leptin and Depressive-Disorder--Major

Topics: Antidepressive Agents; Depressive Disorder, Major; Humans; Ketamine; Leptin; Obesity

Antipsychotic-induced weight gain is the most prevalent somatic adverse event occurring in patients treated by antipsychotics, especially atypical antipsychotics. It is of particular interest because of its repercussion on cardiovascular morbidity and mortality especially now that the use of second-generation antipsychotics has been extended to other mental health illnesses such as bipolar disorders and major depressive disorder. The mechanism underlying antipsychotics-induced weight gain is still poorly understood despite a significant amount of work on the topic. Recently, there has been an on-going debate of tremendous research interest on the relationship between antipsychotic-induced weight gain and body weight regulatory hormones such as leptin. Given that, researchers have brought to light the question of leptin's role in antipsychotic-induced weight gain. Here we summarize and discuss the existing evidence on the link between leptin and weight gain related to antipsychotic drugs, especially atypical antipsychotics.

Topics: Antipsychotic Agents; Depressive Disorder, Major; Female; Humans; Leptin; Male; Weight Gain

Depression and obesity are common conditions with major public health implications that tend to co-occur within individuals. The relationship between these conditions is bidirectional: the presence of one increases the risk for developing the other. It has thus become crucial to gain a better understanding of the mechanisms responsible for the intertwined downward physiological spirals associated with both conditions. The present review focuses specifically on shared biological pathways that may mechanistically explain the depression-obesity link, including genetics, alterations in systems involved in homeostatic adjustments (HPA axis, immuno-inflammatory activation, neuroendocrine regulators of energy metabolism including leptin and insulin, and microbiome) and brain circuitries integrating homeostatic and mood regulatory responses. Furthermore, the review addresses interventional opportunities and questions to be answered by future research that will enable a comprehensive characterization and targeting of the biological links between depression and obesity.

Topics: Brain; Depression; Depressive Disorder; Depressive Disorder, Major; Energy Metabolism; Female; Homeostasis; Humans; Hypothalamo-Hypophyseal System; Inflammation; Insulin; Leptin; Male; Melanocortins; Microbiota; Obesity; Pituitary-Adrenal System

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.. 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).. 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.. The heterogeneity of included studies, small sample sizes, and potential publication bias were significant limitations.. 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).

Topics: Adiponectin; Adult; Asian People; Depressive Disorder, Major; Disease Progression; Female; Humans; Leptin; Male

There are data to suggest low bone mineral density is disproportionately prevalent among those with psychiatric disorders. This paper aims to review the current evidence on the relationship between depression and bone mineral density, and identify potential mechanisms.. Relevant sources were identified from the Pubmed and Web of Science (ISI) databases from the first relevant publication in 1994 to the present, 2007, using a combination of key words and terms including depression, major depressive disorder, osteoporosis, bone mineral density, hypothalamic-pituitary-adrenal axis, cortisol, cytokines, leptin, antidepressants, selective serotonin reuptake inhibitors, smoking, alcohol, physical activity and diet. Reference lists of chosen articles were further reviewed for associated publications.. The possible association between psychiatric illness, in particular depression, and osteoporosis has been the subject of a growing body of research yielding various findings, although most identify some effect on bone. In addition to medication-related processes and/or modifiable lifestyle factors associated with mood disturbances, endocrine and immune alteration secondary to depression may play a pathogenetic role in bone metabolism.. Additional longitudinal studies, with the advantage of temporal sequencing, remain to be conducted, as well as research into potential mechanisms surrounding the association. Nevertheless, the current findings are of clinical relevance, given the health burden of both depression and osteoporosis.

Topics: Bone and Bones; Bone Density; Cytokines; Depressive Disorder, Major; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Leptin; Osteoporosis; Pituitary-Adrenal System; Posture; Prevalence; Smoking

It has been long known that the frequency of overweight and obese people is higher among depressed and bipolar patients than in the general population. The marked alteration of body weight (and appetite) is one of the most frequent of the 9 symptoms of major depressive episode, and these symptoms occur during recurrent episodes of depression with a remarkably high consequence. According to studies with representative adult population samples, in case of obesity (BMI over 30) unipolar or bipolar depression is significantly more frequently (20-45%) observable. Since in case of depressed patients appetite and body weight reduction is observable during the acute phase, the more frequent obesity in case of depressed patients is related (primarily) not only to depressive episodes, but rather to lifestyle factors, to diabetes mellitus also more frequently occurring in depressed patients, to comorbid bulimia, and probably to genetic-biological factors (as well as to pharmacotherapy in case of medicated patients). At the same time, according to certain studies, circadian symptoms of depression give rise to such metabolic processes in the body which eventually lead to obesity and insulin resistance. According to studies in unipolar and bipolar patients, 57-68% of patients is overweight or obese, and the rate of metabolic syndrome was found to be between 25-49% in bipolar patients. The rate of metabolic syndrome is further increased by pharmacotherapy. Low total and HDL cholesterol level increases the risk for depression and suicide and recent studies suggest that omega-3-fatty acids possess antidepressive efficacy. Certain lifestyle factors relevant to healthy metabolism (calorie reduction in food intake, regular exercise) may be protective factors related to depression as well. The depression- and possibly suicide-provoking effect of sibutramine and rimonabant used in the pharmacotherapy of obesity is one of the greatest recent challenges for professionals and patients alike.

Topics: Anti-Obesity Agents; Antidepressive Agents; Appetite Depressants; Appetite Regulation; Bipolar Disorder; Circadian Rhythm; Cyclobutanes; Depression; Depressive Disorder, Major; Dietary Carbohydrates; Energy Intake; Ghrelin; Humans; Hypothalamo-Hypophyseal System; Insulin Resistance; Leptin; Obesity; Piperidines; Pituitary-Adrenal System; Pyrazoles; Rimonabant; Seasonal Affective Disorder; Sleep Wake Disorders; Surveys and Questionnaires; Weight Gain; Weight Loss

Poor appetite and weight loss are common in melancholic depression. Probiotics and prebiotics have the capacity to affect host behaviour, appetite and weight change by modulating the gut microbiome. The aim of this post hoc analysis was to investigate the effect of supplementation with probiotic and prebiotic on appetite, in parallel with body mass index (BMI), weight and energy intake, in patients with major depressive disorder (MDD).. We extracted data from a clinical trial with 81 patients. The participants were randomly assigned to receive probiotic (Lactobacillus helveticus and Bifidobacterium longum), prebiotic (galactooligosaccharide) or placebo for 8 weeks. Appetite, weight, BMI, dietary intake, serum leptin and physical activity were measured. Subjective appetite rating was evaluated every 2 weeks using visual analogue scales (VAS) to assess satiety, hunger, fullness and desire to eat. Serum leptin was measured by an enzyme-linked immunosorbent assay. Physical activity was measured using the international physical activity questionnaire. A repeated measures analysis of variance model was used to analyse VAS data and analysis of variance/analysis of covariance models for dietary intake, BMI, weight and leptin data.. VAS data analyses indicated no significant intervention-time interactions but did show a significant increase over time for desire to eat within the probiotic group (P = 0.025). No significant difference in either BMI or weight was seen among the groups. Energy intake and leptin were significantly increased in the probiotic group compared to the prebiotic.. Overall, probiotic supplementation for 8 weeks among MDD patients resulted in improvement of appetite, whereas prebiotic administration had no significant effect on appetite.

