Impact of environmental stress upon pathophysiology of the metabolic syndrome (MetS) has been substantiated by epidemiological, psychophysiological, and endocrinological studies. This review discusses recent advances in the understanding of causative roles of nutritional factors, sympathomedullo-adrenal (SMA) and hypothalamic-pituitary adrenocortical (HPA) axes, and adipose tissue chronic low-grade inflammation processes in MetS. Disturbances in the neuroendocrine systems for leptin, melanocortin, and neuropeptide Y (NPY)/agouti-related protein systems have been found resulting directly in MetS-like conditions. The review identifies candidate risk genes from factors shown critical for the functioning of each of these neuroendocrine signaling cascades. In its meta-analytic part, recent studies in epigenetic modification (histone methylation, acetylation, phosphorylation, ubiquitination) and posttranscriptional gene regulation by microRNAs are evaluated. Several studies suggest modification mechanisms of early life stress (ELS) and diet-induced obesity (DIO) programming in the hypothalamic regions with populations of POMC-expressing neurons. Epigenetic modifications were found in cortisol (here HSD11B1 expression), melanocortin, leptin, NPY, and adiponectin genes. With respect to adiposity genes, epigenetic modifications were documented for fat mass gene cluster APOA1/C3/A4/A5, and the lipolysis gene LIPE. With regard to inflammatory, immune and subcellular metabolism, PPARG, NKBF1, TNFA, TCF7C2, and those genes expressing cytochrome P450 family enzymes involved in steroidogenesis and in hepatic lipoproteins were documented for epigenetic modifications.

Agomelatine is efficacious in reducing symptoms and preventing relapse in placebo-controlled trials in generalised anxiety disorder (GAD). Nevertheless, fixed dose studies of agomelatine in GAD have not been undertaken. To determine the minimally effective optimal dose of agomelatine in GAD, the efficacy of two doses of agomelatine (10 and 25mg/day) was investigated in a 12-week, placebo-controlled, double-blind, international study in patients with a primary diagnosis of GAD. The primary outcome measure was the Hamilton Anxiety scale (HAM-A). The study was undertaken in 35 clinical centers in Finland, Russia, Poland, Slovakia and Ukraine from August 2013 to January 2015. 131 out-patients were included in the agomelatine 10mg group, 139 in the agomelatine 25mg group, and 142 in the placebo group. Both doses of agomelatine were associated with significant decreases in the HAM-A at week 12 (difference versus placebo of 7.16±1.00 at 10mg and 11.08±0.98 at 25mg, p<0.0001). Significant effects on all secondary measures were found for both doses at week 12; including psychic and somatic HAM-A subscales, response rate, remission on the HAM-A, and functional impairment. Findings were confirmed in subsets of more severely ill patients on all endpoints. The low placebo response rate observed in this study was consistent with an increase in the quality of data collected. Agomelatine was well-tolerated by patients, with minimal distinctions from placebo. There was a dose effect of agomelatine, with a greater placebo-agomelatine difference in the agomelatine 25mg group, compared to the agomelatine 10mg group.The present data support early work indicating the efficacy and tolerability of agomelatine in the treatment of GAD.

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This study examined alcohol consumption in relation to anxiety, depression, and involvement with high risk occupations (HRO; e.g., coal miners), among young adults in the Ukraine (aged 18–25) (N=192; 60.9% male; 100% Caucasian). Participants were grouped based on drinking status: (1) current drinkers (CDs; n=132) or (2) nondrinkers (NDs; n=60). Questionnaires assessed frequency of alcohol use, motives for drinking, problem identification, as well as anxiety and depression (i.e., Hamilton scales). Bivariate analyses showed that CDs were more likely than NDs to be single, have a HRO, and have greater anxiety and depression; for example, 91.7% of CDs had a HRO as compared to 56.7 % of NDs. Drinking status was not significantly related to age or gender. Among CDs, common motives for use included: to reduce anxiety and fears (60.6%), because my friends use alcohol (75.0%), to fight stress (78.8%), and to increase self-esteem (64.4%). Among CDs, past month drinking days were: 25% 1–2 days, 37.9% 3–7 days, 25% 8–21 days, and 12.1% 22–30 days. Regarding problem identification, 29.5% reported not having a problem, 34.8% reported possibly having a problem, 21.9% reported having a problem but not needing help, and 13.6% reported having a problem/needing help. Young adults involved in HRO may be a particularly high risk population given increased likelihood of alcohol use, anxiety, and depression. Early intervention strategies that incorporate motivational interviewing approaches to address coping and social motives for use may be beneficial to address substance use and mental health problems.

Various studies link hypertension with anxiety; however, it remains unclarified if such relations are present in the metabolic syndrome (MetS). We studied cross-sectionally the interrelations of self-reported anxiety (Spielberger STAI), and MetS components in MetS patients. We investigated a nationally sampled treatment cohort for MetS with familial Type 2 diabetes risk. N = 101 patients fulfilling International Diabetes Federation criteria for MetS participated. Both laboratory and nonlaboratory measures were included. Structural equation models (SEM) were adjusted. The final SEM had an R(2)  = .998 with the obesity component linking to waist, BMI, and degree of adiposity, and the hypertension component linking to systolic blood pressure, pulse pressure, total cholesterol, and trait anxiety. For state anxiety, no significant regressive causal path could be estimated. SEM supports the assumption of an interaction of pulse pressure, systolic blood pressure, cholesterol metabolism, and high trait anxiety in the pathophysiology of hypertension in MetS.