leptin and Mood-Disorders

The adipose-derived hormone leptin is well known for its function in the control of energy homeostasis. Recent studies suggest a novel role for this adipokine in the regulation of mood and emotion. Low levels of leptin have been found to be associated with depressive behaviors in rodents and humans. Pharmacological studies indicate that leptin has antidepressant-like efficacy. Both leptin insufficiency and leptin resistance may contribute to alterations of affective status. Identifying the key brain regions that mediate leptin's antidepressant activity and dissecting its intracellular signal transduction pathways may provide new insights into the pathogenesis of depression and facilitate the development of novel therapeutic strategies for the treatment of this illness.

Topics: Animals; Biogenic Monoamines; Depression; Humans; Hypothalamo-Hypophyseal System; Leptin; Mood Disorders; Nerve Growth Factors; Obesity; Pituitary-Adrenal System; Receptors, Leptin

Recent data suggest that chronic low-grade inflammation, a characteristic of obesity, is associated with altered tryptophan (Trp) and tyrosine (Tyr) metabolism and plays a role in neuropsychiatric symptoms. The present study assessed the effect of an extreme short-term diet on Trp breakdown and inflammatory biomarkers in overweight adults.. Thirty-eight overweight participants (16 women, 22 men; average body mass index: 29 kg/m², mean age 52.8 years) were randomized into two diet groups: a very low kcal diet group (VLCD; Ø 600 kcal/day, n = 21) and a low kcal diet group (LCD; Ø 1,200 kcal/day, n = 17). Assays included the measurement of Trp, kynurenine (Kyn), and their ratio, neopterin, phenylalanine (Phe), Tyr, as biologic markers; leptin, plasma insulin, glucose, and homeostatic model assessment-insulin resistance; and interleukin 6, tumor necrosis factor alpha, and C-reactive protein, as biochemical and inflammatory markers at baseline and after 2 weeks of treatment.. Weight loss diet lowered leptin levels in both groups by 46%, although not reaching significance. Trp and Kyn decreased significantly by 21 and 16% for VLCD and by 15 and 17% for the LCD group, respectively. A significant reduction in Phe was only seen after VLCD. Inflammatory biomarkers, neopterin, and Tyr were not significantly altered during the study period. Leptin was significantly correlated with Trp breakdown before and after the intervention (P < 0.02).. Since disturbed metabolism of Trp affects biosynthesis of serotonin and might be associated with increased susceptibility for mood disturbances and carbohydrate craving, strategies to supplement Trp while dieting could be highly useful in treating uncontrolled weight gain or in preventing neuropsychiatric symptoms.

Topics: Austria; Biomarkers; Body Mass Index; Caloric Restriction; Diet, Reducing; Female; Humans; Inflammation Mediators; Kynurenine; Leptin; Male; Middle Aged; Mood Disorders; Neopterin; Overweight; Phenylalanine; Risk; Tryptophan; Tyrosine; Weight Loss

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

Background Anxiety disorders are common psychiatric disorders in childhood and an important health problem that is associated with the risk of serious mental, educational and economical problems. Researchers have mentioned many different mechanisms in the etiopathology of anxiety disorders. This study aimed to investigate ghrelin and leptin levels in children with anxiety disorders and thus to contribute to the clarification of anxiety in children. Methods Forty-three children aged 6-12 years with a diagnosis of the Anxiety Disorder according to DSM 5 and 21 healthy children age- and gender-matched to the study group were included. All the subjects were assessed with Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version (K-SADS-PL) and State-Trait Anxiety Inventory for Children (STAI-C) scale. Blood samples were obtained in the morning and serum ghrelin and leptin levels were measured with enzyme-linked immunosorbent assay (ELISA) kits. Results In the anxiety group the ghrelin levels were higher than the control group (p = 0.037) but there was no significant difference between the leptin levels (p = 0.430). Also, when the girls in the anxiety group and the girls in the control group were compared, ghrelin levels were higher in the anxiety group (p < 0.01). Conclusions These findings suggest that ghrelin may play a significant role in the etiologic mechanisms of anxiety disorders. However, more detailed studies are needed to explain the linkage between anxiety disorders and neuropeptides.