Topics: Accelerometry; Adult; Analysis of Variance; Appetite; Bifidobacterium longum; Body Mass Index; Body Weight; Depressive Disorder, Major; Double-Blind Method; Energy Intake; Exercise; Female; Galactose; Humans; Lactobacillus helveticus; Leptin; Male; Oligosaccharides; Prebiotics; Probiotics; Treatment Outcome; Visual Analog Scale

This study explores whether inflammatory biomarkers act as moderators of clinical response to omega-3 (n-3) fatty acids in subjects with major depressive disorder (MDD). One hundred fifty-five subjects with Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) MDD, a baseline 17-item Hamilton Depression Rating Scale (HAM-D-17) score ⩾ 15 and baseline biomarker data (interleukin (IL)-1ra, IL-6, high-sensitivity C-reactive protein (hs-CRP), leptin and adiponectin) were randomized between 18 May 2006 and 30 June 2011 to 8 weeks of double-blind treatment with eicosapentaenoic acid (EPA)-enriched n-3 1060 mg day(-1), docosahexaenoic acid (DHA)-enriched n-3 900 mg day(-1) or placebo. Outcomes were determined using mixed model repeated measures analysis for 'high' and 'low' inflammation groups based on individual and combined biomarkers. Results are presented in terms of standardized treatment effect size (ES) for change in HAM-D-17 from baseline to treatment week 8. Although overall treatment group differences were negligible (ES=-0.13 to +0.04), subjects with any 'high' inflammation improved more on EPA than placebo (ES=-0.39) or DHA (ES=-0.60) and less on DHA than placebo (ES=+0.21); furthermore, EPA-placebo separation increased with increasing numbers of markers of high inflammation. Subjects randomized to EPA with 'high' IL-1ra or hs-CRP or low adiponectin ('high' inflammation) had medium ES decreases in HAM-D-17 scores vs subjects 'low' on these biomarkers. Subjects with 'high' hs-CRP, IL-6 or leptin were less placebo-responsive than subjects with low levels of these biomarkers (medium to large ES differences). Employing multiple markers of inflammation facilitated identification of a more homogeneous cohort of subjects with MDD responding to EPA vs placebo in our cohort. Studies are needed to replicate and extend this proof-of-concept work.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Depressive Disorder, Major; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Eicosapentaenoic Acid; Female; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-6; Leptin; Male; Middle Aged; Psychiatric Status Rating Scales; Treatment Outcome; Young Adult

This randomized, double-blind, placebo-controlled trial evaluated the efficacy of CP-601,927, an α4β2 nicotinic acetylcholine receptor partial agonist and an augmenting agent of antidepressants in major depressive disorder patients with insufficient response to selective serotonin reuptake inhibitors (SSRIs). After open-label treatment with an SSRI for 8 weeks, subjects with a Hamilton Depression Scale 17 score greater than or equal to 16 were entered into a double-blind phase and randomized to CP-601,927 2 mg twice daily or placebo for 6 weeks. The primary end point was the change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from double-blind baseline to week 14. There was no significant difference in change from baseline to week 14 in the MADRS score for CP-610,927 versus placebo (least square mean difference [80% confidence interval], -1.30 [-3.32-0.71]). Post hoc analyses revealed that the drug-placebo difference in change from baseline (SE) to week 14 in MADRS score was greater in subjects with body mass index (BMI) less than or equal to 35 kg/m (-3.43 [1.87], P = 0.069) than those with BMI greater than 35 kg/m (3.37 [2.8], P = 0.230). Analysis of biomarkers associated with increased BMI suggests that baseline leptin had a significant effect on treatment outcome. P values for the effect of treatment on mean change in MADRS score for subjects with baseline leptin levels below and above the median were 0.055 and 0.0055, respectively. CP-601,927 was equivalent to placebo as an augmenting agent of antidepressants in major depressive disorder patients with insufficient response to SSRIs. However, post hoc analyses suggest that BMI, particularly elevated leptin levels, may have affected the response to CP-601,927; however, further study may be needed to confirm these results.

Topics: Adult; Antidepressive Agents; Biomarkers; Depressive Disorder, Major; Double-Blind Method; Drug Partial Agonism; Female; Follow-Up Studies; Humans; Leptin; Male; Middle Aged; Nicotinic Agonists; Receptors, Nicotinic; Treatment Outcome

Major depressive disorder (MDD) has been associated with adverse medical consequences, including cardiovascular disease and osteoporosis. Patients with MDD may be classified as having melancholic, atypical, or undifferentiated features. The goal of the present study was to assess whether these clinical subtypes of depression have different endocrine and metabolic features and consequently, varying medical outcomes.. Premenopausal women, ages 21 to 45 years, with MDD (N = 89) and healthy controls (N = 44) were recruited for a prospective study of bone turnover. Women with MDD were classified as having melancholic (N = 51), atypical (N = 16), or undifferentiated (N = 22) features. Outcome measures included: metabolic parameters, body composition, bone mineral density (BMD), and 24 hourly sampling of plasma adrenocorticotropin (ACTH), cortisol, and leptin.. Compared with control subjects, women with undifferentiated and atypical features of MDD exhibited greater BMI, waist/hip ratio, and whole body and abdominal fat mass. Women with undifferentiated MDD characteristics also had higher lipid and fasting glucose levels in addition to a greater prevalence of low BMD at the femoral neck compared to controls. Elevated ACTH levels were demonstrated in women with atypical features of depression, whereas higher mean 24-hour leptin levels were observed in the melancholic subgroup.. Pre-menopausal women with various features of MDD exhibit metabolic, endocrine, and BMD features that may be associated with different health consequences.. ClinicalTrials.gov NCT00006180.

Topics: Adrenocorticotropic Hormone; Adult; Alendronate; Biomarkers; Body Composition; Bone Density; Circadian Rhythm; Depressive Disorder, Major; Endocrine System; Female; Humans; Hydrocortisone; Laboratories; Leptin; Middle Aged; Osteoporosis; Premenopause; Reproducibility of Results; Young Adult

Weight gain during treatment with psychotropic drugs is frequently observed and is assumed to be responsible for non-compliance and for an elevated risk to develop a number of somatic co-morbidities including cardiovascular disorders and type 2 diabetes. Absence of weight inducing effects is therefore a major objective for the development of new compounds. Recently, R121919, the first corticotropin releasing hormone receptor 1 (CRH1R) antagonist, was tested in major depression. Clinical efficacy, safety, and tolerability of this compound could be demonstrated. Since CRH is discussed to be involved in the regulation of appetite and weight, directly and via interaction with leptin, CRH1R antagonists are suspected to influence body weight. Effects of 30 days of treatment with the CRH1R antagonist R121919 on weight and leptin levels in 20 patients suffering from major depression were investigated. No significant weight changes during treatment with R121919 were observed. Furthermore, noeffects on plasma leptin concentrations were found. We conclude that treatment with the CRH1R antagonist R121919 does not affect weight or plasma leptin concentrations in patients with major depression. Together with previous findings indicating safety, tolerability, and clinical efficacy CRH1R antagonists are highly promising as a new treatment option in depression.

Topics: Adult; Depressive Disorder, Major; Diabetes Mellitus, Type 2; Female; Humans; Leptin; Male; Middle Aged; Pyrimidines; Receptors, Corticotropin-Releasing Hormone; Receptors, Leptin; Risk Factors; Weight Gain

Leptin is a product of the obese gene and plays an important role in the regulation of body weight and food intake. Weight and appetite are frequently altered in depression. So far, inconsistent results have been reported in terms of leptin levels in depression. Therefore, the authors investigated serum leptin levels in patients with depression and in healthy controls, and whether there was any alteration throughout antidepressant treatment. Female patients showed significantly higher leptin levels than those of the control females both before and after the response to antidepressant treatment, whereas no difference was found between the male patients and the male controls. The improvement from depression with antidepressant treatment caused a further elevation on the leptin levels, in both female and male patients. These findings confirm an increase in leptin levels in depressive patients and presence of a sexual dimorphism. Moreover, clinical response to antidepressant treatment seems to have an additional increasing effect on leptin levels.

Topics: Adolescent; Adult; Antidepressive Agents; Body Mass Index; Depressive Disorder, Major; Female; Humans; Leptin; Male; Middle Aged; Psychiatric Status Rating Scales; Sex Characteristics

Aging and menopause are associated with alterations of the sleep EEG, while age-related changes of the hypothalamo-pituitary-adrenal (HPA) axis remain controversial. Major depression is also associated with typical sleep-endocrine changes, including enhanced activity of the HPA axis, while an influence of age and gender on these alterations is less clear. To test the hypothesis that after menopause sleep-endocrine alterations associated with major depression are accentuated, we examined the sleep EEG and nocturnal hormone secretion (ACTH, cortisol, GH, estradiol, LH, FSH, and leptin) in 16 drug-free female patients, mostly with the first episode of a major depressive disorder (seven pre- and nine postmenopausal subjects) and 19 female controls (10 subjects in the early follicular phase and nine postmenopausal subjects). Nocturnal cortisol secretion was increased in postmenopausal patients with depression, while a decrease was noted in postmenopausal controls. Sleep alterations typically associated with depression, namely a reduction in sleep continuity and slow wave sleep (SWS) and an increase in REM density, were prominent in post- but not in premenopausal patients. An inverse correlation was noted between the decline in SWS and sleep continuity and FSH secretion in patients with depression, suggesting a role of menopause for these sleep-endocrine alterations typically associated with major depression. In contrast, in premenopausal patients we noted primarily a shift in SWS and delta-EEG activity from the first to the second non-REM period, which was not related to age or hormone secretion. Though the relatively small number of subjects per group precludes a definitive conclusion, our data open up the possibility that the sleep-endocrine changes typically associated with major depression are most prominent in postmenopausal patients. Whether the predominant alteration of the distribution of SWS and delta EEG activity in younger patients with a first episode of major depression has a predictive value for the future course of the disease remains to be investigated.

