leptin and Depressive-Disorder

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

Stress is defined as a state that can threaten homeostasis in an organism to initiate the adaptive process. Stress mediators, which include the classic neuroendocrine hormones and a number of neurotransmitters, cytokines, and growth factors, regulate both basal and threatened homeostasis to help control the stress. Severity of stress, as well as malfunctioning of stress pathways, may impair its controllability, leading to the pathogenesis of psychiatric illnesses including depression. Leptin was initially identified as an antiobesity hormone, acting as a negative feedback adiposity signal to control energy homeostasis by binding to its receptors in the hypothalamus. Accumulating evidence has expanded the function of leptin from the control of energy balance to the regulation of other physiological and psychological processes. The aim of this paper is to evaluate the potential role of leptin in stress controllability. To this end, studies on the role of leptin in stress-induced activation of the hypothalamus-pituitary-adrenocortical axis, feeding behavior, learned helplessness, and other depression models have been accumulated. The knowledge accumulated in this article may facilitate the development of alternative treatment strategies, beyond serotonin and noradrenaline reuptake inhibition, for psychiatric care and stress-related disorders.

Topics: Animals; Anxiety Disorders; Brain; Depressive Disorder; Feeding Behavior; Helplessness, Learned; Humans; Leptin; Stress, Psychological

Topics: Biomarkers; Brain; Brain-Derived Neurotrophic Factor; Child; Depressive Disorder; Ghrelin; Humans; Hypothalamo-Hypophyseal System; Inflammation; Leptin; Models, Biological; Neural Pathways; Pituitary-Adrenal System; Sleep Wake Disorders

Impaired appetite and weight changes are commonly seen in patients with depression, but the pathophysiology behind this imbalance between energy intake and energy expenditure remains largely unknown. The aim of this paper is to review the literature regarding a possible role for cytokines in the regulation of appetite and body weight, with special emphasis on depression. There now exists a substantial amount of evidence that depressed patients show signs of immune activation including increased levels of proinflammatory cytokines. Cytokines, which by themselves have anorectic properties, stimulate the release of the cytokine-like anorexogenic peptide leptin. In addition to their anorectic properties, both proinflammatory cytokines and leptin interact with the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic nervous system (SNS) and the immune system. In turn, these systems regulate energy balance as well as they are dysfunctional in depression. Furthermore, both proinflammatory cytokines and leptin can induce anhedonia, one of the cardinal symptoms of depression. In view of the different effects on appetite and/or body weight observed in melancholic versus atypical depression, we suggest that cytokines are differentially altered in these subtypes of depression, and that this may explain some of the inconsistency in the reported findings of cytokine as well as leptin levels in depressed patients. Finally, we propose that the immune system uses the interoceptive pathway projecting to the insular cortex, a brain region where cytokine-induced changes in appetite could be partly mediated, and that this pathway is activated in depression.

Topics: Animals; Anorexia; Appetite Regulation; Brain; Cytokines; Depression; Depressive Disorder; Humans; Leptin

In depressed patients, overstimulation of the hypothalamo-pituitary-adrenocortical (HPA) system, probably caused by glucocorticoid receptor resistance, is the most consistent neurobiological finding. Glucocorticoids themselves are reported to increase leptin synthesis and secretion in humans.. We examined alterations in plasma levels of leptin as well as changes in the HPA system function using the combined dexamethasone/corticotropin-releasing hormone (dex/CRH) test on admission and at discharge in 74 depressed inpatients.. Mean leptin concentration did not change significantly between admission and discharge. However, changes in ACTH response and partial cortisol response to the combined dex/CRH test between admission and discharge were significantly correlated with leptin levels at discharge.. Leptin levels at discharge rise as the HPA axis normalizes. These findings may be explained by an improvement in glucocorticoid receptor sensitivity among depressed patients during antidepressant therapy and a consecutively increased influence of glucocorticoids on leptin levels via the glucocorticoid receptor.

