leptin and Bipolar-Disorder

Antipsychotics (APs) are associated with metabolic syndrome, with increases in leptin proposed as an underlying mechanism of AP-induced weight gain. Currently available meta-analyses on this topic have limited their populations of interest to those diagnosed with schizophrenia. The purpose of this meta-analysis is to explore the relationship between leptin levels and AP use across multiple psychiatric diagnoses, and also in healthy controls.. Systematic electronic searches were conducted using PubMed and OVID: Medline. Longitudinal studies were included if showing leptin levels before and after AP use. We included participants with any psychiatric disorders and mentally healthy participants, if exposed to AP use. The differences in leptin levels were evaluated using Hedges' g with a random effects model.. Forty-two studies were found (36 schizophrenia, 2 bipolar disorder, 1 anorexia nervosa, and 3 healthy controls), encompassing 66 study arms and 1,156 participants. The meta-analysis showed that regardless of diagnoses, leptin levels increase with AP use (Hedges' g = 0.811, p ≤ .001).. Leptin increases induced by APs are present across all diagnoses. More comprehensive research is needed to understand the relationship between AP use and leptin levels across multiple diagnoses.

Topics: Anorexia Nervosa; Antipsychotic Agents; Bipolar Disorder; Humans; Leptin; Metabolic Syndrome; Schizophrenia

Bipolar disorder (BD) is a psychiatric disorder associated with increased rates of obesity and inflammation. Leptin is an adipokine that is mainly produced by the white adipose tissue in response to insulin. It stimulates the immune system, increasing the production of pro-inflammatory cytokines. There is currently uncertainty regarding possible alterations in peripheral leptin levels across the mood states in BD.. This study comprises a between-group meta-analysis comparing serum and plasma leptin levels in people with BD in mania, depression or euthymia and healthy controls. We conducted a systematic search for all possibly eligible-English and non-English peer-reviewed articles. We calculated the effect size (ES) utilizing Hedges' adjusted g using random effects.. Eleven studies were included in the meta-analyses, providing data on 1118 participants. Serum and plasma leptin levels were not altered in subjects with BD when compared to healthy controls in mania (g=-0.99, 95% CI -2.43 to 0.43, P=0.171), in depression (g=0.17, 95% CI -0.45 to 0.79, P=0.584), or in euthymia (g=0.03, 95% CI -0.39 to 0.46, P=0.882). However, we did observe a stronger association between leptin levels and both age and BMI in patients with BD in euthymia compared to healthy controls, such that the greater the age of the individuals, the greater the difference in leptin levels between BD and controls; and the higher the BMI, the greater the difference in leptin levels between BD and controls.. Our meta-analysis provides evidence that leptin levels are not altered in BD across the mood spectrum compared to healthy controls. The disproportionate increase of leptin levels with increase in BMI in BD speaks in favour of a potential inflammatory role of white adipose tissue in BD and a disproportionate increase of leptin levels with increase in age.

Topics: Adult; Bipolar Disorder; Cyclothymic Disorder; Depression; Female; Humans; Leptin; Male

Women with mood disorders, especially bipolar disorder (BD), have been shown to have high rates of reproductive and metabolic dysfunction. The available data on the functional, anatomic, and clinical neuroendocrine abnormalities in women with BD suggest a two-tiered relationship with mood pathology. First, many of the medications commonly used in the treatment of BD can have deleterious effects on blood levels of reproductive hormones and consequently on the hypothalamic-pituitary-gonadal (HPG) axis and reproductive function. Studies that have specifically addressed the association between psychotropic medications and menstrual abnormalities, polycystic ovary syndrome, and overall reproductive endocrine function in women with BD have found high rates of HPG irregularities in women with BD. Second, there is evidence of reproductive dysfunction in women with BD prior to treatment. In addition, many of the psychotropic medications used in the treatment of BD are associated with weight gain, insulin resistance, and dyslipidemia. These metabolic side effects further compound the neuroendocrine system dysregulation in women with BD. Current understanding of the reproductive and metabolic function in women with BD points to vulnerability, which in turn increases the risk of later-life cardiovascular disease and diabetes, among other morbidities, for women with BD.

Topics: Bipolar Disorder; Dyslipidemias; Endocrine System Diseases; Female; Humans; Hypogonadism; Hypothalamo-Hypophyseal System; Leptin; Lithium Carbonate; Menstruation; Obesity; Pituitary-Adrenal System; Polycystic Ovary Syndrome; Psychotropic Drugs; Valproic Acid

