leptin and Mental-Disorders

Insulin and leptin are classically regarded as peptide hormones that play key roles in metabolism. In actuality, they serve several functions in both the periphery and central nervous system (CNS). Likewise, insulin and leptin resistance can occur both peripherally and centrally. Metabolic disorders such as diabetes and obesity share several key features including insulin and leptin resistance. While the peripheral effects of these disorders are well-known (i.e. cardiovascular disease, hypertension, stroke, dyslipidemia, etc.), the CNS complications of leptin and insulin resistance have come into sharper focus. Both preclinical and clinical findings have indicated that insulin and leptin resistance are associated with cognitive deficits and neuropsychiatric diseases such as depression. Importantly, these studies also suggest that these deficits in neuroplasticity can be reversed by restoration of insulin and leptin sensitivity. In view of these observations, this review will describe, in detail, the peripheral and central functions of insulin and leptin and explain the role of insulin and leptin resistance in various metabolic disorders, cognition, and neuropsychiatric diseases.

Topics: Animals; Cognitive Dysfunction; Humans; Insulin; Insulin Resistance; Leptin; Mental Disorders; Metabolic Diseases

The adipocyte-derived hormone leptin is an important regulator of body weight and metabolism through activation of brain leptin receptors expressed in regions such as the hypothalamus. Beyond these well described and characterized activities of leptin in the hypothalamus, it is becoming increasingly clear that the central activities of leptin extend to the hippocampus. Indeed, leptin receptors are expressed in the hippocampus where these receptors are proposed to mediate various aspects of hippocampal synaptic plasticity that ultimately impact cognitive function. This concept is supported by studies demonstrating that leptin promotes hippocampal-dependent learning and memory, as well as studies indicating that leptin resistance is associated with deficits in hippocampal-dependent behaviors and in the induction of depressive-like behaviors. The effects of leptin on cognitive/behavioral plasticity in the hippocampus may be regulated by direct activation of leptin receptors expressed in the hippocampus; additionally, leptin-mediated activation of synaptic networks that project to the hippocampus may also impact hippocampal-mediated behaviors. In view of these previous observations, the goal of this review will be to discuss the mechanisms through which leptin facilitates cognition and behavior, as well as to dissect the loci at which leptin resistance leads to impairments in hippocampal synaptic plasticity, including the development of cognitive deficits and increased risk of depressive illness in metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM).

Topics: Animals; Hippocampus; Humans; Leptin; Mental Disorders; Signal Transduction

Receptors of leptin, the prototypical adipokine, are expressed throughout the cortex and several other areas of the brain. Although typically studied for its role in energy intake and expenditure, leptin plays a critical role in many other neurocognitive processes and interacts with various other hormones and neurotransmitters to perform these functions. Here, we review the literature on how leptin influences brain development, neural degradation, Alzheimer's disease, psychiatric disorders, and more complicated cognitive functioning and feeding behaviors. We also discuss modulators of leptin and the leptin receptor as they relate to normal cognitive functioning and may mediate some of the actions of leptin in the brain. Although we are beginning to better understand the critical role leptin plays in normal cognitive functioning, there is much to be discovered.

Topics: Alzheimer Disease; Animals; Brain; Cognition; Humans; Leptin; Mental Disorders; Receptors, Leptin