Topics: Adrenocorticotropic Hormone; Adult; Analysis of Variance; Antidepressive Agents; Area Under Curve; Corticotropin-Releasing Hormone; Depressive Disorder; Dexamethasone; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Leptin; Male; Middle Aged; Pituitary-Adrenal System

Weight gain is a common side effect of psychotropic medications. Mirtazapine, a widely used antidepressant, induces adverse metabolic effects such as an increase in body weight. The aim of this study was to investigate the influence of mirtazapine treatment on body weight, body fat mass, glucose metabolism, lipoprotein profile, and leptin and its soluble receptor in a prospective, controlled study design.. Seven women who met the ICD-10 diagnostic criteria for a depressive episode (ICD-10: F31-F33) were assigned to monotherapy with mirtazapine and observed for a 6-week period. Seven mentally and physically healthy female volunteers matched for age and body weight served as a control group. Data were collected from November 2002 to December 2003.. The mean +/- SD body weight increased from 63.6 +/- 13.1 kg to 66.6 +/- 11.9 kg during mirtazapine treatment (p = .027). Fat mass increased in study subjects from 20.9 +/- 9.6 kg to 22.1 +/- 9.3 kg (p = .018). Insulin, glucose, and the homeostasis model assessment (HOMA) index for insulin resistance and lipid parameters remained stable. Leptin concentrations increased from 23.0 +/- 17.1 ng/mL to 40.9 +/- 27.2 ng/mL (p = .018), whereas the soluble leptin receptor concentrations remained stable during mirtazapine treatment. In the control subjects, the investigated parameters remained stable. Between-group analyses of change scores revealed significant differences for body weight (p = .010), body mass index (p = .013), fat mass (p = .035), and leptin (p = .013).. The antidepressant therapy with mirtazapine was associated with a significant increase in body weight, body fat mass, and leptin concentration. In contrast to other psychotropic medications inducing weight gain, such as some second-generation antipsychotics, mirtazapine treatment did not influence the glucose homeostasis.

Topics: Adipose Tissue; Adult; Antidepressive Agents, Tricyclic; Blood Glucose; Body Composition; Body Fat Distribution; Body Weight; Depressive Disorder; Female; Follow-Up Studies; Homeostasis; Humans; International Classification of Diseases; Leptin; Lipoproteins; Mianserin; Mirtazapine; Obesity; Prospective Studies; Receptors, Cell Surface; Receptors, Leptin; Treatment Outcome

Major depression in women of reproductive age may be accompanied by multiple endocrine and metabolic disturbances, which, in turn, may affect reproductive functioning. Enhanced cortisol synthesis, impaired leptin production and diminished insulin sensitivity have been reported in some depressed populations. We sought to determine whether an 8-week administration of citalopram would have an effect on these endocrine factors in a group of euglycemic depressed and non-depressed women of reproductive age.. Fourteen depressed and 18 non-depressed women (diagnosed by structured clinical interview) aged between 18 and 45 years completed an 8-week study. All depressed women were treated with citalopram and non-depressed subjects randomized to citalopram or no treatment in an open label cohort study. An oral glucose tolerance test with insulin levels was performed at baseline and at the end of the 8-week trial. Weight, blood pressure, fasting serum cortisol, fasting serum leptin and Beck Depression Inventory were assessed at baseline, 2, 4 and 8 weeks.. Citalopram significantly improved depressive symptoms and Beck Depression Inventory scores in the depressed cohort. Cortisol production was higher in depressed women but did not diminish with citalopram therapy over 8 weeks. Indices of insulin sensitivity and leptin production were similar between depressed and non-depressed women and did not change despite citalopram therapy.. . Insulin sensitivity in moderately depressed women of reproductive age does not differ from that in a similar group of non-depressed women. Insulin sensitivity, cortisol secretion and leptin production do not change significantly in depressed women following an 8-week course of citalopram despite substantial improvement in depression scores.