Topics: Adrenocorticotropic Hormone; Adult; Aged; Depressive Disorder, Major; Electroencephalography; Estradiol; Female; Follicle Stimulating Hormone; Human Growth Hormone; Humans; Hydrocortisone; Leptin; Luteinizing Hormone; Matched-Pair Analysis; Menopause; Middle Aged; Pituitary Hormones, Anterior; Polysomnography; Sleep Wake Disorders; Sleep, REM; Statistics as Topic

Weight gain is a frequent and important side effect of psychopharmacotherapy. Recent studies suggest that the fat-cell-derived hormone leptin and the tumor necrosis factor-alpha (TNF-alpha) cytokine system are pathophysiologically involved. No information is available concerning the influence of the antidepressants mirtazapine and venlafaxine on these immunoendocrine variables. An open-labeled study was performed in 20 patients suffering from major depression treated with either mirtazapine (N = 11) or venlafaxine (N = 9). During 4 weeks, the patients' weight, body mass index (BMI), and plasma levels of leptin, TNF-alpha, sTNF-R p55, and sTNF-R p75 were assessed. Mirtazapine induced a significant increase in weight (mean weight gain: 2.4 kg) that was evident after the first week of treatment. In parallel, the plasma levels of TNF-alpha and both soluble TNF receptors increased. In addition, a slight rise in leptin levels, which occurred slowly and was significant only at the end of the 4 th week of treatment, was observed. Weight decreased slightly but significantly in patients treated with venlafaxine (mean weight loss: 0.4 kg), whereas plasma levels of leptin, TNF-alpha, or soluble TNF receptors did not change significantly. The present results further support the notion that the activation of the TNF-alpha cytokine system is an early, sensitive, and specific marker of weight gain induced by psychotropic agents. In contrast, the effects of such drugs on leptin production seem to be less sensitive with respect to weight gain and more variable.

Topics: Adult; Aged; Antipsychotic Agents; Body Mass Index; Body Weight; Cross-Over Studies; Cyclohexanols; Depressive Disorder, Major; Female; Humans; Leptin; Longitudinal Studies; Male; Mianserin; Middle Aged; Mirtazapine; Tumor Necrosis Factor-alpha; Venlafaxine Hydrochloride

Leptin inhibits appetite by activating several neuroendocrine systems, including the hypothalamo-pituitary-adrenal cortical (HPA) axis. In turn, chronically elevated glucocorticoids increase circulating leptin. HPA axis hyperactivity occurs in 30-50% of patients with major depression, but the few prior reports of leptin measurements in this illness have shown inconsistent results. We, therefore, measured plasma leptin in 12 female and 8 male unipolar major depressives and 12 female and 8 male individually matched normal controls administered low-dose physostigmine (PHYSO) and arginine vasopressin (AVP) to stimulate the HPA axis. The subjects underwent four test sessions 5-7 days apart: PHYSO (8 microg/kg IV); AVP (0-08 U/kg IM); PHYSO+AVP; and saline control. Serial blood samples were taken before and after pharmacologic challenge and analyzed for leptin, ACTH(1-39), cortisol and AVP. Estradiol and testosterone also were measured at each test session. PHYSO and AVP produced no side effects in approximately half the subjects and predominantly mild side effects in the other half, with no significant patient-control differences. Correlations between side effects (absent or present) after PHYSO or AVP and the corresponding leptin responses were non-significant in all groups. Baseline plasma leptin concentrations (mean+/-S.D.) were significantly higher in the female patients compared to the female controls (22.5+/-13.9 ng/ml vs. 12.3+/-9.7 ng/ml), whereas they were similar in the male patients and the male controls (3.9+/-1.4 ng/ml vs. 3.6+/-2.0 ng/ml). Leptin concentrations following PHYSO remained unchanged from baseline, indicating that the short-lived ACTH and cortisol increases produced by PHYSO did not affect leptin secretion. In contrast, AVP administration, while also increasing ACTH and cortisol, significantly suppressed leptin, more so in the women than in the men. Baseline leptin and the leptin decrease after AVP were moderately positively correlated with the Hamilton Depression Scale 'somatization' factor in the female patients (r=0.50) and more strongly correlated with the 'mood-depression' factor in the male patients (r=0.81). These findings indicate a sexual diergism (functional sex difference) in plasma leptin measures between major depressives and matched normal controls.

Topics: Adrenocorticotropic Hormone; Adult; Arginine Vasopressin; Body Mass Index; Cholinesterase Inhibitors; Depressive Disorder, Major; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Leptin; Male; Physostigmine; Pituitary-Adrenal System; Sex Factors; Testosterone; Time Factors; Vasoconstrictor Agents

Major depressive disorder (MDD) is a heterogeneous mental disorder having a very diverse course and causing a significant changes in daily life. Though the exact pathophysiology of depression is still not known, an alteration in the serum levels of cytokines and neurotrophic factors was seen in MDD subjects. In this study, we compared the serum levels of 'pro-inflammatory cytokine leptin and neurotrophic factor EGF' in healthy controls (HCs) and MDD patients. To make the findings more accurate, we eventually looked for a correlation between altered serum leptin and EGF levels and the severity of the disease condition.. For this case-control study, about 205 MDD patients were enrolled from the Department of Psychiatry, Bangabandhu Sheikh Mujib Medical University, Dhaka, and about 195 HCs were enrolled from various parts of Dhaka. The DSM-5 was utilized to evaluate and diagnose the participants. The HAM-D 17 scale was used to measure the severity of depression. After collecting blood samples, they were centrifuged to produce clear serum samples. These serum samples were analyzed using enzyme-linked immunosorbent assay (ELISA) kits to measure serum leptin and EGF levels.. We observed lowered serum EGF levels in MDD patients compared to HCs (524.70 ± 27.25 pg/ml vs. 672.52 ± 49.64 pg/ml, p = 0.009), and HAM-D score was elevated in MDD patients compared to HCs (17.17 ± 0.56 vs. 2.49 ± 0.43, p<0.001). But no correlation was established between serum EGF levels and the severity of depression. However, no significant differences were observed between MDD patients and HCs in the case of serum leptin levels (p = 0.231).. Our study findings suggest that reduced serum EGF levels have an impact on the pathogenesis of depression. But as per our investigation, the severity of depression is not correlated with altered EGF levels. Our findings regarding the association of EGF with MDD would help to use EGF as a risk indicator of depression. We suggest further clinical investigations to determine the precise function of leptin and EGF in depression.

Topics: Bangladesh; Case-Control Studies; Cytokines; Depressive Disorder, Major; Epidermal Growth Factor; Humans; Leptin

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.

Topics: Adiponectin; C-Reactive Protein; Depressive Disorder, Major; Humans; Insulins; Leptin; Magnetic Resonance Imaging; Motivation; Reward

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.. 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.. 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).. 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.. Individuals with MDD and MDD + GAD demonstrate difficulties in regulating eating behaviors, potentially contributing to functional impairment and increased disease burden.