Leptin has long been associated with metabolism as it is a critical regulator of both food intake and energy expenditure, but recently, leptin dysregulation has been proposed as a mechanism of psychopathology. This review discusses the evidence supporting a role for leptin in mental health disorders and describes potential mechanisms that may underlie this association. Leptin plays a critical role in pregnancy and in fetal growth and development. Leptin's role and profile during development is examined in available human studies, and the validity of applying studies conducted in animal models to the human population are discussed. Rodents experience a postnatal leptin surge, which does not occur in humans or larger animal models. This suggests that further research using large mammal models, which have a leptin profile across pregnancy and development similar to humans, are of high importance. Maternal obesity and hyperleptinemia correlate with increased leptin levels in the umbilical cord, placenta, and fetus. Leptin levels are thought to impact fetal brain development; likely by activating proinflammatory cytokines that are known to impact many of the neurotransmitter systems that regulate behavior. Leptin is likely involved in behavioral regulation as leptin receptors are widely distributed in the brain, and leptin influences cortisol release, the mesoaccumbens dopamine pathway, serotonin synthesis, and hippocampal synaptic plasticity. In humans, both high and low levels of leptin are reported to be associated with psychopathology. This inconsistency is likely due to differences in the metabolic state of the study populations. Leptin resistance, which occurs in the obese state, may explain how both high and low levels of leptin are associated with psychopathology, as well as the comorbidity of obesity with numerous mental illnesses. Leptin resistance is likely to influence disorders such as depression and anxiety where high leptin levels have been correlated with symptomatology. Schizophrenia is also associated with both low and high leptin levels. However, as anti-psychotics pharmacotherapy induces weight gain, which elevates leptin levels, drug-naïve populations are needed for further studies. Elevated circulating leptin is consistently found in childhood neurodevelopmental disorders including autism spectrum disorders and Rhett disorder. Further, studies on the impact of leptin and leptin resistance on psychopathology and neurodevelopmental disorder

Topics: Animals; Brain; Female; Humans; Leptin; Mental Disorders; Obesity; Pregnancy; Prenatal Exposure Delayed Effects

To review the literature regarding the role of leptin in psychiatric disorders.. A PubMed search was undertaken using the following keywords: leptin, psychosis, affective disorders, alcohol, psychiatry, depression, dementia, and eating disorders. The articles were restricted to the English language.. The role of leptin in psychiatric populations has been the subject of increasing investigation. Basic science and clinical observations support a role for leptin in mediating cognition and reward processes. The role of leptin in psychiatric illnesses characterized by cognitive deficits has gained increased attention in recent years. Leptin deficiency and resistance have also been associated with eating disorders as well as affective, alcohol dependence, and psychotic disorders. The mechanisms underlining these associations remain to be determined.. Clinical research suggests an important role of leptin in psychiatric illnesses. Given the morbidity associated with mental illness, clinical research on the role of leptin and related novel therapeutic modalities is needed.

Topics: Brain; Brain Chemistry; Cognition; Female; Humans; Learning; Leptin; Male; Mental Disorders; Nootropic Agents; Receptors, Leptin; Reward

We review here our latest results regarding short- and long-term effects of a neonatal maternal deprivation (MD) stress [24h at postnatal day (PND) 9] on diverse psychoneuroimmunoendocrine parameters, pointing out the existence of numerous sexual dimorphisms. Behavioral changes observed in MD animals might be at least in part attributable to neurodevelopmental effects of MD-induced elevated corticosterone levels. Our findings of short-term effects of MD on hippocampal and cerebellar neurons and glial cells appear to support this hypothesis. However, it is important to note that these cellular effects were more marked in males than in females. Moreover, in analyzing the effects of this neonatal stress on the endocannabinoid system (hippocampal endocannabinoid levels and CB1 receptors) we have also found that males were more affected by MD. Since all these sexual dimorphisms were found at an early neonatal age (PND 13), they are attributable to organizational effects of gonadal steroids. We discuss the potential implications of the elevated corticosterone and decreased leptin levels shown by MD animals in their diverse functional alterations, including the above mentioned neural effects as well as the intriguing persistent deficit in their immunological system. We also emphasize the necessity of analyzing the important influence of sex as regards the specific consequences of early life stress.

Topics: Animals; Animals, Newborn; Behavior, Animal; Body Weight; Brain; Cannabinoid Receptor Modulators; Chemotaxis; Corticosterone; Disease Models, Animal; Humans; Leptin; Lymphocyte Activation; Maternal Deprivation; Mental Disorders; Receptors, Cannabinoid; Sex Characteristics; Stress, Psychological

It is suggested that the symptoms of anorexia nervosa are physiological responses to starvation. There is no evidence of a neural or non-neural dysfunction that predisposes women for anorexia nervosa and the endocrine and psychological consequences of starvation are reversed once patients have re-learnt how to eat and regained a normal body weight. Because variability in the supply of food may be a common evolutionary condition, it is more likely that body weight is variable than constant in normal circumstances. The role of the neuroendocrine system in times of feast and famine is to allow the individual to adopt behavioral strategies as needed rather than maintaining body weight homeostasis. Treatment of anorexic patients should aim at reducing their high level of physical activity in order to facilitate eating.