Topics: Administration, Oral; Adolescent; Adult; Citalopram; Cohort Studies; Depressive Disorder; Drug Administration Schedule; Female; Glucose Tolerance Test; Humans; Hydrocortisone; Insulin; Insulin Resistance; Leptin; Middle Aged; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Treatment of depression is often accompanied by weight changes. Previous studies indicate that leptin plays no role in this change despite showing a strong correlation with body mass index (BMI) in healthy people. The aim of this study was to evaluate the effect of imipramine and fluoxetine on BMI and its correlation with leptin. Eighteen depressed female patients randomly received either drug for 3 months. BMI was calculated and fasting blood samples were assayed for glucose, leptin, insulin, free fatty acids (FFA), and lipids. The difference between the changes in BMI (imipramine + 1.0 kg/m2, fluoxetine -0.5 kg/m2) was statistically significant (P < 0.05, t = 2.106). There was a significant positive correlation between overall BMI and leptin (r = 0.784, P < 0.001) but not between BMI and insulin or FFA. However, fasting insulin levels and calculated insulin resistance levels dropped substantially in the imipramine group. We conclude that the use of tricyclic antidepressants (TCAs) in depressed patients at risk for developing type 2 diabetes remains unresolved at this stage.

Topics: Adult; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Black People; Body Mass Index; Depressive Disorder; Female; Fluoxetine; Humans; Imipramine; Leptin; South Africa

Appetite, food intake and weight are frequently altered in psychiatric disorders such as major depression and schizophrenia. The few studies investigating weight and the body mass index (BMI) have yielded variable results. Leptin, a fat cell-derived hormone signalling to the brain the size of the adipose tissue, plays a pivotal role in the regulation of weight and food intake. Moreover, leptin is involved in the control of other behaviors and in brain development. There is almost no information about the amounts of circulating leptin in major depression or schizophrenia. We investigated the BMI and plasma leptin levels in patients with major depression (n = 62), schizophrenia (n = 42), and in healthy controls (n = 64). Mean BMIs did not differ between groups. However, leptin levels were significantly lower in both patient groups compared to healthy controls. Moreover, patients suffering from schizophrenia showed significantly lower leptin levels than depressed patients. Decreased leptin levels were independent of psychotropic medication. We conclude that depression and schizophrenia go along with decreased systemic leptin concentrations that cannot be explained by medication or an altered BMI. Hence, leptin might play an important pathophysiological role in these psychiatric disorders that deserves further scientific attention.

Topics: Adult; Body Mass Index; Depressive Disorder; Female; Humans; Leptin; Male; Middle Aged; Schizophrenia

Leptin is a hormone that regulates fat metabolism and appetite. The secretion of leptin is regulated by adiposity and, in the rodent, by factors such as insulin, beta-adrenergic agonists, and glucocorticoids (GCs). Increased secretion of the endogenous human GC, cortisol, occurs during stress and in disorders such as major depression. Pharmacological GCs can robustly increase plasma leptin concentrations in humans, leading us to hypothesize that cortisol may serve as a physiological regulator of human leptin secretion.. A randomized double-blind placebo-controlled comparison of 2 fixed oral dosages of cortisol (40 mg/d and 160 mg/d), given for 4 days to matched groups of healthy subjects (n=47). Low-dose treatment approximated GC output during mild stress, while high-dose treatment approximated GC output during maximal stress, spanning a range of GC secretion relevant to physiological stress.. Cortisol produced dose-dependent and time-dependent increases in plasma leptin concentrations (time x treatment condition x body mass index; F6,123=10.73; P<.001). Initial treatment-induced increases in plasma leptin concentration returned toward baseline values during 4 treatment days, suggesting tolerance to this GC effect in these healthy subjects.. The results indicate an important role for GCs in the short-term regulation of human leptin secretion. Glucocorticoid-induced increases in leptin secretion suggest a mechanism that may contribute to anorexia and weight loss during stress and disease states such as major depression, if these conditions are associated with sustained increases in plasma leptin concentrations.