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

Excessive body weight gain (BWG) is a clinically relevant side effect of olanzapine administration. The primary objective of this study was to assess whether metformin prevents or reverses BWG in patients with schizophrenia or bipolar disorder under olanzapine administration. Secondarily we evaluated diverse metabolic variables.. Eighty patients taking olanzapine (5-20 mg daily for more than 4 consecutive months) were randomly allocated to metformin (n=40; 850 to 2550 mg daily) or placebo (n=40) group in a 12-week double-blind protocol. Waist circumference (WC) body weight (BW), body mass index (BMI) fasting glucose, glycated hemoglobin (Hb1c), insulin, an insulin resistance index (HOMA-IR) lipids, leptin, c-reactive protein, fibrinogen, cortisol and the growth hormone (GH) were evaluated at baseline and at week 12 of treatment.. The metformin group lost 1.4+/-3.2 kg (p=0.01) and tended to decrease its leptin levels, whereas the placebo group maintained a stable weight: -0.18+/-2.8 kg (p=0.7). The HOMA-IR significantly increased after placebo (p=0.006) and did not change after metformin (p=0.8). No ostensible differences were observed in the other variables, even though metformin did not improve the lipid profile and the Hb1c levels.. Metformin may safely assist olanzapine-treated patients in body weight and carbohydrate metabolism control.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Blood Glucose; Body Mass Index; Body Weight; Brief Psychiatric Rating Scale; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Energy Metabolism; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Resistance; Leptin; Lipids; Male; Metformin; Middle Aged; Olanzapine; Schizophrenia; Statistics as Topic

Atypical antipsychotics (AA)-induced weight gain is associated with increased leptin levels. AA have been increasingly used in the treatment of bipolar disorders. This cross-sectional study aimed to evaluate the association between serum leptin and lipid profiles considering the drug treatments in euthymic bipolar outpatients. Leptin and lipid profiles were compared, and no differences were noted in leptin, cholesterol, and low-density lipoprotein levels among the patients and controls. Glucose, very-low-density lipoprotein, and triglyceride levels in patients were higher than in controls, while high-density lipoprotein levels were low. Patients were divided into three groups according to their type of drug usage: AA users, AA + mood stabilizer users, and mood stabilizer users. Each group of patients was compared with a healthy control group for mentioned biochemical parameters. Lipid profiles were disordered by using both AA and mood stabilizers, but higher leptin levels are associated with AA usage. However, leptin does not seem to be responsible for dyslipidemia caused by AA or mood stabilizers in euthymic bipolar patients.

Topics: Adolescent; Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Blood Glucose; Cholesterol; Female; Humans; In Vitro Techniques; Leptin; Lipoproteins; Middle Aged

Several psychopharmacological agents induce weight gain. Recent studies have suggested that the tumor necrosis factor-alpha (TNF-alpha) cytokine system is pathophysiologically involved. To assess whether carbamazepine and lithium, which have been reported to lead to weight gain, have effects on the circulating levels of cytokines, we measured plasma levels of TNF-alpha, its soluble receptors sTNF-R p55 and p75, and leptin, as well as weight in 25 inpatients receiving lithium (n=10) or carbamazepine (n=15) weekly during the first 4 weeks of treatment. We found an increase in the body mass index and in TNF-alpha and its soluble receptor levels, but not in leptin levels over the 4 weeks of treatment. These changes did not differ between treatment groups. Changes of weight during the first week of treatment, but no other parameter, strongly predicted weight change until endpoint. We conclude that the mood stabilizers carbamazepine and lithium have similar effects on the TNF-alpha system and do not affect leptin levels.

Topics: Adult; Antimanic Agents; Bipolar Disorder; Body Mass Index; Body Weight; Carbamazepine; Female; Humans; Immunologic Factors; Leptin; Lithium Carbonate; Male; Middle Aged; Mood Disorders; Receptors, Leptin; Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha

Novel antipsychotics impart substantial weight gain. Persons with bipolar disorder are frequently treated with these and other agents known to impart substantial weight gain. We sought to describe the influence of adjunctive risperidone and olanzapine on body weight, body mass index (BMI, kg/m2) and serum leptin levels over a prospective observation period of 6 months. Throughout the 6-month investigation, significant increases from baseline to end point in weight were noted with both agents; with significantly greater weight gain with olanzapine (t(10) = 2.761, P = 0.023; t(9) = 4.783, P = 0.001). Leptin levels were highly correlated with increases in weight and were significantly elevated from baseline at 4 months (r = 0.658, P < 0.05). Significant increases in weight and body mass index were apparent at 3 months (P < 0.05). The temporal association between weight increase and leptin changes does not support the notion that leptin is a primary promoter of antipsychotic-induced weight gain; however, a secondary perpetuating role cannot be ruled out.

Topics: Adolescent; Adult; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Body Mass Index; Female; Humans; Leptin; Lithium; Male; Middle Aged; Olanzapine; Pirenzepine; Risperidone; Valproic Acid; Weight Gain

Weight gain is a frequent adverse effect associated with lithium use. Leptin is an adipocyte hormone, regulating food intake and energy balance providing the hypothalamus with information on the amount of body fat. Therefore, we planned to evaluate whether lithium administration was associated with weight gain, and leptin levels. The study consisted of 15 consecutive inpatients with bipolar I disorder according to DSM-III-R. The fasting serum leptin levels were measured. The patients were evaluated at baseline and at the eighth week according to the body mass index, weight, Young Mania Rating (YMRS) and Hamilton Depression Rating (HAM-D) scales, and serum leptin levels. With respect to the leptin levels, a significant difference was observed after lithium treatment. There was a significant positive correlation between the changes in leptin levels and the duration of illness. The change in total YMRS scores correlated with change in leptin levels and that in weight. In conclusion, our result suggest that leptin may be associated with lithium-induced weight gain.