Topics: Anorexia Nervosa; Feeding and Eating Disorders; Female; Humans; Leptin; Mental Disorders; Neurosecretory Systems; Oligopeptides; Pyrrolidonecarboxylic Acid; Starvation

Anorexia is one of the common symptoms caused by various psychiatric disorders. Increasing evidence indicates that neuroleptics can induce weight gain, obesity, and diabetes mellitus. However, the mechanisms underlying these conditions have not been fully elucidated. In this review, we describe molecular neuroanatomic aspects of current biology of energy homeostasis that would help to address the psychiatric issues noted above, focusing on the central leptin/melanocortin system. An adipocyte-derived hormone, leptin acts on the arcuate hypothalamic nucleus (Arc) to inhibit feeding behavior and simultaneously to promote energy expenditure. Leptin activates Arc neurons producing alpha-melanocyte-stimulating hormone (alpha-MSH) and inhibits those producing agouti-related protein (AgRP). alpha-MSH is an endogenous agonist for the melanocortin-4 receptor (MC4-R) that is expressed exclusively in the central nervous system (CNS), whereas AgRP acts as a MC4-R antagonist. It is also established that MC4-R blockade produces an over-eating/obesity syndrome in rodents and humans. Thus, MC4-R-expressing neurons are downstream targets of leptin. Of interest, MC4-R-positive neurons densely populate in CNS sites critical for energy homeostasis and associated with psychiatric disorders, including the paraventricular hypothalamic nucleus and central amygdaloid nucleus. In addition, Arc alpha-MSH neurons receive serotonergic inputs from raphe neurons. Finally, an AgRP gene polymorphism has been associated with anorexia nervosa. These findings suggest that the central melanocortin system is a target for psychiatry.

Topics: Agouti-Related Protein; alpha-MSH; Amygdala; Animals; Antipsychotic Agents; Energy Intake; Energy Metabolism; Feeding and Eating Disorders; Humans; Intercellular Signaling Peptides and Proteins; Lateral Thalamic Nuclei; Leptin; Mental Disorders; Neurons; Polymorphism, Single Nucleotide; Proteins; Receptor, Melanocortin, Type 4; Receptors, Cell Surface; Receptors, Leptin; Serotonin

As early as the beginning of the 20th century, changes in appetite and weight were recognized as important symptoms of severe psychiatric disorders. Particularly in the last decade, understanding of the regulation of appetite and weight has made major progress. In this context, the discovery of the adipose tissue hormone leptin, which signals the size of the peripheral fat stores to the CNS, was crucial. In addition, leptin is also involved in a number of CNS networks regulating behavior and thus of great importance for the pathophysiology of psychiatric disorders. Apart from sexual behavior, those networks include motor activity, sleep, and cognition. Moreover, leptin seems to be involved in the development and maturation of the brain. The present paper summarizes current studies which suggest that, in psychiatric disorders, leptin could be of importance not only for disease-associated or drug-related changes in appetite and weight but also for alterations in behavior and cognition.

Topics: Alcoholism; Animals; Appetite; Body Weight; Brain; Cognition; Humans; Leptin; Mental Disorders; Motor Activity; Schizophrenia; Sexual Behavior; Sleep

