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Tavast IM, Solismaa A, Lyytikäinen LP, Mononen N, Moilanen E, Hämäläinen M, Lehtimäki T, Kampman O. Leptin and leptin receptor gene polymorphisms and depression treatment response. Acta Neuropsychiatr 2024; 37:e38. [PMID: 39529327 DOI: 10.1017/neu.2024.43] [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: 11/16/2024]
Abstract
OBJECTIVE Associations between leptin (LEP) and leptin receptor (LEPR) gene polymorphisms and mood disorders have been found but not yet confirmed in multiple studies. The aim of our study was to study the associations between LEP and LEPR single nucleotide polymorphisms (SNPs) and treatment response of depression. Associations between leptin levels and depression severity were also investigated. METHODS The data included 242 depressed patients in secondary psychiatric care. Symptoms of depression were assessed with the Montgomery–Åsberg Depression Rating Scale (MADRS). Previously found LEP and LEPR SNPs associated with depression and other mood disorders were studied. Furthermore, all available LEP and LEPR SNPs were clumped using proxy SNPs to represent gene areas in r2 > 0.2 linkage disequilibrium and their association with treatment response was analysed with logistic regression. RESULTS Two proxy SNPs of LEPR gene, rs12564738 and rs12029311, were associated with MADRS response at 6 weeks (p adjusted = 0.024, p adjusted = 0.024). SNPs from previous studies were not associated with MADRS response, but LEPR rs12145690 from a previous study was strongly associated with rs12564738 (r2 = 0.94). The positive association between leptin levels and MADRS score at baseline after adjusting with age, sex, body mass index (BMI), Alcohol Use Disorders Identification Test score, and smoking was found (p = 0.011). CONCLUSION Our findings suggest that LEPR polymorphisms are associated with depression treatment response. We also found associations between leptin levels and depression independently of BMI. Further studies and meta-analyses are needed to confirm the significance of found SNPs and the role of leptin in depression.
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Affiliation(s)
- Ida-Maria Tavast
- Department of Psychiatry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Anssi Solismaa
- Department of Psychiatry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Psychiatry, The Pirkanmaa Wellbeing Services County, Tampere, Finland
| | - Leo-Pekka Lyytikäinen
- Department of Clinical Chemistry, Tampere University Hospital and Fimlab Laboratories and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Nina Mononen
- Department of Clinical Chemistry, Tampere University Hospital and Fimlab Laboratories and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Eeva Moilanen
- The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland
| | - Mari Hämäläinen
- The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland
| | - Terho Lehtimäki
- Department of Clinical Chemistry, Tampere University Hospital and Fimlab Laboratories and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Olli Kampman
- Department of Psychiatry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Psychiatry, The Pirkanmaa Wellbeing Services County, Tampere, Finland
- Department of Psychiatry, Department of Clinical Sciences (Psychiatry), Faculty of Medicine, University Hospital of Umeå, Umeå University, Umeå, Sweden
- Department of Clinical Medicine (Psychiatry), Faculty of Medicine, University of Turku, Turku, Finland
- Department of Psychiatry, The Wellbeing Services County of Ostrobothnia, Vaasa, Finland
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Sempach L, Doll JPK, Limbach V, Marzetta F, Schaub AC, Schneider E, Kettelhack C, Mählmann L, Schweinfurth-Keck N, Ibberson M, Lang UE, Schmidt A. Examining immune-inflammatory mechanisms of probiotic supplementation in depression: secondary findings from a randomized clinical trial. Transl Psychiatry 2024; 14:305. [PMID: 39048549 PMCID: PMC11269721 DOI: 10.1038/s41398-024-03030-7] [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: 03/21/2024] [Revised: 07/15/2024] [Accepted: 07/17/2024] [Indexed: 07/27/2024] Open
Abstract
We recently indicated that four-week probiotic supplementation significantly reduced depression along with microbial and neural changes in people with depression. Here we further elucidated the biological modes of action underlying the beneficial clinical effects of probiotics by focusing on immune-inflammatory processes. The analysis included a total of N = 43 participants with depression, from which N = 19 received the probiotic supplement and N = 24 received a placebo over four weeks, in addition to treatment as usual. Blood and saliva were collected at baseline, at post-intervention (week 4) and follow-up (week 8) to assess immune-inflammatory markers (IL-1β, IL-6, CRP, MIF), gut-related hormones (ghrelin, leptin), and a stress marker (cortisol). Furthermore, transcriptomic analyses were conducted to identify differentially expressed genes. Finally, we analyzed the associations between probiotic-induced clinical and immune-inflammatory changes. We observed a significant group x time interaction for the gut hormone ghrelin, indicative of an increase in the probiotics group. Additionally, the increase in ghrelin was correlated with the decrease in depressive symptoms in the probiotics group. Transcriptomic analyses identified 51 up- and 57 down-regulated genes, which were involved in functional pathways related to enhanced immune activity. We identified a probiotic-dependent upregulation of the genes ELANE, DEFA4 and OLFM4 associated to immune activation and ghrelin concentration. These results underscore the potential of probiotic supplementation to produce biological meaningful changes in immune activation in patients with depression. Further large-scale mechanistic trials are warranted to validate and extend our understanding of immune-inflammatory measures as potential biomarkers for stratification and treatment response in depression. Trial Registration: www.clinicaltrials.gov , identifier: NCT02957591.
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Affiliation(s)
- Lukas Sempach
- Translational Neuroscience, Department of Clinical Research (DKF), University of Basel, Basel, Switzerland.
- University Psychiatric Clinics Basel (UPK), University of Basel, Basel, Switzerland.
| | - Jessica P K Doll
- Translational Neuroscience, Department of Clinical Research (DKF), University of Basel, Basel, Switzerland
- University Psychiatric Clinics Basel (UPK), University of Basel, Basel, Switzerland
| | - Verena Limbach
- Translational Neuroscience, Department of Clinical Research (DKF), University of Basel, Basel, Switzerland
- University Psychiatric Clinics Basel (UPK), University of Basel, Basel, Switzerland
| | - Flavia Marzetta
- Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland
| | - Anna-Chiara Schaub
- University Psychiatric Clinics Basel (UPK), University of Basel, Basel, Switzerland
- Translational Psychiatry, Department of Clinical Research (DKF), University of Basel, Basel, Switzerland
| | - Else Schneider
- University Psychiatric Clinics Basel (UPK), University of Basel, Basel, Switzerland
- Experimental Cognitive and Clinical Affective Neuroscience (ECAN) Laboratory, Department of Clinical Research (DKF), University of Basel, Basel, Switzerland
| | - Cedric Kettelhack
- University Psychiatric Clinics Basel (UPK), University of Basel, Basel, Switzerland
| | - Laura Mählmann
- University Psychiatric Clinics Basel (UPK), University of Basel, Basel, Switzerland
| | | | - Mark Ibberson
- Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland
| | - Undine E Lang
- University Psychiatric Clinics Basel (UPK), University of Basel, Basel, Switzerland
| | - André Schmidt
- Translational Neuroscience, Department of Clinical Research (DKF), University of Basel, Basel, Switzerland
- University Psychiatric Clinics Basel (UPK), University of Basel, Basel, Switzerland
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Shell AL, Crawford CA, Cyders MA, Hirsh AT, Stewart JC. Depressive disorder subtypes, depressive symptom clusters, and risk of obesity and diabetes: A systematic review. J Affect Disord 2024; 353:70-89. [PMID: 38432462 DOI: 10.1016/j.jad.2024.02.051] [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: 09/13/2023] [Revised: 02/09/2024] [Accepted: 02/13/2024] [Indexed: 03/05/2024]
Abstract
BACKGROUND Overlapping but divided literatures suggest certain depression facets may pose greater obesity and diabetes risk than others. Our objectives were to integrate the major depressive disorder (MDD) subtype and depressive symptom cluster literatures and to clarify which facets are associated with the greatest cardiometabolic disease risk. METHODS We conducted a systematic review of published studies examining associations of ≥2 MDD subtypes or symptom clusters with obesity or diabetes risk outcomes. We report which facets the literature is "in favor" of (i.e., having the strongest or most consistent results). RESULTS Forty-five articles were included. Of the MDD subtype-obesity risk studies, 14 were in favor of atypical MDD, and 8 showed similar or null associations across subtypes. Of the symptom cluster-obesity risk studies, 5 were in favor of the somatic cluster, 1 was in favor of other clusters, and 5 were similar or null. Of the MDD subtype-diabetes risk studies, 7 were in favor of atypical MDD, 3 were in favor of other subtypes, and 5 were similar or null. Of the symptom cluster-diabetes risk studies, 7 were in favor of the somatic cluster, and 5 were similar or null. LIMITATIONS Limitations in study design, sample selection, variable measurement, and analytic approach in these literatures apply to this review. CONCLUSIONS Atypical MDD and the somatic cluster are most consistently associated with obesity and diabetes risk. Future research is needed to establish directionality and causality. Identifying the depression facets conferring the greatest risk could improve cardiometabolic disease risk stratification and prevention programs.
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Affiliation(s)
- Aubrey L Shell
- Department of Psychiatry, Indiana University Health, United States of America
| | | | - Melissa A Cyders
- Department of Psychology, Indiana University-Indianapolis, United States of America
| | - Adam T Hirsh
- Department of Psychology, Indiana University-Indianapolis, United States of America
| | - Jesse C Stewart
- Department of Psychology, Indiana University-Indianapolis, United States of America.
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AlGhamdi S, Alsulami N, Khoja S, Alsufiani H, Tayeb HO, Alshaibi H, Tarazi FI. Serum Ghrelin and Leptin Concentrations in Patients with Major Depressive Disorder before and after Supplementation with Vitamin D3. Depress Anxiety 2024; 2024:2057881. [PMID: 40226697 PMCID: PMC11918899 DOI: 10.1155/2024/2057881] [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: 12/29/2023] [Revised: 03/06/2024] [Accepted: 03/07/2024] [Indexed: 04/15/2025] Open
Abstract
Aim To determine serum concentrations of leptin and ghrelin in patients with major depressive disorder (MDD) before and after vitamin D3 supplementation. Methods A total of 72 participants were recruited in this study (40 MDD patients and 32 healthy controls). MDD was diagnosed by using Beck's Depression Inventory (BDI) scale. Blood samples were collected from all participants at the beginning of the study to determine baseline serum 25(OH)D3, leptin, and ghrelin concentrations. Patients were then treated weekly with vitamin D3 (50,000 IU) for 3 months, and blood samples were collected again by the end of the study. Results At baseline, serum leptin concentrations were significantly higher in MDD patients than in healthy controls. In contrast, serum ghrelin concentrations were significantly lower compared to those in healthy controls. After supplementation with vitamin D3 for three months, MDD patients showed improvements characterized by a decrease in their BDI's scores and an increase in their serum vitamin D and ghrelin concentrations. No effects of vitamin D3 supplementation were seen on serum leptin concentration. Conclusions The antidepressant effects of vitamin D3 supplementation could be mediated by ghrelin but not leptin.
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Affiliation(s)
- Shareefa AlGhamdi
- Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
- Vitamin D Pharmacogenomics Research Group, King Abdulaziz University, Jeddah, Saudi Arabia
- Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Nabilah Alsulami
- Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Sawsan Khoja
- Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
- Vitamin D Pharmacogenomics Research Group, King Abdulaziz University, Jeddah, Saudi Arabia
- Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Hadeil Alsufiani
- Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
- Vitamin D Pharmacogenomics Research Group, King Abdulaziz University, Jeddah, Saudi Arabia
- Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Haythum O. Tayeb
- The Mind and Brain Studies Initiative, The Neuroscience Research Unit, Division of Neurology, Department of Internal Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Huda Alshaibi
- Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
- Embryonic Stem Cell Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Frank I. Tarazi
- Department of Psychiatry and Neuroscience Program, Harvard Medical School and McLean Hospital, Boston, MA, USA
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McNaughton BA, Burrows K, Choquette E, Poplin T, Kuplicki R, Paulus MP, Ironside M, Stewart JL. Impaired eating behaviors but intact metabolic hormone levels in individuals with major depressive disorder and generalized anxiety disorder. J Psychiatr Res 2023; 168:193-203. [PMID: 37918032 PMCID: PMC10842703 DOI: 10.1016/j.jpsychires.2023.10.042] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 10/23/2023] [Accepted: 10/25/2023] [Indexed: 11/04/2023]
Abstract
BACKGROUND Major depressive disorder (MDD) and generalized anxiety disorder (GAD) contribute significantly to global health burdens. Identifying disease markers for these comorbid disorders can increase understanding of pathogenesis and improve screening and intervention strategies. This study examined the association of physical health factors with MDD and MDD + GAD, across sexes. METHODS Two samples of participants from the Tulsa-1000 study (exploratory cohort: N = 136; confirmatory cohort: N = 185) completed body composition measurements, eating behavior (Three Factor Eating Questionnaire [TFEQ], Eating Disorder Diagnostic Scale [EDDS]), exercise questionnaires, and a blood draw. Metabolic hormone concentrations (leptin, insulin, and adiponectin) were analyzed from blood samples. Within each cohort, a two-way analysis of variance compared three groups (MDD, MDD + GAD, and healthy controls [HC]), sex, and their interaction on dependent variables. Hedges g was calculated to reflect effect size magnitude. RESULTS Medium-to-large group main effects across cohorts indicated that compared to HC: (1) MDD (g = 1.71/0.57) and MDD + GAD (g = 0.93/0.69) reported higher TFEQ Disinhibition scores; (2) MDD endorsed higher TFEQ Hunger scores (g = 0.66/0.48); and (3) MDD (g = 1.60/1.30) and MDD + GAD (g = 0.92/1.72) reported greater EDDS scores. Large sex main effects across cohorts indicated that females exhibited higher levels than males for percent body fat (g = 1.07/1.17), leptin (g = 1.27/1.12), and adiponectin (g=0.82/0.88). LIMITATIONS The power to detect group*sex interactions was limited due to a greater number of females (than males) in the study, and over half of clinical participants were taking medications. CONCLUSIONS Individuals with MDD and MDD + GAD demonstrate difficulties in regulating eating behaviors, potentially contributing to functional impairment and increased disease burden.
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Affiliation(s)
| | | | | | - Tate Poplin
- Laureate Institute of Brain Research, Tulsa, OK, USA
| | | | - Martin P Paulus
- Laureate Institute of Brain Research, Tulsa, OK, USA; The University of Tulsa, Tulsa, OK, USA
| | - Maria Ironside
- Laureate Institute of Brain Research, Tulsa, OK, USA; The University of Tulsa, Tulsa, OK, USA
| | - Jennifer L Stewart
- Laureate Institute of Brain Research, Tulsa, OK, USA; The University of Tulsa, Tulsa, OK, USA.
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Burrows K, McNaughton BA, Figueroa-Hall LK, Spechler PA, Kuplicki R, Victor TA, Aupperle R, Khalsa SS, Savitz JB, Teague TK, Paulus MP, Stewart JL. Elevated serum leptin is associated with attenuated reward anticipation in major depressive disorder independent of peripheral C-reactive protein levels. Sci Rep 2023; 13:11313. [PMID: 37443383 PMCID: PMC10344903 DOI: 10.1038/s41598-023-38410-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 07/07/2023] [Indexed: 07/15/2023] Open
Abstract
Major depressive disorder (MDD) is associated with immunologic and metabolic alterations linked to central processing dysfunctions, including attenuated reward processing. This study investigated the associations between inflammation, metabolic hormones (leptin, insulin, adiponectin), and reward-related brain processing in MDD patients with high (MDD-High) and low (MDD-Low) C-reactive protein (CRP) levels compared to healthy comparison subjects (HC). Participants completed a blood draw and a monetary incentive delay task during functional magnetic resonance imaging. Although groups did not differ in insulin or adiponectin concentrations, both MDD-High (Wilcoxon p = 0.004, d = 0.65) and MDD-Low (Wilcoxon p = 0.046, d = 0.53) showed higher leptin concentrations than HC but did not differ from each other. Across MDD participants, higher leptin levels were associated with lower brain activation during reward anticipation in the left insula (r = - 0.30, p = 0.004) and left dorsolateral putamen (r = -- 0.24, p = 0.025). In contrast, within HC, higher leptin concentrations were associated with higher activation during reward anticipation in the same regions (insula: r = 0.40, p = 0.007; putamen: r = 0.37, p = 0.014). Depression may be characterized by elevated pro-inflammatory signaling via leptin concentrations through alternate inflammatory pathways distinct to CRP.