Topics: Adult; Bipolar Disorder; Body Mass Index; Diet; Female; Humans; Leptin; Lithium; Male; Psychiatric Status Rating Scales; Weight Gain

Metabolic syndrome (MS) is a growing social, economic, and health problem. MS coexists with nearly half of all patients with affective disorders. This study aimed to evaluate the neurobiological parameters (clinical, anthropometric, biochemical, adipokines levels, and ultrasound of carotid arteries) and their relationship with the development of MS in patients with bipolar disorder. The study group consisted of 70 patients (50 women and 20 men) hospitalized due to episodes of depression in the course of bipolar disorders. The Hamilton Depression Rating Scale was used to assess the severity of the depression symptoms in an acute state of illness and after six weeks of treatment. The serum concentration of adipokines was determined using an ELISA method. The main finding of this study is that the following adipokines correlated with MS in the bipolar depression women group: visfatin, S100B, and leptin had a positive correlation, whereas adiponectin, leptin-receptor, and adiponectin/leptin ratio showed a negative correlation. Moreover, the adiponectin/leptin ratio showed moderate to strong negative correlation with insulin level, BMI, waist circumference, triglyceride level, treatment with metformin, and a positive moderate correlation with HDL. The adiponectin/leptin ratio may be an effective tool to assess MS in depressed female bipolar patients.

Topics: Adipokines; Adiponectin; Bipolar Disorder; Female; Humans; Leptin; Male; Metabolic Syndrome

Topics: Adipokines; Adiponectin; Bipolar Disorder; Body Mass Index; Cholesterol, HDL; Female; Humans; Leptin; Lithium; Male; Metabolic Syndrome; Obesity; Valproic Acid

Patients with bipolar disorder (BD) exhibit individual variability in the treatment outcome, and genetic background could contribute to BD itself and the treatment outcome. Leptin levels significantly change in BD patients treated with valproate (VPA), but whether

Topics: Bipolar Disorder; Gene Frequency; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Leptin; Longitudinal Studies; Polymorphism, Single Nucleotide; Receptors, Leptin

Bipolar disorder (BD) and metabolic disturbance represent a chronic state of low-grade inflammation and corticostriatal circuitry alterations. Herein, we aimed to investigate whether plasma leptin, an adipokine that plays a key role in the interplay of metabolism and inflammation, is associated with corticostriatal connectivity in patients with BD. Twenty-eight BD I patients, 36 BD II patients and 66 healthy controls were enrolled and completed the Hamilton Depression Rating Scale, the Young Mania Rating Scale, and the Recent Life Change Questionnaire. Fasting plasma leptin and C-reactive protein (CRP) levels were measured, and corticostriatal connectivity was examined using functional magnetic resonance imaging (fMRI). The relationships between leptin, CRP and body mass index (BMI) identified in the controls and BD II patients were absent in the BD I patients. We did not find a significant group difference in the leptin level; nevertheless, the negative correlation between leptin level and corticostriatal connectivity (ventrolateral prefrontal cortex and inferior temporal gyrus) observed in the healthy controls was absent in the BD patients. The disproportionate increase in leptin level with increasing BMI in BD indicated a potential inflammatory role of white adipose tissue in BD. Furthermore, higher CRP levels in BD I patients might induce leptin resistance. Collectively, our results implied vulnerability to inflammatory and metabolic diseases in patients with BD, especially BD I.

Topics: Bipolar Disorder; Cerebral Cortex; Humans; Inflammation; Leptin; Magnetic Resonance Imaging; Temporal Lobe

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

A potential role for leptin in the pathophysiology of bipolar disorder (BD) has been proposed. We recently investigated the effects of the tumor necrosis factor-alpha (TNF-α) antagonist infliximab in individuals with bipolar depression. Leptin is known to interact with the TNF-α system. Herein, we aimed to explore infliximab's effects on leptin and its relationship with brain structure and function. Sixty adults with bipolar depression were enrolled in this randomized, double-blind, 12-week clinical trial of adjunctive infliximab (n = 29) and saline control (n = 31), which were administered intravenously at weeks 0, 2, and 6. Plasma concentrations of leptin, TNF-α and soluble TNF receptors (sTNFR) 1 and 2 were assessed at weeks 0, 2, 6, and 12. We observed a significant decrease in leptin levels in infliximab-treated patients, relative to placebo. Infliximab treatment also significantly reduced TNF-α and sTNFR2, but not sTNFR1 levels. Changes in sTNR2 levels at week 6 significantly determined changes in leptin at week 12 in infliximab-, but not placebo-treated participants. Improvements in verbal memory and increases in global cortical volume were associated with reduction in leptin levels in the treatment group. Mediation analysis indicated that cognitive improvement in infliximab-treated patients was mediated by reductions in leptin levels, which in its turn were determined by decreases in sTNR2 levels. In conclusion, infliximab treatment reduced plasma leptin levels in individuals with BD, through modulation of sTNFR2. Decreases in leptin signaling were associated with an increase in global cortical volume and better performance in a verbal memory task.

