Psychiatry and Clinical Neurosciences最新文献

Aims: Growing evidence suggests abnormalities of brain structural connectome in psychiatric disorders, but the causal relationships remain underexplored. Therefore, elucidating the causality is critical for deciphering the neurobiological underpinnings of mental illnesses.

Methods: We conducted bidirectional two-sample Mendelian randomization (MR) analyses to investigate the causal links between 206 white-matter connectivity phenotypes (n = 26,333, UK Biobank) and 13 major psychiatric disorders (n = 14,307 to 1,222,882).

Results: Forward MR analyses identified causal effects of five genetically predicted white-matter structural connectivity phenotypes on six psychiatric disorders, with associations being significant or suggestive. For instance, the increase in structural connectivity between the left-hemisphere frontoparietal control network and right-hemisphere default mode network was significantly causally associated with decreased autism spectrum disorder risk, while elevated structural connectivity between the right-hemisphere frontoparietal control network and hippocampus was significantly causally linked to lower risk of both anorexia nervosa and cannabis use disorder. Reverse MR analyses revealed significantly or suggestively causal relationships between the risk of two psychiatric disorders and four different white-matter structural connectivity phenotypes. For example, the heightened susceptibility to anorexia nervosa was found to be significantly causally associated with diminished structural connectivity between the left-hemisphere visual network and pallidum.

Conclusions: These findings offer new insights into the cause of psychiatric disorders and highlight potential biomarkers for early detection and prevention at the brain structural connectome level.

Aim: To investigate the association between serum ergothioneine and risk of developing dementia and its subtypes in a community-dwelling older population.

Methods: In this prospective longitudinal analysis of participants enrolled in the Hisayama Study, 1344 Japanese community-residents aged 65 years and over without dementia at baseline were followed prospectively for a median of 11.2 years (2012-2023). Serum ergothioneine levels were quantified using liquid chromatography-mass spectrometry and divided into quartiles. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and their 95% confidence intervals for the association between serum ergothioneine levels and the risk of dementia subtypes.

Results: During the follow-up, 273 participants developed all-cause dementia. Among them, 201 had Alzheimer's disease (AD) and 72 had non-Alzheimer's disease (non-AD) dementia. The age- and sex-adjusted HRs for all-cause dementia, AD, and non-AD dementia decreased progressively across increasing quartiles of serum ergothioneine (all P for trend <0.05). These associations remained significant after adjustment for a wide range of cardiovascular, lifestyle, and dietary factors, including daily vegetable intake (P for trend <0.05). In subgroup analyses stratified by daily vegetable intake, higher serum ergothioneine levels were consistently associated with lower dementia risk, irrespective of vegetable consumption.

Conclusions: Our findings showed that higher serum ergothioneine levels were associated with a lower risk of developing all-cause dementia, AD, and non-AD dementia in an older Japanese population. Since ergothioneine cannot be synthesized in the human body, a diet rich in ergothioneine may be beneficial in reducing the risk of dementia.

An elderly inpatient with schizophrenia and pica developed bowel obstruction after ingesting plastic gloves; laparotomy removed eleven gloves. The case underscores the need to eliminate seemingly harmless plastic items from the environment of patients with pica, especially those with cognitive or communication impairments.

Aim: The current study investigated the superiority of anxiolytic effects of venlafaxine extended release (ER) compared with placebo and its safety and tolerability in Japanese adult outpatients with generalized anxiety disorder (GAD).

Methods: In this placebo-controlled, double-blind study, 357 eligible participants were randomized to receive venlafaxine ER (75-225 mg/day) or placebo for 8 weeks. The primary endpoint was change from baseline to week 8 in Hamilton Anxiety Rating Scale (HAM-A) total score. Secondary endpoints included changes from baseline to week 8 in scores of HAM-A psychic anxiety factors, HAM-A somatic anxiety factors, Clinical Global Impressions-Severity of Illness (CGI-S), Generalized Anxiety Disorder-7 (GAD-7), Zung Self-Rating Anxiety Scale (Z-SAS), Sheehan Disability Scale (SDS), and the absolute score of Clinical Global Impressions-Global Improvement (CGI-I).

