Psychiatry and Clinical Neurosciences最新文献

Retraction: K. Wang , W. Tang , X. Hao , and H. Liu , "High Consumption of Whole Grain Foods Decreases the Risk of Dementia and Alzheimer's Disease: Framingham Offspring Cohort," Psychiatry and Clinical Neurosciences 77, no. 3 (2023): 141-148, https://doi.org/10.1111/pcn.13509. The above article, published online on 16 November 2022 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal's Editors-in-Chief, Tadafumi Kato and Hidehiko Takahashi; the Japanese Society of Psychiatry and Neurology; and John Wiley & Sons Australia. The retraction has been agreed as the authors did not have the appropriate approvals in place from the National Heart, Lung and Blood Institute (NHLBI) for use of the data in this article. This contravenes the journal's policy on data use and the journal is issuing this retraction as a result.

Aim: This study aimed to explore the comparative risks for dystonia among different second-generation antipsychotics (SGAs), the influence of sex, and the relationship between the time-to-onset of dystonia and its outcomes.

Methods: We analyzed data from the Japanese Adverse Drug Event Report database from April 2004 to November 2023. Cases involving oral SGAs, excluding clozapine, were extracted. We used the odds ratios to assess the reporting proportions among SGAs and sex, analyzed the median time-to-onset and interquartile ranges (IQRs), and conducted a receiver operating characteristic (ROC) curve analysis to investigate the time-to-onset of dystonia and its relationship to outcomes.

Results: We extracted 9837 cases involving oral SGAs. Lurasidone was associated with a significantly higher proportion of dystonia reports than risperidone, aripiprazole, quetiapine, and olanzapine. The reporting proportion of dystonia associated with aripiprazole was lower than that of paliperidone and risperidone, but higher than that of quetiapine and olanzapine. Female sex was significantly associated with a higher reporting proportion of dystonia compared with males. Among the 148 cases of oral SGA-induced dystonia, the median time-to-onset was 125 days (IQR, 19.75-453.25 days). Divided into the three outcome groups (recovered, improved, and unrecovered/residual), those with better outcomes had a shorter time-to-onset than those with poorer outcomes. ROC curve analysis suggested a threshold of 91.5 days for discriminating outcomes, with a sensitivity of 71.7% and specificity of 69.9%.

Conclusions: The risks of dystonia may vary among SGAs and between sexes. SGA-induced dystonia often manifests in the tardive form.

Aim: Despite the clinical importance and significant social burden of neuropsychiatric symptoms (NPS) in dementia, the underlying neurobiological mechanism remains poorly understood. Recently, neuroimaging-derived brain-age estimation by machine-learning analysis has shown promise as an individual-level biomarker. We investigated the relationship between NPS and brain-age in amnestic mild cognitive impairment (MCI) and early dementia.

Methods: In this cross-sectional study, clinical data, including neuropsychiatric inventory (NPI), and structural brain MRI of 499 individuals with clinical diagnoses of amnestic MCI (n = 185), early Alzheimer's disease (AD) (n = 258) or dementia with Lewy bodies (DLB) (n = 56) were analyzed. We established a brain-age prediction model using 694 healthy brain MRIs and a support vector regression model and applied it to the participants' data. Finally, the brain-predicted age difference (brain-PAD: predicted age minus chronological age) was calculated.

Results: All groups showed significantly increased brain-PAD, and the median (IQR) brain-PAD was 4.3 (5.4) years in MCI, 6.3 (6.2) years in AD, and 5.0 (6.5) years in DLB. The NPI scores were subdivided into the following four categories: (i) Agitation and Irritability, (ii) Depression and Apathy, (iii) Delusions and Hallucinations, and (iv) Euphoria and Disinhibition. We found a significantly positive correlation between brain-PAD and the depression/apathy factor (Spearman's rs = 0.156, FDR-corrected P = 0.002), whereas no significance was shown for the other NPS factors.

Conclusion: Higher brain-age may be associated with depression and apathy symptoms presented in MCI to early dementia stages, and brain-age analysis may be useful as a novel biomarker for the assessment or monitoring of NPS.

Aim: As a central component of schizophrenia psychopathology, negative symptoms result in detrimental effects on long-term functional prognosis. However, the neurobiological mechanism underlying negative symptoms remains poorly understood, which limits the development of novel treatment interventions. This study aimed to identify the specific neural fingerprints of negative symptoms in schizophrenia.