Topics: Adult; Bipolar Disorder; Cognition; Double-Blind Method; Female; Humans; Inflammation; Infliximab; Leptin; Male; Middle Aged; Random Allocation; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; Tumor Necrosis Factor-alpha

Obesity and weight gain in bipolar disorder (BD) have multifactorial underlying causes such as medication side effects, atypical depressive symptomatology, genetic variants, and disturbances in the neuro-endocrinal system. Therefore, we aim to explore the associations between food craving (FC), clinical parameters, psychotropic medication, and appetite-related hormones. In this cross-sectional investigation, 139 individuals with BD and 93 healthy controls (HC) completed the food craving inventory (FCI). In addition, blood samples (including leptin and acylated ghrelin) were analyzed and sociodemographic and anthropometric data were collected. Individuals with BD reported higher frequencies of total FC as well as craving for fat and fast food than HC. Additionally, we found a significant negative correlation between FC and ghrelin levels in BD. Smokers with BD reported significantly more craving for high fat foods than non-smokers. Age was significantly associated with FC independent of group. Individuals with BD taking olanzapine and quetiapine reported higher frequencies of craving for sweet food, while patients currently taking lithium reported less total FC compared to those without lithium therapy. Likewise, patients currently taking valproate reported less total FC and less craving for sweets than those not taking valproate. FC appears to be of clinical relevance in individuals with BD. Contrary to previous data, this does not seem to be a female phenomenon only and might encompass more than the specific craving for carbohydrates. Although due to the cross sectional design, causality cannot be determined, the association between depressive symptomatology and fast food craving warrants further research.

Topics: Acylation; Adult; Anthropometry; Appetite; Bipolar Disorder; Craving; Cross-Sectional Studies; Fast Foods; Female; Ghrelin; Hormones; Humans; Leptin; Male; Middle Aged; Non-Smokers; Obesity; Smokers; Valproic Acid; Weight Gain; Young Adult

Topics: Adiponectin; Adult; Bipolar Disorder; Case-Control Studies; Comorbidity; Disease Progression; Female; Humans; Leptin; Male; Middle Aged; Obesity

Obesity and metabolic syndrome (MeS) are more frequently observed in bipolar patients than the general population. This may result from the differences of adipocytokines and ghrelin levels in bipolar disorder.. We evaluated the leptin, adiponectin, resistin and ghrelin levels in bipolar patients (n = 30) in manic episode and in a control group (n = 30). After treatment, the same patients were evaluated again during the euthymic episode. We also measured the insulin, glucose, insulin resistance (HOMA), trygliceride (TG), total cholesterol (TCHOL), high density lipoprotein cholesterol (HDL) and low density lipoprotein cholesterol (LDL) in relation to the (MeS).. When controlling for age, BMI and glucose, leptin levels were higher in the bipolar disorder manic episode group (BD-ME) and bipolar euthymic episode group (BD-EE) than the control group; resistin levels were higher in the BD-ME compared to the control group and it had a positive correlation with Young Mania Rating Scale (YMRS). After treatment, ghrelin levels were higher in the BD-EE compared to the BD-ME group. There was no difference among the groups with respect to adiponectin.. The present results point that high leptin, resistin and ghrelin levels may be involved in the early pathophysiological process which can lead to later obesity and MeS in patients with bipolar disorder.

Topics: Adiponectin; Adult; Bipolar Disorder; Blood Glucose; Female; Ghrelin; Humans; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Resistin; Young Adult

Orexigenic and anorexigenic peptides, especially agouti-related protein (AgRP) and leptin, play important roles in the regulation of energy homeostasis in bipolar disorder. AgRP regulates energy metabolism by increasing appetite and decreasing energy expenditure. The resting energy expenditures of patients with manic bipolar disorder are higher than those of controls. Due to the effects of AgRP on energy expenditure and the increased physical activity of manic patients, we hypothesised that serum AgRP levels may be lower in manic patients than in euthymic patients and controls. There was a total of 112 participants, including 47 patients in the manic group, 35 patients in the euthymic group and 30 healthy controls. For this study, serum AgRP, leptin, cholesterol, and cortisol levels were measured and compared between the groups. The serum AgRP, leptin, and cholesterol levels were significantly different between the groups. The serum AgRP levels of manic group were significantly lower than those of euthymic and control groups. The lower serum AgRP levels of manic patients could be indicators of impaired energy homeostasis during manic episodes. Since the serum AgRP levels of manic patients are lower than those of euthymic patients and controls, AgRP could be a state marker for manic episodes.