Results: Venlafaxine ER showed statistically significant reduction in HAM-A total score at week 8 (difference versus placebo: P = 0.012). The results of all secondary endpoints were consistent with this finding and likewise demonstrated statistical significance in favor of venlafaxine ER in investigator- and patient-rated scales. Venlafaxine ER further showed statistically significant remission in total HAM-A score. These results showed that venlafaxine ER improved patients' functional disabilities along with symptoms more than placebo. Venlafaxine ER was well tolerated, and safety findings were generally consistent with the known safety profile of the drug.

Conclusion: Venlafaxine ER has a favorable benefit-risk profile in adult Japanese patients with GAD, indicating its potential to improve GAD symptoms as well as patients' function and exert superior anxiolytic effects over placebo without any new safety concern.

Trial registration: Japan Registry of Clinical Trials Identifier jRCT2031220156.

Background: Emerging studies link COVID-19 to adverse multi-organ outcomes. To better estimate psychiatric and physical illness after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we analyzed a nationally representative cohort with minimal prior infection (>99% uninfected) and low vaccination coverage (<1%) in Taiwan.

Methods: We conducted a cohort study comprising 11,185 individuals who survived the first 30 days following SARS-CoV-2 infection (alpha variant) between May 1, 2021, and September 30, 2021, confirmed by reverse transcription polymerase chain reaction, along with three age- and sex-matched comparison groups: a contemporary control group (n = 223,700) with no COVID-19 diagnosis, a historical control group (n = 223,700) predating the pandemic, and seasonal influenza group (n = 44,740). We calculated the adjusted incidence rate ratios (aIRRs) of specific psychiatric and physical illnesses to compare their occurrence between the COVID-19 cohort and comparison groups.

Results: During the 6 months after the first COVID-19 diagnosis, aIRRs for psychiatric illnesses in the COVID-19 group were higher across diagnostic categories than those of comparison groups. Moreover, aIRRs of physical illnesses in the COVID-19 group were higher across nearly all major organ systems compared to the comparison ones. The absolute rate difference for overall psychiatric illnesses was 7921.0 (COVID-19 vs contemporary control) and 7226.9 per 100,000 person-years (COVID-19 vs historical control), respectively.

Conclusions: SARS-CoV-2-immunologically naïve individuals have heightened risks of psychiatric illnesses across diagnostic categories and physical illnesses spanning nearly all major organ systems after the infection. Future studies warrant to explore the pathogenesis of these postacute effects.

Aim: Changes in neurometabolites are believed to have a significant impact on the underlying mechanisms of obsessive-compulsive disorder (OCD). However, current findings regarding the neurometabolite levels of OCD patients remain inconsistent. To address this issue, we conducted a comprehensive meta-analysis of proton magnetic resonance spectroscopy studies to investigate the differences in neurometabolite levels in OCD patients relative to healthy controls (HCs).

Methods: A systematic search of PubMed, Web of Science, and Embase included 55 original studies that compared the levels of eight in vivo neurometabolites in OCD patients (n = 1270) and HCs (n = 1186). Hedge's g with random effects model was employed to calculate the effect sizes for the between-group differences in neurometabolite levels. Meta-regression and subgroup analyses were conducted to examine confounding effects.

Results: Compared to HCs, OCD patients exhibited decreased N-acetylaspartate compounds (NAA) in the striatum, as well as elevated choline-containing compounds (Cho) levels in the thalamus. The symptom severity of OCD patients showed positive associations with Cho in the striatum. Subgroup analyses showed that decreased striatal NAA in OCD patients remained evident in both the medicated and 1.5T subgroups. Additionally, significantly increased thalamic Cho in OCD patients was also observed in the unmedicated, adult, 3.0T, and non-comorbid subgroups.