Topics: Adipose Tissue; Adult; Anorexia; Body Mass Index; Depressive Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hydrocortisone; Leptin; Male; Placebos; Proteins; Stress, Physiological; Weight Loss

Phytoestrogens, such as daidzein and genistein, may be used to treat various hormone-dependent disorders. Daidzein can be metabolized by intestinal microbes to S-equol. However, not all individuals possess bacteria producing this metabolite, resulting in categorization of equol vs nonequol producers. Past human and rodent studies have suggested that supplementation of this compound might yield beneficial metabolic and behavioral effects. We hypothesized that administration of S-equol to diet-induced obese male and female mice would mitigate potential diet-induced metabolic and comorbid neurobehavioral disorders. To test this possibility, we placed 5-week-old C57 mice on a high-fat diet (HFD) to mimic the diet currently consumed by many Western adults. Animals were randomly assigned to S-equol supplementation (10 mg/kg body weight) or vehicle control group. After 4 weeks on HFD with or without S-equol supplementation, metabolic and behavioral phenotyping was performed. Although the initial hypothesis proposed that S-equol treatment would improve metabolic and neurobehavioral outcomes, this supplementation instead exacerbated aspects of HFD-induced metabolic disease, as indicated by suppressed physical activity in treated individuals, reduced energy expenditure in treated males, and serum chemistry changes (hyperglycemia in treated individuals; hyperinsulinemia and hypoleptinemia in treated males). Conversely, S-equol individuals exhibited less anxiety-like and depressive-like behaviors, as evidenced by increased exploratory time in the elevated plus maze by treated males and increased time spent mobile in the tail suspension test for treated individuals. In summary, S-equol may be beneficial in mitigating depression and anxiety disorders in individuals, but for indeterminate reasons, supplementation may worsen facets of metabolic disorders in obese individuals.

Topics: Animals; Anxiety; Anxiety Disorders; Behavior, Animal; Blood Glucose; Depression; Depressive Disorder; Dietary Supplements; Equol; Female; Hindlimb Suspension; Insulin; Isoflavones; Leptin; Male; Maze Learning; Metabolic Diseases; Metabolic Syndrome; Mice, Inbred C57BL; Phytoestrogens; Sex Factors

Associations between suicidality and lipid dysregulation are documented in mental illness, but the potential role of leptin remains unclear. We examined the association between leptin and suicidal behaviour in schizophrenia, together with the influence of other clinical and biological indices.. We recruited a sample of 270 participants with schizophrenia spectrum diagnoses. Blood samples were analysed for leptin, while symptom severity was assessed by Positive and Negative Syndrome Scale (PANSS) and Inventory of Depressive Symptomatology (IDS-C). Patients' history of suicidal behaviour was categorized into three subgroups based on IDS-C suicide subscale: No suicidal behaviour, mild/moderate suicidal behaviour and severe suicidal behaviour with/without attempts.. Mild/moderate suicidal behaviour was present in 17.4% and severe suicidal behaviour in 34.8%. Both groups were significantly associated with female gender (OR = 6.0, P = 0.004; OR = 5.9, P = 0.001), lower leptin levels (OR = 0.4, P = 0.008; OR = 0.5, P = 0.008) and more severe depression (OR = 1.2, P < 0.001; OR = 1.1, P < 0.001) respectively. Smoking (OR = 2.6, P = 0.004), younger age of onset (OR = 0.9, P = 0.003) and less use of leptin-increasing medications (OR = 0.5, P = 0.031) were associated with severe/attempts group, while higher C-reactive protein CRP (OR = 1.3, P = 0.008) was associated with mild/moderate group.. Lower leptin levels were associated with higher severity of suicidal behaviour in schizophrenia.

