We found significant predictive relationships between AWS and HDL-C, LDL-C, and triglycerides. While extreme-high HDL-C, (≥100 mg/dL), conferred the highest odds for moderate (4.405, 95% CI, 2.572-7.546, P less then 0.001) and severe AWS (5.494, 95% CI, 3.541-8.523, P less then 0.001), lowest odds ratios for moderate AWS (0.493, 95% CI, 0.248-0.981, P = 0.044) and severe AWS (0.303, 95% CI, 0.223-0.411, P less then 0.001) were associated with high LDL-C (≥ 160 mg/dL). The present study demonstrates that altered lipid levels, measured upon admission for inpatient AUD treatment, may help to predict individuals at risk for medically relevant moderate-to-severe AWS. This suggest that further research into the role of lipid biomarkers in AWS may be beneficial for identifying biologically determined risk profiles in AUD. Published by Elsevier Inc.Glutathione (GSH) and GSH/glutathione peroxidase (GPX) enzyme system is essential for normal intracellular homeostasis and gets disturbed under pathophysiologic conditions including endothelial dysfunction. Overproduction of reactive oxidative species (ROS) and reactive nitrogen species (RNS) including superoxide (O2•-), and the loss of nitric oxide (NO) bioavailability is a characteristic of endothelial dysfunction. The GSH/GPX system play an important role in eliminating ROS/RNS. Studies have provided important information regarding the interactions of ROS/RNS with the GSH/GPX in biological systems; however, it is not clear how this cross talk affect these reactive species and GSH/GPX enzyme system, under physiologic and oxidative/nitrosative stress conditions. In the present study, we developed a detailed endothelial cell kinetic model to understand the relationship amongst the key enzyme systems including GSH, GPX, peroxiredoxin (Prx) and reactive species, such as hydrogen peroxide (H2O2), peroxynitrite (ONOO-), and dinitrogen trioxide (N2O3). Our simulation results showed that the alterations in the generation rates of O2•- and NO led to the formation of a wide range of ROS and RNS. Simulations performed by varying the ratio of O2•- to NO generation rates as well as GSH and GPX concentrations showed that the GPX reducing capacity was dependent on GSH availability, level of oxidative/nitrosative stress, and can be attributed to N2O3 levels, but not to H2O2 and ONOO-. Our results showed that N2O3 mediated switch-like depletion in GSH and the incorporation of Prx had no considerable effect on the ROS/RNS species other than ONOO- and H2O2. The analysis presented in this study will improve our understanding of vascular diseases in which the levels and oxidation states of GSH, GPX and/or Prx are significantly altered and pharmacological interventions show limited benefits. BACKGROUND Antipsychotics, especially most of the second-generation antipsychotics, have a high risk for metabolic syndrome and antipsychotic-induced weight gain (AIWG). A promoter variant of the leptin (LEP) gene, -2548G/A (rs7799039), has been associated with AIWG in several studies. The aim of this study was to evaluate this association in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) sample, followed by meta-analysis. METHODS We investigated the association between rs7799039 and AIWG in a sub-sample of European (N = 164) individuals from the CATIE study. Body mass index (BMI) change and weight gain (presence or absence) was analyzed using ANCOVA and logistic regression, respectively. For the meta-analysis, a literature search was conducted using MEDLINE, Embase, and PsycINFO up to October 2019. The pooled odds ratio was calculated for presence or absence of weight gain (≥7% weight change) using a random effects model. RESULTS We did not detect an association between rs7799039 and BMI change or weight gain (presence or absence) in the CATIE sample. As for the meta-analysis, we included 12 studies. No significant associations between the LEP rs7799039 polymorphism and AIWG were observed under the allelic genetic model (allele A vs. allele G) (OR = 1.10 [0.71, 1.70], p = .68). In the subgroup analyses of first-episode schizophrenia patients, a significant association between the A-allele and weight gain was observed, respectively (OR = 2.32 [1.41, 3.82], p = .0009). CONCLUSIONS The present meta-analysis showed no significant effect of rs7799039 on AIWG. However, this variant may influence AIWG in first-episode schizophrenia patients. Further investigation of a larger and more homogenous sample is required to elucidate the role of the LEP gene in AIWG. selleck OBJECTIVE Major depressive disorder (MDD) is a neuropsychiatric disorder associated with functional dysconnectivity in emotion regulation system. State characteristics which measure the current presence of depressive symptoms, and trait characteristics which indicate the long-term vulnerability to depression are two important features of MDD. However, the relationships between trait and state characteristics of MDD and functional connectivity (FC) within the emotion regulation system still remain unclear. METHODS This study aims to examine the neural biological mechanisms of trait characteristics measured by the Affective Neuroscience Personality Scale (ANPS) and state anhedonia measured by the Snaith-Hamilton Pleasure Scale (SHAPS) in MDD. Sixty-three patients with MDD and 63 well-matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. A spatial pairwise clustering and the network-based analysis approaches were adopted to identify the abnormal FC networks. Support vector regression was utilized to predict the trait and state characteristics based on abnormal FCs. RESULTS Four disrupted subnetworks mainly involving the prefrontal-limbic-striatum system were observed in MDD. Importantly, the abnormal FC between the left amygdala (AMYG)/hippocampus (HIP) and right AMYG/HIP could predict the SADNESS scores of ANPS (trait characteristics) in MDD. While the aberrant FC between the medial prefrontal cortex (mPFC)/anterior cingulate gyrus (ACC) and AMYG/parahippocampal gyrus could predict the state anhedonia scores (state characteristics). CONCLUSIONS The present findings give first insights into the neural biological basis underlying the trait and state characteristics associated with functional dysconnectivity within the emotion regulation system in MDD.