Methods: Based on resting-state functional connectivity data obtained in a large sample (n = 132) of first-episode drug-naïve schizophrenia patients (DN-FES), connectome-based predictive modeling (CPM) with cross-validation was applied to identify functional networks that predict the severity of negative symptoms. The generalizability of identified networks was then validated in an independent sample of n = 40 DN-FES.

Results: A connectivity pattern significantly driving the prediction of negative symptoms (ρ = 0.28, MSE = 81.04, P = 0.012) was identified within and between networks implicated in motivation (medial frontal, subcortical, sensorimotor), cognition (default mode, frontoparietal, medial frontal) and error processing (medial frontal and cerebellum). The identified networks also predicted negative symptoms in the independent validation sample (ρ = 0.37, P = 0.018). Importantly, the predictive model was symptom-specific and robust considering the potential effects of demographic characteristics and validation strategies.

Conclusions: Our study discovers and validates a comprehensive network model as the unique neural substrates of negative symptoms in schizophrenia, which provides a novel and comprehensive perspective to the development of target treatment strategies for negative symptoms.

Aim: Autistic traits exhibit neurodiversity with varying behaviors across developmental stages. Brain complexity theory, illustrating the dynamics of neural activity, may elucidate the evolution of autistic traits over time. Our study explored the patterns of brain complexity in autistic individuals from childhood to adulthood.

Methods: We analyzed functional magnetic resonance imaging data from 1087 autistic participants and neurotypical controls aged 6 to 30 years within the ABIDE I (Autism Brain Imaging Data Exchange) data set. Sample entropy was calculated to measure brain complexity among 90 brain regions, utilizing an automated anatomical labeling template for voxel parcellation. Participants were grouped using sliding age windows with partial overlaps. We assessed the average brain complexity of the entire brain and brain regions for both groups across age categories. Cluster analysis was conducted using generalized association plots to identify brain regions with similar developmental complexity trajectories. Finally, the relationship between brain region complexity and autistic traits was examined.

Results: Autistic individuals may tend toward higher whole-brain complexity during adolescence and lower complexity during childhood and adulthood, indicating possible distinct developmental trajectories. However, these results do not remain after Bonferroni correction. Two clusters of brain regions were identified, each with unique patterns of complexity changes over time. Correlations between brain region complexity, age, and autistic traits were also identified.

Conclusion: The study revealed brain complexity trajectories in autistic individuals, providing insight into the neurodiversity of autism and suggesting that age-related changes in brain complexity could be a potential neurodevelopmental marker for the dynamic nature of autism.

Aims: Schizophrenia, a debilitating mental disorder, is characterized by persistent negative symptoms such as avolition and anhedonia. Currently, there are no effective treatments available for these symptoms. Thus, our study aims to assess the efficacy of online high-definition transcranial direct current stimulation (online HD-tDCS) in addressing the negative symptoms of schizophrenia, utilizing a double-blind, randomized, sham-controlled trial design.

Methods: Fifty-nine patients with schizophrenia were randomized to receive either active HD-tDCS or sham stimulation, targeting the left dorsolateral prefrontal cortex. Outcomes were measured by changes in the Positive and Negative Syndrome Scale Factor Score for Negative Symptom (PANSS-FSNS). Exact low-resolution electromagnetic tomography was used to assess the functional connectivity.

Results: All 59 participants, including 50.84% females with an average age of 43.36 years, completed the trial. In the intention-to-treat analysis, patients receiving active HD-tDCS showed greater improvement in PANSS-FSNS scores compared to those receiving the sham procedure. The differences were 2.34 (95% confidence interval [CI], 1.28-3.40), 4.28 (95% CI, 2.93-5.62), and 4.91 (95% CI, 3.29-6.52) after the intervention, as well as at 1-week and 1-month follow-ups, respectively. A tingling sensation on the scalp was more common in the active group (63.3%) compared to the sham group (10.3%). Additionally, HD-tDCS was associated with a decrease in delta-band connectivity within the default mode network.

Conclusions: High-definition transcranial direct current stimulation was effective and safe in ameliorating negative symptoms in patients with schizophrenia when combined with online functional targeting.

Aim: Whole-exome sequencing (WES) studies have revealed that germline de novo variants (gDNVs) contribute to the genetic etiology of schizophrenia. However, the contribution of mosaic DNVs (mDNVs) to the risk of schizophrenia remains to be elucidated. In the present study, we systematically investigated the gDNVs and mDMVs that contribute to the genetic etiology of schizophrenia in a Japanese population.