Topics: Anxiety Disorders; Biomarkers; Child; Child Behavior Disorders; Female; Follow-Up Studies; Ghrelin; Humans; Leptin; Male; Mood Disorders; Prognosis

Dietary factors have significant effects on the brain, modulating mood, anxiety, motivation and cognition. To date, no attention has been paid to the consequences that the combination of ethanol (EtOH) and a high-fat diet (HFD) have on learning and mood disorders during adolescence. The aim of the present work was to evaluate the biochemical and behavioral consequences of ethanol binge drinking and an HFD consumption in adolescent mice.. Animals received either a standard diet or an HFD (ad libitum vs. binge pattern) in combination with ethanol binge drinking and were evaluated in anxiety and memory. The metabolic profile and gene expression of leptin receptors and clock genes were also evaluated.. Excessive white adipose tissue and an increase in plasma insulin and leptin levels were mainly observed in ad libitum HFD + EtOH mice. An upregulation of the Lepr gene expression in the prefrontal cortex and the hippocampus was also observed in ad libitum HFD groups. EtOH-induced impairment on spatial memory retrieval was absent in mice exposed to an HFD, although the aversive memory deficits persisted. Mice bingeing on an HFD only showed an anxiolytic profile, without other alterations. We also observed a mismatch between. Our results confirm the bidirectional influence that occurs between the composition and intake pattern of a HFD and ethanol consumption during adolescence, even when the metabolic, behavioral and chronobiological effects of this interaction are dissociated.

Topics: Adiposity; Animals; ARNTL Transcription Factors; Bulimia; CLOCK Proteins; Diet, High-Fat; Ethanol; Hippocampus; Learning; Leptin; Male; Mice; Mood Disorders; Prefrontal Cortex; Receptors, Leptin; Weight Gain

Bulimia nervosa (BN) is characterized by dysregulated eating behaviour and present data suggest adipokines may regulate food intake. We investigated a possible association between BN and adipokine levels and hypothesized that plasma (P)-adiponectin would be elevated and P-leptin and P-leptin-adiponectin-ratio would be reduced in women with BN.. The study was designed as a cross-sectional study with a longitudinal arm for patients with BN. Plasma-adiponectin and leptin was measured in 148 female patients seeking psychiatric ambulatory care and 45 female controls. Fifteen patients were diagnosed with BN and the remaining with other affective and anxiety disorders. P-adiponectin and P-leptin levels were compared between patients with BN, patients without BN and controls. At follow-up 1-2years later, adipokines were reassessed in patients with BN and the Eating Disorder Examination Questionnaire was used to assess symptom severity.. P-adiponectin was elevated in patients with BN at baseline and at follow-up when compared to patients without BN and controls (P<0.004 and <0.008 respectively). The difference remained significant after controlling for body mass index. P-adiponectin was correlated to symptom severity at follow-up in patients with BN without morbid obesity (ρ=0.72, P<0.04). P-leptin-adiponectin-ratio was significantly lower in patients with BN compared to controls (P<0.04) and P-leptin non-significantly lower.. Findings indicate a stable elevation of P-adiponectin in women with BN. P-adiponectin at follow-up correlates to eating disorder symptom severity in patients without morbid obesity, indicating that P-adiponectin should be further investigated as a possible potential prognostic biomarker for BN.

Topics: Adiponectin; Adult; Body Mass Index; Bulimia Nervosa; Cross-Sectional Studies; Feeding Behavior; Female; Humans; Leptin; Longitudinal Studies; Mood Disorders; Psychiatric Status Rating Scales; Statistics as Topic; Sweden

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 Ca(2+)/calmodulin stimulated adenylyl cylcase 8 (AC8) is a pure Ca(2+) sensor, catalyzing the conversion of ATP to cAMP, with a critical role in neuronal plasticity. A role for AC8 in modulating complex behavioral outcomes has been demonstrated in AC8 knock out (KO) mouse models in which anxiety-like responses were differentially modulated following repeated stress experiences, suggesting an involvement of AC8 in stress adaptation and mood disorders. To further investigate the role of this enzyme in phenotypes relevant for psychiatric conditions, AC8 KO mice were assessed for baseline behavioral and hormonal parameters, responses to repeated restraint stress experience, and long-term effects of chronic social defeat stress. The lack of AC8 conferred a hyperactive-phenotype both in home-cage behaviors and the forced swim test response as well as lower leptin plasma levels and adrenal hypertrophy. AC8 KO mice showed baseline "anxiety" levels similar to wild type littermates in a variety of procedures, but displayed decreased anxiety-like responses following repeated restraint stress. This increased stress resilience was not seen during the chronic social defeat procedure. AC8 KO did not differ from wild type mice in response to social stress; similar alterations in body weight, food intake and increased social avoidance were found in all defeated subjects. Altogether these results support a complex role of cAMP signaling pathways confirming the involvement of AC8 in the modulation of stress responses. Furthermore, the hyperactivity and the increased risk taking behavior observed in AC8 KO mice could be related to a manic-like behavioral phenotype that warrants further investigation.

Topics: Adenylyl Cyclases; Adrenal Glands; Animals; Behavior, Animal; Biomarkers; Disease Models, Animal; Hypertrophy; Leptin; Male; Mice; Mice, Knockout; Mood Disorders; Stress, Psychological

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