leptin and Stress-Disorders--Post-Traumatic

Recent research strongly supports the hypothesis that posttraumatic stress disorder (PTSD) can be accompanied by obesity and related metabolic disturbances. The mechanisms of these associations are however still not well defined, although disturbed functions in the sympathetic-adrenergic nervous system together with the disturbed release of hormones via the endocrine HPA (hypothalamic-pituitary-adrenal) axis apparently play a role. Leptin resistance and ghrelin excesses might contribute to a disturbed hypothalamic function, and also disturb other cerebral functions, leading to dysfunctional reward signaling and uncontrolled appetite combined with a tendency to alcohol abuse. Secondarily, cortisol stimulation will contribute to the development of central obesity which is known to facilitate the development of metabolic syndrome, including slightly increased levels of inflammatory biomarkers such as C-reactive protein and fibrinogen. While previous therapeutic strategies have focused on early psychotherapeutic interventions in PTSD, the present review emphasizes the importance of better therapeutic approaches regarding the somatic correlates of the syndrome. Strict regulation of dietary meals and food composition with minimal intake of sweets and saturated fat, as well as alcohol avoidance, can provide a basic therapeutic framework. A cognitive psychotherapeutic approach with graduated desensitization toward trigging factors, combined with pharmacotherapy, is discussed in the present review.

Topics: Anxiety; Cytokines; Humans; Leptin; Obesity; Stress Disorders, Post-Traumatic

Accumulating evidence suggests that the activation of nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome contributes to the pathophysiology of post-traumatic stress disorder (PTSD). Astrocytes, the homeostatic cells of the central nervous system are intimately involved into pathophysiology of various mental disorders including PTSD. We demonstrated previously that leptin exerts neuroprotection and ameliorates chronic sleep deprivation-induced depressive-like behaviours. Here, we extended the study of therapeutic effects of leptin to PTSD model mice. We discovered that PTSD is associated with significant activation of NLRP3 inflammasome in astrocytes sorted from GFAP-GFP transgenic mice, while administration of leptin markedly suppressed the activation of astrocytic NLRP3 inflammasome. Leptin effectively improved PTSD-associated behavioural alterations including fear memory, cognitive impairments, and depressive-like behaviours. Therapeutic effects of leptin were mediated by the signal transducer and activator of transcription 3 (STAT3) in astrocytes. In addition, the PTSD-related activation of NLRP3 inflammasome impairs astrocytic mitochondria suppressing ATP synthesis and leading to an increased ROS production. Leptin reversed mitochondrial inhibition by stimulating STAT3 in astrocytes. We propose leptin as a novel candidate for the pharmacological treatment of PTSD.

Topics: Animals; Astrocytes; Fear; Inflammasomes; Leptin; Mice; NLR Family, Pyrin Domain-Containing 3 Protein; Stress Disorders, Post-Traumatic

Posttraumatic stress disorder (PTSD) is very common after exposure to trauma, mental stress or violence. Because objective biological markers for PTSD are lacking, exactly diagnosing PTSD is a challenge for clinical psychologists. In-depth research on the pathogenesis of PTSD is a key for solving this problem. In this work, we used male Thy1-YFP transgenic mice, in which neurons are fluorescently labeled, to research the effects of PTSD on neurons in vivo. We initially discovered that pathological stress associated with PTSD increased the activation of glycogen synthesis kinase-beta (GSK-3β) in neurons and induced the translocation of the transcription factor forkhead box-class O3a (FoxO3a) from the cytoplasm to the nucleus, which decreased the expression of uncoupling protein 2 (UCP2) and increased mitochondrial production of reactive oxygen species (ROS) to trigger neuronal apoptosis in the prefrontal cortex (PFC). Furthermore, the PTSD model mice showed increased freezing and anxiety-like behaviors and more severe decrease of memory and exploratory behavior. Additionally, leptin attenuated neuronal apoptosis by increasing the phosphorylation of signal transducer and activator of transcription 3 (STAT3), which further elevated the expression of UCP2 and inhibited the mitochondrial production of ROS induced by PTSD, thus reducing neuronal apoptosis and ameliorating PTSD-related behaviors. Our study is expected to promote the exploration of PTSD-related pathogenesis in neural cells and the clinical effectiveness of leptin for PTSD.