Topics: Adiponectin; Anxiety Disorders; Comorbidity; Depressive Disorder, Major; Feeding Behavior; Female; Humans; Leptin; Male

Social anhedonia, a loss of interest and pleasure in social interactions, is a common symptom of major depression as well as other psychiatric disorders. Depression can occur at any age, but typically emerges in adolescence or early adulthood, which represents a sensitive period for social interaction that is vulnerable to stress. In this study, we evaluated social interaction reward using a conditioned place preference (CPP) paradigm in adolescent male and female mice. Adolescent mice of both sexes exhibited a preference for the social interaction-associated context. Chronic unpredictable stress (CUS) impaired the development of CPP for social interaction, mimicking social anhedonia in depressed adolescents. Conversely, administration of leptin, an adipocyte-derived hormone, enhanced social interaction-induced CPP in non-stressed control mice and reversed social anhedonia in CUS mice. By dissecting the motivational processes of social CPP into social approach and isolation avoidance components, we demonstrated that leptin treatment increased isolation aversion without overt social reward effect. Further mechanistic exploration revealed that leptin stimulated oxytocin gene transcription in the paraventricular nucleus of the hypothalamus, while oxytocin receptor blockade abolished the leptin-induced enhancement of socially-induced CPP. These results establish that chronic unpredictable stress can be used to study social anhedonia in adolescent mice and provide evidence that leptin modulates social motivation possibly via increasing oxytocin synthesis and oxytocin receptor activation.

Topics: Anhedonia; Animals; Depressive Disorder, Major; Female; Leptin; Male; Mice; Motivation; Oxytocin; Receptors, Oxytocin; Reward; Stress, Psychological

Depression is a highly prevalent and heterogeneous disorder. This study aims to determine whether depression with atypical features shows different heritability and different degree of overlap with polygenic risk for psychiatric and immuno-metabolic traits than other depression subgroups.. Data included 30 069 European ancestry individuals from the UK Biobank who met criteria for lifetime major depression. Participants reporting both weight gain and hypersomnia were classified as ↑WS depression (N = 1854) and the others as non-↑WS depression (N = 28 215). Cases with non-↑WS depression were further classified as ↓WS depression (i.e. weight loss and insomnia; N = 10 142). Polygenic risk scores (PRS) for 22 traits were generated using genome-wide summary statistics (Bonferroni corrected p = 2.1 × 10-4). Single-nucleotide polymorphism (SNP)-based heritability of depression subgroups was estimated.. ↑WS depression had a higher polygenic risk for BMI [OR = 1.20 (1.15-1.26), p = 2.37 × 10-14] and C-reactive protein [OR = 1.11 (1.06-1.17), p = 8.86 × 10-06] v. non-↑WS depression and ↓WS depression. Leptin PRS was close to the significance threshold (p = 2.99 × 10-04), but the effect disappeared when considering GWAS summary statistics of leptin adjusted for BMI. PRS for daily alcohol use was inversely associated with ↑WS depression [OR = 0.88 (0.83-0.93), p = 1.04 × 10-05] v. non-↑WS depression. SNP-based heritability was not significantly different between ↑WS depression and ↓WS depression (14.3% and 12.2%, respectively).. ↑WS depression shows evidence of distinct genetic predisposition to immune-metabolic traits and alcohol consumption. These genetic signals suggest that biological targets including immune-cardio-metabolic pathways may be relevant to therapies in individuals with ↑WS depression.

Topics: Alcohol Drinking; Depression; Depressive Disorder, Major; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Leptin; Multifactorial Inheritance; Polymorphism, Single Nucleotide

Lithium-treated patients often suffer from weight gain as a common adverse event. In an earlier investigation, we found an impact of two single-nucleotide polymorphisms (rs10487506 and rs2278815) at the leptin gene on weight gain but not on leptin protein levels in serum under lithium augmentation. A recent genome-wide association study identified a polymorphism at the leptin gene locus (rs10487505) associated with circulating leptin protein levels. To characterize potential effects of this variant in acute major depressive disorder, we investigated body mass indices from 180 lithium-augmented patients and serum concentrations of leptin protein from 89 patients using linear mixed model analyses and rs6979832, a proxy SNP of rs10487505. Body mass index was measured before and after 4 weeks of lithium augmentation, in a subsample also after 4 and 7 months. Leptin serum levels were measured before and during lithium augmentation. G-allele homozygotes of rs6979832 had a significantly lower body mass index increase during observation compared to A-allele hetero- and homozygotes. However, we found no influence on leptin serum levels. Joint analyses of rs6979832 with the previously investigated polymorphisms rs10487506 and rs2278815, and expressed quantitative trait data, suggest a complex interplay between SNP alleles at the leptin locus. These results strongly support our earlier findings that common genetic variation at the leptin gene locus may be involved in lithium augmentation-associated weight gain in major depressive disorder.

Topics: Body Mass Index; Depression; Depressive Disorder, Major; Genome-Wide Association Study; Humans; Leptin; Lithium; Polymorphism, Single Nucleotide; Weight Gain

The association of appetite hormones with cognitive function in patients with affective disorders remains unknown.. All total, 58 adult patients with bipolar I disorder, 36 with bipolar II disorder, 40 with major depressive disorder were enrolled and age and sex-matched with 40 controls. The levels of appetite hormones leptin, ghrelin, insulin and adiponectin were assessed. Wisconsin Card Sorting Test was used to assess executive function.. A general linear model, adjusted for demographic data and clinical symptoms, demonstrated the ghrelin levels were higher in patients with bipolar I or II disorder than in those with major depressive disorder and controls (. Patients with bipolar I or II disorder were more likely to have high levels of ghrelin than patients with major depressive disorder and controls, which may have a positive correlation on the cognitive function of patients with bipolar I or II disorder.

Topics: Adult; Appetite; Bipolar Disorder; Cognition; Depressive Disorder, Major; Humans; Leptin

Dimensional psychopathology and its neurobiological underpinnings could provide important insights into major psychiatric disorders, including major depressive disorder, bipolar disorder and schizophrenia. In a dimensional transdiagnostic approach, we examined depressive symptoms and their relationships with regional homogeneity and leptin across major psychiatric disorders. A total of 728 participants (including 403 patients with major psychiatric disorders and 325 age-gender-matched healthy controls) underwent resting-state functional magnetic resonance imaging at a single site. We obtained plasma leptin levels and depressive symptom measures (Hamilton Depression Rating Scale (HAMD)) within 24 h of scanning and compared the regional homogeneity (ReHo), plasma leptin levels and HAMD total score and factor scores between patients and healthy controls. To reveal the potential relationships, we performed correlational and mediational analyses. Patients with major psychiatric disorders had significant lower ReHo in primary sensory and visual association cortices and higher ReHo in the frontal cortex and angular gyrus; plasma leptin levels were also elevated. Furthermore, ReHo alterations, leptin and HAMD factor scores had significant correlations. We also found that leptin mediated the transdiagnostic relationships among ReHo alterations in primary somatosensory and visual association cortices, core depressive symptoms and body mass index. The transdiagnostic associations we demonstrated support the common neuroanatomical substrates and neurobiological mechanisms. Moreover, leptin could be an important association among ReHo, core depressive symptoms and body mass index, suggesting a potential therapeutic target for dimensional depressive symptoms across major psychiatric disorders.

Topics: Brain; Brain Mapping; Depression; Depressive Disorder, Major; Humans; Leptin; Magnetic Resonance Imaging

Topics: Depressive Disorder, Major; Humans; Insulin; Leptin; ortho-Aminobenzoates; Plasma; Proteomics; Schizophrenia

A link between brain-derived neurotrophic factor (BDNF) expression and the mood regulatory effect of leptin has been suggested in the pathophysiology of major depressive disorder (MDD). We investigated treatment response and pre-treatment leptin and BDNF in patients with MDD and with panic disorder (PD).. We recruited 41 patients with MDD, 52 patients with PD, and 59 matched healthy controls. All subjects completed five visits (at baseline, 2, 4, 8, and 12 weeks), and both MDD and PD patients were treated with standard pharmacotherapy for 12 weeks. Plasma BDNF (pBDNF) and blood leptin levels were obtained along with a 17-item Hamilton Depression Scale rating (HDRS-17) score at every visit.. The ratio of pre-treatment pBDNF to leptin was significantly lower in patients with MDD and PD compared to healthy controls (p = 0.024), but was not associated with severity of depressive or anxiety symptoms. Pre-treatment pBDNF:leptin ratio was significantly higher in treatment responders than in non-responders (p = 0.012) in MDD but not in PD. This difference was larger in MDD patients with appetite loss (p = 0.034). In multivariate analysis, pre-treatment pBDNF:leptin ratio was significantly associated with treatment responsiveness (Adjusted Odds Ration [AOR] = 2.50, 95% CI 1.02-6.14) in MDD.. small sample size; limited information on detailed pharmacological effects.. A relatively higher ratio of pre-treatment pBDNF to leptin was associated with greater treatment response in MDD but not in PD. Further research should focus on exploration of a link between BDNF and leptin underlying neuronal plasticity in depression.