Adverse effects of antipsychotics (AP) contribute to cardiovascular disease (CVD) risk in patients with severe mental disorders (SMD). We investigated sex differences in AP-related CVD risk factors and the role of metabolic hormones.. Patients with SMD (N = 1791) receiving AP with different CVD risk were recruited and grouped into olanzapine and/or clozapine (N = 532), other APs (N = 744) or no use of APs (N = 515). Associations between CVD risk factor (total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), body mass index (BMI), glucose, blood pressure), sex and AP groups were tested in multiple linear regression with interactions, controlling for diagnostic group, lifestyle factors, polypharmacy, age and ethnicity. Next, we tested associations between sex differences in AP-related CVD risk factors and metabolic regulatory hormones.. AP groups and male sex were significantly associated with higher levels of LDL-C, TG and BMI, and lower levels of HDL-C. Significant interaction between AP groups and sex were found for TG (p = 0.017), with larger increase in males. Serum adiponectin, insulin, cortisol, leptin, testosterone, free thyroxine and thyroid-stimulating hormone (TSH) were associated with TG levels (all p ≤ 0.001), and a significant interaction with sex for insulin (p = 0.005), cortisol (p = 0.016), leptin (p < 0.001) and TSH (p = 0.001).. We found more severe AP-related CVD risk factors in male patients with SMD. The male-dependent increase in TG levels was associated with leptin, insulin, cortisol and TSH levels. Clinicians treating patients with SMD should be aware of increased vulnerability for AP-related lipid abnormalities in males.

Topics: Antipsychotic Agents; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Female; Heart Disease Risk Factors; Humans; Hydrocortisone; Insulin; Leptin; Male; Mental Disorders; Sex Factors; Thyrotropin; Triglycerides

Athlete health, training continuity and performance can be impeded as a result of Relative Energy Deficiency in Sport (RED-S). Here we report the point prevalence of symptoms described by the RED-S model in a mixed-sport cohort of Australian female athletes.. Elite and pre-elite female athletes (n=112) from eight sports completed validated questionnaires and underwent clinical assessment to assess the point prevalence of RED-S symptoms. Questionnaires included the Depression, Anxiety and Stress Questionnaire (DASS-21), Generalized Anxiety Disorder (GAD-7), Center for Epidemiological Studies Depression Scale (CES-D), SCOFF questionnaire for disordered eating, Low Energy Availability in Females Questionnaire (LEAF-Q), and a custom questionnaire on injury and illness. Clinical assessment comprised resting metabolic rate (RMR) assessment, dual-energy X-ray absorptiometry-derived body composition and bone mineral density, venous and capillary blood samples, and the Mini International Neuropsychiatric Interview (MINI 7.0.2). Descriptive prevalence statistics are presented.. Almost all (80%) participants (age 19 (range 15-32) years; mass 69.5±10.3 kg; body fat 23.1%±5.0%) demonstrated at least one symptom consistent with RED-S, with 37% exhibiting between two and three symptoms. One participant demonstrated five symptoms. Impaired function of the immunological (28%, n. Symptoms described by the RED-S model were prevalent in this cohort, supporting the need for improved awareness, monitoring and management of these symptoms in this population.

Topics: Absorptiometry, Photon; Adolescent; Adult; Australia; Basal Metabolism; Biomarkers; Cardiorespiratory Fitness; Competitive Behavior; Cross-Sectional Studies; Female; Health Surveys; Humans; Interview, Psychological; Leptin; Mental Disorders; Prevalence; Relative Energy Deficiency in Sport; Risk Factors; Young Adult

The prevalence of obesity, metabolic syndrome and type 2 diabetes mellitus is increased among patients with severe mental disorders, and particularly use of second generation antipsychotic drugs is associated with metabolic side effects. Antipsychotics have been found to alter levels of adipokines which regulate insulin sensitivity, but their role in antipsychotic-associated insulin resistance is not established, and it is unclear whether adipokines affect insulin resistance independently of body mass index (BMI).. We included 1050 patients with severe mental disorders and 112 healthy controls aged 18-65 years from the Oslo area, Norway. Clinical variables, BMI and use of medication were assessed, fasting blood samples were obtained for calculation of the leptin/adiponectin ratio (L/A ratio) and estimate of insulin resistance using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Case-control analyses were followed by mediation analyses to evaluate the possible direct effect of antipsychotics on HOMA-IR and indirect effect mediated via the L/A ratio. This was performed both with and without adjustment for BMI, in the total sample and in an antipsychotic monotherapy subsample (N = 387).. BMI, L/A ratio and HOMA-IR were significantly higher in patients than controls (p < 0.001-p = 0.01). There was a significant direct effect from use of antipsychotics in general on HOMA-IR both without (b = 0.03, p = 0.007) and with adjustment for BMI (b = 0.03, p = 0.013), as well as a significant mediating effect via L/A ratio both without (b = 0.03, p < 0.001) and with adjustment for BMI (b = 0.01, p = 0.041). Use of olanzapine (b = 0.03, p < 0.001) or aripiprazole (b = 0.04, p < 0.001) in monotherapy showed significant effects on HOMA-IR mediated via L/A ratio.. The study suggests that use of antipsychotics may alter adipokine levels, and that increased L/A ratio may play a role in the development of insulin resistance associated with use of antipsychotics also independently of BMI.