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Affiliation(s)
- Kaiping Burrows
- Laureate Institute for Brain Research, 6655 South Yale Ave, Tulsa, OK, 74136, USA.
| | - Breanna A McNaughton
- Laureate Institute for Brain Research, 6655 South Yale Ave, Tulsa, OK, 74136, USA
| | - Leandra K Figueroa-Hall
- Laureate Institute for Brain Research, 6655 South Yale Ave, Tulsa, OK, 74136, USA
- Oxley College of Health Sciences, University of Tulsa, Tulsa, OK, USA
| | - Philip A Spechler
- Laureate Institute for Brain Research, 6655 South Yale Ave, Tulsa, OK, 74136, USA
| | - Rayus Kuplicki
- Laureate Institute for Brain Research, 6655 South Yale Ave, Tulsa, OK, 74136, USA
| | - Teresa A Victor
- Laureate Institute for Brain Research, 6655 South Yale Ave, Tulsa, OK, 74136, USA
| | - Robin Aupperle
- Laureate Institute for Brain Research, 6655 South Yale Ave, Tulsa, OK, 74136, USA
- Oxley College of Health Sciences, University of Tulsa, Tulsa, OK, USA
| | - Sahib S Khalsa
- Laureate Institute for Brain Research, 6655 South Yale Ave, Tulsa, OK, 74136, USA
- Oxley College of Health Sciences, University of Tulsa, Tulsa, OK, USA
| | - Jonathan B Savitz
- Laureate Institute for Brain Research, 6655 South Yale Ave, Tulsa, OK, 74136, USA
- Oxley College of Health Sciences, University of Tulsa, Tulsa, OK, USA
| | - T Kent Teague
- Departments of Surgery and Psychiatry, School of Community Medicine, The University of Oklahoma, Tulsa, OK, USA
- Department of Biochemistry and Microbiology, The Oklahoma State University Center for Health Sciences, Tulsa, OK, USA
- Department of Pharmaceutical Sciences, The University of Oklahoma College of Pharmacy, Oklahoma City, OK, USA
| | - Martin P Paulus
- Laureate Institute for Brain Research, 6655 South Yale Ave, Tulsa, OK, 74136, USA
- Oxley College of Health Sciences, University of Tulsa, Tulsa, OK, USA
| | - Jennifer L Stewart
- Laureate Institute for Brain Research, 6655 South Yale Ave, Tulsa, OK, 74136, USA
- Oxley College of Health Sciences, University of Tulsa, Tulsa, OK, USA
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Refisch A, Sen ZD, Klassert TE, Busch A, Besteher B, Danyeli LV, Helbing D, Schulze-Späte U, Stallmach A, Bauer M, Panagiotou G, Jacobsen ID, Slevogt H, Opel N, Walter M. Microbiome and immuno-metabolic dysregulation in patients with major depressive disorder with atypical clinical presentation. Neuropharmacology 2023; 235:109568. [PMID: 37182790 DOI: 10.1016/j.neuropharm.2023.109568] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 03/24/2023] [Accepted: 04/30/2023] [Indexed: 05/16/2023]
Abstract
Depression is highly prevalent (6% 1-year prevalence) and is the second leading cause of disability worldwide. Available treatment options for depression are far from optimal, with response rates only around 50%. This is most likely related to a heterogeneous clinical presentation of major depression disorder (MDD), suggesting different manifestations of underlying pathophysiological mechanisms. Poorer treatment outcomes to first-line antidepressants were reported in MDD patients endorsing an "atypical" symptom profile that is characterized by preserved reactivity in mood, increased appetite, hypersomnia, a heavy sensation in the limbs, and interpersonal rejection sensitivity. In recent years, evidence has emerged that immunometabolic biological dysregulation is an important underlying pathophysiological mechanism in depression, which maps more consistently to atypical features. In the last few years human microbial residents have emerged as a key influencing variable associated with immunometabolic dysregulations in depression. The microbiome plays a critical role in the training and development of key components of the host's innate and adaptive immune systems, while the immune system orchestrates the maintenance of key features of the host-microbe symbiosis. Moreover, by being a metabolically active ecosystem commensal microbes may have a huge impact on signaling pathways, involved in underlying mechanisms leading to atypical depressive symptoms. In this review, we discuss the interplay between the microbiome and immunometabolic imbalance in the context of atypical depressive symptoms. Although research in this field is in its infancy, targeting biological determinants in more homogeneous clinical presentations of MDD may offer new avenues for the development of novel therapeutic strategies for treatment-resistant depression.
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Affiliation(s)
- Alexander Refisch
- Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany; Center for Intervention and Research on Adaptive and Maladaptive Brain Circuits Underlying Mental Health (C-I-R-C), Jena-Magdeburg-Halle, Germany.
| | - Zümrüt Duygu Sen
- Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany; Center for Intervention and Research on Adaptive and Maladaptive Brain Circuits Underlying Mental Health (C-I-R-C), Jena-Magdeburg-Halle, Germany; Clinical Affective Neuroimaging Laboratory (CANLAB), Magdeburg, Germany
| | - Tilman E Klassert
- Host Septomics Group, Centre for Innovation Competence (ZIK) Septomics, University Hospital Jena, 07745, Jena, Germany; Respiratory Infection Dynamics, Helmholtz Centre for Infection Research (HZI), Inhoffenstr, Braunschweig, Germany
| | - Anne Busch
- Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany; Center for Sepsis Control and Care, Jena, Germany
| | - Bianca Besteher
- Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany; Center for Intervention and Research on Adaptive and Maladaptive Brain Circuits Underlying Mental Health (C-I-R-C), Jena-Magdeburg-Halle, Germany
| | - Lena Vera Danyeli
- Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany; Center for Intervention and Research on Adaptive and Maladaptive Brain Circuits Underlying Mental Health (C-I-R-C), Jena-Magdeburg-Halle, Germany; Clinical Affective Neuroimaging Laboratory (CANLAB), Magdeburg, Germany
| | - Dario Helbing
- Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany; Center for Intervention and Research on Adaptive and Maladaptive Brain Circuits Underlying Mental Health (C-I-R-C), Jena-Magdeburg-Halle, Germany; Leibniz Institute on Aging-Fritz Lipmann Institute, 07745, Jena, Germany; Institute of Molecular Cell Biology, Jena University Hospital, Friedrich Schiller University Jena, 07745, Jena, Germany
| | - Ulrike Schulze-Späte
- Section of Geriodontics, Department of Conservative Dentistry and Periodontology, Jena University Hospital, Jena, Germany
| | - Andreas Stallmach
- Department of Internal Medicine IV (Gastroenterology, Hepatology and Infectious Diseases), Jena University Hospital, Germany
| | - Michael Bauer
- Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany; Center for Sepsis Control and Care, Jena, Germany; Theoretical Microbial Ecology, Friedrich Schiller University Jena, Jena, Germany
| | - Gianni Panagiotou
- Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Jena, Germany
| | - Ilse D Jacobsen
- Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany, and Institute of Microbiology, Friedrich Schiller University Jena, Jena, Germany
| | - Hortense Slevogt
- Host Septomics Group, Centre for Innovation Competence (ZIK) Septomics, University Hospital Jena, 07745, Jena, Germany; Respiratory Infection Dynamics, Helmholtz Centre for Infection Research (HZI), Inhoffenstr, Braunschweig, Germany; Department of Pulmonary Medicine, Hannover Medical School, 30625, Hannover, Germany
| | - Nils Opel
- Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany; Center for Intervention and Research on Adaptive and Maladaptive Brain Circuits Underlying Mental Health (C-I-R-C), Jena-Magdeburg-Halle, Germany; German Center for Mental Health (DZPG), Site Jena-Magdeburg-Halle, Germany
| | - Martin Walter
- Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany; Center for Intervention and Research on Adaptive and Maladaptive Brain Circuits Underlying Mental Health (C-I-R-C), Jena-Magdeburg-Halle, Germany; Clinical Affective Neuroimaging Laboratory (CANLAB), Magdeburg, Germany; German Center for Mental Health (DZPG), Site Jena-Magdeburg-Halle, Germany; Center for Behavioral Brain Sciences, Magdeburg, Germany
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Choi W, Kim JW, Kang HJ, Kim HK, Kang HC, Lee JY, Kim SW, Stewart R, Kim JM. Interactive Effects of Serum Leptin Levels and Physical Comorbidity on the Pharmacotherapeutic Response of Depressive Disorders. CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE : THE OFFICIAL SCIENTIFIC JOURNAL OF THE KOREAN COLLEGE OF NEUROPSYCHOPHARMACOLOGY 2022; 20:662-674. [PMID: 36263641 PMCID: PMC9606432 DOI: 10.9758/cpn.2022.20.4.662] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 06/13/2021] [Accepted: 06/15/2021] [Indexed: 01/12/2023]
Abstract
OBJECTIVE To investigate individual and interactive associations of baseline serum leptin levels and physical comorbidity with short- and long-term treatment outcomes in outpatients with depressive disorders who received stepwise antidepressant treatment in a naturalistic prospective study design. METHODS Baseline serum leptin levels were measured, and the number of concurrent physical disorders ascertained from 1,094 patients. These patients received initial antidepressant monotherapy; then, for patients with an insufficient response or who experienced uncomfortable side effects, treatment was administered using alternative strategies every 3 weeks in the acute treatment phase (at 3, 6, 9, and 12 weeks) and every 3 months in the continuation treatment phase (at 6, 9, and 12 months). Then, 12-week and 12-month remission, defined as a Hamilton Depression Rating Scale score of ≤7, was estimated. RESULTS In multivariable logistic regression analyses, individual effects were found only between higher baseline serum leptin levels and 12-week non-remission. Significant interactive effects between higher leptin levels and fewer physical disorders (< 2 physical disorders) on 12-week non-remission were observed. However, neither individual nor interactive effects between leptin levels and physical comorbidity were associated with 12-month remission. CONCLUSION The combination of serum leptin level and number of physical disorders may be a useful predictor of short-term treatment responses in patients with depressive disorders receiving pharmacotherapy.
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Affiliation(s)
- Wonsuk Choi
- Department of Internal Medicine, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea
| | - Ju-Wan Kim
- Department of Psychiatry, Chonnam National University Medical School, Gwangju, Korea
| | - Hee-Ju Kang
- Department of Psychiatry, Chonnam National University Medical School, Gwangju, Korea
| | - Hee Kyung Kim
- Department of Internal Medicine, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea
| | - Ho-Cheol Kang
- Department of Internal Medicine, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea
| | - Ju-Yeon Lee
- Department of Psychiatry, Chonnam National University Medical School, Gwangju, Korea
| | - Sung-Wan Kim
- Department of Psychiatry, Chonnam National University Medical School, Gwangju, Korea
| | - Robert Stewart
- King’s College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK,South London and Maudsley NHS Foundation Trust, London, UK
| | - Jae-Min Kim
- Department of Psychiatry, Chonnam National University Medical School, Gwangju, Korea,Address for correspondence: Jae-Min Kim Department of Psychiatry, Chonnam National University Medical School, 160 Baekseo-ro, Dong-gu, Gwangju 61469, Korea, E-mail: , ORCID: https://orcid.org/0000-0001-7409-6306
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9
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Tasci G, Kaya S, Kalayci M, Atmaca M. Increased ghrelin and decreased leptin levels in patients with antisocial personality disorder. J Affect Disord 2022; 317:22-28. [PMID: 36028010 DOI: 10.1016/j.jad.2022.08.048] [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] [Received: 01/26/2022] [Revised: 07/25/2022] [Accepted: 08/20/2022] [Indexed: 10/31/2022]
Abstract
OBJECTIVE The study aimed to compare acyl ghrelin (AG), des-acyl ghrelin (DAG), and leptin levels considered to be used as biological markers in the etiopathogenesis of antisocial personality disorder (ASPD) with healthy controls, and to investigate the relationship between these hormones and aggression and impulsivity. METHOD The study included 45 patients with ASPD and 61 healthy people in the control group. Sociodemographic data form, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Barratt Impulsiveness Scale (BIS-11), and Buss-Durkee Aggression Scale (BDAS) were applied to all participants. Fasting venous blood samples were taken from all participants at the same time of the day and the height and weight of the participants were measured. RESULTS It was found that the mean serum AG and DAG levels were significantly higher than that of healthy controls whereas leptin hormone levels were significantly lower in patients compared to healthy controls. BDI, BAI, BIS-11, and BDAS scores of the patients were significantly higher compared to healthy controls. There was a positive correlation between AG and DAG hormone levels and impulsivity and aggression. DISCUSSION The present study is the first in the literature to examine AG, DAG, and leptin hormone levels of patients diagnosed with ASPD. According to the results of the study, it is believed that changes in serum leptin and ghrelin levels will bring a new perspective in terms of understanding the pathophysiological mechanism of ASPD. Further studies are required to explain the definitive roles of these hormones in ASPD.
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Affiliation(s)
- Gulay Tasci
- Elazig Fethi Sekin City Hospital, Elazig, Turkey.
| | - Suheda Kaya
- Elazig Mental Health Hospital, Elazig, Turkey
| | | | - Murad Atmaca
- Firat University School of Medicine Department of Psychiatry, Elazig, Turkey
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10
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Chompre G, Sambolin L, Cruz ML, Sanchez R, Rodriguez Y, Rodríguez-Santiago RE, Yamamura Y, Appleyard CB. A one month high fat diet disrupts the gut microbiome and integrity of the colon inducing adiposity and behavioral despair in male Sprague Dawley rats. Heliyon 2022; 8:e11194. [PMID: 36387539 PMCID: PMC9663868 DOI: 10.1016/j.heliyon.2022.e11194] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 06/17/2022] [Accepted: 10/17/2022] [Indexed: 11/05/2022] Open
Abstract
High-fat diet (HFD) is associated with gut microbiome dysfunction and mental disorders. However, the time-dependence as to when this occurs is unclear. We hypothesized that a short-term HFD causes colonic tissue integrity changes resulting in behavioral changes. Rats were fed HFD or low-fat diet (LFD) for a month and gut microbiome, colon, and behavior were evaluated. Behavioral despair was found in the HFD group. Although obesity was absent, the HFD group showed increased percent weight gain, epididymal fat tissue, and leptin expression. Moreover, the HFD group had increased colonic damage, decreased expression of the tight junction proteins, and higher lipopolysaccharides (LPS) in serum. Metagenomic analysis revealed that the HFD group had more Bacteroides and less S24-7 which correlated with the decreased claudin-5. Finally, HFD group showed an increase of microglia percent area, increased astrocytic projections, and decreased phospho-mTOR. In conclusion, HFD consumption in a short period is still sufficient to disrupt gut integrity resulting in LPS infiltration, alterations in the brain, and behavioral despair even in the absence of obesity.
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Affiliation(s)
- Gladys Chompre
- Biology and Biotechnology Department, Pontifical Catholic University of Puerto Rico, Ponce, Puerto Rico
- Basic Sciences Department, Division of Physiology, Ponce Health Sciences University/Ponce Research Institute, Ponce, Puerto Rico
| | - Lubriel Sambolin
- Basic Sciences Department, Division of Pharmacology, Ponce Health Sciences University/Ponce Research Institute, Ponce, Puerto Rico
| | - Myrella L. Cruz
- Basic Sciences Department, Division of Physiology, Ponce Health Sciences University/Ponce Research Institute, Ponce, Puerto Rico
| | - Rafael Sanchez
- AIDS Research Infrastructure Program, Ponce Health Sciences University/Ponce Research Institute, Ponce, Puerto Rico
| | - Yarelis Rodriguez
- Basic Sciences Department, Division of Physiology, Ponce Health Sciences University/Ponce Research Institute, Ponce, Puerto Rico
| | - Ronald E. Rodríguez-Santiago
- AIDS Research Infrastructure Program, Ponce Health Sciences University/Ponce Research Institute, Ponce, Puerto Rico
| | - Yasuhiro Yamamura
- AIDS Research Infrastructure Program, Ponce Health Sciences University/Ponce Research Institute, Ponce, Puerto Rico
| | - Caroline B. Appleyard
- Basic Sciences Department, Division of Physiology, Ponce Health Sciences University/Ponce Research Institute, Ponce, Puerto Rico
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11
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Wittekind DA, Kratzsch J, Biemann R, Mergl R, Riedel-Heller S, Witte V, Villringer A, Kluge M. Association Between Self-rating Depression Scores and Total Ghrelin and Adipokine Serum Levels in a Large Population-Based Sample. Front Psychiatry 2022; 13:891325. [PMID: 35633817 PMCID: PMC9130496 DOI: 10.3389/fpsyt.2022.891325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 04/14/2022] [Indexed: 11/13/2022] Open
Abstract
Background Ghrelin and the adipokines leptin and adiponectin have been suggested to be involved in mood and anxiety regulation and to be altered in affective disorders. However, studies investigating the association between ghrelin, leptin and adiponectin and depressive symptomatology are scarce but might contribute to a better understanding of their involvement in mood regulation. We thus aimed investigating the association between depressive symptomatology and total ghrelin as well as leptin and adiponectin serum levels in a large population-based sample. Methods Total serum ghrelin, adiponectin and leptin levels were determined in 1666 subjects of a population-based cross-sectional study ("LIFE"). The Center for Epidemiological Studies Depression Scale (CES-D) and the Inventory of Depressive Symptoms - Self Rating (IDS-SR) were administered. Multiple linear regression analyses were conducted to examine the association between total serum ghrelin, leptin and adiponectin and the intensity of depressive symptoms. Results In the total sample (n = 1,092), neither ghrelin nor leptin or adiponectin serum levels showed a significant association with CES-D or IDS-SR sum scores (N = 1,092) or in depressed/non-depressed subjects. Leptin serum levels showed a significantly positive association with IDS-SR sum scores in elderly men (≥60 years; β = 0.122, 95% CI: 0.009; 0.236; p = 0.035). Conclusion Our study suggests that peripheral levels of ghrelin and adipokines in a cross-sectional study design might not be sufficient to measure their involvement in depression, suggesting that associations are more complex and multi-layered.