Topics: Animals; Glycogen Synthase Kinase 3 beta; Leptin; Male; Mice; Mice, Transgenic; Reactive Oxygen Species; Stress Disorders, Post-Traumatic

The study's aim was to examine the prevalence and severity of posttraumatic stress disorder (PTSD) longitudinally among high school students with different genotypes of the leptin gene (LEP) rs7799039 after the 2008 Wenchuan earthquake in China.. The symptoms of PTSD were measured by the PTSD Checklist-Civilian Version (PCL-C) based on DSM-IV-TR criteria in 462 students at 6, 12, and 18 months after the earthquake. The genotypes of LEP rs7799039 were identified by polymerase chain reaction-restriction fragment length polymorphism analyses in 2018 using genomic DNA prepared in 2008 and stored at -80°C and verified by DNA sequencing. The association of LEP genotypes with PTSD was then analyzed by various statistical methods.. The AA homozygotes had higher prevalence of PTSD than the G allele carriers at 12 months (22.30% vs 10.53%, P = .013) and higher median (interquartile range [IQR]) PCL-C scores at 12 (27.00 [24.00-35.75] vs 26.00 [22.00-31.25], P = .010) and 18 months (27.00 [21.00-32.00] vs 24.00 [19.00-29.00], P = .003) post-earthquake among female subjects. Female students had higher PCL-C scores than male subjects at 6 and 12 months regardless of the genotypes but only among the AA homozygotes at 18 months (27.00 [21.00-32.00] vs 22.00 [18.00-26.00], P = .000). The potential risk factors for and predictors of PTSD severity differed at different time points during follow-up. LEP rs7799039 was a potential factor for PTSD at 12 months and a predictor of PTSD severity at 18 months post-earthquake.. An association of LEP rs7799039 with the prevalence and severity of PTSD in Chinese adolescents was observed. These results indicate that females with the LEP rs7799039 AA genotype had more severe PTSD characteristics compared to female G allele carriers, suggesting that psychosocial or pharmacologic managements may particularly be needed by these female subjects.

Topics: Adolescent; China; Earthquakes; Female; Gene Frequency; Genotype; Humans; Leptin; Longitudinal Studies; Male; Natural Disasters; Polymorphism, Single Nucleotide; Prevalence; Stress Disorders, Post-Traumatic; Time Factors

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

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

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

Leptin (OB protein) is an important signal in the regulation of energy balance. Leptin levels correlate with adiposity, but also decrease acutely with caloric restriction and increase with refeeding. The brain is an established critical site of leptin function, yet little is known about leptin concentrations in the central nervous system relative to plasma levels, psychiatric diagnoses, and other endocrine parameters. Therefore, using a novel ultrasensitive leptin assay, we explored relationships of human plasma and cerebrospinal fluid (CSF) leptin levels to body mass index, smoking, posttraumatic stress disorder diagnosis, and levels of dopamine, monoamine metabolites, beta-lipotropin, glucocorticoid, and thyroid and cytokine hormones. A strong linear relation between CSF and plasma leptin levels in the am (r = 0.63; P < 0.002) and afternoon (r = 0.90; P < 0.0001) was revealed. CSF and plasma leptin concentrations decreased during a 12- to 20-h period of fasting. A strong association was found between plasma leptin and CSF dopamine levels (r = 0.74; P < 0.01) as well as between CSF leptin levels and urinary free cortisol (r = 0.73; P < 0.01). Both of these parameters covaried with leptin independently of adiposity, as estimated by body mass index. Implications for leptin transport, regulation, and its potential role in therapeutic strategies for obesity and diabetes are discussed.

Topics: Adult; Body Mass Index; Circadian Rhythm; Dopamine; Fasting; Humans; Hydrocortisone; Leptin; Male; Middle Aged; Smoking; Stress Disorders, Post-Traumatic