Topics: Adult; Affect; Agouti-Related Protein; Biomarkers; Bipolar Disorder; Case-Control Studies; Cholesterol; Energy Metabolism; Female; Humans; Leptin; Male; Rest

An increased risk for metabolic syndrome (MS) has been described for people with psychotic and mood disorders. The aim of this study was to determine the influence of valproic acid (VPA) treatment on adiponectin, leptin levels and oxidative stress in bipolar disorder (BD).. Forty patients with BD receiving VPA monotherapy and 20 healthy control subjects were included in this study. BD patients were divided into two groups with and without MS as group 1 and group 2, respectively. Twenty BD patients diagnosed according to the Diagnostic and Statistical Manual for Mental Disorders (DSM IV) were assessed for MS according to the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP III) criteria. Adiponectin, leptin, protein carbonyls, sulfhydryl (-SH) and malondialdehyde (MDA) levels were measured in 40 BD patients and 20 control subjects.. Serum adiponectin levels were significantly lower in group 1 patients than in group 2 and control subjects ( p<.001). Serum leptin levels were significantly higher in group 1 patients than in group 2 and control subjects ( p<.001). Serum -SH levels were significantly lower in group 2 patients than in group 1 ( p<.001) and control subjects ( p<.05). Serum carbonyl levels were significantly higher in group 1 and group 2 patients than in control subjects ( p<.001). Serum MDA levels were significantly higher in group 1 patients than in group 2 and control subjects ( p<.001).. These results provide further evidence that VPA treatment for patients with BD contributed to the metabolic disturbances, such as the decreased serum adiponectin and -SH levels, as well as the increased serum leptin, MDA and carbonyl levels.

Topics: Adiponectin; Adult; Bipolar Disorder; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Oxidative Stress; Risk Factors; Valproic Acid

This longitudinal study aimed to investigate the associations between the polymorphisms of guanine nucleotide-binding protein subunit β-3 (GNB3) C825T and metabolic disturbance in bipolar II disorder (BP-II) patients being treated with valproate (VPA). A 100 BP-II patients received a 12-week course of VPA treatment, and their body weight and metabolic indices were measured. At baseline, the GNB3 C825T polymorphisms were associated with the triglyceride level (P=0.032) in BP-II patients. During the VPA treatment course, the polymorphisms were not only associated with body mass index (BMI) and waist circumference (P-values=0.009 and 0.001, respectively), but also with total cholesterol, triglyceride, low-density lipoprotein and leptin levels (P-values=0.004, 0.002, 0.031 and 0.015, respectively). Patients with the TT genotype had a lower BMI, smaller waist circumference, and lower levels of lipids and leptin than those with the CT or CC genotypes undergoing the VPA treatment course.

Topics: Adult; Antimanic Agents; Biomarkers; Bipolar Disorder; Body Mass Index; Case-Control Studies; Dyslipidemias; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Heterotrimeric GTP-Binding Proteins; Heterozygote; Homozygote; Humans; Leptin; Lipids; Longitudinal Studies; Male; Middle Aged; Obesity; Pharmacogenomic Variants; Phenotype; Polymorphism, Single Nucleotide; Risk Factors; Time Factors; Treatment Outcome; Valproic Acid; Waist Circumference; Young Adult

Replicated evidence indicates that individuals with BD are differentially affected by metabolic comorbidities and that its occurrence is a critical mediator and/or moderator of BD outcomes. This study aimed to explore the role of adipokines on bipolar disorder (BD) course and its relationship with metabolic comorbidities (i.e. type 2 diabetes mellitus, obesity). We measured plasma levels of adiponectin and leptin, as well as anthropometric and metabolic parameters of 59 patients with BD and 28 healthy volunteers. Our results showed that, in female participants, adiponectin was lower in individuals with BD, relative to healthy controls (p = 0.017). In the BD population, adiponectin levels were correlated with fasting glucose (r = -0.291, p = 0.047), fasting insulin (r = -0.332, p = 0.023), C-peptide (r = 0.040, p = 0.040), homeostatic model assessment-insulin resistance (r = -0.411, p = 0.004), HDL (r = 0.508, p < 0.001), VLDL (r = -0.395, p = 0.005) and triglycerides (r = -0.310, p = 0.030). After adjustment for age, gender and BMI, individuals with BD and low adiponectin levels (i.e. < 7.5 μg/ml), had a higher number of mood episodes (p < 0.001), lower number of psychiatric hospitalizations (p = 0.007), higher depressive symptoms (p < 0.001) and lower levels of functioning (p = 0.020). In conclusion, adiponectin levels, either directly or as a proxy of metabolic dysfunction, is independently associated with an unfavorable course of illness in BD.

Topics: Adiponectin; Adult; Bipolar Disorder; Diabetes Mellitus, Type 2; Female; Humans; Leptin; Male; Middle Aged; Obesity

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

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

Patients with bipolar disorder (BD) are more frequently affected by metabolic syndrome (MetS) than the general population, but the neurobiological correlates underlying such association are still not clarified and few studies in BD have evaluated the role of regulators of lipid and glucose metabolism. The present study was aimed to investigate putative alterations in markers linked to metabolic dysfunctions as C-peptide, Ghrelin, GIP, GLP-1, Glucagon, Insulin, Leptin, PAI-1 (total), Resistin and Visfatin in a sample of BD patients compared to controls. Furthermore, associations between changes of metabolic markers and relevant clinical features, such as severity of symptomatology, number and type of past mood episodes, drug treatments and presence/absence of metabolic alterations (MetS, diabetes and cardiovascular disease) were analyzed. A total of 57 patients with BD and 49 healthy controls were recruited. The main results showed lower serum levels of Glucagon, GLP-1, Ghrelin, and higher levels of GIP in BD patients as compared to controls (p = 0.018 for Ghrelin; p < 0.0001 for Glucagon; p < 0.0001 for GLP-1; p < 0.0001 for GIP). Further, Glucagon and GLP-1 levels were significantly associated with the number of past mood episodes. These findings support the hypothesis that alterations in Glucagon, GLP-1, GIP and Ghrelin might be involved in BD pathogenesis and might represent useful biomarkers for the development of preventive and personalized therapies in this disorder.