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Affiliation(s)
| | - Jürgen Kratzsch
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Leipzig, Germany
| | - Ronald Biemann
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Leipzig, Germany
| | - Roland Mergl
- Institute of Psychology, Universität der Bundeswehr München, Neubiberg, Germany
| | - Steffi Riedel-Heller
- Faculty of Medicine, Institute of Social Medicine, Occupational Health and Public Health, University of Leipzig, Leipzig, Germany
| | - Veronika Witte
- Department of Neurology, Max Planck Institute for Cognitive and Brain Sciences, Leipzig, Germany
| | - Arno Villringer
- Department of Neurology, Max Planck Institute for Cognitive and Brain Sciences, Leipzig, Germany
| | - Michael Kluge
- Department of Psychiatry and Psychotherapy, University of Leipzig, Leipzig, Germany
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12
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Krishna AG, Goyal N, Ram D, Rajan AK, Kshitiz KK. Hunger Hormones in Disruptive Mood Dysregulation Disorder in Adolescents: An Exploratory Study. ADOLESCENT PSYCHIATRY 2022. [DOI: 10.2174/2210676612666220415112851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Background:
Hunger hormones, including ghrelin and leptin, are associated with appetitive behaviors in various psychiatric disorders. Biochemical and hormonal status in disruptive mood dysregulation disorder (DMDD) in adolescents is largely unexplored.
Objectives:
The study aimed to assess levels of leptin and ghrelin and find their association with lipid profiles in adolescents with DMDD.
Methods:
Twenty adolescents with a DSM 5 diagnosis of DMDD with age and gender-matched 19 healthy controls were recruited, followed by clinical assessment. They were assessed for leptin, ghrelin, and lipid profiles, respectively.
Results:
Adolescents with DMDD were comparable in age, education, family income, domicile status, psychiatric illness in the family, and body mass index (BMI) with matched controls. There was no difference in mean lipid profile and ghrelin in both groups. However, the DMDD group had statistically significant higher mean level of leptin as compared to the control group (t=1.84, p < 0.05). As measured by the Modified Overt Aggression Scale in DMDD, aggression showed a significant positive correlation with measures of lipid profile.
Conclusion:
Adolescents with DMDD have elevated serum leptin levels. Further research is needed to confirm this finding.
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Affiliation(s)
| | - Nishant Goyal
- Associate Professor of Psychiatry, Centre for Child and Adolescent Psychiatry, Central Institute of Psychiatry, Ranchi
| | - Dushad Ram
- Associate Professor of Psychiatry, College of Medicine, Shaqra University, Shaqra
| | | | - K. K. Kshitiz
- Professor of Biochemistry, Central Institute of Psychiatry, Ranchi
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13
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Ha GE, Cheong E. Chronic Restraint Stress Decreases the Excitability of Hypothalamic POMC Neuron and Increases Food Intake. Exp Neurobiol 2021; 30:375-386. [PMID: 34983879 PMCID: PMC8752322 DOI: 10.5607/en21037] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 12/08/2021] [Accepted: 12/11/2021] [Indexed: 11/19/2022] Open
Abstract
Stress activates the hypothalamic-pituitary-adrenal system, and induces the release of glucocorticoids, stress hormones, into circulation. Many studies have shown that stress affects feeding behavior, however, the underlying circuitry and molecular mechanisms are not fully understood. The balance between orexigenic (simulating appetite) and anorexigenic (loss of appetite) signals reciprocally modulate feeding behavior. It is suggested that proopiomelanocortin (POMC) and neuropeptide Y (NPY) neurons in the arcuate nucleus (ARC) of the hypothalamus are the first-order neurons that respond to the circulating signals of hunger and satiety. Here, we examined a chronic restraint stress model and observed an increase in food intake, which was not correlated with anhedonia. We investigated whether stress affects the properties of POMC and NPY neurons and found that chronic restraint stress reduced the excitatory inputs onto POMC neurons and increased the action potential threshold. Therefore, our study suggests that chronic stress modulates the intrinsic excitability and excitatory inputs in POMC neurons, leading to changes in feeding behavior.
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Affiliation(s)
- Go Eun Ha
- Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea
| | - Eunji Cheong
- Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea
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14
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Sen ZD, Danyeli LV, Woelfer M, Lamers F, Wagner G, Sobanski T, Walter M. Linking atypical depression and insulin resistance-related disorders via low-grade chronic inflammation: Integrating the phenotypic, molecular and neuroanatomical dimensions. Brain Behav Immun 2021; 93:335-352. [PMID: 33359233 DOI: 10.1016/j.bbi.2020.12.020] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Revised: 12/11/2020] [Accepted: 12/17/2020] [Indexed: 12/13/2022] Open
Abstract
Insulin resistance (IR) and related disorders, such as T2DM, increase the risk of major depressive disorder (MDD) and vice versa. Current evidence indicates that psychological stress and overeating can induce chronic low-grade inflammation that can interfere with glutamate metabolism in MDD as well as insulin signaling, particularly in the atypical subtype. Here we first review the interactive role of inflammatory processes in the development of MDD, IR and related metabolic disorders. Next, we describe the role of the anterior cingulate cortex in the pathophysiology of MDD and IR-related disorders. Furthermore, we outline how specific clinical features of atypical depression, such as hyperphagia, are more associated with inflammation and IR-related disorders. Finally, we examine the regional specificity of the effects of inflammation on the brain that show an overlap with the functional and morphometric brain patterns activated in MDD and IR-related disorders.
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Affiliation(s)
- Zümrüt Duygu Sen
- Department of Psychiatry and Psychotherapy, University Tuebingen, Calwerstraße 14, 72076 Tuebingen, Germany; Department of Psychiatry and Psychotherapy, Jena University Hospital, Philosophenweg 3, 07743 Jena, Germany
| | - Lena Vera Danyeli
- Department of Psychiatry and Psychotherapy, Jena University Hospital, Philosophenweg 3, 07743 Jena, Germany; Clinical Affective Neuroimaging Laboratory (CANLAB), Leipziger Str. 44, Building 65, 39120 Magdeburg, Germany; Leibniz Institute for Neurobiology, Brenneckestr. 6, 39118 Magdeburg, Germany
| | - Marie Woelfer
- Clinical Affective Neuroimaging Laboratory (CANLAB), Leipziger Str. 44, Building 65, 39120 Magdeburg, Germany; Leibniz Institute for Neurobiology, Brenneckestr. 6, 39118 Magdeburg, Germany
| | - Femke Lamers
- Department of Psychiatry, Amsterdam UMC, Vrije Universiteit, Oldenaller 1, 1081 HJ Amsterdam, the Netherlands
| | - Gerd Wagner
- Department of Psychiatry and Psychotherapy, Jena University Hospital, Philosophenweg 3, 07743 Jena, Germany
| | - Thomas Sobanski
- Department of Psychiatry, Psychotherapy and Psychosomatic Medicine, Thueringen-Kliniken "Georgius Agricola" GmbH, Rainweg 68, 07318 Saalfeld, Germany
| | - Martin Walter
- Department of Psychiatry and Psychotherapy, University Tuebingen, Calwerstraße 14, 72076 Tuebingen, Germany; Department of Psychiatry and Psychotherapy, Jena University Hospital, Philosophenweg 3, 07743 Jena, Germany; Clinical Affective Neuroimaging Laboratory (CANLAB), Leipziger Str. 44, Building 65, 39120 Magdeburg, Germany; Leibniz Institute for Neurobiology, Brenneckestr. 6, 39118 Magdeburg, Germany.
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15
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Amadio P, Zarà M, Sandrini L, Ieraci A, Barbieri SS. Depression and Cardiovascular Disease: The Viewpoint of Platelets. Int J Mol Sci 2020; 21:E7560. [PMID: 33066277 PMCID: PMC7589256 DOI: 10.3390/ijms21207560] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 10/08/2020] [Accepted: 10/09/2020] [Indexed: 02/06/2023] Open
Abstract
Depression is a major cause of morbidity and low quality of life among patients with cardiovascular disease (CVD), and it is now considered as an independent risk factor for major adverse cardiovascular events. Increasing evidence indicates not only that depression worsens the prognosis of cardiac events, but also that a cross-vulnerability between the two conditions occurs. Among the several mechanisms proposed to explain this interplay, platelet activation is the more attractive, seeing platelets as potential mirror of the brain function. In this review, we dissected the mechanisms linking depression and CVD highlighting the critical role of platelet behavior during depression as trigger of cardiovascular complication. In particular, we will discuss the relationship between depression and molecules involved in the CVD (e.g., catecholamines, adipokines, lipids, reactive oxygen species, and chemokines), emphasizing their impact on platelet activation and related mechanisms.
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Affiliation(s)
- Patrizia Amadio
- Unit of Brain-Heart Axis: Cellular and Molecular Mechanism, Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy; (M.Z.); (L.S.)
| | - Marta Zarà
- Unit of Brain-Heart Axis: Cellular and Molecular Mechanism, Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy; (M.Z.); (L.S.)
| | - Leonardo Sandrini
- Unit of Brain-Heart Axis: Cellular and Molecular Mechanism, Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy; (M.Z.); (L.S.)
| | - Alessandro Ieraci
- Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Department of Pharmaceutical Sciences, University of Milan, 20133 Milan, Italy;
| | - Silvia Stella Barbieri
- Unit of Brain-Heart Axis: Cellular and Molecular Mechanism, Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy; (M.Z.); (L.S.)
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16
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Sang YM, Wang LJ, Mao HX, Lou XY, Zhu YJ, Zhu YH. Correlation of lower 2 h C-peptide and elevated evening cortisol with high levels of depression in type 2 diabetes mellitus. BMC Psychiatry 2020; 20:490. [PMID: 33023555 PMCID: PMC7539383 DOI: 10.1186/s12888-020-02901-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2020] [Accepted: 09/28/2020] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND A number of studies have explored the association between depression and ghrelin, leptin, and cortisol; further, postprandial C-peptide levels have a therapeutic effect on type 2 diabetes mellitus (T2DM). However, the relationship between C-peptide and depression in patients with diabetes, remains unclear. The aim of this study was to explore the association between depression and ghrelin, leptin, cortisol, and C-peptide in patients with diabetes. METHODS We enrolled 50 adults without T2DM, 77 non-depressed adults with T2DM (free of Axis-I psychiatric disorders as assessed using the Mental Illness Needs Index (MINI), Patient Health Questionnaire (PHQ-9 score ≤ 4)) and 59 patients with T2DM and depression (PHQ-9 ≥ 7 and positive by the Structured Clinical Interview for DSM-5). The age range of the participants was 45-59 years of age. We compared the above three groups and explored the association between ghrelin, leptin, cortisol, C-peptide, and depression in patients with diabetes. A post-hoc power-analysis was finished. RESULTS Compared with the non-depression T2DM group, the depression T2DM group had significantly higher blood glucose fluctuations. Further, compared with the non-depression T2DM and non-diabetic groups, the depression T2DM group had significantly lower levels of post-meal 2-h C-peptide and elevated evening cortisol (p < 0.01). Regression analysis revealed a significant negative correlation between depression severity and 2-h postprandial C-peptide in patients with diabetes (p < 0.01) and a significant positive correlation with midnight cortisol levels (p < 0.01). A post hoc power analysis showed that we had an adequate sample size and met the minimum requirement to attain 80% power. A post hoc power calculation also demonstrated that this study basically achieved power of 80% at 5% alpha level. CONCLUSIONS Our findings indicate a correlation of low fasting levels of 2-h C-peptide as well as higher midnight cortisol levels with higher depression severity in middle-aged patients with T2DM.
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Affiliation(s)
- Yu Ming Sang
- grid.452555.60000 0004 1758 3222Department of Endocrinology, Jinhua Central Hospital, 351 Mingyue Street, Jinhua City, 321000 Zhejiang Province China
| | - Li Jun Wang
- Department of Psychology, Zhejiang Normal University, 688 Yingbin Road, Jinhua, 321004, Zhejiang Province, China.
| | - Hong Xian Mao
- grid.452555.60000 0004 1758 3222Department of Endocrinology, Jinhua Central Hospital, 351 Mingyue Street, Jinhua City, 321000 Zhejiang Province China
| | - Xue Yong Lou
- grid.452555.60000 0004 1758 3222Department of Endocrinology, Jinhua Central Hospital, 351 Mingyue Street, Jinhua City, 321000 Zhejiang Province China
| | - Yi Jun Zhu
- The Central Laboratory, Jinhua Central Hospital, 351 Mingyue Street, Jinhua City, 321000 Zhejiang Province China
| | - Yue Hua Zhu
- grid.452555.60000 0004 1758 3222Department of Psychiatry, Jinhua Central Hospital, 351 Mingyue Street, Jinhua City, 321000 Zhejiang Province China
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17
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Akram F, Gragnoli C, Raheja UK, Snitker S, Lowry CA, Sterns-Yoder KA, Hoisington AJ, Brenner LA, Saunders E, Stiller JW, Ryan KA, Rohan KJ, Mitchell BD, Postolache TT. Seasonal affective disorder and seasonal changes in weight and sleep duration are inversely associated with plasma adiponectin levels. J Psychiatr Res 2020; 122:97-104. [PMID: 31981963 PMCID: PMC7024547 DOI: 10.1016/j.jpsychires.2019.12.016] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Revised: 12/25/2019] [Accepted: 12/30/2019] [Indexed: 12/15/2022]
Abstract
Overlapping pathways between mood and metabolic regulation have increasingly been reported. Although impaired regulation of adiponectin, a major metabolism-regulating hormone, has been implicated in major depressive disorder, its role in seasonal changes in mood and seasonal affective disorder-winter type (SAD), a disorder characterized by onset of mood impairment and metabolic dysregulation (e.g., carbohydrate craving and weight gain) in fall/winter and spontaneous alleviation in spring/summer, has not been previously studied. We studied a convenience sample of 636 Old Order Amish (mean (± SD), 53.6 (±14.8) years; 50.1% males), a population with self-imposed restriction on network electric light at home, and low prevalence of total SAD (t-SAD = syndromal + subsyndromal). We calculated the global seasonality score (GSS), estimated SAD and subsyndromal-SAD after obtaining Seasonal Pattern Assessment Questionnaires (SPAQs), and measured overnight fasting plasma adiponectin levels. We then tested associations between plasma adiponectin levels and GSS, t-SAD, winter-summer difference in self-reported sleep duration, and self-reported seasonal weight change, by using analysis of co-variance (ANCOVA) and linear regression analysis after adjusting for age, gender, and BMI. Participants with t-SAD (N = 14; 2.2%) had significantly lower plasma adiponectin levels (mean ± SEM, 8.76 ± 1.56 μg/mL) than those without t-SAD (mean ± SEM, 11.93 ± 0.22 μg/mL) (p = 0.035). In addition, there was significant negative association between adiponectin levels and winter-summer difference in self-reported sleep duration (p = 0.025) and between adiponectin levels and self-reported seasonal change in weight (p = 0.006). There was no significant association between GSS and adiponectin levels (p = 0.88). To our knowledge, this is the first study testing the association of SAD with adiponectin levels. Replication and extension of our findings longitudinally and, then, interventionally, may implicate low adiponectin as a novel target for therapeutic intervention in SAD.