Topics: Adult; Age of Onset; C-Reactive Protein; Cross-Sectional Studies; Depressive Disorder; Female; Humans; Leptin; Male; Psychotropic Drugs; Risk Factors; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Smoking; Suicidal Ideation; Suicide

Environmental stress (ES) is commonly used in producing chronic unpredictable mild stress to study pathogenesis of depression, including the regulatory role of circadian system on depression. However, the direct effect of ES on the circadian system has been rarely explored. The present study was aimed to investigate the effect of ES on depression-like behaviors and diurnal rhythm of plasma hormone/peptide levels in male rats. Rats were allocated into control group (CON group), low frequency ES group (LF group) and high frequency ES group (HF group). Sucrose preference test (SPT), open field test (OFT), weight gain, food and water intake were conducted to assess depression- and anxiety-like behaviors. A total of 7 times of the tail venous blood was collected with an interval of 4 h during 24 h from other rats who subjected to the same procedures of ES but not the behavioral tests. The alterations of diurnal rhythm of peripheral plasma corticosterone (CORT) and melatonin, and changes of the cholecystokinin (CCK), neuropeptide Y and leptin levels at zeitgeber time (ZT) 0 were detected by using enzyme-linked immunosorbent assay (ELISA). We found that ES led to a disturbance of diurnal rhythm of CORT and melatonin in the plasma. Besides, it also increased plasma leptin level and decreased body weight gain, but it did not produce depression- and anxiety-like behaviors compared with those rats in the control group. In short, our findings indicated that the ES could induce a disturbance of diurnal rhythm of plasma CORT and melatonin in male rats.

Topics: Animals; Anxiety; Behavior, Animal; Circadian Rhythm; Corticosterone; Depression; Depressive Disorder; Leptin; Male; Melatonin; Neuropeptide Y; Rats; Stress, Physiological

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.

Topics: Adult; beta 2-Microglobulin; Case-Control Studies; Complement C3; Depressive Disorder; Fatty Acid-Binding Proteins; Female; GPI-Linked Proteins; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 2; Leptin; Linear Models; Male; Mesothelin; Middle Aged; Netherlands; Proteomics

The present study investigated whether peripheral leptin levels are associated with current depressive episodes in a cross-sectional study nested within a population-based study.. The Mini-International Neuropsychiatric Interview (MINI) 5.0 was used to assess the presence of current depressive episodes. The sample was composed of 206 subjects (103 controls and 103 subjects with a current depressive episode) paired by gender, BMI and age. Medication use and lifestyle characteristics were self-reported.. Serum leptin levels were lower in currently depressive subjects (10.9 ± 12.0 ng/ml) than in the control group (20.3 ± 24.0 ng/ml; p = 0.023). According to the clinical diagnosis, individuals with bipolar depression present lower leptin levels (8.4 ± 8.1 ng/ml) than those with unipolar depression (12.0 ± 13.4 ng/ml) and the control group (20.3 ± 24.0 ng/ml; p = 0.031). In addition, ANCOVA showed that leptin is an independent factor associated with current depressive episodes (p = 0.018).. A decreased leptin level might be a useful peripheral marker associated with depressive episodes in the context of bipolar disorder.

Topics: Adolescent; Adult; Bipolar Disorder; Cross-Sectional Studies; Depressive Disorder; Female; Humans; Leptin; Male; Neuropsychological Tests; Young Adult

Chronic stress is a potential contributing factor for depression, accompanying with metabolic and inflammatory response. Exercise is considered as a treatment for depression, but mechanisms underlying its beneficial effects still remain unknown. The objectives of present study were to confirm that metabolic factors-triggered inflammatory response mediates the antidepressant actions of exercise in chronic unpredictable mild stress (CUMS) rats. It has been found that CUMS stimulated expression of ghrelin and its receptor Ghsr, but inhibited expression of leptin and its receptor LepRb. Ghrelin, via binding to Ghsr, induced phosphorylation of GSK-3β on Tyr216 and decreased phosphorylation on Ser9, thus increasing GSK-3β activity. Conversely, ghrelin binding to Ghsr decreased STAT3 activity, through decreasing phosphorylation of STAT3 on Tyr705 and increasing Ser727 phosphorylation. Negatively correlated with ghrelin, leptin binding to LepRb had opposite effects on the activity of GSK-3β and STAT3 via phosphorylation. In addition, decreased leptin level initiated NLRP3 activity via LepRb. Furthermore, GSK-3β inhibited STAT3 activation, thus promoting the expression of NLRP3. Meanwhile, swim improved metabolic and inflammatory response both in CUMS and control rats. Our findings suggest that exercise not only ameliorates metabolic disturbance and inflammatory response in depression, but also contributes to metabolic and inflammatory function in normal conditions.