Topics: Adult; Antidepressive Agents; Brain-Derived Neurotrophic Factor; Case-Control Studies; Depressive Disorder, Major; Female; Follow-Up Studies; Humans; Leptin; Male; Middle Aged; Panic Disorder; Treatment Outcome

Peripheral biomarkers have been studied to predict treatment response of panic symptoms. We hypothesized that depressive disorder (MDD) vs. panic disorder (PD) would exhibit different peripheral biomarkers, and their correlation with severity of panic attacks (PA) would also differ.. Forty-one MDD patients, 52 PD patients, and 59 healthy controls were followed for 12 weeks. We measured peripheral biomarkers along with the Panic Disorder Severity Scale (PDSS) at each visit-pre-treatment, 2, 4, 8, and 12 weeks on a regular schedule. Peripheral biomarkers including serum cytokines, plasma and serum brain-derived neurotrophic factor (BDNF), leptin, adiponectin, and C-reactive protein (CRP) were quantified using enzyme-linked immunosorbent assay (ELISA).. Patients with MDD and PD demonstrated significantly higher levels of pre-treatment IL-6 compared to controls, but no differences were seen in plasma and serum BDNF, leptin, adiponectin, and CRP. Pre-treatment leptin showed a significant clinical correlation with reduction of panic symptoms in MDD patients at visit 5 (p=0.011), whereas pre-treatment IL-6 showed a negative correlation with panic symptom reduction in PD patients (p=0.022). An improvement in three panic-related items was observed to be positively correlated with pre-treatment leptin in MDD patients: distress during PA, anticipatory anxiety, and occupational interference.. Higher pre-treatment leptin was associated with better response to treatment regarding panic symptoms in patients with MDD, while higher IL-6 was associated with worse response regarding panic symptoms in PD patients. Different predictive peripheral biomarkers observed in MDD and PD suggest the need for establishing individualized predictive biomarkers, even in cases of similar symptoms observed in different disorders.

Topics: Adiponectin; Adult; Biomarkers; Brain-Derived Neurotrophic Factor; C-Reactive Protein; Case-Control Studies; Depressive Disorder, Major; Female; Follow-Up Studies; Humans; Interleukin-6; Leptin; Male; Middle Aged; Panic; Panic Disorder; Time Factors

Weight gain is a common adverse effect of lithium augmentation. Previous studies indicate an impact of genetic variants at the leptin gene on weight gain as a consequence of psychopharmacological treatment. The primary aim of our study was to identify variants at the leptin locus that might predict lithium-induced weight gain. The secondary aim was to investigate if these variants modulate leptin levels. In 180 patients with acute major depressive disorder, body mass index was measured before and after 4 weeks of lithium augmentation, in a subsample also after 4 and/or 7 months. In a subsample of 89 patients, leptin serum concentrations were measured before and during lithium augmentation. We used linear mixed model analyzes to investigate the effects of 2 polymorphisms at the leptin locus (rs4731426 and rs7799039, employing the respective proxy SNPs rs2278815 and rs10487506) on changes in body mass index and leptin levels. For both polymorphisms, which are in high linkage disequilibrium, body mass index was significantly lower in homozygous A-allele carriers than in carriers of other genotypes at baseline. Over the follow-up period, body mass index increased less in homozygous A-allele carriers of rs4731426 than in carriers of other genotypes. This was not the case for rs7799039. Neither polymorphism modulated leptin protein expression. Our study strongly supports the hypothesis that genetic variability at the leptin locus is involved in lithium augmentation-associated weight gain in major depressive disorder. Furthermore, Genotype-Tissue Expression data provide strong evidence that rs4731426 influences the expression of leptin messenger ribonucleic acid in fibroblasts.

Topics: Adult; Depressive Disorder, Major; Female; Genotype; Humans; Ideal Body Weight; Leptin; Lithium; Male; Middle Aged; Polymorphism, Single Nucleotide; Psychiatric Status Rating Scales; Retrospective Studies; Weight Gain

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.

Topics: Adiponectin; Adult; Biomarkers; Depression; Depressive Disorder, Major; Female; Humans; Leptin; Male; Psychiatric Status Rating Scales; Severity of Illness Index; Sex Factors; Young Adult

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.

Topics: Adolescent; Adult; Appetite; Biomarkers; Cross-Sectional Studies; Depressive Disorder, Major; Feeding and Eating Disorders; Female; Ghrelin; Humans; Leptin; Male; Middle Aged; Surveys and Questionnaires; Weight Gain; Young Adult

Leptin is produced in the adipose tissue. It controls energy homeostasis by reducing food intake and increasing energy expenditure. According to the "leptin hypothesis of depression", chronic stress leads to reduced leptin concentration and leptin insufficiency may underlie depressive symptoms. However, it is also hypothesized that observed in depressed patients differences in leptin levels may be secondary to differences in adiposity. The aim of this case-control study is to evaluate fasting serum leptin levels in elderly women with major depression disorder and to compare them with non-depressed elderly women.. We measured fasting serum leptins levels and body composition in 32 elderly (age ≥60 years) European Caucasian women with major depression disorder and in 49 non-depressed elderly (age ≥ 60 years) European Caucasian women.. There was no statistically significant difference (p=0.14) in fasting serum leptin level between patients with depression (3.04±1.79 ng/mL) and control subjects (2.46±1.70 ng/mL).. In two groups of subjects with comparable adiposity parameters we did not confirm that leptin level is changed in patients with depression. We assume that changes in leptin level in patients with depression may be mediated by adiposity.

Topics: Aged; Body Composition; Body Mass Index; Case-Control Studies; Depressive Disorder, Major; Fasting; Female; Humans; Leptin; Middle Aged

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.

Topics: Adolescent; Adult; Case-Control Studies; Depressive Disorder, Major; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Proteomics; Schizophrenia; Young Adult

Identification of biomarkers in major depressive disorder (MDD) has proceeded in an extemporised manner. No single biomarker has been identified with utility in screening, diagnosis, prognosis, or monitoring, and screening tests have different characteristics than the other functions. Using chaos, bifurcation, and perturbation (CBP) theories, the aim is to identify biomarkers to aid clinicians in screening for MDD.. MDD is a complex disorder; consequently, a reductionist approach to characterize the complex system changes found in MDD will be inchoate and unreliable. A holistic approach is used to identify biomarkers reflecting the tipping points seen before the catastrophic bifurcation that results in MDD.. Applying CBP theories revealed skew, resistance to change, flickering, increased variance and autocorrelation as patterns of biomarkers. Integrals and differentials of extracellular and intracellular biomarkers were identified, specifically focussed on hypothalamo-pituitary axis (HPA) dysfunction, metabolic dysfunction, inflammation and mitochondrial oxidative stress, and tryptophan metabolism.. Applying CBP theories to the dysfunctional complex biological systems in MDD led to development of integrals and differentials of biomarkers that can be used in screening for MDD and planning future biomarker research, targeting intracellular and extracellular inflammation, HPA axis dysfunction, and tryptophan metabolism.

Topics: Biomarkers; Blood Glucose; C-Reactive Protein; Depressive Disorder, Major; Early Diagnosis; Ghrelin; Glycated Hemoglobin; Humans; Hypothalamo-Hypophyseal System; Inflammation; Interleukin-6; Leptin; Oxidative Stress; Tumor Necrosis Factor-alpha

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.

Topics: Adipokines; Adiponectin; Adult; Cross-Sectional Studies; Depression; Depressive Disorder, Major; Female; Humans; Leptin; Longitudinal Studies; Middle Aged; Psychological Tests; Women's Health

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.. 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.. 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.. The study is limited by a cross sectional design and a small sample size in the subset analysis of eating behaviours.. 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.

Topics: Adult; Appetite; Case-Control Studies; Cross-Sectional Studies; Depressive Disorder, Major; Feeding and Eating Disorders; Female; Humans; Leptin; Male; Middle Aged; Sex Characteristics; Weight Gain; Weight Loss

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.. 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.. 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.. 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.