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Affiliation(s)
- Faisal Akram
- Mood and Anxiety Program, University of Maryland School of Medicine, Baltimore, MD, USA,Saint Elizabeths Hospital, DC Department of Behavioral Health, Washington, DC, USA
| | - Claudia Gragnoli
- Division of Endocrinology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA,Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA,Molecular Biology Laboratory, Bios Biotech Multi-Diagnostic Health Center, Rome, Italy
| | - Uttam K. Raheja
- Mood and Anxiety Program, University of Maryland School of Medicine, Baltimore, MD, USA,Saint Elizabeths Hospital, DC Department of Behavioral Health, Washington, DC, USA
| | - Soren Snitker
- Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA,Amish Research Clinic of the University of Maryland, Lancaster, PA, USA
| | - Christopher A. Lowry
- Veterans Health Administration, Rocky Mountain Mental Illness Research Education and Clinical Center (MIRECC), Rocky Mountain Regional Veterans Affairs Medical Center (RMRVAMC), Aurora, CO, USA,Department of Physical Medicine & Rehabilitation and Center for Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, CO, USA,Military and Veteran Microbiome: Consortium for Research and Education (MVM-CoRE), Aurora, CO, USA,Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA
| | - Kelly A. Sterns-Yoder
- Veterans Health Administration, Rocky Mountain Mental Illness Research Education and Clinical Center (MIRECC), Rocky Mountain Regional Veterans Affairs Medical Center (RMRVAMC), Aurora, CO, USA,Military and Veteran Microbiome: Consortium for Research and Education (MVM-CoRE), Aurora, CO, USA,Department of Physical Medicine & Rehabilitation, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Andrew J. Hoisington
- Military and Veteran Microbiome: Consortium for Research and Education (MVM-CoRE), Aurora, CO, USA,Department of Systems Engineering, Air Force Institute of Technology, Wright-Patterson AFB, OH, USA
| | - Lisa A. Brenner
- Veterans Health Administration, Rocky Mountain Mental Illness Research Education and Clinical Center (MIRECC), Rocky Mountain Regional Veterans Affairs Medical Center (RMRVAMC), Aurora, CO, USA,Military and Veteran Microbiome: Consortium for Research and Education (MVM-CoRE), Aurora, CO, USA,Department of Physical Medicine & Rehabilitation, University of Colorado Anschutz Medical Campus, Aurora, CO, USA,Departments of Psychiatry & Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Erika Saunders
- Department of Psychiatry, Penn State University, Hershey, PA, USA
| | - John W. Stiller
- Mood and Anxiety Program, University of Maryland School of Medicine, Baltimore, MD, USA,Saint Elizabeths Hospital, DC Department of Behavioral Health, Washington, DC, USA
| | - Kathleen A. Ryan
- Program for Personalized and Genomic Medicine, Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland, School of Medicine, Baltimore, MD, USA,Geriatrics Research and Education Clinical Center, Baltimore, MD, USA,Baltimore Veterans Administration Medical Center, Baltimore, MD, USA
| | - Kelly J. Rohan
- Department of Psychological Science, University of Vermont, Burlington, VT, USA
| | - Braxton D. Mitchell
- Program for Personalized and Genomic Medicine, Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland, School of Medicine, Baltimore, MD, USA,Geriatrics Research and Education Clinical Center, Baltimore, MD, USA,Baltimore Veterans Administration Medical Center, Baltimore, MD, USA
| | - Teodor T. Postolache
- Mood and Anxiety Program, University of Maryland School of Medicine, Baltimore, MD, USA,Saint Elizabeths Hospital, DC Department of Behavioral Health, Washington, DC, USA,Veterans Health Administration, Rocky Mountain Mental Illness Research Education and Clinical Center (MIRECC), Rocky Mountain Regional Veterans Affairs Medical Center (RMRVAMC), Aurora, CO, USA,Department of Physical Medicine & Rehabilitation, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
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18
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Silva DA, Coutinho EDSF, Ferriani LO, Viana MC. Depression subtypes and obesity in adults: A systematic review and meta-analysis. Obes Rev 2020; 21:e12966. [PMID: 31724325 DOI: 10.1111/obr.12966] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Revised: 08/17/2019] [Accepted: 09/16/2019] [Indexed: 11/30/2022]
Abstract
Examining clinical features of depressive episodes may help elucidating the nature of association between depression and obesity, related to specific symptoms such as appetite and weight changes. This meta-analysis of observational studies evaluated whether subtypes of depression are associated with specific anthropometric profiles in adults. We searched MEDLINE, LILACS, PsycINFO, Scopus, Web of Science databases, and Grey Literature for articles published up to October 2016 that examined depressive subtypes and adiposity measures among adults. The pooled effect size was estimated with random effects models. The PRISMA guidelines were adopted to reporting results, and this review was registered in PROSPERO (CRD42016035685). A total of 22 articles were included in this systematic review, of which eight had data included in the meta-analysis, assessing 14 757 individuals with depression. Patients with atypical depression presented a 2.55 higher BMI score compared with those with melancholic depression. Subgroup analysis identified a differential distribution of anthropometric measures in studies conducted with Chinese populations. Among the remainder studies, only one reported discrepant results, possibly due to the exclusion of "weight change" in defining subtypes of depression. Atypical depression was significantly associated with elevated BMI compared with melancholic depression, deserving particular attention due to its clinical importance.
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Affiliation(s)
- Daniela Alves Silva
- Postgraduate Program in Public Health, Federal University of Espírito Santo, Vitória, Brazil.,Department of Health Integrated Education, Federal University of Espírito Santo, Vitória, Brazil
| | | | - Lara Onofre Ferriani
- Postgraduate Program in Public Health, Federal University of Espírito Santo, Vitória, Brazil
| | - Maria Carmen Viana
- Postgraduate Program in Public Health, Federal University of Espírito Santo, Vitória, Brazil.,Department of Social Medicine, Federal University of Espírito Santo, Vitória, Brazil
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19
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The brain-adipocyte-gut network: Linking obesity and depression subtypes. COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE 2019; 18:1121-1144. [PMID: 30112671 DOI: 10.3758/s13415-018-0626-0] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Major depressive disorder (MDD) and obesity are dominant and inter-related health burdens. Obesity is a risk factor for MDD, and there is evidence MDD increases risk of obesity. However, description of a bidirectional relationship between obesity and MDD is misleading, as closer examination reveals distinct unidirectional relationships in MDD subtypes. MDD is frequently associated with weight loss, although obesity promotes MDD. In contrast, MDD with atypical features (MDD-AF) is characterised by subsequent weight gain and obesity. The bases of these distinct associations remain to be detailed, with conflicting findings clouding interpretation. These associations can be viewed within a systems biology framework-the psycho-immune neuroendocrine (PINE) network shared between MDD and metabolic disorders. Shared PINE subsystem perturbations may underlie increased MDD in overweight and obese people (obesity-associated depression), while obesity in MDD-AF (depression-associated obesity) involves more complex interactions between behavioural and biomolecular changes. In the former, the chronic PINE dysfunction triggering MDD is augmented by obesity-dependent dysregulation in shared networks, including inflammatory, leptin-ghrelin, neuroendocrine, and gut microbiome systems, influenced by chronic image-associated psychological stress (particularly in younger or female patients). In MDD-AF, behavioural dysregulation, including hypersensitivity to interpersonal rejection, fundamentally underpins energy imbalance (involving hyperphagia, lethargy, hypersomnia), with evolving obesity exaggerating these drivers via positive feedback (and potentially augmenting PINE disruption). In both settings, sex and age are important determinants of outcome, associated with differences in emotional versus cognitive dysregulation. A systems biology approach is recommended for further research into the pathophysiological networks underlying MDD and linking depression and obesity.
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20
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Mills JG, Larkin TA, Deng C, Thomas SJ. Weight gain in Major Depressive Disorder: Linking appetite and disordered eating to leptin and ghrelin. Psychiatry Res 2019; 279:244-251. [PMID: 30878306 DOI: 10.1016/j.psychres.2019.03.017] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Revised: 03/08/2019] [Accepted: 03/09/2019] [Indexed: 01/12/2023]
Abstract
Major Depressive Disorder (MDD) involves changes in appetite and weight, with a subset of individuals at an increased risk of weight gain. Pathways to weight gain may include appetite disturbances, excess eating, and dysregulation of appetite hormones. However, little research has simultaneously examined relationships between hormones, eating behaviours and MDD symptoms. Plasma ghrelin and leptin, biometrics, eating behaviours and psychopathology were compared between depressed (n = 60) and control (n = 60) participants. Depressed participants were subcategorised into those with increased or decreased appetite/weight for comparison by subtype. The Dutch Eating Behaviours Questionnaire and Yale Food Addiction Scale measured eating behaviours. Disordered eating was higher in MDD than controls, in females than males, and in depressed individuals with increased, compared to decreased, appetite/weight. Leptin levels were higher in females only. Leptin levels correlated positively, and ghrelin negatively, with disordered eating. The results provide further evidence for high levels of disordered eating in MDD, particularly in females. The correlations suggest that excessive eating in MDD is significantly linked to appetite hormones, indicating that it involves physiological, rather than purely psychological, factors. Further, longitudinal, research is needed to better understand whether hormonal factors play a causal role in excessive eating in MDD.
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Affiliation(s)
- Jessica G Mills
- Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, Australia; Illawarra Health and Medical Research Institute, University of Wollongong, Australia.
| | - Theresa A Larkin
- Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, Australia; Illawarra Health and Medical Research Institute, University of Wollongong, Australia
| | - Chao Deng
- Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, Australia; Illawarra Health and Medical Research Institute, University of Wollongong, Australia; Antipsychotic Research Laboratory, University of Wollongong, Australia
| | - Susan J Thomas
- Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, Australia; Illawarra Health and Medical Research Institute, University of Wollongong, Australia
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21
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Taheri E, Heshmat R, Esmaeil Motlagh M, Ardalan G, Asayesh H, Qorbani M, Kelishadi R. Association of Physical Activity and Screen Time with Psychiatric Distress in Children and Adolescents: CASPIAN-IV Study. J Trop Pediatr 2019; 65:361-372. [PMID: 30561678 DOI: 10.1093/tropej/fmy063] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND There are limited studies about the association of physical activity (PA) and screen time (ST) with psychiatric distress (PD) among children and adolescents including Iranian populations. OBJECTIVE We aimed to examine the independent and combined associations of PA and ST with PD among children and adolescents. METHOD This school-based nationwide survey was carried out among 14 880 students (50.8% boys and 75.6% urban inhabitants), of age 6-18 years by cluster and the stratified multistage sampling method from 30 provinces of Iran. The students and their parents completed two sets of questionnaires obtained from Global School Health Survey with several questions about the PD. The time spent on watching TV/video and computer games and PA were assessed by self-administered validated questionnaires. RESULTS The study had a participation rate of 90.6%. Of the studied students, 45.85%, 83.62%, 37.81% and 23.92% had depression, anger, insomnia and worthlessness, respectively. The prevalence of confusion, anxiety and worry was reported in 19.6%, 55.17% and 75.31% of the students, respectively. The combined effect of PA and that of ST showed that students with high PA and low ST had the lowest prevalence of PD, while the highest prevalence of these PD was observed among students with low PA combined with high ST (p < 0.05 for all). CONCLUSIONS Increasing PA and reducing ST should both be considered for improving the mental health status of children and adolescents.
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Affiliation(s)
- Ehsaneh Taheri
- Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.,Osteoporosis Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Ramin Heshmat
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinics Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Gelayol Ardalan
- Child Department of Pediatrics, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Hamid Asayesh
- Department of Medical Emergencies, Qom University of Medical Sciences, Qom, Iran
| | - Mostafa Qorbani
- Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran.,Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Roya Kelishadi
- Child Department of Pediatrics, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
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22
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Amer AAA, Zhu Y, Wei S, Zhang R, Wang Y, Duan J, Jiang X, Tang Y, Wang F. Relationship Between White Matter Integrity and Plasma Leptin Levels in Drug-Naïve and Medicated Patients With Major Depressive Disorder. Front Neurosci 2019; 13:707. [PMID: 31354416 PMCID: PMC6639733 DOI: 10.3389/fnins.2019.00707] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Accepted: 06/24/2019] [Indexed: 01/17/2023] Open
Abstract
Many previous studies have noticed obvious alterations in different white matter tracts among patients with major depressive disorder (MDD). Growing evidence also strongly suggest a role of leptin in the pathogenesis of MDD, but with conflicting results of leptin levels. However, no previous studies have examined the relationship between leptin and white matter integrity of patients with MDD. Therefore, we aimed in this study to investigate the relationship between white matter alterations and plasma leptin levels in both drug-naïve and medicated MDD patients. We measured plasma leptin levels and white matter integrity using diffusion tensor imaging (DTI) and voxel-based analysis (VBA) in 140 participants (40 drug-naïve MDD patients; 40 medicated MDD patients; 60 healthy controls) aged between 18 and 49 years old. A significant reduced fractional anisotropy (FA) value in the dorsomedial thalamus was found for both drug-naïve and medicated MDD patients compared to the healthy non-depressed participants (p < 0.01, corrected). In addition, leptin levels were significantly higher in the drug-naïve MDD patients and were negatively correlated with the detected white matter alteration. Our results suggest that the elevated plasma leptin levels in the drug-naïve MDD group might be associated with the changes of the white matter integrity in the dorsomedial thalamus region.
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Affiliation(s)
- Abdulrahman A. A. Amer
- Department of Psychiatry, First Affiliated Hospital, China Medical University, Shenyang, China
| | - Yue Zhu
- Department of Psychiatry, First Affiliated Hospital, China Medical University, Shenyang, China
| | - Shengnan Wei
- Brain Function Research Section, First Affiliated Hospital, China Medical University, Shenyang, China
- Department of Radiology, First Affiliated Hospital, China Medical University, Shenyang, China
| | - Ran Zhang
- Department of Psychiatry, First Affiliated Hospital, China Medical University, Shenyang, China
| | - Yang Wang
- Department of Psychiatry, First Affiliated Hospital, China Medical University, Shenyang, China
| | - Jia Duan
- Department of Psychiatry, First Affiliated Hospital, China Medical University, Shenyang, China
| | - Xiaowei Jiang
- Department of Psychiatry, First Affiliated Hospital, China Medical University, Shenyang, China
- Brain Function Research Section, First Affiliated Hospital, China Medical University, Shenyang, China
- Department of Radiology, First Affiliated Hospital, China Medical University, Shenyang, China
| | - Yanqing Tang
- Department of Psychiatry, First Affiliated Hospital, China Medical University, Shenyang, China
- Brain Function Research Section, First Affiliated Hospital, China Medical University, Shenyang, China
- Department of Geriatric Medicine, First Affiliated Hospital, China Medical University, Shenyang, China
| | - Fei Wang
- Department of Psychiatry, First Affiliated Hospital, China Medical University, Shenyang, China
- Brain Function Research Section, First Affiliated Hospital, China Medical University, Shenyang, China
- Department of Radiology, First Affiliated Hospital, China Medical University, Shenyang, China
- Department of Psychiatry, Yale School of Medicine, New Haven, CT, United States
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23
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Increased serum levels of leptin and insulin in both schizophrenia and major depressive disorder: A cross-disorder proteomics analysis. Eur Neuropsychopharmacol 2019; 29:835-846. [PMID: 31230885 DOI: 10.1016/j.euroneuro.2019.05.010] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Revised: 03/15/2019] [Accepted: 05/29/2019] [Indexed: 12/12/2022]
Abstract
We investigated whether there are similar serum alterations in schizophrenia and major depressive disorder (MDD). We investigated serum analytes in two epidemiological studies on schizophrenia (N = 121) and MDD (N = 1172) versus controls. Serum analytes (N = 109) were measured with a multi-analyte profiling platform and analysed using linear regression models, adjusted for site, age, gender, ethnicity, anti-inflammatory agents, smoking, cardiovascular disease and diabetes, and adjusted for multiple comparisons. An increase in leptin and insulin levels was observed for both schizophrenia patients (Cohen's d (d): 0.26 and 0.65, respectively) and MDD patients (d: 0.29 and 0.12, respectively) compared to their respective controls. Lower angiopoietin-2 levels were seen in both schizophrenia (d: -0.22) and MDD (d: -0.13). Four analytes differed in only schizophrenia patients (increased levels of C-peptide and prolactin, and decreased levels of CD5 antigen-like and sex hormone binding globulin) and one analyte differed in only MDD patients (increased angiotensinogen levels) compared to their respective controls. Restricting analyses to patients with a current episode of disease showed even more marked elevations of insulin and leptin. Our results suggest the presence of insulin and leptin resistance as cross-disorder mechanisms that could contribute to the higher somatic comorbidity and decreased life-span seen in both disorders.
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24
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The role of hormonal, metabolic and inflammatory biomarkers on sleep and appetite in drug free patients with major depression: A systematic review. J Affect Disord 2019; 250:249-259. [PMID: 30870775 DOI: 10.1016/j.jad.2019.03.015] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Revised: 01/30/2019] [Accepted: 03/03/2019] [Indexed: 01/08/2023]
Abstract
BACKGROUND Major depressive disorder (MDD) is a complex and heterogeneous disorder in which clinical symptoms can widely differ among patients. Neurovegetative symptoms, i.e. decreased or increased appetite, changes in body weight and sleep disturbances, described as 'melancholic' or 'atypical' features of a depressive episode, are the most variable symptoms among patients with MDD. We hypothesized biomarkers differences underlying this neurovegetative variability in major depression. METHODS We systematically reviewed, according to the PRISMA guidelines, the role of specific metabolic, hormonal and inflammatory biomarkers in drug-free MDD patients, that could have neurobiological effects on appetite, weight regulation and circadian rhythms, influencing eating behaviour and sleep patterns. All studies regarding the co-occurrence of disturbed sleep and appetite were examined. RESULTS Besides the well-known leptin and ghrelin, other biomarkers such as BDNF, VEGF, NPY, orexin, and the recent discovered nesfatin-1 seem to be involved in neurovegetative changes in depressive disorders playing a role in the regulation of affective states, stress reactions and sleep patterns. Interestingly, based on the existing evidence, ghrelin, orexin and nesfatin-1 could be linked both to sleep and appetite regulation in depressed patients. LIMITATIONS Heterogeneous studies with low sample size. CONCLUSIONS Despite the wide heterogeneity of results, studies on biomarkers of appetite and sleep in MDD are an interesting field of research to explain the neurobiological substrates of depressive symptoms that deserve further investigation.