Topics: Animals; Antidepressive Agents; Depression; Depressive Disorder; Drive; Exercise Therapy; Exploratory Behavior; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Leptin; Male; Motor Activity; Phosphorylation; Phosphotransferases; Physical Conditioning, Animal; Rats; Stress, Psychological; Swimming

Topics: Animals; Brain; Depressive Disorder; Eating; Ghrelin; Humans; Leptin; Obesity

Leptin, involved in energy regulation and contributor to cardiovascular disease, has been implicated to play a role in depression and sleep disturbances, two closely intertwined conditions. Previous results investigating leptin level alterations either in sleep disorders or in depression have been inconsistent. We investigate the association between leptin levels and the different combinations of depressed mood and sleep disturbances in 1369 subjects (706 men, 663 women), derived from the population-based MONIKA/KORA study. As leptin regulation is known to differ by sex and weight, analyses were performed in normal weight and overweight men and women separately. We found a highly significant association between leptin levels and the combination of depressed mood and sleep disturbances in normal-weight women (BMI ≤ 25) (p<0.01). No associations were found in men and in overweight women. Our results suggest that leptin regulation in depressed mood and sleep disturbances very much depend on sex and weight.

Topics: Adult; Aged; Analysis of Variance; Association; C-Reactive Protein; Chi-Square Distribution; Cholesterol; Cholesterol, HDL; Cohort Studies; Community Health Planning; Depressive Disorder; Female; Humans; Immunoradiometric Assay; Leptin; Male; Middle Aged; Obesity; Psychometrics; Retrospective Studies; Risk Factors; Sleep Wake Disorders; Surveys and Questionnaires

Animal models suggest that impaired leptin production, or leptin resistance despite increased leptin levels, may contribute to depression. The link between leptin and depression could be mediated by obesity, which is more common in depression and increases leptin production.. We administered the Beck Depression Inventory-II (BDI-II) to 537 participants (mean [standard deviation (SD)] age = 51 [9] years; female, 61%) enrolled in the Morehouse and Emory Team up to Eliminate Health Disparities (META-Health) study. Leptin levels were examined as continuous log-transformed values.. Participants with moderate to severe depression had higher levels of leptin (median [interquartile range] 37.7 [17.6-64.9] ng/mL) than those with mild depression (22.9 [7.0-57.9] ng/mL) or minimal to no depression (19.8 ng/mL [7.8-39.1], p = .003). Participants with moderate to severe depression had higher body mass index (BMI) than those with mild or minimal depression (mean [SD] = 33 [8] versus 31 [9] versus 29 [7] kg/m(2), p = .001). After multivariate adjustment for age, sex, race, smoking status, hypertension, diabetes, blood pressure, lipids, and C-reactive protein, the BDI-II score remained a significant predictor of leptin levels (β = 0.093, p = .01). Further adjustment for BMI eliminated the association between the BDI-II score and leptin (β = 0.03, p = .3). Adjusting for waist circumference in place of BMI revealed similar findings.. The association between depression and leptin seems to be mediated by increased adiposity in depressed individuals.

Topics: Adiposity; Adolescent; Adult; Aged; Animals; Black or African American; Body Mass Index; Cross-Sectional Studies; Depressive Disorder; Female; Homeostasis; Humans; Leptin; Linear Models; Male; Mice; Middle Aged; Obesity; Psychiatric Status Rating Scales; Risk Factors; Severity of Illness Index; Waist Circumference; Young Adult

