Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

Background: Individuals with eating disorders are at high risk of suicide attempts (SA), yet nutritional correlates remain underexplored. Selenium, an essential micronutrient with antioxidant and neuroprotective functions, is often deficient in eating disorders. We examined the association between baseline plasma selenium and subsequent SA.

Methods: We analyzed 658 patients with eating disorders recruited at the University Hospital Center of Montpellier (2012-2014 and 2017-2020). Baseline plasma selenium was quantified by the hospital's biochemistry laboratory. SA occurring after baseline were identified through review of electronic Emergency Department records up to December 1, 2024. Semi-parametric Cox proportional hazards models estimated hazard ratios (HR) for time to first SA.

Results: Median plasma selenium was 82.9 μg/L. Over a median 82-month follow-up, 40 participants (6.1%) attempted suicide. Higher selenium levels were associated with lower hazard of SA (HR per 1 SD = 0.59, 95% CI 0.42-0.83, p = 0.002). Results were similar across models adjusted for age, sex, and BMI and, separately, past SA, global eating disorder severity, current depression, psychotropic medication use, and additional C-reactive protein, albumin, zinc, and iron indices. Sensitivity analyses using ≤83 and ≤ 70 μg/L thresholds, restricting to women, and excluding extreme values yielded similar results. Exploratory analyses suggested modest attenuation of associations between purging, tobacco use, alcohol/substance use disorder and SA after adding selenium.

Conclusions: Lower baseline selenium was associated with higher subsequent SA hazard. If replicated, selenium status could inform future risk models.

Albeit different in their clinical presentations, schizophrenia (SZ) and autism spectrum disorder (ASD) share different features, with mounting evidence supporting a neurodevelopmental origin for both disorders and a common genetic susceptibility. Among associated genes, G protein-coupled receptors (GPCR) have frequently been related to both disorders. The aim of this systematic review is to gather evidence of the association between GPCR polymorphisms and the manifestation of SZ and ASD, and the potential effect of GPCR polymorphisms in treatment response to antipsychotics, the main pharmacological therapy used in both disorders. A total number of 301 polymorphisms within GPCR coding loci were reported as risk variants for SZ and/or ASD. Among these, association studies identified 171 polymorphisms associated with SZ, most frequently in DRD2 and DRD3 genes and 55 polymorphisms associated with ASD, mainly in OXTR and AVPR1A. GPCR variants have been shown to affect antipsychotic treatment response. In our analysis of the SZ population, mutations in the DRD2 gene were most frequently associated with clozapine and risperidone treatment response, whereas HTR2A mutations were more commonly linked to olanzapine response. In contrast, for antipsychotic treatment in ASD, response to risperidone appeared to be more strongly influenced by mutations in the HTR2C gene. Additionally, a further literature search was conducted to determine whether these polymorphisms had any known functional consequences affecting gene or protein expression, signalling, activity, binding, structure, or chemical properties. Functional biological mechanisms have been described for 59 polymorphisms, with DRD2 being the most extensively studied. In conclusion, this systematic review brings together compelling evidence highlighting the genetic influence of GPCRs in these two mental disorders.

Previous studies have demonstrated increased inflammatory markers and altered quantitative electroencephalography (qEEG) findings in schizophrenia. This study explores the relationship between systemic inflammation and electrophysiological changes in drug-naïve first-episode schizophrenia to understand the disorder's etiopathogenesis better. Eighty-two patients with first-episode schizophrenia (DSM-5) and 62 healthy, age- and sex-matched controls were included. Absolute spectral power (ASP) of frequency bands and slow-to-fast frequency ratios were analyzed using qEEG. Inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-albumin ratio (NAR), were measured and correlated with qEEG indices. Inflammatory markers such as neutrophil count, NLR, MLR, and NAR were significantly elevated in patients. Theta wave power increased globally, delta wave power was higher in parietal and occipital regions, and alpha power was elevated in frontal, parietal, and central regions. Inflammatory markers were negatively correlated with theta power and theta/beta ratios, linking systemic inflammation to altered brain activity. These findings support the inflammatory hypothesis of schizophrenia and suggest that qEEG indices and inflammatory markers may serve as potential biomarkers. The negative correlation between inflammatory markers and theta wave power indicates that inflammation affects electrophysiological processes in schizophrenia. Larger multicenter studies are needed to confirm these results.

The serotonin type 3 receptor (5-HT₃R) is a ligand-gated ion channel with a unique position within the serotonergic system, yet its relevance to schizophrenia (SCZ) and its frequent psychiatric comorbidities remains underappreciated. The aim of this review is to critically synthesize preclinical and clinical evidence supporting the role of 5-HT₃Rs in the pathophysiology and treatment of SCZ, with particular emphasis on negative and cognitive symptoms, as well as comorbid depressive symptoms and substance use disorders (SUDs). We summarize data demonstrating that 5-HT₃R antagonists (setrons), widely used and well tolerated in non-psychiatric indications, exert circuit-level effects through modulation of mesolimbic dopaminergic signaling, cortical excitation-inhibition balance, cholinergic transmission, and neuroinflammatory and oxidative stress pathways. Clinical studies and meta-analyses suggest statistically significant but heterogeneous improvements in negative symptoms with adjunctive setron treatment in SCZ, with less consistent findings for total and cognitive outcomes and minimal or no robust effects on positive symptoms. Preclinical and clinical evidence further suggests that 5-HT₃R antagonism may attenuate depressive symptomatology and reduce craving and relapse vulnerability in SUDs, highlighting its potential transdiagnostic relevance. In addition, recent advances in medicinal chemistry have yielded multifunctional ligands combining 5-HT₃R antagonism with dopaminergic or other serotonergic activities, illustrating a rational polypharmacological strategy for next-generation antipsychotic development. In conclusion, we propose that 5-HT₃Rs function as circuit-level modulatory hubs rather than classical antipsychotic targets. Targeting these receptors may represent a potentially well-tolerated and mechanistically distinct adjunctive strategy to address unmet therapeutic needs in SCZ, particularly negative symptoms, cognitive dysfunction, and psychiatric comorbidities.