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25
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Syk M, Ellström S, Mwinyi J, Schiöth HB, Ekselius L, Ramklint M, Cunningham JL. Plasma levels of leptin and adiponectin and depressive symptoms in young adults. Psychiatry Res 2019; 272:1-7. [PMID: 30562581 DOI: 10.1016/j.psychres.2018.11.075] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Revised: 09/18/2018] [Accepted: 11/30/2018] [Indexed: 01/09/2023]
Abstract
Circulating levels of adipokines are known to be associated with depression. This study aimed to investigate a possible association between leptin, adiponectin and dimensional measures of depressive symptoms in young adults with and without psychiatric illness. Total plasma adiponectin and leptin levels were measured in 194 young adults seeking psychiatric ambulatory care and 57 healthy controls. Depressive symptoms were assessed using the Montgomery-Åsberg Depression Self-Rating Scale (MADRS-S). Analysis was performed on men and women separately. P-leptin levels were significantly elevated in patients compared with controls and correlated with total MADRS-S scores in the women. Women with P-leptin in the highest quartile reached a significantly higher MADRS-S score than women in the lowest quartile, but this difference disappeared after adjusting for body mass index (BMI) and antidepressant use. MADRS-S score was associated with P-leptin in female patients without antidepressant use, independently of BMI. There was no association between P-leptin levels and current major depression. P-adiponectin levels were not associated with depressive symptoms or current major depression. The findings indicate that P-leptin levels are associated with depressive symptom severity in young women; however, the association is linked to other factors, which challenges its usefulness as a biomarker for depression in clinical psychiatry.
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Affiliation(s)
- Mikaela Syk
- Department of Neuroscience, Psychiatry, Uppsala University, Akademiska sjukhuset, 751 85, Uppsala, Sweden
| | - Sofie Ellström
- Department of Neuroscience, Psychiatry, Uppsala University, Akademiska sjukhuset, 751 85, Uppsala, Sweden
| | - Jessica Mwinyi
- Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, Box 593, 751 24, Uppsala, Sweden
| | - Helgi B Schiöth
- Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, Box 593, 751 24, Uppsala, Sweden
| | - Lisa Ekselius
- Department of Neuroscience, Psychiatry, Uppsala University, Akademiska sjukhuset, 751 85, Uppsala, Sweden
| | - Mia Ramklint
- Department of Neuroscience, Psychiatry, Uppsala University, Akademiska sjukhuset, 751 85, Uppsala, Sweden
| | - Janet L Cunningham
- Department of Neuroscience, Psychiatry, Uppsala University, Akademiska sjukhuset, 751 85, Uppsala, Sweden.
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26
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Kasyanov ED, Mazo GE, Kibitov AO. The role of family studies in research of neurobiological basis of depressive disorders. Zh Nevrol Psikhiatr Im S S Korsakova 2019; 119:87-93. [DOI: 10.17116/jnevro201911902187] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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27
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Everson-Rose SA, Clark CJ, Wang Q, Guo H, Mancuso P, Kravitz HM, Bromberger JT. Depressive symptoms and adipokines in women: Study of women's health across the nation. Psychoneuroendocrinology 2018; 97:20-27. [PMID: 30005278 PMCID: PMC6300165 DOI: 10.1016/j.psyneuen.2018.07.011] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2018] [Revised: 06/27/2018] [Accepted: 07/04/2018] [Indexed: 01/10/2023]
Abstract
Small clinical studies suggest depression is associated with alterations in adiponectin and leptin, adipocyte-derived secretory proteins involved in metabolic regulation; however, longitudinal data on these association are lacking. This study examined cross-sectional and longitudinal associations of depressive symptoms and major depressive disorder (MDD) with adiponectin and leptin in healthy middle-aged women (mean (SD) age, 45.6 (2.5) years). Cross-sectional analyses included 575 women with baseline adipokine data; longitudinal analyses included 262 women with 2-4 adipokine measurements over 5 years. The 20-item Center for Epidemiologic Studies Depression scale (CES-D) was used to assess depressive symptoms; history of MDD was determined by the Structured Clinical Interview for DSM-IV. Adipokines were assayed from stored serum specimens; values were log-transformed for analyses. Linear and repeated measure random effects regression models evaluated associations of baseline CES-D scores with baseline adipokine concentrations and changes over time, respectively. Secondary analyses evaluated the relation of MDD history with adipokine concentrations. Mean (SD) baseline concentrations of adiponectin and leptin were 9.90 (4.92) μg/mL and 27.02 (20.06) ng/mL; both increased over time (p < .0001). CES-D scores were associated with lower adiponectin at baseline (per 1-SD: estimate=-0.04, SE=.02, p=.03) and over time (per 1-SD: estimate=-0.055, SE = .024, p=.02). Associations were unchanged in risk factor-adjusted models. Women with elevated CES-D scores (≥16) had 6.9% (95% CI: -1.1%, 14.3%; p = .089) lower median adiponectin at baseline and 11.5% (95% CI: 1.5%, 20.4%, p = .025) lower median adiponectin over time in adjusted models, compared to women with CES-D<16. Rate of change in adipokines did not vary by baseline depressive symptoms or MDD history. Depressive symptoms and MDD history were unrelated to leptin. In women at midlife, depressive symptoms are associated with lower adiponectin, a critical anti-inflammatory biomarker involved in metabolic and cardiovascular conditions.
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Affiliation(s)
- Susan A. Everson-Rose
- Department of Medicine and Program in Health Disparities Research, University of Minnesota Medical School, Minneapolis, MN
| | - Cari J. Clark
- Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA
| | - Qi Wang
- Biostatistical Design & Analysis Center, Clinical and Translational Science Institute, University of Minnesota, Minneapolis, MN
| | - Hongfei Guo
- Division of Biostatistics, School of Public Health, and Clinical and Translational Science Institute, University of Minnesota, Minneapolis, MN
| | - Peter Mancuso
- Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI
| | - Howard M. Kravitz
- Department of Psychiatry and Department of Preventive Medicine, Rush Medical College, Rush University Medical Center, Chicago, IL
| | - Joyce T. Bromberger
- Departments of Epidemiology and Psychiatry, University of Pittsburgh, Pittsburgh, PA
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28
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Mills JG, Thomas SJ, Larkin TA, Pai NB, Deng C. Problematic eating behaviours, changes in appetite, and weight gain in Major Depressive Disorder: The role of leptin. J Affect Disord 2018; 240:137-145. [PMID: 30071417 DOI: 10.1016/j.jad.2018.07.069] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2017] [Revised: 06/22/2018] [Accepted: 07/22/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Appetite and weight changes are core symptoms of Major Depressive Disorder (MDD), and those with MDD are at increased risk of obesity, cardiovascular disease and metabolic disorders. Leptin promotes satiety, with leptin dysregulation and resistance noted in obesity. However, the role of leptin in weight changes in MDD is not established. This study investigates leptin levels in relation to appetite and weight changes and problematic eating behaviours in MDD. METHODS Plasma leptin levels, psychopathology and biometrics were compared between participants meeting DSM-5 diagnostic criteria for MDD (n = 63) and healthy controls (n = 60). Depressed participants were also sub-categorised according to increased, decreased or unchanged appetite and weight. The Dutch Eating Behaviour Questionnaire and Yale Food Addiction Scale were examined in a subset of participants with MDD. RESULTS Females with increased appetite/weight had higher leptin levels than those with stable or reduced appetite/weight, however males showed the opposite effect. Leptin levels were positively correlated with problematic eating behaviours. One quarter of the depressed subset, all females, met the Yale criteria for food addiction, approximately double the rates reported in general community samples. LIMITATIONS The study is limited by a cross sectional design and a small sample size in the subset analysis of eating behaviours. CONCLUSIONS The results provide new information about associations between leptin, sex-specific weight and appetite changes and problematic eating behaviours, which may be risk factors for cardiovascular and metabolic diseases in MDD, particularly in females. Future longitudinal research investigating leptin as a risk factor for weight gain in MDD is warranted, and may lead to early interventions aimed at preventing weight gain in at-risk individuals.
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Affiliation(s)
- Jessica G Mills
- School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, Australia; Illawarra Health and Medical Research Institute, University of Wollongong, Australia.
| | - Susan J Thomas
- School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, Australia; Illawarra Health and Medical Research Institute, University of Wollongong, Australia
| | - Theresa A Larkin
- School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, Australia; Illawarra Health and Medical Research Institute, University of Wollongong, Australia
| | - Nagesh B Pai
- School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, Australia; Illawarra Health and Medical Research Institute, University of Wollongong, Australia
| | - Chao Deng
- School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, Australia; Illawarra Health and Medical Research Institute, University of Wollongong, Australia; Antipsychotic Research Laboratory, University of Wollongong, Australia
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29
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Leptin in depression: a potential therapeutic target. Cell Death Dis 2018; 9:1096. [PMID: 30367065 PMCID: PMC6203758 DOI: 10.1038/s41419-018-1129-1] [Citation(s) in RCA: 64] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2018] [Revised: 06/02/2018] [Accepted: 07/04/2018] [Indexed: 12/15/2022]
Abstract
Leptin, produced and secreted by white adipose tissue, plays a critical role in regulating body weight, food intake, and energy metabolism. Recently, several studies have identified an underlying role for leptin in regulation of mood and cognition via regulation of synaptic changes in the brain that have been associated with antidepressant-like actions. Brain neural plasticity occurs in response to a range of intrinsic and extrinsic stimuli, including those that may mediate the effects of antidepressants. Neural plasticity theories of depression are thought to explain multiple aspects of depression and the effects of antidepressants. It is also well documented that leptin has effects on neural plasticity. This review summarizes the recent literature on the role of leptin in neural plasticity in order to elaborate the possible mechanism of leptin’s antidepressant-like effects. Recent findings provide new insights into the underlying mechanisms of neural plasticity in depression. Leptin may influence these mechanisms and consequently constitute a possible target for novel therapeutic approaches to the treatment of depression.
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30
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Cao B, Chen Y, Brietzke E, Cha D, Shaukat A, Pan Z, Park C, Subramaniapillai M, Zuckerman H, Grant K, Mansur RB, McIntyre RS. Leptin and adiponectin levels in major depressive disorder: A systematic review and meta-analysis. J Affect Disord 2018; 238:101-110. [PMID: 29870819 DOI: 10.1016/j.jad.2018.05.008] [Citation(s) in RCA: 66] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2018] [Revised: 04/24/2018] [Accepted: 05/13/2018] [Indexed: 12/15/2022]
Abstract
OBJECTIVES To explore differences in adipokine levels (i.e., leptin and adiponectin levels) between adults with Major Depressive Disorder (MDD) and healthy controls (HC), and to discuss the possible role of adipokine regulation in the development and progression of MDD. METHODS A systematic review and meta-analysis were conducted based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A systematic search was conducted for all English and Chinese peer-reviewed articles from inception to November 2017. A random effects model was used to calculate the standardized mean difference (SMD) of leptin and/or adiponectin levels in subjects diagnosed with MDD versus HC within a 95% confidence interval (CI). RESULTS Thirty-three studies were included in this meta-analysis. In total, 4,372 (52.3%) subjects with MDD and 3,984 (47.7%) HC were compared. We identified significant lower adiponectin levels in MDD compared to HC with a small effect size (ES) (SMD = -0.25; 95% CI: -0.48, -0.02; P < 0.001). However, no significant difference was observed in leptin levels between MDD subjects and HC (SMD = 0.13; 95% CI: -0.06, 0.31; P = 0.170). The heterogeneity in the results of our meta-analysis could not be completely explained by dividing subjects into subgroups. Results from subgroup analyses suggested that studies involving samples with BMI ≥ 25 had lower adiponectin levels in subjects with MDD compared to HC, and older age samples (i.e., age ≥ 40) with BMI ≥ 25 had both higher leptin levels and lower adiponectin levels in MDD subjects as compared to HC. LIMITATIONS The heterogeneity of included studies, small sample sizes, and potential publication bias were significant limitations. CONCLUSIONS The current systematic review and meta-analysis indicated that lower adiponectin levels may be associated with MDD. Moreover, the results suggest that males expressing lower adiponectin and leptin levels have an increased likelihood of developing MDD. Future studies should aim to investigate the manifestation of depressive phenotypes in older, obese populations with altered metabolic profiles resulting from adipokine dysregulation. The review has been registered with PROSPERO (registration number CRD42018082733).
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Affiliation(s)
- Bing Cao
- Department of Laboratorial Science and Technology, School of Public Health, Peking University, Beijing 100191, PR China; Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Canada
| | - Yan Chen
- Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Canada
| | - Elisa Brietzke
- Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Canada; Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Danielle Cha
- Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Canada; Faculty of Medicine, School of Medicine, University of Queensland, Brisbane, QLD, Australia
| | - Aisha Shaukat
- Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Canada
| | - Zihang Pan
- Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Canada
| | - Caroline Park
- Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Canada
| | | | - Hannah Zuckerman
- Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Canada
| | - Kiran Grant
- Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Canada
| | - Rodrigo B Mansur
- Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Canada
| | - Roger S McIntyre
- Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Department of Pharmacology, University of Toronto, Toronto, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada.
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Yürümez E, Uğur Ç, Sertçelik M. The assessment of serum omentin levels of children with autism spectrum disorder and attention-deficit/hyperactivity disorder. PSYCHIAT CLIN PSYCH 2018. [DOI: 10.1080/24750573.2017.1421397] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
Affiliation(s)
- Esra Yürümez
- Department of Child and Adolescent Psychiatry, Ankara University School of Medicine, Ankara, Turkey
| | - Çağatay Uğur
- Department of Child and Adolescent Psychiatry, Ankara Pediatric Hematology–Oncology Training and Research Hospital, Ankara, Turkey
| | - Mehmet Sertçelik
- Child and Adolescent Psychiatry Division, Hitit University Çorum Training and Research Hospital, Çorum, Turkey
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Sang YM, Wang LJ, Mao HX, Lou XY, Zhu YJ. The association of short-term memory and cognitive impairment with ghrelin, leptin, and cortisol levels in non-diabetic and diabetic elderly individuals. Acta Diabetol 2018; 55:531-539. [PMID: 29492658 DOI: 10.1007/s00592-018-1111-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2017] [Accepted: 01/29/2018] [Indexed: 01/02/2023]
Abstract
AIMS This study assessed short-term memory and biochemical indicators with the levels of ghrelin, leptin, and cortisol between cognitive impairment and normal older adults with or without diabetes. METHODS We enrolled 286 older adults (aged 65-85 years) with or without diabetes from the local community. Short-term memory was assessed using pictures of common objects; cognitive functioning was assessed using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). The physiological indexes assessed were plasma levels of fasting ghrelin and leptin, ghrelin level at 2_h after breakfast, 24-h urinary cortisol value, body mass index, and plasma cortisol levels at 8:00 a.m., 4:00 p.m., and 12:00 p.m. RESULTS In both non-diabetic and diabetic subjects, short-term memory was significantly lower in the impaired cognition group (5.99 ± 2.90 in non-diabetic subjects and 4.71 ± 2.14 in diabetic subjects) than in the normal cognition group (8.14 ± 2.23 in non-diabetic subjects and 7.82 ± 3.37 in diabetic subjects). Baseline ghrelin level was significantly lower in the impaired cognition group (9.07 ± 1.13 ng/mL in non-diabetic subjects and 7.76 ± 1.34 ng/mL in diabetic subjects) than in the normal cognition group (10.94 ± 1.53 ng/mL in non-diabetic subjects and 9.93 ± 1.76 ng/mL in diabetic subjects); plasma cortisol levels at 8:00 a.m., 4:00 p.m., and 12:00 p.m. were significantly higher in the impaired cognition group than in the normal cognition group, while no significant difference was observed in plasma levels of fasting leptin between different groups. CONCLUSIONS Fasting plasma ghrelin and cortisol levels may be markers of cognitive decline and memory loss. It is possible that adjusting their levels may have a therapeutic effect, and this should be investigated in future studies.