Topics: Biomarkers; Bipolar Disorder; Blood Glucose; C-Peptide; Case-Control Studies; Female; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon; Glucagon-Like Peptide 1; Humans; Insulin; Leptin; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Plasminogen Activator Inhibitor 1; Resistin

Obesity is more frequent in bipolar disorder. Adipokines are associated with depression and obesity via the inflammatory process. Twenty-six DSM-IV patients with BD and 39 controls were enrolled to assess the relationship between serum leptin and adiponectin with hippocampal volumes. Among patients, there was a significant negative correlation between right hippocampal volume and serum leptin levels. This result sum for the hypothesis of a pro-inflammatory state associated with BD and the prevalent co-morbid obesity.

Topics: Adipokines; Adiponectin; Adult; Biomarkers; Bipolar Disorder; Female; Hippocampus; Humans; Leptin; Male; Middle Aged; Organ Size; Pilot Projects

Lithium, a first line treatment for bipolar disorder (BD), has been associated with significant weight gain, but the mechanisms underlying this phenomenon are still unclear. It has been suggested that changes in production/release of adipokines - molecules secreted by adipose tissue presenting anti-inflammatory (adiponectin) and pro-inflammatory (leptin, resistin) properties - might be implicated. Adiponectin, resistin and leptin were assessed in 25 acutely depressed BD individuals (88% medication-free and 68% treatment-naive) at baseline and after 6 weeks of lithium therapy, and in 23 healthy controls matched by age. The 21-item Hamilton Depression Rating Scale was used to assess depression severity. Levels of adiponectin significantly decreased after lithium monotherapy, while the levels of resistin and leptin remained stable after the follow-up period. Adipokine levels during depressive episodes in BD did not differ compared to controls. Pretreatment levels of leptin were higher in remitters and changes in resistin levels were negatively correlated to improvement of depressive symptoms with lithium. Our findings shed light in this pathophysiological process, which might be associated with metabolic syndrome, inflammation and other medical comorbidities in BD.

Topics: Adiponectin; Adult; Antipsychotic Agents; Bipolar Disorder; Female; Humans; Leptin; Lithium; Male; Resistin; Young Adult

A proinflammatory phase with various immunomodulatory mechanisms has been noted in bipolar mania and major depression. Weight gain and increased production of leptin may be associated with immunomodulation and insulin resistance in bipolar disorder. However, immunomodulation and its linkage with leptin and insulin in the depressive episode of bipolar disorder remain unclear. We investigated alterations in inflammatory markers and their relationship with leptin and insulin levels in patients with phases of bipolar disorder from acute depression to full remission.. Thirty-two physically healthy bipolar I depressed patients aged <45 years and age- and sex-matched healthy controls participated in this study. We measured their circulating levels of leptin, insulin, high-sensitivity C-reactive protein (hs-CRP), soluble interleukin-2 receptor (sIL-2R), soluble interleukin-6 receptor (sIL-6R), soluble tumor necrosis factor receptor 1 (sTNF-R1), and interleukin-1 receptor antagonist (IL-1Ra) in three phases, i.e., acute depression, subsequent partial remission, and full remission.. In acute depression, subsequent partial remission, and full remission, patients with bipolar disorder had significantly higher mean levels of hs-CRP, IL-1Ra, sTNF-R1, and sIL-2R compared with control subjects. The IL-1Ra and sTNF-R1 levels in various affective phases were significantly correlated to body mass index, leptin level, circulating lipids, and medication status. The sIL-2R levels in the three affective phases were all independent of other inflammatory markers and clinical and laboratory variables. Patients showed no alteration of sIL-6R levels through the depressive episode.. Patients with bipolar disorder in depressive episodes may exhibit persistent inflammation with elevated levels of hs-CRP, IL-1Ra, sTNF-R1, and sIL-2R but not sIL-6R from the acute phases to full remission. Only sIL-2R production seems to be tightly linked with the pathophysiology of bipolar depression and is independent of insulin and leptin levels.

