p = 0.002). Conclusions: This study observed improved synchronization of personal and social rhythms in individuals with BD after a virtual reality cognitive remediation intervention, particularly in social activity, daily activities, and chronotype, with greater benefits in the younger population.

This study addresses the challenge of differentiating between bipolar disorder II (BD II) and borderline personality disorder (BPD), which is complicated by overlapping symptoms. To overcome this, a multimodal machine learning approach was employed, incorporating both electroencephalography (EEG) patterns and cognitive abnormalities for enhanced classification. Data were collected from 45 participants, including 20 with BD II and 25 with BPD. Analysis involved utilizing EEG signals and cognitive tests, specifically the Wisconsin Card Sorting Test and Integrated Cognitive Assessment. The k-nearest neighbors (KNN) algorithm achieved a balanced accuracy of 93%, with EEG features proving to be crucial, while cognitive features had a lesser impact. Despite the strengths, such as diverse model usage, it's important to note limitations, including a small sample size and reliance on DSM diagnoses. The study suggests that future research should explore multimodal data integration and employ advanced techniques to improve classification accuracy and gain a better understanding of the neurobiological distinctions between BD II and BPD.

Cognitive impairment is a recognized fundamental deficit in individuals diagnosed with schizophrenia (SZ), bipolar II disorder (BD II), and major depressive disorder (MDD), among other psychiatric disorders. However, limited research has compared cognitive function among first-episode drug-naïve individuals with SZ, BD II, or MDD.

This study aimed to address this gap by assessing the cognitive performance of 235 participants (40 healthy controls, 58 SZ patients, 72 BD II patients, and 65 MDD patients) using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) before and after 12 weeks of treatment in SZ, BD II, and MDD patients. To clarify, the healthy controls only underwent RBANS testing at baseline, whereas the patient groups were assessed before and after treatment. The severity of symptoms in SZ patients was measured using the Positive and Negative Syndrome Scale (PANSS), and depression in BD II and MDD patients was assessed using the Hamilton Depression Scale-24 items (HAMD-24 items).

Two hundred participants completed the 12-week treatment period, with 35 participants dropping out due to various reasons. This group included 49 SZ patients, 58 BD II patients, and 53 MDD patients. Among SZ patients, significant improvements in immediate and delayed memory were observed after 12 weeks of treatment compared to their initial scores. Similarly, BD II patients showed significant improvement in immediate and delayed memory following treatment. However, there were no significant differences in RBANS scores for MDD patients after 12 weeks of treatment.

In conclusion, the findings of this study suggest that individuals with BD II and SZ may share similar deficits in cognitive domains. It is important to note that standardized clinical treatment may have varying degrees of effectiveness in improving cognitive function in patients with BD II and SZ, which could potentially alleviate cognitive dysfunction.

Bipolar depression is the major cause of morbidity in patients with bipolar disorder. It affects psychosocial functioning and markedly impairs occupational productivity. Anhedonia is one of the most debilitating symptoms of depression contributing to treatment resistance. It correlates with suicidality, low quality of life, social withdrawal, and poor treatment response. Currently, there is no approved treatment specifically targeting anhedonia. Emerging evidence suggests that ketamine possesses anti-anhedonic properties in individuals with depression.

The aim of this naturalistic open-label study was to investigate the effect of add-on ketamine treatment on anhedonia in treatment resistant bipolar depression.

Our main interest was the change in patient-reported (Snaith-Hamilton Pleasure Scale) and rater-based anhedonia measure (Montgomery-Åsberg Depression Rating Scale-anhedonia subscale). The secondary aim was to analyze the score change in three Inventory of Depressive Symptomatology-Self Report (IDS-SR) domains: mood/cognition, anxiety/somatic, and sleep. Patients underwent assessments at several time points, including baseline, after the third, fifth, and seventh ketamine infusions. Additionally, a follow-up assessment was conducted 1 week following the final ketamine administration.

We found improvement in anhedonia symptoms according to both patient-reported and rater-based measures. The improvement in IDS-SR domains was most prominent in anxiety/somatic factor and mood/cognition factor, improvement in sleep factor was not observed. No serious adverse events occurred.

Add-on ketamine seems to be a good choice for the treatment of anhedonia in treatment resistant bipolar depression. It also showed a good effect in reducing symptoms of anxiety in this group of patients. Considering unmet needs and the detrimental effect of anhedonia and anxiety, more studies are needed on ketamine treatment in resistant bipolar depression.