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Affiliation(s)
- Yu Ming Sang
- Department of Endocrinology, Jinhua Central Hospital, Jinhua, Zhejiang province, China.
| | - Li Jun Wang
- Department of Psychology, Zhejiang Normal University, Jinhua, China
| | - Hong Xian Mao
- Department of Endocrinology, Jinhua Central Hospital, Jinhua, Zhejiang province, China
| | - Xue Yong Lou
- Department of Endocrinology, Jinhua Central Hospital, Jinhua, Zhejiang province, China
| | - Yi Jun Zhu
- The Central Laboratory, Jinhua Central Hospital, Jinhua, Zhejiang province, China
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Lamers F, Milaneschi Y, de Jonge P, Giltay EJ, Penninx BWJH. Metabolic and inflammatory markers: associations with individual depressive symptoms. Psychol Med 2018; 48:1102-1110. [PMID: 28889804 DOI: 10.1017/s0033291717002483] [Citation(s) in RCA: 121] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Literature has shown that obesity, metabolic syndrome and inflammation are associated with depression, however, evidence suggests that these associations are specific to atypical depression. Which of the atypical symptoms are driving associations with obesity-related outcomes and inflammation is unknown. We evaluated associations between individual symptoms of depression (both atypical and non-atypical) and body mass index (BMI), metabolic syndrome components and inflammatory markers. METHODS We included 808 persons with a current diagnosis of depression participating in the Netherlands Study of Depression and Anxiety (67% female, mean age 41.6 years). Depressive symptoms were derived from the Composite International Diagnostic Interview and the Inventory of Depressive Symptomatology. Univariable and multivariable regression analyses adjusting for sex, age, educational level, depression severity, current smoking, physical activity, anti-inflammatory medication use, and statin use were performed. RESULTS Increased appetite was positively associated with BMI, number of metabolic syndrome components, waist circumference, C-reactive protein and tumor necrosis factor-α. Decreased appetite was negatively associated with BMI and waist circumference. Psychomotor retardation was positively associated with BMI, high-density lipoprotein cholesterol and triglycerides, and insomnia with number of metabolic syndrome components. CONCLUSION Increased appetite - in the context of a depressive episode - was the only symptom that was associated with both metabolic as well as inflammatory markers, and could be a key feature of an immuno-metabolic form of depression. This immuno-metabolic depression should be considered in clinical trials evaluating effectiveness of compounds targeting metabolic and inflammatory pathways or lifestyle interventions.
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Affiliation(s)
- F Lamers
- Department of Psychiatry,Amsterdam Public Health Research Institute and Amsterdam Neuroscience research institute,VU University Medical Center/GGZ inGeest,Amsterdam,the Netherlands
| | - Y Milaneschi
- Department of Psychiatry,Amsterdam Public Health Research Institute and Amsterdam Neuroscience research institute,VU University Medical Center/GGZ inGeest,Amsterdam,the Netherlands
| | - P de Jonge
- Interdisciplinary Center Psychopathology and Emotion regulation (ICPE),University of Groningen, University Medical Center,Groningen,the Netherlands
| | - E J Giltay
- Department of Psychiatry,Leiden University Medical Center,Leiden,the Netherlands
| | - B W J H Penninx
- Department of Psychiatry,Amsterdam Public Health Research Institute and Amsterdam Neuroscience research institute,VU University Medical Center/GGZ inGeest,Amsterdam,the Netherlands
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Çeri V, Aykutlu HC, Görker I, Akça ÖF, Tarakçıoğlu MC, Aksoy UM, Kaya H, Sertdemir M, İnce E, Kadak MT, Yalçın GY, Guliyev C, Bilgiç A, Çiftçi E, Tekin K, Tuna ZO, Oğuzdoğan B, Duman NS, Semerci B, Üneri ÖŞ, Karabekiroglu K, Mutluer T, Nebioglu M, Başgül ŞS, Naharcı Mİ, Maden Ö, Hocaoğlu Ç, Durmaz O, Usta H, Boşgelmez Ş, Puşuroğlu M, Eser HY, Kaçar M, Çakır M, Karatepe HT, Işık Ü, Kara H, Yeloğlu ÇH, Yazıcı E, Gündüz A, Karataş KS, Yavlal F, Uzun N, Yazici AB, Bodur Ş, Aslan EA, Batmaz S, Çelik F, Açıkel SB, Topal Z, Altunsoy N, Tulacı ÖD, Demirel ÖF, Çıtak S, Çak HT, Artık AB, Özçetin A, Özdemir I, Çelik FGH, Kültür SEÇ, Çipil A, Ay R, Arman AR, Yazıcı KU, Yuce AE, Yazıcı İP, Kurt E, Kaçar AŞ, Erbil N, Poyraz CA, Altın GE, Şahin B, Kılıç Ö, Turan Ş, Aydın M, Kuru E, Bozkurt A, Güleç H, İnan MY, Şevik AE, Baykal S, Karaer Y, Yanartaş O, Aksu H, Ergün S, Görmez A, Yıldız M, Bag S, Özkanoğlu FK, Caliskan M, Yaşar AB, Konuk E, Altın M, Bulut S, Bulut GÇ, Tulacı RG, Küpeli NY, Enver N, Tasci İ, Kani AS, et alÇeri V, Aykutlu HC, Görker I, Akça ÖF, Tarakçıoğlu MC, Aksoy UM, Kaya H, Sertdemir M, İnce E, Kadak MT, Yalçın GY, Guliyev C, Bilgiç A, Çiftçi E, Tekin K, Tuna ZO, Oğuzdoğan B, Duman NS, Semerci B, Üneri ÖŞ, Karabekiroglu K, Mutluer T, Nebioglu M, Başgül ŞS, Naharcı Mİ, Maden Ö, Hocaoğlu Ç, Durmaz O, Usta H, Boşgelmez Ş, Puşuroğlu M, Eser HY, Kaçar M, Çakır M, Karatepe HT, Işık Ü, Kara H, Yeloğlu ÇH, Yazıcı E, Gündüz A, Karataş KS, Yavlal F, Uzun N, Yazici AB, Bodur Ş, Aslan EA, Batmaz S, Çelik F, Açıkel SB, Topal Z, Altunsoy N, Tulacı ÖD, Demirel ÖF, Çıtak S, Çak HT, Artık AB, Özçetin A, Özdemir I, Çelik FGH, Kültür SEÇ, Çipil A, Ay R, Arman AR, Yazıcı KU, Yuce AE, Yazıcı İP, Kurt E, Kaçar AŞ, Erbil N, Poyraz CA, Altın GE, Şahin B, Kılıç Ö, Turan Ş, Aydın M, Kuru E, Bozkurt A, Güleç H, İnan MY, Şevik AE, Baykal S, Karaer Y, Yanartaş O, Aksu H, Ergün S, Görmez A, Yıldız M, Bag S, Özkanoğlu FK, Caliskan M, Yaşar AB, Konuk E, Altın M, Bulut S, Bulut GÇ, Tulacı RG, Küpeli NY, Enver N, Tasci İ, Kani AS, Bahçeci B, Oğuz G, Şenyuva G, Ünal GT, Yektaş Ç, Örüm MH, Göka E, Gıca Ş, Şahmelikoğlu Ö, Dinç GŞ, Erşan S, Erşan E, Ceylan MF, Hesapçıoğlu ST, Solmaz M, Balcioglu YH, Cetin M, Tosun M, Yurteri N, Ulusoy S, Karadere ME, Kivrak Y, Görmez V. Symposium Oral Presentations. PSYCHIAT CLIN PSYCH 2018. [DOI: 10.1080/24750573.2018.1464274] [Show More Authors] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/14/2022] Open
Affiliation(s)
- Veysi Çeri
- Marmara University Pendik Research and Training Hospital, Child and Adolescent Psychiatry Clinic, Istanbul, Turkey
| | - Hasan Cem Aykutlu
- Department of Child and Adolescent Psychiatry, Trakya University School of Medicine, Edirne, Turkey
| | - Işık Görker
- Department of Child and Adolescent Psychiatry, Trakya University School of Medicine, Edirne, Turkey
| | - Ömer Faruk Akça
- Department of Child and Adolescent Psychiatry, Necmettin Erbakan University Meram School of Medicine, Konya, Turkey
| | - Mahmut Cem Tarakçıoğlu
- Health Sciences University Kanuni Sultan Süleyman Research and Training Hospital, Istanbul, Turkey
| | - Umut Mert Aksoy
- Health Sciences University Kanuni Sultan Süleyman Research and Training Hospital, Istanbul, Turkey
| | - Heysem Kaya
- Department of Computer Engineering, Çorlu Faculty of Engineering, Namık Kemal University, Çorlu, Tekirdağ, Turkey
| | - Merve Sertdemir
- Department of Child and Adolescent Psychiatry, Necmettin Erbakan University Meram School of Medicine, Konya, Turkey
| | - Ezgi İnce
- Department of Psychiatry, Istanbul University Istanbul School of Medicine, Istanbul, Turkey
| | - Muhammed Tayyib Kadak
- Department of Child and Adolescent Psychiatry, Istanbul University Cerrahpaşa School of Medicine, Istanbul, Turkey
| | | | | | - Ayhan Bilgiç
- Department of Child and Adolescent Psychiatry, Necmettin Erbakan University Meram School of Medicine, Konya, Turkey
| | - Elvan Çiftçi
- Department of Psychiatry, Erenkoy Research and Training Hospital, Istanbul, Turkey
| | | | | | | | | | - Bengi Semerci
- Department of Psychology, Hasan Kalyoncu University, Gaziantep, Turkey
| | - Özden Şükran Üneri
- Department of Child and Adolescent Psychiatry, Yıldırım Beyazıt University School of Medicine, Ankara, Turkey
| | | | - Tuba Mutluer
- Koç University Hospital, Department of Child and Adolescent Psychiatry, Istanbul, Turkey
| | - Melike Nebioglu
- Health Sciences University, Haydarpaşa Numune Research and Training Hospital, Istanbul, Turkey
| | | | - Mehmet İlkin Naharcı
- Division of Geriatrics, Department of Internal Medicine, Health Sciences University, Ankara, Turkey
| | - Özgür Maden
- SBÜ Sultan Abdülhamid Han Education and Training Hospital, Department of Psychiatry, Istanbul, Turkey
| | - Çiçek Hocaoğlu
- Department of Psychiatry, Recep Tayyip Erdogan University School of Medicine, Rize, Turkey
| | - Onur Durmaz
- Erenköy Mental Health and Neurology Research and Training Hospital, Department of Psychiatry, Istanbul, Turkey
| | - Haluk Usta
- Erenköy Mental Health and Neurology Research and Training Hospital, Department of Psychiatry, Istanbul, Turkey
| | - Şükriye Boşgelmez
- Kocaeli Derince Research and Training Hospital, Psychiatry Clinic, Kocaeli, Turkey
| | | | - Hale Yapıcı Eser
- KOÇ University School of Medicine, Istanbul, Turkey
- KOÇ University Research Center FOR Translational Medicine (Kuttam), Istanbul, Turkey
- Koç University School of Medicine Department of Psychiatry, Istanbul, Turkey
- Koç University Research Center for Translational Medicine (KUTTAM), Istanbul, Turkey
| | - Murat Kaçar
- Department of Child and Adolescent Psychiatry, Recep Tayyip Erdogan University School of Medicine, Rize, Turkey
| | - Mahmut Çakır
- Child Psychiatry Clinic, Health Sciences University, Amasya Research and Training Hospital, Amasya, Turkey
| | - Hasan Turan Karatepe
- Department of Psychiatry, Istanbul Medeniyet University, School of Medicine, Istanbul, Turkey
| | - Ümit Işık
- Department of Child and Adolescent Psychiatry, Yozgat State Hospital, Yozgat, Turkey
| | - Halil Kara
- Department of Child and Adolescent Psychiatry, Aksaray University Research and Training Hospital, Aksaray, Turkey
| | | | - Esra Yazıcı
- Department of Psychiatry, Sakarya University School of Medicine, Sakarya, Turkey
| | - Anıl Gündüz
- Health Sciences University, Haydarpaşa Numune Research and Training Hospital, Istanbul, Turkey
| | - Kader Semra Karataş
- Recep Tayyip Erdogan University School of Medicine Psychiatry Department, Rize, Turkey
| | - Figen Yavlal
- Department of Neurology, School of Medicine, Bahcesehir University, Istanbul, Turkey
- Department of Neurology, Bahcesehir University School of Medicine, Istanbul, Turkey
| | - Necati Uzun
- Department of Child and Adolescent Psychiatry, Elazığ Psychiatry Hospital, Elazığ, Turkey
| | - Ahmet Bulent Yazici
- Department of Psychiatry, Sakarya University School of Medicine, Sakarya, Turkey
| | - Şahin Bodur
- Health Sciences University, Gulhane Research and Training Hospital, Child and Adolescent Psychiatry Clinic, Ankara, Turkey
| | - Esma Akpınar Aslan
- Department of Psychiatry, Gaziosmanpaşa University School of Medicine, Tokat, Turkey
| | - Sedat Batmaz
- Department of Psychiatry, Gaziosmanpasa University School of Medicine, Tokat, Turkey
| | - Feyza Çelik
- Department of Psychiatry, Dumlupınar University School of Medicine, Evliya Çelebi Research and Training Hospital, Kütahya, Turkey
| | - Sadettin Burak Açıkel
- Dr. Sami Ulus Research and Training Hospital, Child and Adolescent Psychiatry Department, Ankara, Turkey
| | | | | | | | - Ömer Faruk Demirel
- Department of Psychiatry, Cerrahpaşa Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Serhat Çıtak
- Department of Psychiatry, Istanbul Medeniyet University, School of Medicine, Istanbul, Turkey
| | - Halime Tuna Çak
- Department of Child and Adolescent Psychiatry, Hacettepe University School of Medicine, Ankara, Turkey
| | - Abdül Baki Artık
- Department of Child and Adolescent Psychiatry, Hacettepe University School of Medicine, Ankara, Turkey
| | - Adnan Özçetin
- Department of Psychiatry, Duzce University School of Medicine, Duzce, Turkey
| | - Ilker Özdemir
- Giresun University Prof. Dr. A. İlhan Özdemir Research and Training Hospital, Giresun, Turkey
| | | | | | - Arif Çipil
- Health Sciences University, Haydarpaşa Numune Research and Training Hospital, Istanbul, Turkey
| | - Rukiye Ay
- Malatya Research and Training Hospital, Malatya, Turkey
| | - Ayşe Rodopman Arman
- Department of Child and Adolescent Psychiatry, Marmara University School of Medicine, Istanbul
| | - Kemal Utku Yazıcı
- Department of Child and Adolescent Psychiatry, Firat University School of Medicine, Elazig, Turkey
| | | | - İpek Perçinel Yazıcı
- Department of Child and Adolescent Psychiatry, Firat University School of Medicine, Elazig, Turkey
| | - Emel Kurt
- Psychiatry Clinic, Hisar Intercontinental Hospital, Istanbul, Turkey
| | - Anıl Şafak Kaçar
- Koc University, Research Center for Translational Medicine, Istanbul, Turkey
| | - Nurhan Erbil
- Department of Biophysics, Hacettepe University School of Medicine, Ankara, Turkey
| | - Cana Aksoy Poyraz
- Department of Psychiatry, Istanbul University Cerrahpaşa School of Medicine, Istanbul, Turkey
| | | | - Berkan Şahin
- Iğdır State Hospital, Child and Adolescent Psychiatry Clinic, Iğdır, Turkey
| | - Özge Kılıç
- Department of Psychiatry, Koç University Hospital, Istanbul, Turkey
| | - Şenol Turan
- Department of Psychiatry, Istanbul University Cerrahpaşa School of Medicine, Istanbul, Turkey
| | - Memduha Aydın
- Department of Psychiatry, Selçuk University School of Medicine, Konya, Turkey
| | - Erkan Kuru
- Özel Boylam Psychiatry Hospital, Ankara, Turkey
| | - Abdullah Bozkurt
- Department of Child and Adolescent Psychiatry, Konya Research and Training Hospital, Konya, Turkey
| | - Hüseyin Güleç
- Erenköy Mental Health and Neurology Research and Training Hospital, Department of Psychiatry, Istanbul, Turkey
| | | | - Ali Emre Şevik
- Department of Psychiatry, Çanakkale 18 Mart University School of Medicine, Çanakkale, Türkiye
| | - Saliha Baykal
- Department of Child and Adolescent Psychiatry, Namık Kemal University School of Medicine, Tekirdağ, Turkey
| | - Yusuf Karaer
- Department of Child and Adolescent Psychiatry, Hacettepe University School of Medicine, Ankara, Turkey
| | - Omer Yanartaş
- Department of Psychiatry, Marmara Medical School, Istanbul, Turkiye
| | - Hatice Aksu
- Department of Child and Adolescent Psychiatry, Adnan Menderes University School of Medicine, Aydın, Turkey
| | - Serhat Ergün
- Department of Psychiatry, Marmara University Pendik Research and Training Hospital, Istanbul, Turkey
| | - Aynur Görmez
- Department of Child and Adolescent Psychiatry, Istanbul Medeniyet University School of Medicine, Istanbul, Turkey
| | - Mesut Yıldız
- Department of Psychiatry, School of Medicine, Marmara University, Istanbul, Turkey
| | - Sevda Bag
- Bakirkoy Research and Training Hospital for Psychiatry, Neurology and Neurosurgery, Istanbul, Turkey
| | | | - Mecit Caliskan
- Health Sciences University, Haydarpaşa Numune Research and Training Hospital, Istanbul, Turkey
| | - Alişan Burak Yaşar
- Health Sciences University, Haydarpaşa Numune Research and Training Hospital, Istanbul, Turkey
- Behavioral Sciences Institute, Istanbul, Turkey
| | - Emre Konuk
- Health Sciences University, Haydarpaşa Numune Research and Training Hospital, Istanbul, Turkey
- Behavioral Sciences Institute, Istanbul, Turkey
| | - Murat Altın
- Istinye University Hospital, Psychiatry Clinic, Istanbul, Turkey
| | - Serkut Bulut
- Psychiatry Clinic, Health Sciences University Sakarya Research and Training Hospital, Sakarya, Turkey
| | | | - Rıza Gökçer Tulacı
- Uşak University School of Medicine Research and Training Hospital, Uşak, Turkey
| | - Neşe Yorguner Küpeli
- Department of Psychiatry, Marmara University Pendik Research and Training Hospital, Istanbul, Turkey
| | - Necati Enver
- Department of Otolaryngology, Marmara University Pendik Research and Training Hospital, Istanbul, Turkey
| | - İlker Tasci
- Health Sciences University, Gulhane School of Medicine, Department of Internal Medicine, Ankara, Turkey
| | - Ayşe Sakallı Kani
- Marmara University Pendik Research and Training Hospital, Istanbul, Turkey
| | - Bülent Bahçeci
- Department of Psychiatry, Recep Tayyip Erdogan University, Rize, Turkey
| | | | | | - Gülşen Teksin Ünal
- Bakirkoy Prof. Dr. Mazhar Osman Research and Training Hospital for Psychiatry, Neurology, and Neurosurgery, Istanbul, Turkey
| | - Çiğdem Yektaş
- Duzce University School of Medicine, Department of Child and Adolescent Psychiatry, Duzce, Turkey
| | - Mehmet Hamdi Örüm
- Department of Psychiatry, Adiyaman University School of Medicine, Adiyaman, Turkey
| | - Erol Göka
- SBÜ Ankara Numune Eğitim ve Araştırma Hastanesi
| | - Şakir Gıca
- Bakirkoy Prof. Dr. Mazhar Osman Research and Training Hospital for Psychiatry, Neurology, and Neurosurgery, Istanbul, Turkey
| | - Özge Şahmelikoğlu