Inflammation might link posttraumatic stress disorder (PTSD) with an increased risk of cardiovascular events. We explored the association between PTSD and inflammatory biomarkers related to cardiovascular morbidity and the role of co-morbid depressive symptoms in this relationship.. We investigated 15 patients with interviewer-rated PTSD caused by myocardial infarction (MI) and 29 post-MI patients with no PTSD. All patients completed the depression subscale of the Hospital Anxiety and Depression Scale and had blood collected to determine inflammatory markers of increased cardiovascular risk.. Controlling for demographic and medical covariates, patients with PTSD had higher leptin levels than patients with no PTSD (p = 0.038, explained variance 10.4%); this difference became nonsignificant when controlling for depressive symptoms. After controlling for depressive symptoms, PTSD patients had higher interleukin-6 (p = 0.041; explained variance 10%), lower C-reactive protein (p = 0.022, explained variance 12.1%), and lower soluble CD40 ligand (p = 0.016, explained variance 13.4%) than patients without PTSD. After controlling for PTSD status, depressive symptoms correlated with soluble CD40 ligand (r = 0.45, p = 0.002) and with C-reactive protein (r = 0.29, p < 0.07).. The findings provide further evidence for altered inflammation in PTSD. Comorbid depressive symptoms ought to be considered to disentangle the unique associations of PTSD caused by MI and systemic inflammation.

Topics: Aged; Biomarkers; CD40 Ligand; Comorbidity; Depressive Disorder; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Leptin; Male; Middle Aged; Myocardial Infarction; Neuropsychological Tests; Stress Disorders, Post-Traumatic; Surveys and Questionnaires

Epidemiologic data suggest an association between obesity and depression, however findings vary considerably across different studies. Both depression and obesity are disabling disorders associated with loss over appetite control, influenced by genetic and environmental factors and are risk factors for diseases like hypertension, cardiovascular disorders, etc. This study attempts to establish a link between the symptoms of depression, metabolic disorders, and obesity, to unravel the underlying association/s.. This exploratory case-control study comprises 133 clinically diagnosed depressed individuals and 136 age matched controls. DNA from all 269 subjects was genotyped for D7S1875 repeat polymorphism in the promoter region of Leptin (LEP) gene using polymerase chain reaction.. Frequency of the shorter allele of D7S1875 (<208 bp) was 0.73 in the depressive group versus 0.67 in the control group (P=.01). Cases homozygous for D7S1875> or =208 bp alleles had significantly higher value of systolic (130 versus 122; P<.009) and diastolic (85.4 versus 81; P=.01) blood pressure (SBP and DBP) than the individuals homozygous for<208 bp allele. A similar trend was observed for SBP (127.8 versus 123.6; P=.03) among controls homozygous for the longer or the shorter allele. Thus, the LEP gene appears to be an important genetic determinant for susceptibility to depression in the Indian population (OR=1.4913, 95% CI=1.0334-2.1522; P=.04).. Our findings suggest that LEP gene variants could be related to depression and associated co-morbidities such as hypertension.

Topics: Adult; Alleles; Blood Pressure; Body Mass Index; Case-Control Studies; Depressive Disorder; Female; Gene Frequency; Genetic Carrier Screening; Genetic Predisposition to Disease; Genotype; Homozygote; Humans; Hypertension; India; Leptin; Male; Middle Aged; Obesity; Polymerase Chain Reaction; Polymorphism, Genetic; Promoter Regions, Genetic

To investigate the relationship between leptin and cytokines in depressed patients.. Thirty-three unmedicated patients (24 female, nine male) with depressive disorder and 23 healthy controls (16 female, seven male) were assessed for serum levels of interleukin (IL)-6, IL-1beta, tumour necrosis factor-alpha (TNF-alpha) and leptin.. Levels of IL-6 and TNF-alpha in depressed patients were higher than in normal controls. There were significantly lower leptin levels in depressed patients than in normal controls. There were also significant differences in the leptin levels, being higher in female than in male patients, and in female than in male controls.. IL-6 and TNF-alpha cytokines and leptin are important in the psychoimmunology of depressed patients. There were gender differences in leptin levels in depression.

