Neuropsychobiology最新文献

Introduction: Bipolar 2 disorder (BD2) is an independent disease with specific familial aggregation, significant functional impairment, specific treatment challenges, and several distinctive clinical features. However, unlike bipolar 1 disorder, studies investigating causal and functional genes are lacking. This study aimed to identify and prioritize causal genetic variants and genes for BD2 by analysing brain-specific gene expression markers, improve the understanding of its genetic underpinnings, and support advancements in diagnosis, treatment, and prognosis.

Method: We used FUMA, a genome-wide association study (GWAS) annotation tool, to pinpoint potential causal variants and genes from the largest BD2 GWAS data. Candidate causal variants most likely affecting brain gene expression were prioritized using the following criteria: (1) variants identified as eSNPs in any brain region within any brain expression quantitative trait loci (eQTL) dataset; (2) variants annotated in the Regulome database with a score <5, indicating likely functional localization; (3) the most common 15-core chromatin state across all cell types in the Roadmap Epigenomics data being ≤7, reflecting an open chromatin state; (4) localization in genomic regions with evidence of 3D chromatin interactions, as such interactions mediate genetic effects on gene expression.

Results: We identified AGRN, ORMDL3, SLC25A39, RUNDC3A, NOS2, C1orf159, RP11-5407.18, RP11-465B22.3, RP11-5407.17 as candidate causal genes. These genes are associated with important pathways such as synapse formation, mitochondrial and oxidative metabolism, intracellular transport, neurotransmission, and lipid metabolism-related pathways.

Conclusion: This study provides a guide for further experimental validation of functional variants, BD2-associated genes, and novel drug targets.

Introduction: Although lithium has long been considered the gold standard for mood stabilization in the treatment of bipolar disorder, growing concerns about its adverse events have significantly undermined its once-trusted status. This study aims to conduct a pharmacovigilance analysis of lithium to provide a more comprehensive understanding of its safety profile.

Methods: Four disproportionality analysis methods, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM), were employed to detect potential signals between lithium and various adverse events.

Results: Analysis of 6,909 adverse event reports from the FDA Adverse Event Reporting System (FAERS) showed that lithium-related adverse events occur in the endocrine, renal or urinary, nervous, and psychiatric systems. Well-known adverse events, such as hypothyroidism, nephrogenic diabetes insipidus, and ataxia, were found. In addition, several previously overlooked adverse events, such as renal oncocytoma, benign parathyroid tumor, and Adams-Stokes syndrome, were identified.

Conclusion: By analyzing real-world data, this study provides a comprehensive evaluation of lithium's safety profile, offering critical evidence for its clinical risk. However, given the inherent limitations of FAERS, such as underreporting of minor symptoms, the findings should be interpreted cautiously.

Introduction: Depression is a prevalent mental health disorder. miR-27a regulates neuronal development. This study aimed to investigate the association between the miR-27a rs895819 polymorphism and antidepressant treatment response in patients with depression.

Methods: The expression level of miR-27a was detected by reverse transcription-polymerase chain reaction. The genotype of rs895819 was performed by PCR-restriction fragment length polymorphism. The condition of patients was evaluated by a 17-item Hamilton Depression Rating Scale (HAMD-17) (reduction rate = [HAMD-17 baseline - HAMD-17 8 weeks]/HAMD-17 baseline × 100%). Effective response was defined as a reduction rate of ≥50%. Remission was defined as HAMD-17 ≤17. The association between SNP and depression risk was calculated by the χ2 test. Logistic regression analysis was performed to evaluate the effects of SNP on antidepressant treatment response.

Results: There were 173 patients with depression and 186 healthy controls. rs895819 was negatively correlated with depression under CC versus TT (p = 0.044, OR = 0.412, 95% CI = 0.170-0.996), CC + TC versus TT (OR = 0.607, 95% CI = 0.397-0.927), and C versus T (OR = 0.633, 95% CI = 0.448-0.896) models. miR-27a expression was significantly decreased in individuals with TC/CC genotypes than TT genotypes. rs895819 (TC/CC) was positively correlated with the effective response (p = 0.005, OR = 2.551, 95% CI = 1.322-4.920).

Conclusion: rs895819 TC/CC genotypes were significantly correlated with depression and associated with increased effective response.

Introduction: As a late proinflammatory factor, the role of high-mobility group box 1 (HMGB-1) in nervous system inflammation has been widely studied. The inflammatory response mediated by HMGB-1 plays an important role in the pathophysiological mechanism of depression. This study aimed to investigate the antidepressant effects of forced running on chronic unpredictable mild stress (CUMS) mice by examining the impact on hippocampal HMGB-1.