- Bakirkoy Prof. Dr. Mazhar Osman Research and Training Hospital for Psychiatry, Neurology, and Neurosurgery, Istanbul, Turkey
| | - Gülser Şenses Dinç
- Department of Child and Adolescent Psychiatry, Ankara Children’s Hematology Oncology Research and Training Hospital, Ankara Turkey
| | - Serpil Erşan
- Cumhuriyet University Advanced Technology Research and Application Center, Sivas, Turkey
| | - Erdal Erşan
- Sivas Numune Hospital, Community Mental Health Center, Sivas, Turkey
| | - Mehmet Fatih Ceylan
- Department of Child and Adolescent Psychiatry, Yıldırım Beyazıt University School of Medicine, Ankara, Turkey
| | - Selma Tural Hesapçıoğlu
- Department of Child and Adolescent Psychiatry, Yıldırım Beyazıt University School of Medicine, Ankara, Turkey
| | - Mustafa Solmaz
- Health Sciences University Bagcilar Research and Training Hospital, Department of Psychiatry, Istanbul, Turkey
- Bakirkoy Prof. Mazhar Osman Training and Research Hospital for Psychiatry, Neurology, and Neurosurgery, Forensic Psychiatry Unit, Istanbul, Turkey
| | - Yasin Hasan Balcioglu
- Health Sciences University Bagcilar Research and Training Hospital, Department of Psychiatry, Istanbul, Turkey
- Bakirkoy Prof. Mazhar Osman Training and Research Hospital for Psychiatry, Neurology, and Neurosurgery, Forensic Psychiatry Unit, Istanbul, Turkey
| | | | - Musa Tosun
- Istanbul University Cerrahpaşa School of Medicine, Department of Child and Adolescent Psychiatry, Istanbul, Turkey
| | - Nihal Yurteri
- Duzce University School of Medicine, Department of Child and Adolescent Psychiatry, Duzce, Turkey
| | - Sevinc Ulusoy
- Bakirkoy Prof. Dr. Mazhar Osman Research and Training Hospital for Psychiatry and Neurology, Istanbul, Turkey
| | | | - Yüksel Kivrak
- Department of Psychiatry, Kafkas University School of Medicine, Kars, Turkey
| | - Vahdet Görmez
- Bezmialem Vakif University, Department of Child and Adolescent Psychiatry, Istanbul, Turkey
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Simanek AM, Parry A, Dowd JB. Differences in the association between persistent pathogens and mood disorders among young- to middle-aged women and men in the U.S. Brain Behav Immun 2018; 68:56-65. [PMID: 28965957 DOI: 10.1016/j.bbi.2017.09.017] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2017] [Revised: 09/08/2017] [Accepted: 09/27/2017] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND A growing literature supports the role of immune system alterations in the etiology of mood regulation, yet there is little population-based evidence regarding the association between persistent pathogens, inflammation and mood disorders among younger women and men in the U.S. METHODS We used data from the National Health and Nutrition Examination Survey III on individuals 15-39 years of age assessed for major depression, dysthymia, and/or bipolar disorder I and tested for cytomegalovirus (N=6825), herpes simplex virus (HSV)-1 (N=5618) and/or Helicobacter pylori (H. pylori) (N=3167) seropositivity as well as C-reactive protein (CRP) level (N=6788). CMV immunoglobulin G (IgG) antibody level was also available for a subset of women (N=3358). We utilized logistic regression to estimate the odds ratio (OR) and 95% confidence interval (CI) for the association between pathogens, CRP levels and each mood disorder overall and among women and men, separately. RESULTS H. pylori seropositivity was associated with increased odds of dysthymia (OR 2.37, 95% confidence interval (CI): 1.07, 5.24) among women, but decreased odds among men (OR 0.51, 95% CI: 0.28, 0.92). CMV seropositivity was also associated with lower odds of depression (OR 0.54, 95% CI: 0.32, 0.91) among men, while elevated CMV IgG level was marginally associated with increased odds of mood disorders among women. Associations were not mediated by CRP level. CONCLUSIONS Our findings suggest that persistent pathogens such as CMV and H. pylori may differentially influence mood disorders among women and men, warranting further investigation into biological and/or sociocultural explanations for the contrasting associations observed.
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Affiliation(s)
- Amanda M Simanek
- Joseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI, United States.
| | - Amy Parry
- Joseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI, United States
| | - Jennifer B Dowd
- Department of Global Health and Social Medicine, King's College London, London, UK; Department of Epidemiology and Biostatistics, CUNY Graduate School of Public Health and Health Policy, New York, NY, United States
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Horne R, Foster JA. Metabolic and Microbiota Measures as Peripheral Biomarkers in Major Depressive Disorder. Front Psychiatry 2018; 9:513. [PMID: 30405455 PMCID: PMC6204462 DOI: 10.3389/fpsyt.2018.00513] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2018] [Accepted: 09/28/2018] [Indexed: 12/21/2022] Open
Abstract
Advances in understanding the role of the microbiome in physical and mental health are at the forefront of medical research and hold potential to have a direct impact on precision medicine approaches. In the past 7 years, we have studied the role of microbiota-brain communication on behavior in mouse models using germ-free mice, mice exposed to antibiotics, and healthy specific pathogen free mice. Through our work and that of others, we have seen an amazing increase in our knowledge of how bacteria signal to the brain and the implications this has for psychiatry. Gut microbiota composition and function are influenced both by genetics, age, sex, diet, life experiences, and many other factors of psychiatric and bodily disorders and thus may act as potential biomarkers of the gut-brain axis that could be used in psychiatry and co-morbid conditions. There is a particular need in major depressive disorder and other mental illness to identify biomarkers that can stratify patients into more homogeneous groups to provide better treatment and for development of new therapeutic approaches. Peripheral outcome measures of host-microbe bidirectional communication have significant translational value as biomarkers. Enabling stratification of clinical populations, based on individual biological differences, to predict treatment response to pharmacological and non-pharmacological interventions. Here we consider the links between co-morbid metabolic syndrome and depression, focusing on biomarkers including leptin and ghrelin in combination with assessing gut microbiota composition, as a potential tool to help identify individual differences in depressed population.
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Affiliation(s)
- Rachael Horne
- Department of Psychiatry & Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada
| | - Jane A Foster
- Department of Psychiatry & Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.,Department of Psychiatry, St. Michael's Hospital, Toronto, ON, Canada
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Woo YS, Bahk WM. The Link Between Obesity and Depression: Exploring Shared Mechanisms. UNDERSTANDING DEPRESSION 2018:203-220. [DOI: 10.1007/978-981-10-6577-4_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Milaneschi Y, Lamers F, Bot M, Drent ML, Penninx BWJH. Leptin Dysregulation Is Specifically Associated With Major Depression With Atypical Features: Evidence for a Mechanism Connecting Obesity and Depression. Biol Psychiatry 2017; 81:807-814. [PMID: 26742925 DOI: 10.1016/j.biopsych.2015.10.023] [Citation(s) in RCA: 146] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2015] [Revised: 10/27/2015] [Accepted: 10/27/2015] [Indexed: 10/22/2022]
Abstract
BACKGROUND Obesity-related dysregulation of leptin signaling (e.g., hyperleptinemia due to central functional resistance) may affect mood. However, evidence for leptin dysregulation in major depressive disorder (MDD) is conflicting. Inconclusive findings may be attributable to heterogeneity of MDD, aggregating biologically different subtypes. We examined the relationship of leptin with MDD, its common subtypes (typical and atypical), and clinical features. METHODS The sample consisted of participants (aged 18 to 65 years) from the Netherlands Study of Depression and Anxiety with current (n = 1062) or remitted (n = 711) MDD and healthy control subjects (n = 497). Diagnoses of MDD and subtypes were based on DSM-IV symptoms. Additional symptoms were measured with the Inventory of Depressive Symptomatology. Blood levels of leptin and adiposity indexes (body mass index and waist circumference) were assessed. RESULTS As compared to control subjects, higher leptin was associated with the atypical MDD subtype both for remitted (n = 144, odds ratio = 1.53, 95% confidence interval = 1.16-2.03, p = .003) and current (n = 270, odds ratio = 1.90, 95% confidence interval = 1.51-2.93, p = 5.3e-8) cases. This association was stronger for increasing adiposity levels (leptin by body mass index interaction, p < .02), strengthening the hypothesis of the involvement of leptin resistance. No association with leptin was found for overall MDD or the typical subtype. Among currently depressed patients, higher leptin was associated with key symptoms identifying the atypical subtype, such as hyperphagia, increased weight, and leaden paralysis. CONCLUSIONS Leptin dysregulation (resistance) may represent an underlying mechanism connecting obesity and MDD with atypical features. Development of treatment effectively targeting leptin resistance may benefit patients with atypical depression characterized by obesity-related metabolic alterations.
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Affiliation(s)
- Yuri Milaneschi
- Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center/GGZ ingest, Amsterdam, The Netherlands.
| | - Femke Lamers
- Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center/GGZ ingest, Amsterdam, The Netherlands
| | - Mariska Bot
- Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center/GGZ ingest, Amsterdam, The Netherlands
| | - Madeleine L Drent
- Department of Internal Medicine, Endocrine Section, VU University Medical Center, Department of Clinical Neuropsychology, Faculty of Psychology and Education, VU University, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands
| | - Brenda W J H Penninx
- Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center/GGZ ingest, Amsterdam, The Netherlands
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Yildiz G, Senturk MB, Yildiz P, Cakmak Y, Budak MS, Cakar E. Serum serotonin, leptin, and adiponectin changes in women with postpartum depression: controlled study. Arch Gynecol Obstet 2017; 295:853-858. [PMID: 28224268 DOI: 10.1007/s00404-017-4313-0] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2016] [Accepted: 02/01/2017] [Indexed: 12/31/2022]
Abstract
PURPOSE Postpartum depression (PPD) affects nearly 10% of mothers after delivery and has many serious results. Although many factors associated with PPD, the etiology, and pathophysiology of PPD are not known completely. The relationship between serum serotonin concentration and depression is well known, but there are no enough data regarding the serum change of leptin and adiponectin. The aims of this study are to research the level of serum serotonin, leptin,s and adiponectin concentrations in women with PPD. MATERIALS AND METHODS A controlled trial has been conducted in three centers. Two hundred and forty four women were evaluated at postpartum day 10 with the Edinburgh Postnatal Depression Scale (EPDD). Venous blood samples were collected and serotonin, and leptin and adiponectin levels were studied using human enzyme-linked immunosorbent assay. Mann-Whitney U test was used for comparison of serum levels of serotonin, leptin, and adiponectin between women with PPD and without. A p value of <0.05 was considered significant. RESULTS PPD was detected in 70 postpartum women. The mean serum serotonin level was significantly lower in the group with PPD (p = 0.001), while mean serum adiponectin level was higher (p = 0.001). The mean serum leptin level was not different (p = 0.133). CONCLUSIONS The serum adiponectin and leptin levels were high in women with PPD. This could play important role in the pathophysiology of PPD. Elevation of serum levels also may play antidepressant role against PPD, especially the early postpartum period.
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Affiliation(s)
- Gazi Yildiz
- Department of Obstetrics and Gynecology, Muş Şifa Private Hospital, Kültür district, 168 th street, Muş, Turkey
| | - Mehmet Baki Senturk
- Department of Obstetrics and Gynecology, Zeynep Kamil Gynecologic and Pediatric Training and Research Hospital, Opr. Dr. Burhanettin Ustunel street, No: 10, 34668, Uskudar, Istanbul, Turkey.
| | - Pinar Yildiz
- Department of Obstetrics and Gynecology, Muş Şifa Private Hospital, Kültür district, 168 th street, Muş, Turkey
| | - Yusuf Cakmak
- Department of Obstetrics and Gynecology, Batman State Hospital, Ziya Gokalp district, 72060, Batman, Turkey
| | - Mehmet Sukru Budak
- Department of Obstetrics and Gynecology, Diyarbakir Women and Child Hospital, Bagcılar district, 21060, Baglar, Diyarbakir, Turkey
| | - Erbil Cakar
- Department of Obstetrics and Gynecology, Zeynep Kamil Gynecologic and Pediatric Training and Research Hospital, Opr. Dr. Burhanettin Ustunel street, No: 10, 34668, Uskudar, Istanbul, Turkey
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Pathogen-Host Defense in the Evolution of Depression: Insights into Epidemiology, Genetics, Bioregional Differences and Female Preponderance. Neuropsychopharmacology 2017; 42:5-27. [PMID: 27629366 PMCID: PMC5143499 DOI: 10.1038/npp.2016.194] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2016] [Revised: 08/28/2016] [Accepted: 09/08/2016] [Indexed: 12/25/2022]
Abstract
Significant attention has been paid to the potential adaptive value of depression as it relates to interactions with people in the social world. However, in this review, we outline the rationale of why certain features of depression including its environmental and genetic risk factors, its association with the acute phase response and its age of onset and female preponderance appear to have evolved from human interactions with pathogens in the microbial world. Approaching the relationship between inflammation and depression from this evolutionary perspective yields a number of insights that may reveal important clues regarding the origin and epidemiology of the disorder as well as the persistence of its risk alleles in the modern human genome.
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Li L, Gower BA, Shelton RC, Wu X. Gender-Specific Relationship between Obesity and Major Depression. Front Endocrinol (Lausanne) 2017; 8:292. [PMID: 29176959 PMCID: PMC5686049 DOI: 10.3389/fendo.2017.00292] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Accepted: 10/12/2017] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVE Prior research suggests a bidirectional relationship between obesity and major depressive disorder (MDD), but the results have been heterogeneous. Differences between males and females in the association of MDD with obesity may contribute to inconsistent results. Thus, this study was designed to determine whether sex has a differential effect on the relationship between MDD and obesity, and to explore the potential mechanisms. METHODS All participants were diagnosed with MDD, and depression severity was measured using the 17-item Hamilton Depression Rating Scale. Body weight and height were measured to calculate body mass index (BMI). Body composition, including total fat, trunk fat, android fat, and visceral fat mass, was measured by dual-energy X-ray absorptiometry. Subjects provided blood samples, and serum was extracted for measuring the inflammatory factors using human immunoassay kits. RESULTS Among all obesity measures, depressed women had greater BMI and total body fat. By contrast, depressed men had greater visceral fat mass. However, only in depressed women was depression correlated with several measures of obesity, including BMI, total body fat, and visceral fat mass. A stepwise multiple regression analysis was conducted, and only visceral fat entered the regression model and was most predictive of depression in women (β = 0.60, p = 0.007). Moreover, compared with depressed men, depressed women had higher leptin levels after controlling for BMI, total body fat, and visceral fat. CONCLUSION These results highlight gender differences in determining the association between obesity and depression, and elevated leptin level is a potential mechanism linking MDD to obesity in depressed women. Understanding a gender-specific relationship between obesity and MDD would allow clinicians to target and personalize therapies in the hope of improving health outcomes.
