Differential effects of alcohol-drinking patterns on the structure and function of the brain and cognitive performance in young adult drinkers: A pilot study.

INTRODUCTION: This study was aimed to determine how different patterns of alcohol consumption drive changes to brain structure and function and their correlation with cognitive impairments in young adult alcohol drinkers. METHODS: In this study, we enrolled five groups participants and defined as: long-term abstinence from alcohol (LA), binge drinking (BD), long-term low dosage alcohol consumption but exceeding the safety drinking dosage (LD), long-term alcohol consumption of damaging dosage (LDD), and long-term heavy drinking (HD). All participants underwent magnetic resonance imaging (MRI) and functional MRI (fMRI) to acquire data on brain structure and function, including gray matter volume (GMV), fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), functional connectivity (FC), and brain network properties. The cognitive ability was evaluated with the California Verbal Learning Test (CVLT), intelligence quotient (IQ), and short delay free recall (SDFR). RESULTS: Compared to LA, GMV significantly decreased in the brain regions in VN, SMN, and VAN in the alcohol-drinking groups (BD, LD, LDD, and HD). ReHo was significantly enhanced in the brain regions in VN, SMN, and VAN, while fALFF significantly increased in the brain regions in VN and SMN. The number of intra- and inter-modular connections within networks (VN, SMN, sensory control network [SCN], and VAN) and their connections to other modules were abnormally changed. These changes adversely affected cognition (e.g., IQ, CVLT, SDFR). CONCLUSION: Despite the small sample size, this study provides new evidence supporting the need for young people to abstain from alcohol to protect their brains. These findings present strong reasoning for updating anti-alcohol slogans and guidelines for young people in the future.

Safety and Efficacy of High-Dose Vitamin B6 as an Adjunctive Treatment for Antipsychotic-Induced Hyperprolactinemia in Male Patients With Treatment-Resistant Schizophrenia.

This study aimed to investigate the safety and efficacy of high-dose vitamin B6 (vB6) as an adjunct treatment for antipsychotic-induced hyperprolactinemia (AIHP) in male patients with treatment-resistant schizophrenia (TRS). In this randomized double-blinded controlled study, patients were randomized (1:1) into a control group given aripiprazole (ARI; 10 mg/day; n = 100) or an intervention group given vB6 (300 mg/12 h for 16 weeks; n = 100). Prolactin levels, psychotic symptoms [Positive and Negative Syndrome Scale (PANSS)], cognitive function [MATRICS Consensus Cognitive Battery (MCCB)], liver function, kidney function, growth hormone level, micronutrient levels, blood lipids, and adverse secondary effects (ASEs)[Treatment Emergent Symptom Scale (TESS) and Barnes-Akathisia scale] were monitored. After a 16-week treatment period, the vB6 group showed a 68.1% reduction in serum prolactin levels (from 95.52 ± 6.30 µg/L to 30.43 ± 18.65 µg/L) while the ARI group showed only a 37.4% reduction (from 89.07 ± 3.59 µg/L to 55.78 ± 7.39 µg/L). During weeks 1-4, both treatments reduced prolactin similarly. Subsequently, the ARI effect plateaued, while the vB6 effect remained robust. The vB6 group showed better alleviation of psychotic symptoms and cognitive impairment. No serious ASEs were observed; ASEs were more frequent in the ARI group. AIHP reduction efficacy of vB6 was associated with baseline prolactin and triglyceride levels, total vB6 dosage, and education level. In conclusion, compared with the ARI group, TRS patients given vB6 showed better attenuation of AIHP, lower ASE scores, and greater improvements in clinical symptoms and cognitive impairments. These results support further consideration of vB6 as a putative treatment for AIHP. Trial Registration: ChiCTR1800014755.

Clozapine induces metformin-resistant prediabetes/diabetes that is associated with poor clinical efficacy in patients with early treatment-resistant schizophrenia.

BACKGROUND: Two distinct subtypes of treatment-resistant schizophrenia (TRS) have been recently reported, including early-treatment resistance (E-TR) and late-treatment resistance (L-TR). This study was to assess clozapine-induced metformin-resistant prediabetes/diabetes and its correlation with clinical efficacy in schizophrenia E-TR subtype. METHODS: This prospective cohort study enrolled 230 patients with schizophrenia E-TR subtype and they were treated with adequate doses of clozapine for 16 weeks, during which patients with prediabetes/diabetes were assigned to receive add-on metformin. The main outcomes and measures included incidence of clozapine-induced prediabetes/diabetes and metformin-resistant prediabetes/diabetes, and the efficacy of clozapine as assessed by the Positive and Negative Syndrome Scale (PANSS) score. RESULTS: Clozapine-induced prediabetes/diabetes occurred in 76.52% of patients (170 prediabetes and 6 diabetes), of which the blood sugar of 43 (24.43%) patients was controlled with metformin. Despite add-on metformin, 47.06% (74/170) of prediabetes patients progressed to diabetes. In total, the incidence of clozapine-induced metformin-resistant prediabetes/diabetes was 75.57% (133/176). On completion of 16-week clozapine treatment, 16.52% (38/230) patients showed clinical improvement with PANSS scores of ≥50% declining. Furthermore, clozapine-induced prediabetes/diabetes was significantly correlated with the poor clinical efficacy of clozapine for schizophrenia E-TR subtype. CONCLUSIONS: The incidence of clozapine-induced metformin-resistant prediabetes/diabetes was considerably high in the schizophrenia E-TR subtype. Clozapine-induced metformin-resistant prediabetes/diabetes represents an independent risk factor that adversely affects the clinical efficacy of clozapine for the schizophrenia E-TR subtype. This study provided new evidence for re-evaluating the use of clozapine for TRS, especially E-TR subtype, and the use of metformin for the glycemic control of clozapine-induced prediabetes/diabetes.