Topics: Adiposity; Adolescent; Adult; Aged; Body Mass Index; Depressive Disorder, Major; Female; Humans; Leptin; Male; Middle Aged; Netherlands; Obesity; Young Adult

A large number of diabetes patients suffer from major depression and are at high risk of mortality. In view of a role of leptin in diabetes, depression and energy homeostasis, the present study concerns circulating levels of leptin in different BMI groups of un-depressed and depressed diabetes patients. Six hundred thirty male and female patients with a primary diagnosis of diabetes were grouped according to BMI and with or without clinical symptoms of depression. Age matched healthy, normal weight male and female volunteers without clinical symptoms of depression or diabetes were taken as controls. Blood samples were obtained after an overnight fast of 12 h. Serum was stored for the determination of leptin and glucose. We found that there were more female than male diabetes patients with comorbid depression. Fasting leptin was higher in normal weight non-diabetes women than men; but comparable in normal weight men and women diabetes patients. Fasting glucose levels were higher in diabetes than non diabetes groups; values were comparable in men and women. Depression was associated with a decrease and increase in leptin respectively in normal-overweight and obese men and women diabetes patients. Glucose levels were also higher in obese depressed than un-depressed diabetes patients. The results suggested that the female gender is at greater risk to comorbid diabetes with depression. Adipo-insular axis plays an important role in diabetes, associated depression and in the greater risk of the female gender to comorbid diabetes with depression.

Topics: Adult; Aged; Biomarkers; Blood Glucose; Body Composition; Body Mass Index; Depressive Disorder, Major; Diabetes Mellitus, Type 2; Fasting; Female; Humans; Leptin; Male; Middle Aged; Obesity; Overweight; Sex Characteristics

Meta-analytical data show lithium augmentation (LA) as an effective treatment strategy in major depression. Weight-gain is a common side effect of LA. The proteohormone leptin is discussed to be involved in the pathophysiology of weight gain induced by psychopharmacological treatment. The purpose of our study was to investigate the association of leptin and body mass index (BMI) during LA in a prospective cohort study.. Leptin serum concentrations and body mass index (BMI) were measured in a total of 89 acute depressive patients before and then after four weeks of LA.. In a linear mixed model analysis the following variables had a significant positive effect on BMI: time (equal with "treatment effect of LA"; F1.83=6.05; p=0.016) and leptin (F1.111=13.83; p=0.0003) as well as the covariates male gender (F1.89=5.08; p=0.027) and adiposity (F1.85=105.13; p<0.0001).. If the reported effect of leptin on BMI is specific to LA remains unclear without a control group.. Leptin signalling might be involved in lithium-induced weight-gain.

Topics: Adult; Aged; Body Mass Index; Body Weight; Cohort Studies; Depressive Disorder, Major; Female; Humans; Leptin; Lithium; Male; Middle Aged; Obesity; Prospective Studies; Weight Gain

Leptin plays a key role in the pathogenesis of obesity and depression via the long form of leptin receptor (LepRb). An animal model of comorbid obesity and depression induced by high-fat diet (HFD) combined with chronic unpredictable mild stress (CUMS) was developed to study the relationship between depression/anxiety-like behavior, levels of plasma leptin and LepRb in the brains between four groups of rats, the combined obesity and CUMS (Co) group, the obese (Ob) group, the CUMS group and controls. Our results revealed that the Co group exhibited most severe depression-like behavior in the open field test (OFT), anxiety-like behavior in elevated plus maze test (EMT) and cognitive impairment in the Morris water maze (MWM). The Ob group had the highest weight and plasma leptin levels while the Co group had the lowest levels of protein of LepRb in the hypothalamus and hippocampus. Furthermore, depressive and anxiety-like behaviors as well as cognitive impairment were positively correlated with levels of LepRb protein and mRNA in the hippocampus and hypothalamus. The down-regulation of leptin/LepRb signaling might be associated with depressive-like behavior and cognitive impairment in obese rats facing chronic mild stress.

Topics: Animals; Anxiety; Behavior, Animal; Depression; Depressive Disorder, Major; Diet, High-Fat; Disease Models, Animal; Down-Regulation; Hippocampus; Hypothalamus; Leptin; Male; Obesity; Rats; Rats, Wistar; Receptors, Leptin; RNA, Messenger; Stress, Psychological

Many peripheral biomarkers, including low cholesterol and its fractions, have been examined to identify suicidal behavior. Herein, we assessed serum lipid profile and some proteins putatively associated with suicidal behavior in subjects with mood disorder (bipolar disorder or major depressive disorder) with a recent suicide attempt and with no lifetime history of suicide attempts.. Fifty subjects had presented an episode of attempted suicide during the last 15 days, and 36 subjects had no history of any suicide attempt. We measured total cholesterol, HDL, LDL and triglycerides as well as serum leptin, brain-derived neurotrophic factor (BDNF), S100B and C-reactive protein (CRP).. Individuals that had attempted suicide presented decreased body mass index (BMI) and waist circumference. After adjusting for these confounders, we found that triglycerides were decreased in attempted suicide subjects. We found no differences among total cholesterol, LDL, and HDL or leptin, S100B, CRP and BDNF.. This is a cross-sectional study, and we cannot therefore assess whether a decrease in triglycerides caused a mood episode with suicidal ideation that led to a suicide attempt or if the presence of a mood episode originated a loss of appetite and consequent loss of weight, therefore decreasing triglyceride levels.. These results do not support the hypothesis that lower levels of cholesterol are associated with suicidal behavior in a mood disorder sample. However, our data support the idea that adiposity is differentiated in these patients (reduced BMI, waist circumference and serum triglycerides), which could lead to an altered communication between the adipose tissue and brain.

Topics: Adult; Biomarkers; Bipolar Disorder; Brain-Derived Neurotrophic Factor; C-Reactive Protein; Cholesterol; Cross-Sectional Studies; Depressive Disorder, Major; Female; Humans; Leptin; Male; Middle Aged; Mood Disorders; Suicidal Ideation; Suicide, Attempted; Triglycerides

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.

Topics: Adiposity; Adult; Body Mass Index; Depressive Disorder, Major; Female; Humans; Leptin; Male; Middle Aged; Nutrition Surveys; Obesity; Odds Ratio; Sex Factors; Waist-Hip Ratio; Young Adult

Many people with major depressive disorder (MDD) show evidence of systemic inflammation, including elevations in inflammatory factors, but the cause is unclear. The purpose of this analysis was to determine if obesity might contribute to the pro-inflammatory state in MDD patients. Blood was obtained from 135 MDD patients and 50 controls. Serum was extracted and assayed for interleukin (IL) -1β, IL-2, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, interferon-γ (IFNγ), tumor necrosis factor α (TNFα), C-reactive protein (CRP), leptin, and adiponectin using single- or multi-plex human immunoassay kits. The primary analysis contrasted IL-6, TNFα, and CRP between MDD and control groups with body mass index (BMI) as a covariate. The other analytes were compared in an exploratory fashion. IL-6 (but not TNFα or CRP) showed significant differences between MDD and controls even after covarying for BMI. Obese controls and obese MDD groups were significantly higher in IL-6 than both lean groups, but the two obese groups did not differ from each other. In the exploratory analyses, the IL-2 level showed robust and significant differences between MDD and controls even after covarying for BMI. Both lean and obese MDD were higher than lean and obese controls. Adiponectin levels were also lower in the MDD sample than controls. Prior findings of higher IL-6, and CRP in MDD patients may be explained, at least in part, based on obesity. High IL-2, however, was associated with depression and not obesity. The results have significant implications for the understanding of pathophysiology and, potentially treatment of MDD.

Topics: Adiponectin; Adult; C-Reactive Protein; Depressive Disorder, Major; Female; Humans; Interleukin-6; Leptin; Male; Middle Aged; Obesity; Tumor Necrosis Factor-alpha

The relationship between leptin and affective disorders is still unknown. We measured free and bound leptin in 13 drug naïve subjects. Leptin did not significantly differ between patients and controls. As part of future studies, it also appears useful to distinguish between free and bound leptin.