Topics: Adult; Bipolar Disorder; Body Weight; C-Reactive Protein; Case-Control Studies; Cytokines; Disease Progression; Female; Humans; Inflammation; Insulin; Leptin; Male; Psychiatric Status Rating Scales; Recurrence; Smoking; Statistics as Topic; Young Adult

Patients with bipolar disorder are at a high risk for becoming obese. Adipokines are associated with depression and obesity via the inflammatory process. However, few studies have investigated the associations between depression and leptin, adiponectin and resistin levels in patients with bipolar disorder. We explored the associations between serum levels of leptin, adiponectin and resistin and mood and metabolic status in patients with bipolar disorder.. Body mass index (BMI) and serum leptin, adiponectin and resistin levels were assessed in 94 Korean patients with bipolar disorder. The Hamilton Rating Scale for Depression-17 and the Young Mania Rating Scale were used to assess mood state.. Leptin (17.19 ± 13.08 vs. 10.47 ± 10.05 ng/ml; p = 0.008) and adiponectin (10.51 ± 8.37 vs. 5.91 ± 2.82 μg/ml; p = 0.001) levels were higher in female than in male patients. After adjusting for mood state, age, smoking, alcohol habit, and BMI in a multivariate analysis of covariance (MANCOVA), leptin (17.86 ± 1.22 vs. 10.05 ± 1.48 ng/ml; p < 0.001) and adiponectin (10.18 ± 0.98 vs. 6.40 ± 1.19 μg/ml; p = 0.027) levels were still higher in female than in male patients. Compared to euthymic patients, depressed patients had higher levels of leptin (17.37 ± 14.69 vs. 11.65 ± 9.04 ng/ml; p = 0.024), but there was no significant difference in adiponectin and resistin levels between the two groups. After adjusting for age, gender and BMI in the MANCOVA, leptin levels were also significantly higher in depressed (16.78 ± 1.34 ng/ml) than in euthymic patients (10.73 ± 1.22 ng/ml; p = 0.001).. Leptin is closely associated with the regulation of mood and metabolic homeostasis in patients with bipolar disorder.

Topics: Adiponectin; Adult; Affect; Bipolar Disorder; Depression; Female; Homeostasis; Humans; Leptin; Male; Resistin

Weight gain and increased production of leptin may be associated with immuno-modulation and insulin resistance in bipolar disorder. The links among inflammatory markers, leptin, and insulin of bipolar patients from acute mania to full remission remain unclear.. Thirty-three healthy, bipolar I patients under 45 years of age were enrolled. We measured the circulating levels of high-sensitivity C-reactive protein (hs-CRP), anti-inflammatory mediators (interleukin-1 receptor antagonist [IL-1Ra] and soluble tumor necrosis factor receptor 1 [sTNF-R1]), leptin, and insulin during acute mania and subsequent partial and full remission. The results were compared with 33 age- and gender-matched healthy subjects.. The levels of IL-1Ra and hs-CRP of bipolar patients in both acute mania and partial remission were significantly higher than their levels of control subjects. The hs-CRP level of bipolar patients was also elevated in full remission. The elevation of IL-1Ra and hs-CRP levels in acute mania was independent of each other. They were also independent of the body mass index (BMI) and levels of leptin and insulin measurements. The levels of leptin were all positively associated with insulin levels in the normal subjects and bipolar patients in three phases. However, a significant relationship between leptin and immunoparameter was only seen in full remission with sTNF-R1 (r=0.51). Furthermore, IL-1Ra was inversely correlated with sTNF-R1 (r=-0.37, p<0.05) during partly remission, and while levels of IL-1Ra tended to normalize when patients remitted, levels of hs-CRP and sTNF-R1 showed the opposite trend.. Activated inflammation was found in acute mania, as evidenced by high levels of IL-1Ra, hs-CRP, and sTNF-R1. The production of leptin may be more tightly linked to insulin than the immunomodulators. Chronic inflammation may exist in bipolar patients and is reflected by elevations of IL-1Ra and hs-CRP levels in acute mania and persistent higher hs-CRP in full remission.

Topics: Adult; Biomarkers; Bipolar Disorder; Body Mass Index; C-Reactive Protein; Female; Humans; Inflammation; Insulin; Insulin Resistance; Interleukin 1 Receptor Antagonist Protein; Leptin; Male; Receptors, Tumor Necrosis Factor, Type I; Remission Induction; Young Adult

Valproate (VPA) is a mood stabilizer for treating patients with bipolar disorder (BD). It may cause metabolic abnormalities in certain bipolar patients. However, the genetic factors that influence the susceptibility remain unclear. Genetic polymorphism of the G-protein β3 subunit (GNB3) is reported to be associated with metabolic phenotypes. In the current study, we investigated the possible associations between the GNB3 variation and VPA-induced metabolic abnormalities.. Subjects (n = 96) who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for BD were recruited from the National Cheng Kung University Hospital. Their metabolic indices were measured.. The variation of GNB3 C825T showed an association with higher plasma total cholesterol (P = 0.037), triglyceride (P = 0.014), and leptin (P < 0.001) levels in BD patients treated with VPA. After adjusting for age, sex, types of BDs, and serum concentration of VPA, the variation of GNB3 C825T remained significantly associated with the levels of serum leptin and body mass index (BMI; P < 0.001 and P = 0.030, respectively). In addition, the GNB3 C825T showed significant drug-single-nucleotide polymorphism interactions with insulin levels (P = 0.033), triglyceride levels (P = 0.013), leptin levels (P = 0.013), and BMI (P = 0.018). These results indicated that the T allele may be associated with lower serum leptin levels and BMI in BD patients treated with VPA.. The current study provides evidence that BD patients who are T allele carriers of the GNB3 C825T polymorphism have a lower risk for VPA-induced metabolic abnormalities. Further studies about the underlying mechanisms of G protein in VPA-induced metabolic abnormalities are warranted.