Topics: Adipokines; Adult; Antipsychotic Agents; Blood Glucose; Body Mass Index; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Mental Disorders; Metabolic Syndrome; Middle Aged; Norway; Obesity

Leptin is essential for the control of energy homeostasis and eating behaviour. We investigated potential associations between serum leptin levels and food addiction in adolescent psychiatric inpatients (n = 228). The most frequent psychiatric diagnoses were mood disorders, anxiety disorders, and substance use disorders. More than three quarters of the study group suffered from more than one psychiatric disorder. Food addiction was assessed with the Yale Food Addiction Scale. Leptin was determined in serum. Analyses were conducted for the whole body weight range and for distinct weight categories to evaluate a potential impact of known nonlinearity between leptin levels and satiety due to leptin resistance in obese. A weak negative association between food addiction and leptin in normal weight patients (ß = -0.11, p = .022) was detected. In contrast, food addiction was associated with a significantly higher serum leptin (ß = 0.16. p = .038) in overweight patients. Food addiction in normal weight patients might be associated with restrained eating, previously shown to involve reduced leptin levels. The small positive association of food addiction with higher serum leptin in overweight patients might reflect leptin resistance and overeating.

Topics: Adolescent; Body Weight; Female; Food Addiction; Humans; Inpatients; Leptin; Male; Mental Disorders

To evaluate body mass index (BMI) and its correlate plasma leptin levels that have been associated with psychiatric morbidity and suicidal behaviour, in relation to clinical features in psychiatric patients after a suicide attempt.. BMI and plasma leptin were assessed in 198 patients (66 males, age range of 21 to 80 years) who were admitted to the hospital after a suicide attempt, 98 with major depressive disorder, 28 with bipolar disorder, 30 with psychosis, and 42 with personality or adjustment disorder, compared to data of 134 healthy subjects, and evaluated in relation to gender, diagnosis, mode of attempt, and pharmacological treatment before attempt. The ratio leptin/BMI was used as a measure of adipocyte leptin secreting activity.. Drugs taken for treatment before attempt, among them atypical neuroleptics, were not associated either to BMI or to plasma leptin. The positive correlation between BMI and leptin was significant in all groups. Compared to same gender controls, significant differences were found only for female patients, namely higher BMI for patients with psychosis and patients with bipolar disorder, while leptin/BMI ratio was higher only in females with bipolar disorder.. BMI and plasma leptin in psychiatric suicide attempters are elevated in certain diagnostic groups in females, not related to previous pharmacologic treatment. The lack of a control group without a history of suicide attempts does not allow the attribution of enhanced leptin secreting activity found in female bipolar attempters specifically to suicidal behavior or to the disorder as a diagnostic entity.

Topics: Adult; Aged; Aged, 80 and over; Body Mass Index; Female; Humans; Leptin; Male; Mental Disorders; Middle Aged; Sex Factors; Suicide, Attempted; Young Adult