Topics: Adult; Depressive Disorder, Major; Female; Humans; Leptin; Male; Middle Aged; Receptors, Leptin; Young Adult

Leptin and ghrelin have been implicated in the pathogenesis of major depression. However, evidence is lacking among apparently healthy people. This study examined the relationship of these appetite hormones to depressive symptoms in a Japanese working population.. A cross-sectional study was conducted in 2009 among 497 Japanese employees (287 men and 210 women) aged 20-68 years. Fasting serum leptin and ghrelin levels were measured using a Luminex suspension bead-based multiplexed array. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. Logistic regression analysis was performed to estimate odds ratio (OR) and 95% confidence interval (CI) for depressive symptoms with adjustment for potential confounders.. The prevalence of depressive symptoms (CES-D ≥16) was 26.5% and 33.3% among men and women, respectively. Women in the middle and highest tertiles of leptin levels showed lower odds for depressive symptoms compared with those in the lowest level, although the trend association was not statistically significant (Ptrend = 0.14). Higher ghrelin levels were associated with increased odds for depressive symptoms in women (Ptrend = 0.02). The multivariable adjusted OR (95% CI) of having depressive symptoms for the lowest through highest tertiles of ghrelin levels were 1.00 (reference), 1.71 (0.76 - 3.86), and 2.69 (1.16 - 6.28), respectively. Neither leptin nor ghrelin was associated with depressive symptoms in men.. Results suggest that lower leptin and higher ghrelin levels may be related to higher prevalence of depressive status among Japanese women.

Topics: Adult; Aged; Asian People; Cross-Sectional Studies; Depressive Disorder, Major; Female; Ghrelin; Humans; Japan; Leptin; Male; Middle Aged; Odds Ratio; Prevalence; Young Adult

This study aimed to describe the prevalence of psychiatric disorders and to identify the factors associated with Current Suicide Risk (CSR) in the first trimester of pregnancy. The Mini-International Neuropsychiatric Interview (M.I.N.I.) was employed to diagnose mental disorders in 239 women enrolled in a prospective cohort in Rio de Janeiro, Brazil. Serum lipids, leptin and socio-economic status were the independent variables. CSR, the dependent variable, was entered as binary (yes/no) variable into crude and adjusted Poisson regression models with robust variances. CSR was found to be the main psychiatric syndrome (18.4%), followed by agoraphobia (17.2%), major depressive disorder (15.1%) and generalized anxiety disorder (10.5%). Women with CSR showed higher mean levels of cholesterol (169.2 vs. 159.2; p=0.017), high density lipoprotein (50.4 vs. 47.7; p=0.031) and low density lipoprotein (102.8 vs. 95.6; p=0.022) when compared to women without CSR. The adjusted regression model showed a higher prevalence ratio (PR) of CSR among pregnant women with generalized anxiety disorder (PR=2.70, 95% CI: 1.36-5.37), with ≥ two parturitions (PR=2.46, 95% CI: 1.22-4.93), and with major depressive disorder (PR=2.11, 95% CI: 1.08-4.12). We have shown that generalized anxiety disorder, major depressive disorder and higher parity are associated with CSR in the first trimester of pregnancy.

Topics: Adult; Agoraphobia; Brazil; Cross-Sectional Studies; Depressive Disorder, Major; Female; Humans; Leptin; Lipids; Mental Disorders; Neuropsychological Tests; Pregnancy; Pregnancy Trimester, First; Prevalence; Prospective Studies; Risk Factors; Socioeconomic Factors; Suicide; Violence; Young Adult

Major depressive disorder (MDD) is associated with immune system dysfunction and disruption of multiple circadian systems. Adiponectin is an adipocytokine with anti-inflammatory and antiatherogenic effects. Circulating concentrations are inversely related to adiposity and risks of metabolic syndrome and diabetes mellitus. Our goals were (1) to establish whether premenopausal women with MDD exhibit decreased plasma adiponectin concentrations and/or disruption of circadian adiponectin rhythmicity; (2) to assess whether there is a relationship between adiponectin and MDD; and (3) to explore the temporal relationships among adiponectin, leptin, corticotropin, and cortisol secretion.. We conducted a case-control study of community-dwelling premenopausal women with DSM-IV MDD (n = 23) and age- and body mass index (BMI)-matched control subjects (n = 23). Main outcome measures were circulating concentrations of adiponectin, leptin, corticotropin, and cortisol measured hourly for 24 hours. Subjects were recruited from July 1, 2001, to February 28, 2003.. Women with MDD had approximately 30% lower mean 24-hour concentration of adiponectin than did control subjects. Adiponectin concentration was inversely related to depression severity and total duration of disease, suggesting a causal link. In contrast, mean nocturnal leptin concentration was higher in the MDD versus control groups. Mean leptin concentration was inversely related to cortisol and adiponectin concentrations, both in subjects with depression and in control subjects. In cross-correlation analyses, the relationship between corticotropin and cortisol concentrations was stronger in women with MDD than in control subjects, a finding consistent with hypothalamic-pituitary-adrenal (HPA) axis activation in MDD.. In premenopausal women with MDD, reduced daily adiponectin production may increase the risk of diabetes mellitus, and elevated leptin may contribute to osteoporosis.

Topics: Adiponectin; Adrenocorticotropic Hormone; Adult; Alendronate; Body Mass Index; Case-Control Studies; Circadian Rhythm; Depressive Disorder, Major; Diabetes Mellitus, Type 2; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Hydrocortisone; Leptin; Middle Aged; Osteoporosis; Premenopause; Psychiatric Status Rating Scales; Risk Factors; Women's Health

Depression is a frequent mood disorder that affects around 33% of stroke patients and has been associated with both poorer outcome and increased mortality. Our aim was to test the possible association between inflammatory and neurotrophic molecular markers and the development of post-stroke depression.. We studied 134 patients with a first episode of ischemic stroke without previous history of depression or speech disorders. We screened for the existence of major depression symptoms in accordance with DSM-IV criteria and a Yesavage Geriatric Depression Scale (GDS) score >11 at discharge and 1 month after stroke. At these times, serum levels of molecular markers of inflammation [interleukin (IL)-1beta, IL-6, intracellular adhesion molecule 1 (ICAM-1), tumor necrosis factor (TNF)-alpha, leptin and high-sensitivity C-reactive protein (hs-CRP)] and neurotrophic factors [brain-derived neurotrophic factor (BDNF)] were measured by enzyme-linked immunosorbent assay (ELISA).. Twenty-five patients (18.7%) were diagnosed as having major depression at discharge. Out of 104 patients who completed the follow-up period, 23 were depressed at 1 month (22.1%). Patients with major depression showed higher serum leptin levels at discharge [43.4 (23.4-60.2) v. 6.4 (3.7-16.8) ng/ml, p<0.001] and at 1 month after stroke [46.2 (34.0-117.7) v. 6.4 (3.4-12.2) ng/ml, p<0.001). Serum levels of leptin >20.7 ng/ml were independently associated with post-stroke depression [odds ratio (OR) 16.4, 95% confidence interval (CI) 5.2-51.5, p<0.0001]. Leptin levels were even higher in the eight patients who developed depression after discharge [114.6 (87.6-120.2) v. 7.2 (3.6-13.6) ng/ml, p<0.0001].. Serum leptin levels at discharge are found to be associated with post-stroke depression and may predict its development during the next month.

Topics: Aged; Aged, 80 and over; Biomarkers; Cerebral Infarction; Depressive Disorder, Major; Female; Follow-Up Studies; Humans; Inflammation Mediators; Leptin; Male; Middle Aged; Odds Ratio; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Factors; Statistics as Topic; Tomography, X-Ray Computed

There is conflicting evidence regarding levels of leptin in depression. In this study we aimed to investigate the relationship between serum leptin level and depression in a community sample of women using both cross-sectional and longitudinal data.. From among 510 women aged 20-78 yr, 83 were identified with a lifetime history of major depressive disorder or dysthymia, ascertained using the Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition (SCID-I/NP). Serum leptin levels were measured by radioimmunoassay. Medication use and lifestyle were self-reported and body mass index (BMI) determined from measures of height and weight.. Using multiple linear regression, serum leptin levels were greater among women with a lifetime history of depression compared to women without any history of depression, independent of BMI. Adjusted geometric mean values of serum leptin were 16.37 (95%CI 14.70-18.23) ng/mL for depressed and 14.46 (95%CI 13.79-15.16) ng/mL for non-depressed women (P=0.039). The hazard ratio (HR) for a de novo depressive disorder over five years increased 2.56-fold for each standard deviation increase in log-transformed serum leptin among non-smokers and this was not explained by differences in BMI, medications or other lifestyle factors (HR=2.56, 95%CI 1.52-4.30). No association was observed for smokers.. There is potential for unrecognised confounding, recall bias and transient changes in body composition.. Women with a lifetime history of depression have elevated levels of serum leptin, and elevated serum leptin predicts subsequent development of a depressive disorder.