Methods: The experiment included a comparison with the traditional broad-spectrum antidepressant fluoxetine to evaluate the potential benefits of forced exercise or combined therapy. Mice were divided into different groups - control, forced running + fluoxetine (FR + FLU), CUMS, CUMS + forced running (CUMS + FR), CUMS + fluoxetine (CUMS + FLU), and CUMS + forced running + fluoxetine combined therapy (CUMS + FR + FLU). The study used the tail suspension test (TST), forced swimming test (FST), and sucrose preference test (SPT) to assess depression-like behavior. Following the experiment, the levels of hippocampal HMGB-1 and associated proteins and cytokines were measured.

Results: The results revealed that 4 weeks of forced running significantly attenuated depression-like behavior and reduced the expression of HMGB-1-associated inflammatory proteins and cytokines in CUMS mice. Conversely, fluoxetine showed limited effectiveness in reversing depression-like behavior but demonstrated a reduction in the expression of hippocampal HMGB-1-associated inflammatory proteins and cytokines. The combined therapy also exhibited significant antidepressant effects and reduced levels of HMGB-1-associated inflammatory proteins and cytokines, with a faster response compared to forced running alone.

Conclusion: Forced running may offer potential benefits in modulating the anti-inflammatory response associated with HMGB-1, providing insights into the potential therapeutic role of physical exercise in managing depression.

Introduction: Anorexia nervosa (AN) is a severe and complex eating disorder (ED), whose incidence has increased following the COVID-19 pandemic, straining specialized healthcare systems worldwide. Although patients often resort to compulsive exercise as a means of weight control, prolonged fasting intensifies the urge to move, leading to increased motor restlessness. Despite progress in understanding AN, interventions often overlook the crucial role that the urge to be physically active plays in reinforcing the ED itself. This case series tested the feasibility of a Virtual Reality-based Running Exposure (VR-RE) protocol to target the acute urge to be physically active in inpatients with severe AN undergoing rehabilitation.

Methods: Three female inpatients with severe AN (body mass index ≤15 kg/m2), aged 21, 23, and 26, participated in a 4-week VR-RE protocol, involving four sessions of simulated jogging in a VR environment. Pre- and post-intervention assessments evaluated ED symptoms and traits characteristics, such as compulsive exercise and physical activity addiction.

Results: Although treatment outcomes were only partially achieved and there was little change observed in clinical parameters such as weight and body mass index, reductions in the acute urge to move were observed for all after each VR session. Additionally, reliable and clinically relevant changes were observed in drive for thinness, body image dissatisfaction, interoceptive deficits, and emotional regulation. Two patients also reported a decrease in both trait and addictive physical activity at the end of the protocol and rehabilitation program. Qualitative feedback revealed perceived synchronization with the avatar and endorsed the protocol's potential for outpatient settings. No cybersickness was reported.

Conclusion: This study presents a structured VR-based protocol targeting the acute urge to be physically active in severe AN, integrated into a rehabilitation setting. Future research with longer, personalized, and controlled trials is needed to validate its clinical utility.

Introduction: There is some evidence for hypothalamic-pituitary-adrenal (HPA) axis hypofunction in chronic tinnitus, but findings are contradicting possibly due to clinical heterogeneity. This study aimed to assess differential effects of childhood trauma and anxiety on HPA-axis functioning in adults suffering from chronic subjective tinnitus with distress.

Methods: Salivary cortisol data were collected in 22 chronic subjective tinnitus sufferers (without major depression) and 29 healthy controls after awakening, at baseline, and after a low-dose (0.5 mg) dexamethasone challenge. A factorial ANCOVA was conducted to compare the main effects of group (tinnitus versus. controls), trauma, and their interaction effect on the cortisol awakening response (CAR). Linear mixed models were fitted for baseline and post-dexamethasone cortisol levels with group, sampling time, trauma, and their interactions as fixed factors and subject as the random effect. The Beck Anxiety Index, Anxiety Sensitivity Index, and Panic Disorder Severity Scale were included to investigate effects of anxiety.

Results: A significant interaction between group and trauma (F [1, 47] = 6.9755, p = 0.0112) was found, with the tinnitus group showing lower CARs (M = 5.1808, SD = 0.5821) than the comparison group (M = 5.9974, SD = 0.5251) in traumatized individuals only. No effects were found for baseline or post-dexamethasone cortisol. Anxiety scores had no effects on any of the outcome variables.

Conclusion: A differential effect of childhood trauma, but not anxiety, on the HPA-axis function in chronic subjective tinnitus was partly confirmed by the finding of a blunted CAR in tinnitus sufferers reporting early-life adversity.