Methods: We performed deep WES (depth: 460×) of 73 affected offspring and WES (depth: 116×) of 134 parents from 67 families with schizophrenia. Prioritized rare nonsynonymous gDNV and mDNV candidates were validated using Sanger sequencing and ultra-deep targeted amplicon sequencing (depth: 71,375×), respectively. Subsequently, we performed a Gene Ontology analysis of the gDNVs and mDNVs to obtain biological insights. Lastly, we selected DNVs in known risk genes for psychiatric and neurodevelopmental disorders.

Results: We identified 62 gDNVs and 98 mDNVs. The Gene Ontology analysis of mDNVs implicated actin filament and actin cytoskeleton as candidate biological pathways. There were eight DNVs in known risk genes: splice region gDNVs in AKAP11 and CUL1; a frameshift gDNV in SHANK1; a missense gDNV in SRCAP; missense mDNVs in CTNNB1, GRIN2A, and TSC2; and a nonsense mDNV in ZFHX4.

Conclusion: Our results suggest the potential contributions of rare nonsynonymous gDNVs and mDNVs to the genetic etiology of schizophrenia. This is the first report of the mDNVs in schizophrenia trios, demonstrating their potential relevance to schizophrenia pathology.

Aim: Bipolar disorder (BD) is a common psychiatric disorder characterized by alterations between manic/hypomanic and depressive states. Rare pathogenic copy number variations (CNVs) that overlap with exons of synaptic genes have been associated with BD. However, no study has comprehensively explored CNVs in synaptic genes associated with BD. Here, we evaluated the relationship between BD and rare CNVs that overlap with synaptic genes, not limited to exons, in the Japanese population.

Methods: Using array comparative genome hybridization, we detected CNVs in 1839 patients with BD and 2760 controls. We used the Synaptic Gene Ontology database to identify rare CNVs that overlap with synaptic genes. Using gene-based analysis, we compared their frequencies between the BD and control groups. We also searched for synaptic gene sets related to BD. The significance level was set to a false discovery rate of 10%.

Results: The RNF216 gene was significantly associated with BD (odds ratio, 4.51 [95% confidence interval, 1.66-14.89], false discovery rate < 10%). The BD-associated CNV that corresponded with RNF216 also partially overlapped with the minimal critical region of the 7p22.1 microduplication syndrome. The integral component of the postsynaptic membrane (Gene Ontology:0099055) was significantly associated with BD. The CNV overlapping with the intron region of GRM5 in this gene set showed a nominal significant association between cases and controls (P < 0.05).

Conclusion: We provide evidence that CNVs in RNF216 and postsynaptic membrane-related genes confer a risk of BD, contributing to a better understanding of the pathogenesis of BD.

Aim: This study examined the efficacy of AST-001 for the core symptoms of autism spectrum disorder (ASD) in children.

Methods: This phase 2 clinical trial consisted of a 12-week placebo-controlled main study, a 12-week extension, and a 12-week follow-up in children aged 2 to 11 years with ASD. The participants were randomized in a 1:1:1 ratio to a high-dose, low-dose, or placebo-to-high-dose control group during the main study. The placebo-to-high-dose control group received placebo during the main study and high-dose AST-001 during the extension. The a priori primary outcome was the mean change in the Adaptive Behavior Composite (ABC) score of the Korean Vineland Adaptive Behavior Scales II (K-VABS-II) from baseline to week 12.

Results: Among 151 enrolled participants, 144 completed the main study, 140 completed the extension, and 135 completed the follow-up. The mean K-VABS-II ABC score at the 12th week compared with baseline was significantly increased in the high-dose group (P = 0.042) compared with the placebo-to-high-dose control group. The mean CGI-S scores were significantly decreased at the 12th week in the high-dose (P = 0.046) and low-dose (P = 0.017) groups compared with the placebo-to-high-dose control group. During the extension, the K-VABS-II ABC and CGI-S scores of the placebo-to-high-dose control group changed rapidly after administration of high-dose AST-001 and caught up with those of the high-dose group at the 24th week. AST-001 was well tolerated with no safety concern. The most common adverse drug reaction was diarrhea.

Conclusions: Our results provide preliminary evidence for the efficacy of AST-001 for the core symptoms of ASD.