Topics: Adolescent; Adult; Body Mass Index; Depressive Disorder; Female; Humans; Interleukin-1beta; Interleukin-6; Leptin; Male; Middle Aged; Patient Admission; Reference Values; Sex Factors; Statistics as Topic; Tumor Necrosis Factor-alpha

The effects of electroconvulsive therapy (ECT), which is a widely used treatment for psychiatric disorders, have not yet been established. Therefore, we aimed to explore whether the patients' serum ghrelin and leptin levels are associated with the action of ECT treatment. In the case of the mood disorders, which occurred in 16 patients with major depressive episode (MDE) and 12 patients with bipolar disorder-manic episode (BD-me) and 25 healthy controls, we have determined the serum levels of ghrelin, leptin and cholesterol before ECT and 2 days after ECT. The BMI was also calculated in all subjects. Although ECT treatment did not change mean the BMI and serum leptin level, the mean serum ghrelin level decreased and the total cholesterol level increased after ECT compared with before ECT. While the leptin levels in the patient group were significantly lower than the controls before and after ECT, the mean serum ghrelin and total cholesterol levels differed statistically only before ECT, but not after ECT than those in controls. The ghrelin levels have decreased significantly after ECT in both sub-groups MDE and BB-me. However, the mean serum total cholesterol level increased statistically after ECT only in the MDE sub-group, and the leptin levels did not differ in both sub-groups after ECT compared with before ECT. In conclusion, ECT treatment seems to be associated with decreased ghrelin levels and increased cholesterol levels but not leptin levels. However, more comprehensive and detailed studies are needed to decipher the exact role of ECT on ghrelin, leptin and total cholesterol in mood disorders.

Topics: Adult; Biomarkers; Bipolar Disorder; Brain; Brain Chemistry; Cholesterol; Depressive Disorder; Down-Regulation; Electroconvulsive Therapy; Female; Ghrelin; Humans; Leptin; Male; Middle Aged; Mood Disorders; Treatment Outcome; Up-Regulation

Topics: Adult; Brain; Cerebrovascular Circulation; Depressive Disorder; Female; Humans; Leptin; Male; Middle Aged; Suicide

The aim of the present study was to evaluate serum leptin levels to demonstrate whether or not its eventual alterations might have an etiopathogenetic significance in patients with obsessive-compulsive disorder (OCD). Thus, it was planned to examine whether serum leptin levels were affected by pure OCD (OCD-D), pure depression (D) or the comorbidity of OCD and depression (OCD+D). Forty-four patients with OCD (27 with OCD-D and 17 with OCD+D), 38 depressed patients and 30 control subjects were enrolled and serum leptin and cortisol levels were measured. According to the mean leptin levels, no significant difference was found between the OCD-D and control groups and between the OCD+D and D groups, while statistically significantly lower levels were found in the OCD+D and D groups than in control group. Significant difference in the mean leptin levels was found among groups even after controlling for body mass index or sex. The present study confirms the strong relationship between serum leptin and cortisol values and suggests that reduced leptin levels, rather than having an etiopathogenetic significance in patients with OCD, seem to be associated with patients with OCD and depression but not with pure OCD patients, and that OCD may be a heterogeneous subtype containing some biological indications of anxiety and affective disorders.

Topics: Adolescent; Adult; Depressive Disorder; Female; Humans; Hydrocortisone; Leptin; Male; Middle Aged; Obsessive-Compulsive Disorder; Reference Values

Leptin is thought to be related to vegetative symptoms of depression such as alterations in food intake and weight. Fifty-seven drug-free patients and 26 healthy controls were enrolled in this study. We have found that the serum leptin levels were higher in patients with atypical depressive disorder than in controls, but not in patients with non-atypical depressive disorder, however, body mass index, age, and gender were not significantly different between these groups. Probably, these findings seem to be associated with some features of the atypical depressive disorders such as weight gain, a result of hyperphagia.

Topics: Adult; Body Mass Index; Depressive Disorder; Female; Human Growth Hormone; Humans; Hydrocortisone; Insulin; Leptin; Male; Weight Gain

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