Topics: Adult; Alleles; Bipolar Disorder; Body Mass Index; Female; Genetic Carrier Screening; Heterotrimeric GTP-Binding Proteins; Humans; Leptin; Male; Middle Aged; Polymorphism, Single Nucleotide; Protein Subunits; Valproic Acid; Young Adult

Leptin dysregulation has been implicated in the body weight gain and metabolic dysfunction observed with the second generation antipsychotic drugs (SGAD) olanzapine and clozapine.. This study quantified the frequency of subjects with abnormal correlation between leptin and the body mass index controlling for gender (defined as being out of the upper or lower 95% confidence interval in the regression line when combining each group with the drug-free subjects) after prolonged treatment with olanzapine (n=126), clozapine (n=62), first generation antiypsychotics (n=91), other SGAD (n=22), other psychotropic drugs (n=65) and drug-free subjects (n=229).. None of the analysis was significant (p>0.05). In fact, in 17 out of 20 comparisons, the drug-free group had numerically higher frequencies of outliers than the corresponding treatment group. There were 28 outliers (4.7% of the total sample). In agreement with previous studies, cross-sectional analysis did not report gross alterations in serum leptin levels during olanzapine or clozapine administration.. Longitudinal studies should focus on leptin regulation early on treatment, on the frequency of abnormal leptin receptor sensitivity and/or specific polymorphisms in the leptin allele and on several confounding factors in order to design personalized preventive and therapeutic measures.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Body Mass Index; Body Weight; Clozapine; Cross-Sectional Studies; Female; Humans; Insulin Resistance; Leptin; Male; Mental Disorders; Middle Aged; Olanzapine; Outliers, DRG; Receptors, Leptin; Schizophrenia; Sex Factors; Weight Gain

Hyperinsulinaemia, a pre-clinical condition which is considered to predict insulin resistance and metabolic syndrome, has not been sufficiently investigated in bipolar disorder, despite evidence to suggest that bipolar patients are at risk of developing insulin resistance. This study was set out to determine the alteration in fasting insulin levels and evaluate the factors associated with hyperinsulinaemia during manic episodes. Measurements were taken of the fasting plasma insulin and leptin levels, as well as the body mass index (BMI), amongst 42 physically healthy bipolar I manic (DSM-IV) patients aged < or =45 with Young Mania Rating Scale (YMRS) scores of > or =26. These were then compared with their values in subsequent remission (YMRS < or =12). A total of 14 patients (33.3%) in acute mania and 30 patients (71.4%) in subsequent remission met the Taiwanese criteria for hyperinsulinaemia of > or =8.7 microIU/ml for men, and > or =11.3 microIU/ml for women. Multiple analyses were then undertaken, without correction, as the exploratory analyses. The measurement, by logistic regression, of the use of propranolol in remission (odds ratio [OR]=10.04, 95% confidence interval [95% CI]=1.03-97.96) and the increase in BMI (OR=1.35, 95% CI=1.01-1.80) were found to have independent associations with hyperinsulinaemia in subsequent remission. Our results suggest that medicated bipolar manic patients are vulnerable to hyperinsulinaemia in early remission, particularly those gaining bodyweight or those using beta-adrenoceptor antagonist (beta-blockers), irrespective of the types of mood stabilizers or antipsychotics used.

Topics: Acute Disease; Adrenergic beta-Antagonists; Adult; Bipolar Disorder; Body Mass Index; Female; Humans; Hyperinsulinism; Insulin; Leptin; Male; Propranolol; Psychiatric Status Rating Scales

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

Low cholesterol levels have been reported in patients with manic episodes. Leptin seems to be strongly associated with lipid metabolism. In the present study, therefore, serum total cholesterol and leptin levels were compared in 16 patients with manic episodes, 16 with bipolar I disorder in full remission and 16 healthy controls. The serum total cholesterol and leptin levels were measured and Young Mania Rating (YMRS) and Hamilton Depression Rating Scales (HAM-D) were administered for each subject. Both the patients with manic episodes and the patients with bipolar I disorder in full remission had markedly low serum cholesterol and leptin levels compared with controls, though the difference was more obvious in patients with manic episodes. In addition, there were negative correlations between YMRS scores and serum cholesterol or leptin levels in the patients with manic episodes. Our results suggest that the patients with manic episodes and those with bipolar I disorder in full remission seem to be associated with decreased serum cholesterol and leptin levels.

Topics: Adolescent; Adult; Bipolar Disorder; Body Mass Index; Case-Control Studies; Cholesterol; Female; Humans; Leptin; Male; Psychiatric Status Rating Scales

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