Computational markers of risky decision-making predict for relapse to alcohol.

BACKGROUND: Relapse remains the major challenge in treatment of alcohol use disorder (AUD). Aberrant decision-making has been found as important cognitive mechanism underlying relapse, but factors associated with relapse vulnerability are unclear. Here, we aim to identify potential computational markers of relapse vulnerability by investigating risky decision-making in individuals with AUD. METHODS: Forty-six healthy controls and fifty-two individuals with AUD were recruited for this study. The risk-taking propensity of these subjects was investigated using the balloon analog risk task (BART). After completion of clinical treatment, all individuals with AUD were followed up and divided into a non-relapse AUD group and a relapse AUD group according to their drinking status. RESULTS: The risk-taking propensity differed significantly among healthy controls, the non-relapse AUD group, and the relapse AUD group, and was negatively associated with the duration of abstinence in individuals with AUD. Logistic regression models showed that risk-taking propensity, as measured by the computational model, was a valid predictor of alcohol relapse, and higher risk-taking propensity was associated with greater risk of relapse to drink. CONCLUSION: Our study presents new insights into risk-taking measurement and identifies computational markers that provide prospective information for relapse to drink in individuals with AUD.

A Retrospective Analysis of Death Among Chinese Han Patients with Schizophrenia from Shandong.

Purpose: To describe the mortality rate and cause of death among Han Chinese schizophrenia patients and to explore the risk factors affecting survival. Methods: We performed a retrospective analysis of death among patients with schizophrenia from Jan 1, 2012, to Dec 31, 2019, using the Severe Mental Disorders Information System of Shandong Province (henceforth referred to as the SMDI system) in Shandong, China. The cohort included 72,102 patients, and 11,766 patients died during follow-up. The data in this cohort study were derived from the SMDI system. We calculated the crude mortality rate and standardized mortality rate (SMR, standardized according to the sex and age composition of the population in Shandong Province) for patients with schizophrenia. Cox regression analysis was used to analyze the risk factors affecting patient survival, and the statistical index was the hazard ratio (HR). Results: The mean age of the cohort patients was 47.21±14.05 years; 51.79% were males, and 48.21% were females. Among them, 68.98% (49,735) had only a primary education level, 85.36% (61,549) were farmers, 64.37% (46,413) were married, and 94.01% (67,775) received community management. A total of 16.32% of the cohort died. The SMR in patients with schizophrenia was 4.9, and it was higher for males than females (4.99 versus 4.82). Among the 6 registered causes of death, physical illness had the highest SMR (5.15), followed by other causes of death (4.86), mental illness-related complications (4.57), homicide (4.31), accidents (4.13), and suicide (3.87). Higher levels of education, employment (in-service status), marriage, and urban residence were protective factors for survival among patients with schizophrenia. Conclusion: In China, the SMR of schizophrenia is relatively high, and physical diseases are the main cause of death. We suggest that a variety of measures should be taken early to treat somatic diseases and reduce SMR in patients with schizophrenia.

Antagonistic effects of ultra-low-molecular-weight heparin on Aß25-35-induced apoptosis in cultured rat cortical neurons.

Low-molecular-weight heparin (LMWH) and ultra-low-molecular-weight heparin (ULMWH) are heparin's derivatives, having various pharmacological effects. The present study aims to investigate the effect of ULMWH on amyloid ß peptide (Aß25-35)-induced neurotoxicity in cultured rat cortical neurons, and LMWH was employed as a positive control agent. The neurons were incubated with Aß25-35 (35µM), Aß25-35 plus ULMWH (2, 10, 50 µg/ml) or LMWH (10 µg/ml) for 24h. The cell viability was assessed by MTT and LDH release. FITC-Annexin V/PI double staining, Hoechst 33258 staining, TUNEL and Western blotting for bcl-2 and caspase-3 were employed to measure the neuron apoptosis. Furthermore, the intracellular Ca(2+) concentration was measured by a fluorescent dye, Fura-2/AM. The results showed that ULMWH significantly increased cell viability and the protein expression levels of bcl-2 and decreased the LDH release, the number of apoptotic cells, the concentration of intracellular Ca(2+) and the protein expression levels of caspase-3 in cortical neurons, suggesting that ULMWH can obviously reduce Aß25-35-induced neurotoxic effects and might act as a potential agent for Alzheimer's disease.

Protective effect of ultra low molecular weight heparin on glutamate-induced apoptosis in cortical cells.

PURPOSE: To investigate the effect of ultra low molecular weight heparin (ULMWH) on glutamate induced apoptosis in rat cortical cells and to explore the possible mechanisms. MATERIALS AND METHODS: Cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis was first analyzed with Hoechst 33258 and then confirmed by DNA fragmentation. The concentration of free intracellular calcium ([Ca(2+)](i)) was determined with fura-2/AM fluorometry. The expression of Bcl-2 family protein and caspase-3 were evaluated with Western blot. RESULTS: Typical apoptotic morphological change in rat cortical cells treated with 100 micromol/L glutamate for 24h was detected by Hoechst 33258 staining, which was then confirmed by the DNA ladder of agarose gel electrophoresis. The apoptotic rate of the glutamate treated cells was up to 33.21%, and 24 h of treatment with glutamate increased [Ca(2+)](i), down-regulated Bcl-2 expression, up-regulated Bax expression, and increased caspase-3 activation in rat cortical cells. Our research demonstrated that ULMWH pretreatment can prevent the glutamate-induced apoptosis, attenuate the increase of [Ca(2+)](i) not only in medium containing Ca(2+) but also in Ca(2+)-free medium, up-regulate the expression of Bcl-2, down-regulate the expression of Bax, and decrease caspase-3 activation. CONCLUSION: ULMWH has neuroprotective capacity to antagonize glutamate-induced apoptosis in cortical cells, through decrease of Ca(2+) release and modulation of apoptotic processes.