Previous studies have shown that rats fed a high calorie diet rich in saturated fat for 12weeks exhibit peripheral insulin resistance and impairments of behavioural flexibility when switched from an operant delayed matching to place (DMTP) schedule to a delayed non-matching to place (DNMTP) schedule. However, the metabolic changes evoked by feeding a high fat (HF) diet can be observed within two weeks of commencing the diet. The current study has confirmed that 4weeks exposure to an HF diet resulted in increased body weight, peripheral insulin resistance and plasma leptin. Studies performed during weeks 3 and 4 on the HF diet revealed suppressed lever pressing rates and impaired behavioural flexibility in the operant DMTP/DNMTP task. When animals fed the HF diet were then returned to a standard chow (SC) diet for 5weeks their weight and blood biochemistry no longer differed from those measured in animals that had never been exposed to the HF diet. The animals restored to the SC diet exhibited a clear ability to acquire the DNMTP schedule of reinforcement although these animals continued to lever press at a lower rate when compared with animals that received the SC diet throughout. The data suggest that exposure to an HF diet diminishes the motivation to respond for a reward and, thus, the capacity to adapt behavioural performance. This deficit was ameliorated, but not totally reversed, by the dietary intervention. If also true for humans, the results suggest that deficits in behavioural flexibility develop after only a short period on a high calorie diet but may be largely reversible through simple dietary intervention, at least in the early stages of deficit development. However, the putative effects of short-term exposure to an HF diet on behavioural motivation may persist for some time after switching to a healthier low fat diet and remain a problem for those seeking to adopt a healthier diet.

Topics: Analysis of Variance; Animals; Blood Glucose; Body Weight; Conditioning, Operant; Diet, High-Fat; Disease Models, Animal; Fasting; Insulin; Leptin; Male; Mental Disorders; Metabolic Diseases; Rats; Rats, Wistar; Reinforcement, Psychology; Time Factors

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

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

Dyslipidemia independent of body mass has previously been reported in humans after antipsychotic treatment. The present study investigated the levels of several metabolic regulatory hormones in psychiatric outpatients treated with different antipsychotics under real-life conditions.. The study included cross-sectional data from 234 subjects on stable monotherapy with any of the following: olanzapine (n = 72), any other antipsychotic (n = 80), or no medications (n = 82). Groups were well matched for sex, body mass index (BMI), ethnicity, and smoking. After adjustment for differences in age and illness duration, groups were compared for the insulin resistance index (homeostatic model assessment of insulin resistance) and fasting concentrations of glucose, lipids, insulin, sex hormone-binding globulin (SHBG), adiponectin, leptin, and cortisol. Correlations were examined between serum olanzapine and hormonal levels, and between leptin concentrations and BMI in both sexes.. Significant intergroup differences in concentrations of insulin (P = 0.025), SHBG (P = 0.001), adiponectin (P = 0.017), and cortisol (P = 0.003) but no significant difference for homeostatic model assessment of insulin resistance (P = 0.051) were found, independent of body mass. Olanzapine-treated subjects had the highest insulin concentrations and the lowest SHBG, adiponectin, and cortisol concentrations. Olanzapine-treated female subjects had significantly higher leptin (P = 0.005) and lower SHBG (P = 0.023) concentrations than other subjects. In female subjects, serum olanzapine concentrations were correlated with hormonal levels, and a significant proportion of olanzapine-treated female subjects had abnormal correlations between serum leptin levels and BMI.. Alterations in several interrelated metabolic hormonal markers were associated with olanzapine treatment, independent of body mass, particularly in female subjects.

Topics: Adiponectin; Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Controlled Clinical Trials as Topic; Cross-Sectional Studies; Female; Humans; Hydrocortisone; Insulin; Leptin; Male; Mental Disorders; Middle Aged; Olanzapine; Severity of Illness Index; Sex Factors; Sex Hormone-Binding Globulin; Young Adult

The pathogenesis of anorexia nervosa (AN) is still poorly understood. The Diagnostic and Statistical Manual of Mental Disorders (4th edition) classification differentiates 2 AN types: the restricting type (AN-R) and the binge eating/purging type (AN-BP). We investigated 4 young women suffering from AN (2 with AN-R and 2 with AN-BP). Four women, age matched, with other psychiatric disorders (paranoid schizophrenia, adjustment disorder, mental retardation) served as the reference group. The oligonucleotide microarray method (HG-U133A, Affymetrix) was used to determine the expression profile of 13 genes connected with the orexigenic and anorexigenic system: leptin, leptin receptor-coding gene, hypocretin (orexin) receptor-coding gene, hypocretin (orexin) neuropeptide precursor-coding gene and growth hormone secretagogue receptor. A hierarchical analysis of the results showed that AN-BP and AN-R patients were grouped into different clusters. Also, expression levels of leptin receptor-coding gene showed significant differences between AN-BP and AN-R patients and between AN-R and control subjects. This preliminary study suggests that the microarray technique may contribute to elucidating molecular genetics of the pathogenesis of both types of AN.