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Affiliation(s)
- Li Li
- Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, United States
- *Correspondence: Li Li,
| | - Barbara A. Gower
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Richard C. Shelton
- Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Xiaoyan Wu
- Department of Nephrology, Wuhan University, Wuhan, China
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Serum proteomic profiles of depressive subtypes. Transl Psychiatry 2016; 6:e851. [PMID: 27404283 PMCID: PMC5545705 DOI: 10.1038/tp.2016.115] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2015] [Revised: 03/21/2016] [Accepted: 03/29/2016] [Indexed: 01/10/2023] Open
Abstract
Depression is a highly heterogeneous disorder. Accumulating evidence suggests biological and genetic differences between subtypes of depression that are homogeneous in symptom presentation. We aimed to evaluate differences in serum protein profiles between persons with atypical and melancholic depressive subtypes, and compare these profiles with serum protein levels of healthy controls. We used the baseline data from the Netherlands Study of Depression and Anxiety on 414 controls, 231 persons with a melancholic depressive subtype and 128 persons with an atypical depressive subtype for whom the proteomic data were available. Depressive subtypes were previously established using a data-driven analysis, and 171 serum proteins were measured on a multi-analyte profiling platform. Linear regression models were adjusted for several covariates and corrected for multiple testing using false discovery rate q-values. We observed differences in analytes between the atypical and melancholic subtypes (9 analytes, q<0.05) and between atypical depression and controls (23 analytes, q<0.05). Eight of the nine markers differing between the atypical and melancholic subtype overlapped with markers from the comparison between atypical subtype and controls (mesothelin, leptin, IGFBP1, IGFBP2, FABPa, insulin, C3 and B2M), and were mainly involved in cellular communication and signal transduction, and immune response. No markers differed significantly between the melancholic subtype and controls. To conclude, although some uncertainties exist in our results as a result of missing data imputation and lack of proteomic replication samples, many of the identified analytes are inflammatory or metabolic markers, which supports the notion of atypical depression as a syndrome characterized by metabolic disturbances and inflammation, and underline the importance and relevance of subtypes of depression in biological and genetic research, and potentially in the treatment of depression.
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43
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Jeon SW, Kim YK. Molecular Neurobiology and Promising New Treatment in Depression. Int J Mol Sci 2016; 17:381. [PMID: 26999106 PMCID: PMC4813239 DOI: 10.3390/ijms17030381] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2016] [Revised: 03/03/2016] [Accepted: 03/07/2016] [Indexed: 01/04/2023] Open
Abstract
The limited effects of currently available antidepressants are becoming an urgent issue in depression research. It takes a long time to determine treatment effects, and the overall remission rate is low. Although we expect the development of non-monoamine antidepressants in the near future, efforts in this regard over the past several decades have not yet been compensated. Thus, researchers and clinicians should clarify the neurobiological mechanisms of integrated modulators that regulate changes in genes, cells, the brain, and behaviors associated with depression. In this study, we review molecular neurobiological theories and new treatments for depression. Beyond neuroanatomy and monoamine theory, we discuss cells and molecules, neural plasticity, neurotrophisms, endocrine mechanisms, immunological mechanisms, genetics, circadian rhythms, and metabolic regulation in depression. In addition, we introduce the possibility of new antidepressant drug development using protein translation signaling (mTOR) pathways.
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Affiliation(s)
- Sang Won Jeon
- Department of Psychiatry, College of Medicine, Korea University, Ansan Hospital, 123, Jeokgeum-ro, Danwon-gu, Ansan-si, Gyeonggi-do, Seoul 15355, Korea.
| | - Yong-Ku Kim
- Department of Psychiatry, College of Medicine, Korea University, Ansan Hospital, 123, Jeokgeum-ro, Danwon-gu, Ansan-si, Gyeonggi-do, Seoul 15355, Korea.
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Ubani CC, Zhang J. The role of adiposity in the relationship between serum leptin and severe major depressive episode. Psychiatry Res 2015; 228:866-70. [PMID: 26032460 DOI: 10.1016/j.psychres.2015.05.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2015] [Accepted: 05/07/2015] [Indexed: 01/22/2023]
Abstract
To assess the role that adiposity plays in the association between leptin and major depressive episode (MDE), we analyzed the data of 1046 men and 1359 women aged 20-39 years, who completed an interview and had blood collected as a part of the National Health and Nutrition Examination Survey (NHANES) between 1991 and 1994. Waist-hip ratio (WHR) was used as an indicator of adiposity. MDE was assessed with the Diagnostic Interview Schedule. For normal-WHR women, the prevalence of MDE was reversely associated with leptin levels, 13.7(4.4)%, 12.2(4.0)% and 2.3(1.8)% respectively for lower, interquartile, and upper quartile. For abnormal-WHR women, the prevalence of MDE was positively associated with leptin, 6.1(2.3)%, 9.1(2.4)% and 20.0 (3.8) respectively for the three leptin levels. Compared to women with lower quartile of leptin, the odds ratio of MDE for women with upper quartile was 0.09 (0.01-0.98) for normal-WHR women but 4.35 (1.55-12.2) for abnormal-WHR women. No moderating effects were observed among men. Using BMI in place of WHR revealed similar findings. The association between MDE and leptin is moderated by adiposity. High leptin levels are associated with low odds of MDE among women with normal adiposity but high odds among women with abnormal adiposity.
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Affiliation(s)
- Chinedu C Ubani
- Department of Epidemiology, Jiann-Ping Hsu College of Public Health, Georgia Southern University, Statesboro, GA 30456, USA
| | - Jian Zhang
- Department of Epidemiology, Jiann-Ping Hsu College of Public Health, Georgia Southern University, Statesboro, GA 30456, USA.
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Neri Calixto M, Ayllón Alvarez D, Vieyra Reyes P, Hernández-González M, Jiménez-Garcés C, Flores Ocampo P. Influencia de grelina y leptina sobre alteraciones psiquiátricas en sujetos con obesidad. ACTA ACUST UNITED AC 2015. [DOI: 10.1016/j.mei.2015.02.017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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Zarouna S, Wozniak G, Papachristou AI. Mood disorders: A potential link between ghrelin and leptin on human body? World J Exp Med 2015; 5:103-109. [PMID: 25992324 PMCID: PMC4436933 DOI: 10.5493/wjem.v5.i2.103] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2014] [Revised: 12/28/2014] [Accepted: 02/02/2015] [Indexed: 02/06/2023] Open
Abstract
Leptin and ghrelin are two hormones associated with multiple physiological functions, especially energy balance. Leptin is an adipocyte-secreted hormone discovered in 1950 and ghrelin which was found in 1999, is a peptide hormone produced and secreted in the stomach. A number of previous studies showed that these hormones could be associated with different types of mood disorders. The results of previous studies, nevertheless, are confounded by diverse sample selection and different methodologies. A search for related articles in the PubMed database was attempted. The search covered studies, reports, reviews and editorials published in the last ten years. Older references served as auxiliary sources for comparison purposes. However, due to the different results of the studies, there is a need for more investigation in order to establish the exact biochemical mechanisms that are responsible for these diseases and ghrelin’s and leptin’s effects on mood.
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de Carvalho-Ferreira JP, Masquio DCL, da Silveira Campos RM, Dal Molin Netto B, Corgosinho FC, Sanches PL, Tock L, Tufik S, de Mello MT, Finlayson G, Dâmaso AR. Is there a role for leptin in the reduction of depression symptoms during weight loss therapy in obese adolescent girls and boys? Peptides 2015; 65:20-8. [PMID: 25629253 DOI: 10.1016/j.peptides.2014.11.010] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 11/18/2014] [Accepted: 11/18/2014] [Indexed: 01/04/2023]
Abstract
Several studies have sought to clarify the association between adolescent obesity and psychological distress. Recently, a biological link between leptin resistance and depression has been proposed. The aim of the present study was to examine changes in leptin concentrations as a potential predictor of reduced depression symptoms in obese adolescents during long-term interdisciplinary weight loss therapy. Seventy-five obese adolescents (age: 16.28±2.37 years; BMI: 35.65±4.64 kg/m2) engaged in a long-term interdisciplinary therapy for weight loss. They were evaluated at baseline and after 1 year of treatment for body composition, serum analyses and depression symptomatology. After therapy, body mass BMI, fat mass (% and kg), waist circumference, visceral, subcutaneous and visceral/subcutaneous fat and depression symptoms decreased and lean mass (%) increased significantly. There was an improvement in inflammatory profiles with a significant reduction in leptin and increase in adiponectin. Regression analyses showed that decreased leptin predicted amelioration in depression symptoms independent of age, gender and changes in visceral fat, body mass, fat mass (%) and leptin/adiponectin ratio. These associations appear stronger in girls than boys. The attenuation of hyperleptinemia appears to play an important role in the association between weight loss and depression, particularly in obese girls.
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Affiliation(s)
| | | | | | - Bárbara Dal Molin Netto
- Post-Graduate Program of Nutrition - Universidade Federal de São Paulo, São Paulo, SP, Brazil
| | | | - Priscila L Sanches
- Post-Graduate Program of Nutrition - Universidade Federal de São Paulo, São Paulo, SP, Brazil
| | - Lian Tock
- Weight Science, São Paulo, SP, Brazil
| | - Sergio Tufik
- Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, SP, Brazil
| | - Marco Túlio de Mello
- Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, SP, Brazil
| | - Graham Finlayson
- Institute of Psychological Sciences, University of Leeds, Leeds, West Yorkshire, United Kingdom
| | - Ana R Dâmaso
- Post-Graduate Program of Interdisciplinary Health Sciences, Universidade Federal de São Paulo, Santos, SP, Brazil; Post-Graduate Program of Nutrition - Universidade Federal de São Paulo, São Paulo, SP, Brazil.
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Wittekind DA, Kluge M. Ghrelin in psychiatric disorders - A review. Psychoneuroendocrinology 2015; 52:176-94. [PMID: 25459900 DOI: 10.1016/j.psyneuen.2014.11.013] [Citation(s) in RCA: 77] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2014] [Revised: 11/13/2014] [Accepted: 11/13/2014] [Indexed: 12/21/2022]
Abstract
Ghrelin is a 28-amino-acid peptide hormone, first described in 1999 and broadly expressed in the organism. As the only known orexigenic hormone secreted in the periphery, it increases hunger and appetite, promoting food intake. Ghrelin has also been shown to be involved in various physiological processes being regulated in the central nervous system such as sleep, mood, memory and reward. Accordingly, it has been implicated in a series of psychiatric disorders, making it subject of increasing investigation, with knowledge rapidly accumulating. This review aims at providing a concise yet comprehensive overview of the role of ghrelin in psychiatric disorders. Ghrelin was consistently shown to exert neuroprotective and memory-enhancing effects and alleviated psychopathology in animal models of dementia. Few human studies show a disruption of the ghrelin system in dementia. It was also shown to play a crucial role in the pathophysiology of addictive disorders, promoting drug reward, enhancing drug seeking behavior and increasing craving in both animals and humans. Ghrelin's exact role in depression and anxiety is still being debated, as it was shown to both promote and alleviate depressive and anxiety-behavior in animal studies, with an overweight of evidence suggesting antidepressant effects. Not surprisingly, the ghrelin system is also implicated in eating disorders, however its exact role remains to be elucidated. Its widespread involvement has made the ghrelin system a promising target for future therapies, with encouraging findings in recent literature.
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Affiliation(s)
| | - Michael Kluge
- Department of Psychiatry and Psychotherapy, University of Leipzig, Leipzig, Germany
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Stieg MR, Sievers C, Farr O, Stalla GK, Mantzoros CS. Leptin: A hormone linking activation of neuroendocrine axes with neuropathology. Psychoneuroendocrinology 2015; 51:47-57. [PMID: 25290346 DOI: 10.1016/j.psyneuen.2014.09.004] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2014] [Revised: 09/03/2014] [Accepted: 09/06/2014] [Indexed: 11/24/2022]
Abstract
Leptin, a peptide hormone secreted by adipocytes, plays a central role in controlling appetite and weight in both rodents and humans. Basic science and clinical research suggest that this hormone not only affects the regulation of the neuroendocrine axes, but also exerts effects on the central nervous system with subsequent alterations in psychological functions. For instance, leptin suppresses cortisol secretion during stress-related activation of the adrenal axis. As psychiatric disorders like depression are associated with hypercortisolism, leptin is proposed to exert anti-depressant-like effects due to its inhibition of chronically overactive hypothalamo-pituitary-adrenal axis function. Moreover, leptin status of depressed patients could serve as a prognostic marker for therapy response. Besides its influence on neuroendocrine pathways leptin seems to have direct central effects on brain development and neuroplasticity. Low leptin levels have been shown to be associated with increased risk of developing dementia, supporting the idea of a pro-cognitive effect of leptin. These areas may have direct clinical implications and deserve to be studied further in the future.
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Affiliation(s)
- Mareike R Stieg
- Max-Planck-Institute of Psychiatry, Kreapelinstr. 2-10, 80804 Munich, Germany.
| | - Caroline Sievers
- Max-Planck-Institute of Psychiatry, Kreapelinstr. 2-10, 80804 Munich, Germany
| | - Olivia Farr
- Division of Endocrinology, Diabetes & Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA; Section of Endocrinology, Boston VA Healthcare System, Boston, USA
| | - Günter K Stalla
- Max-Planck-Institute of Psychiatry, Kreapelinstr. 2-10, 80804 Munich, Germany
| | - Christos S Mantzoros
- Division of Endocrinology, Diabetes & Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA; Section of Endocrinology, Boston VA Healthcare System, Boston, USA.
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Carvalho AF, Rocha DQC, McIntyre RS, Mesquita LM, Köhler CA, Hyphantis TN, Sales PMG, Machado-Vieira R, Berk M. Adipokines as emerging depression biomarkers: a systematic review and meta-analysis. J Psychiatr Res 2014; 59:28-37. [PMID: 25183029 DOI: 10.1016/j.jpsychires.2014.08.002] [Citation(s) in RCA: 101] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2014] [Revised: 08/06/2014] [Accepted: 08/07/2014] [Indexed: 12/15/2022]
Abstract
Adiponectin, leptin and resistin may play a role in the pathophysiology of major depressive disorder (MDD). However, differences in peripheral levels of these hormones are inconsistent across diagnostic and intervention studies. Therefore, we performed meta-analyses of diagnostic studies (i.e., MDD subjects versus healthy controls) and intervention investigations (i.e., pre-vs. post-antidepressant treatment) in MDD. Adiponectin (N = 1278; Hedge's g = -0.35; P = 0.16) and leptin (N = 893; Hedge's g = -0.018; P = 0.93) did not differ across diagnostic studies. Meta-regression analyses revealed that gender and depression severity explained the heterogeneity observed in adiponectin diagnostic studies, while BMI and the difference in BMI between MDD individuals and controls explained the heterogeneity of leptin diagnostic studies. Subgroup analyses revealed that adiponectin peripheral levels were significantly lower in MDD participants compared to controls when assayed with RIA, but not ELISA. Leptin levels were significantly higher in individuals with mild/moderate depression versus controls. Resistin serum levels were lower in MDD individuals compared to healthy controls (N = 298; Hedge's g = -0.25; P = 0.03). Leptin serum levels did not change after antidepressant treatment. However, heterogeneity was significant and sample size was low (N = 108); consequently meta-regression analysis could not be performed. Intervention meta-analyses could not be performed for adiponectin and resistin (i.e., few studies met inclusion criteria). In conclusion, this systematic review and meta-analysis underscored that relevant moderators/confounders (e.g., BMI, depression severity and type of assay) should be controlled for when considering the role of leptin and adiponectin as putative MDD diagnostic biomarkers.
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Affiliation(s)
- André F Carvalho
- Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil.
| | - Davi Q C Rocha
- Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil
| | - Roger S McIntyre
- Departments of Pharmacology and Psychiatry, University of Toronto, Toronto, ON, Canada; Mood Disorders Psychopharmacology Unit, University of Toronto, Toronto, ON, Canada
| | - Lucas M Mesquita
- Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil
| | - Cristiano A Köhler
- Memory Research Laboratory, Brain Institute (ICe), Federal University of Rio Grande do Norte (UFRN), Natal, RN, Brazil
| | - Thomas N Hyphantis
- Department of Psychiatry, Medical School, University of Ioaninna, Ioaninna, Greece
| | - Paulo M G Sales
- Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil
| | - Rodrigo Machado-Vieira
- National Institute of Mental Health (NIMH), Bethesda, USA; Laboratory of Neuroscience, LIM-27, Department and Institute of Psychiatry, University of São Paulo, USP, Brazil; Center for Interdisciplinary Research in Applied Neuroscience (NAPNA), USP, Brazil
| | - Michael Berk
- IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Vic., Australia; Florey Institute of Neuroscience and Mental Health, Australia; Orygen Youth Health Research Centre, University of Melbourne, Parkville, Vic., Australia
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