Conclusion: This study reveals neurometabolic dysregulation within the cortico-striatal-thalamo-cortical circuits in OCD, offering integrated insights into its underlying neurobiological mechanisms.

Schizophrenia is a complex psychiatric disorder characterized by positive, negative, and general psychopathological symptoms. While antipsychotic drugs are effective for positive symptoms, they provide limited benefit for negative symptoms, which are often persistent and strongly associated with functional disability. Additionally, up to 30% of patients exhibit resistance to current treatments, including clozapine. These challenges underscore the need for novel adjunctive strategies. This systematic review and meta-analysis, preregistered in PROSPERO (CRD42022359199), evaluated the efficacy and safety of repurposed antihypertensive drugs (AHTs) as adjunctive treatments for schizophrenia. PubMed, Web of Science, and Scopus were searched for double-blind, randomized controlled trials (RCTs) published since 2000. Twelve studies were included (n = 436; sodium nitroprusside = 6; diuretics = 4; telmisartan = 1; clonidine = 1). Meta-analyses were conducted on Positive and Negative Syndrome Scale (PANSS) outcomes and adverse event (AE) rates. Standardized mean differences (SMDs) were calculated as Hedges' g using a restricted maximum likelihood estimator. Incidence rate ratios modeled AE rates. AHTs significantly improved negative symptoms (SMD = -0.37 [-0.59, -0.15]; I² = 43.8%), positive symptoms (SMD = -0.29 [-0.53, -0.06]; I² = 25.1%), general psychopathology (SMD = -0.28 [-0.48, -0.08]; I² = 0.0%), and total symptoms (SMD = -0.44 [-0.66, -0.21]; I² = 0.0%). No significant increase in AEs was observed. Overall, repurposed AHTs-particularly sodium nitroprusside-may offer adjunctive therapeutic benefits for schizophrenia treatments. Some diuretics also showed preliminary signals of efficacy. However, findings are preliminary and require confirmation in larger, long-term RCTs.

A randomized, double-blinded, placebo-controlled study by Otsubo et al. demonstrated a statistically significant effect of venlafaxine in patients with generalized anxiety disorder. However, the magnitude of improvement may have little clinical value. Methodological factors-including the exclusion of placebo responders, the inclusion of participants with comorbid depressive disorders, and a higher rate of discontinuation due to adverse events-further diminish the clinical significance of the findings. Overall, although venlafaxine achieved statistical efficacy, it may lack a clinically meaningful risk-benefit balance.

Aim: Previous studies have found that patients with major depressive disorder (MDD) exist in a subcritical state, impairing information processing. However, the mechanisms behind these abnormalities remain unclear, as biomolecular explanations offer only a partial explanation. The brain's efficiency depends not only on molecular networks but also on peripheral physiological rhythms, particularly cardiac signals. Given that MDD involves deficits in heart-brain interactions, this study aims to examine how resting-state neural avalanche dynamics vary across cardiac cycles in MDD.

Methods: We collected 5-min resting-state magnetoencephalography and electrocardiogram data from 60 patients with MDD and 60 healthy control participants. We defined neural avalanches during different phases of the cardiac cycle (systole versus diastole). Avalanche criticality metrics were computed to measure individuals' deviations from criticality. A mixed-design two-way anova was conducted to examine the main effects and interaction effects of cardiac phase and depression on avalanche criticality metrics.

Results: The avalanche metrics move toward from the critical point during diastole compared with systole in both groups at the whole-brain level. However, the $\beta$ -band avalanche metrics in patients with MDD move further from the critical point during diastole compared with systole in the default mode network.

Conclusion: Our findings suggest that, when the cardiac cycle fails to dynamically regulate default mode network excitability fluctuations through phase-specific inputs, $\beta$ -band activity becomes decoupled from the physiological cardiac rhythm, leading to a persistent bias of the network toward a subcritical state.