Topics: Adolescent; Adult; Anorexia Nervosa; Case-Control Studies; Cluster Analysis; Female; Gene Expression Profiling; Genetic Linkage; Ghrelin; Humans; Intracellular Signaling Peptides and Proteins; Leptin; Matched-Pair Analysis; Mental Disorders; Neuropeptides; Oligonucleotide Array Sequence Analysis; Orexin Receptors; Orexins; Receptors, G-Protein-Coupled; Receptors, Leptin; Receptors, Neuropeptide; Statistics, Nonparametric

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

The aim of this study was to investigate serum leptin, adiponectin and paraoxonase1 levels in adult females receiving pharmacotherapy for various psychiatric disorders.. The study group consisted of 32 obese females (mean age 40.53 +/- 11.00 years, mean body mass index 35.44 +/- 5.33 kg/m(2)) who were receiving treatment for psychiatric disorders, and the control group included 22 obese females (mean age 35.95 +/- 9.16 years, mean body mass index 30.78 +/- 3.33 kg/m(2)) who were free of psychiatric disorders. Analyses were performed using a bioelectrical impedance device. Fasting blood samples were obtained for complete blood count and various biochemical tests, including determination of leptin, adiponectin and paraoxonase1 activity.. Body mass index, waist and hip circumference, body fat percentage, fasting blood glucose, insulin, glycosylated hemoglobin, homeostasis model assesement of insulin resistance, alanine transaminase, aspartate tarnsaminase, and leptin levels were significantly higher in the study group than in controls. Although body weight was positively correlated with leptin levels in both groups, body weight was negatively correlated with adiponectin levels in the control group and positively correlated with adiponectin levels in the study group. In the study group, body mass index and hip circumference correlated positively with leptin levels, hip circumference correlated positively with adiponectin levels, and waist to hip ratio correlated positively with paraoxonase levels. In the control group, body mass index as well as waist and hip circumferences were positively correlated with leptin levels. Weight, body mass index, and hip circumference were also negatively correlated with the adiponectin/leptin ratio in the control group.. This study indicates a higher risk for obesity-related disorders, particularly metabolic syndrome, diabetes and cardiovascular disease, in patients treated with psychiatric drugs.

Topics: Adiponectin; Adult; Antidepressive Agents; Aryldialkylphosphatase; Biomarkers; Body Mass Index; Cardiovascular Diseases; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Humans; Leptin; Mental Disorders; Metabolic Syndrome; Obesity; Waist-Hip Ratio

Topics: Antidepressive Agents; Antipsychotic Agents; Humans; Leptin; Mental Disorders; Prognosis; Psychotropic Drugs; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha; Weight Gain

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

Leptin is produced by fat cells and is presumed to signal the size of the adipose tissue to the brain. The authors investigated whether antipsychotic drugs that often induce weight gain affect circulating levels of leptin.. Weight, body mass index, and leptin plasma level were measured weekly over 4 weeks in psychiatric inpatients who received clozapine (N = 11), olanzapine (N = 8), haloperidol (N = 13), or no psychopharmacological treatment (N = 12).. In patients receiving clozapine or olanzapine, significant increases in weight, body mass index, and leptin level were found, whereas these measures remained stable in patients who received haloperidol or no pharmacological treatment.. Weight gain induced by clozapine or olanzapine appears to be associated with an increase in leptin level that cannot be attributed to dietary changes upon hospitalization.

Topics: Adipose Tissue; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Body Weight; Clozapine; Haloperidol; Hospitalization; Humans; Leptin; Mental Disorders; Olanzapine; Pirenzepine; Proteins; Weight Gain

Topics: Disease; Humans; Leptin; Mental Disorders; Obesity