Topics: Adult; Aged; Australia; Body Mass Index; Comorbidity; Cross-Sectional Studies; Depressive Disorder, Major; Dysthymic Disorder; Female; Humans; Leptin; Life Style; Longitudinal Studies; Male; Middle Aged; Prognosis; Proportional Hazards Models; Psychiatric Status Rating Scales; Radioimmunoassay; Recurrence; Risk Factors; Smoking; Surveys and Questionnaires

Appetite, food intake and weight are frequently altered in psychiatric disorders such as major depression and schizophrenia. Leptin is an adipocyte hormone, as the product of the ob gene, regulating food intake and energy balance providing the hypothalamus with information on the amount of body fat. Leptin seems to be strongly associated with lipid metabolism. Moreover, leptin is involved in the control of other behaviors and in brain development. There are few studies about the amounts of plasma leptin in mood disorder and schizophrenia with inconsistent findings. The relationship between leptin and major depressive disorder is still unknown. We planned to investigate the relationship of the serum leptin concentration, cholesterol, and BMI between patients with major depressive disorder, schizophrenic patients and healthy control subjects.. In the present study, the BMI, plasma cholesterol and leptin levels, BDI, and BPRS were compared in 69 patients with major depressive disorder, 78 schizophrenic patients, and 51 healthy controls.. The major findings of our study included (1) leptin and cholesterol levels were low in patients with major depressive disorder, but high in schizophrenic patients; (2) negative correlations between BDI scores and serum cholesterol or leptin levels in the patients with major depressive disorder; (3) an inconsistently positive correlation between mean leptin levels, cholesterol, and BMI among different groups; (4) positive correlations between serum cholesterol or leptin levels and the length of illness in the schizophrenic patients.. In this study, our results indicate that that leptin and cholesterol might play differently important pathophysiological roles in these psychiatric disorders.

Topics: Adult; Body Mass Index; Brief Psychiatric Rating Scale; Cholesterol; Depressive Disorder, Major; Female; Humans; Leptin; Male; Schizophrenia

Topics: Anxiety Disorders; Comorbidity; Depressive Disorder, Major; Follow-Up Studies; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Leptin; Obsessive-Compulsive Disorder; Pituitary-Adrenal System; Stress Disorders, Post-Traumatic

The pathogenesis of bone loss in major depressive disorder is a matter of debate. Studies of bone loss in nonpsychiatric medical disorders have found an association between the activation of osteoclastic cells and an imbalance of pro- and antiinflammatory cytokines. Since major depressive disorder is also associated with alterations in serum cytokine concentrations, the authors hypothesized that bone loss in patients with major depressive disorder and comorbid borderline personality disorder may be associated with cytokines capable of activating osteoclastic cells.. Twenty-two patients with borderline personality disorder and comorbid current or lifetime major depressive disorder were compared with 16 patients with borderline personality disorder who did not have major depressive disorder and 20 healthy volunteers. Bone mineral density was assessed by means of dual-energy x-ray absorptiometry. Markers of bone turnover as well as endocrine and immune measures were determined.. The bone mineral density of 10 patients with borderline disorder plus current major depressive episode was significantly lower than that of the healthy subjects and the patients with borderline personality disorder without depression. Values of crosslaps, osteocalcin, serum cortisol, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 were significantly higher in the patients with borderline disorder plus current major depressive episode than in the healthy subjects. Crosslaps correlated positively with TNF-alpha but negatively with bone mineral density at the lumbar spine. Patients with borderline personality disorder who did not have current or lifetime depression displayed no alterations of either bone mineral density or the immunological and hormonal measures examined.. Young women with comorbid borderline personality disorder and major depressive disorder have an elevated risk for osteoporosis. Borderline personality disorder per se is not associated with low bone mineral density. These data suggest that the immune and endocrine disturbances associated with depressive disorders in the context of borderline personality disorder may play a role in the pathophysiological process underlying bone loss in the patients studied.

Topics: Absorptiometry, Photon; Adult; Biomarkers; Bone and Bones; Bone Density; Borderline Personality Disorder; Collagen; Comorbidity; Cytokines; Depressive Disorder, Major; Female; Humans; Insulin-Like Growth Factor I; Leptin; Osteoclasts; Osteoporosis; Peptide Fragments; Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha

Leptin is a hormone known to participate in the regulation of weight and appetite and is therefore of interest to examine in the context of major depressive disorder (MDD). Studies of circulating leptin have yielded variable results. We therefore decided to study leptin in cerebrospinal fluid (CSF).. We measured leptin in cerebrospinal fluid (CSF) in 72 patients admitted after a suicide attempt. They were divided in two groups: patients with major depressive disorder (MDD) and patients with other diagnoses (non-MDD). They were also subgrouped according to the number of suicide attempts (one or repeated) and whether the suicide attempt method was classified as violent or nonviolent. Since CSF leptin was considerably lower in men than in women, statistical calculations were made for men and women separately.. We found that in spite of having similar body mass index (BMI) (P = 0.1), women in the MDD group had lower CSF leptin than those in the non-MDD group (P < 0.01). In contrast, no such difference was found among men. No significant differences were found between women with a first suicide attempt compared to those with a repeated one, or between women with a violent attempt compared to those with a nonviolent attempt.. The heterogeneity of the non-MDD group including patients with various diagnoses is the most important limitation of our study.. CSF leptin is involved in the neuroendocrine dysfunction in women with suicide attempt and MDD. This finding contributes to the understanding of the metabolic symptoms in MDD.

Topics: Adult; Body Mass Index; Depressive Disorder; Depressive Disorder, Major; Female; Humans; Leptin; Male; Middle Aged; Reference Values; Risk Factors; Sex Factors; Suicide, Attempted

The growing number of studies examining the relationship between suicide and lipid metabolism are based upon studies suggesting that cholesterol-lowering procedures may increase the risk of death due to suicide or impulsive-aggressive behavior. Leptin seems to be strongly associated with lipid metabolism. In the present study, serum total cholesterol and leptin levels were compared in 24 suicide attempters and 24 healthy controls. The patients with suicide attempts had significantly lower serum cholesterol and leptin levels than controls. There was a positive correlation between cholesterol and leptin levels in both groups. Our results suggest that suicide attempts seem to be associated with decreased serum cholesterol and leptin levels.

Topics: Adult; Alcoholism; Bipolar Disorder; Borderline Personality Disorder; Cholesterol; Depressive Disorder, Major; Female; Humans; Leptin; Male; Mental Disorders; Middle Aged; Schizophrenia; Suicide, Attempted

Recently, hypocretins have been implicated in the pathophysiology of narcolepsy, a sleep disorder characterized particularly by the occurrence of excessive daytime sleepiness and cataplexy. Hypocretins, which stimulate food intake, have been reported to be absent in the cerebrospinal fluid (CSF) of the majority of patients suffering from narcolepsy. Because these patients also display an increased body mass index (BMI), it has been suggested that disturbances in metabolism and food intake regulation may be present. To further investigate these presumed alterations, we studied the production of leptin, a fat-cell-derived hormone signaling to the brain the size of the adipose tissue. We measured the levels of leptin in serum and CSF from 15 narcoleptic patients and compared the results to those from age-, sex- and BMI-matched control groups of depressive patients and patients suffering from a noninflammatory neurological disorder. Compared to both control groups, leptin levels in serum, but not in the CSF, were significantly reduced in narcoleptic patients by more than 50%. These results support the hypothesis that human narcolepsy is accompanied by complex alterations of the regulation of food intake and metabolism. The significance of these alterations for the core symptomatology of narcolepsy should be a target of future research.

Topics: Depressive Disorder, Major; Humans; Leptin; Narcolepsy; Nervous System Diseases; Osmolar Concentration; Reference Values