Psychiatry and Clinical Neurosciences最新文献

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: Empirical research investigating hyperorality in syndromes associated with frontotemporal lobar degeneration (FTLD) is limited. The present study aims to assess and describe hyperorality and its clinical and imaging correlates in patients with FTLD-associated syndromes.

Methods: This retrospective longitudinal study included consecutive patients with FTLD who underwent a clinical, cognitive, and behavioral assessment. The presence and severity of hyperorality was assessed using the Frontal Behavior Inventory.

Results: A total of 712 patients with FTLD were included in the study. Hyperorality was reported by 29% (204 of 712 [95% CI: 25-32%]) of patients; was more frequent in those with severe dementia than in those with prodromal or mild to moderate dementia (P < 0.05); was associated with younger age (odds ratio [OR] = 0.96 [95% CI: 0.94-0.99]), (P = 0.003) and positive family history for dementia (OR = 2.03 [95% CI: 1.18-3.49], P = 0.010); was overall more probable in the behavioral variant of frontotemporal dementia (bvFTD) and frontotemporal dementia with amyotrophic lateral sclerosis phenotypes, and less probable in other language or motor phenotypes; and was associated with higher severity of neuropsychiatric symptoms (OR = 1.08 [95% CI: 1.06-1.10], P < 0.001) and with the presence of several behavioral symptoms (P < 0.05). Moreover, hyperorality severity increased over time only in patients with bvFTD (β = +0.15, P = 0.011) or semantic variant of primary progressive aphasia (β = +0.34, P = 0.010). Finally, the presence of hyperorality was significantly associated with greater atrophy in the right anterior insula and right orbitofrontal region (false discovery rate-corrected P < 0.05).

Conclusion: Hyperorality is common in certain FTLD-associated syndromes. Understanding its correlates can help clinicians define pharmacological and educational interventions and clarify related anatomical circuits.

Aim: Current treatments for obsessive-compulsive disorder (OCD) encounter resistance and limiting adverse events, necessitating novel therapeutic strategies. This study aimed to investigate the benefits of naproxen, a medication with effects on inflammation and neuronal function, on OCD.

Methods: One hundred and four OCD outpatients with a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score of >21 were equally assigned to receive fluoxetine plus either naproxen 250 mg or matched placebo q12hr. Patients were assessed using the Y-BOCS by recording the subscale scores at baseline and weeks 5 and 10 to evaluate efficacy. They were also assessed in terms of tolerability.

Results: Data from 96 patients were analyzed. The baseline characteristics were comparable between the groups. There were significant time-treatment interaction effects on the obsession subscale ( ${\eta }_P^2$  = 0.055) and total ( ${\eta }_P^2$  = 0.043) scores of Y-BOCS. Reductions in the obsession subscale and total scores of Y-BOCS were significantly greater in the fluoxetine plus naproxen group until the endpoint (Cohen's d = 0.560 and Cohen's d = 0.477, respectively). However, the difference in compulsion subscale score changes between the groups was not significant. Respondents with a reduction of ≥35% in Y-BOCS total scores were significantly more in the fluoxetine plus naproxen group (80.0% versus 47.8%). The side effect frequencies were comparable between the groups.

Conclusion: Naproxen, adjunct to fluoxetine, outperformed adjunctive placebo in treating obsession and total symptoms of OCD patients in a safe and tolerable manner.

Clinical trial registration: The study protocol was registered and published in the Iranian Registry of Clinical Trials (http://www.irct.ir; registration number IRCT20090117001556N139).

Psilocybin is a classic psychedelic with demonstrated preliminary clinical efficacy in a range of psychiatric disorders. Evaluating the impact of psilocybin on cognitive function is essential to unravel its potential benefits and risks. In this systematic review, we assessed psilocybin's effect on cognitive function through a comprehensive search of electronic databases from inception to January 2024, identifying 20 articles involving 2,959 participants. While 85% of studies were conducted in healthy volunteers, most of these studies (85%) used macrodoses, ranging from 45 μg/kg to 30 mg/70 kg. Various cognitive aspects were evaluated and yielded mixed results. Global cognitive function, and processing speed remained mostly unchanged in healthy individuals; However, a limited number of studies reported improvements in certain areas such as sustained attention, working memory, and executive function especially in patients with treatment-resistant depression (TRD). Emotional processing was positively modified, particularly in TRD patients. Psilocybin was observed to enhance emotional empathy without significantly altering cognitive empathy and social cognition. Cognitive flexibility and creative cognition were noted to initially decline but could potentially improve over time. Additionally, with respect to learning and memory skills, psilocybin showed promise in improving specific memory types such as semantic associations and associative learning, while its effects on episodic and verbal memory have been less pronounced compared to other cognitive enhancers. The observed mixed findings underscore the complexity of psilocybin's cognitive influence. Further research is essential to provide a clearer understanding of psilocybin's impact on cognitive domains and to guide the development of safe and effective interventions.

Aims: Decreases in suicide rates during the coronavirus disease 2019 (COVID-19) pandemic were found in several countries, including Taiwan and South Korea. We investigated the pattern of the reduction in suicide by sex, age, method, and outbreak period in the two countries.

Methods: Suicide data for Taiwan (2015-2021) and South Korea (2017-2021) stratified by sex, age, method, and month were extracted from national mortality data files in the two countries. Negative binomial regression was used to estimate suicide rate ratios and 95% confidence intervals across outbreak and inter-outbreak periods during the pandemic, relative to that expected based on pre-pandemic trends, and their associations with economic and outbreak control stringency indicators.

Results: There were fewer-than-expected suicides in Taiwan (7%-16% fewer suicides over outbreaks and inter-outbreaks) and South Korea (17% fewer suicides in outbreaks III and IV). Fewer-than-expected suicides were found primarily in the working-age populations aged 25 to 64 years in Taiwan and those aged 45 to 64 years in South Korea. In both countries, fewer-than-expected suicides by charcoal burning during the pandemic were consistently found; the greatest reduction occurred when the outbreak control measures were most restricted. Increased time at residence was associated with decreased suicide rates in South Korea.

Conclusion: Taiwan and South Korea showed reduced suicide rates during the COVID-19 pandemic in 2020-2021. Potential reasons for the decrease in suicides may include reduced access to suicide means during outbreaks in the two countries.

Aim: Mental health issues in adolescence contribute to various disease burdens later in life and are associated with violence, crime, and suicide. Activities such as sleep, diet, exercise, and time spent using electronic devices are related to declining mental health. However, few studies have examined the association between commuting times to school and mental health. This study tested the hypothesis that high school students' long commuting times are associated with poor mental health.

Method: A cross-sectional study was conducted between October and December 2022 among 2067 students at two private high schools. Survey items included participant information (sex, grade, school), commuting time, mental health status (Patient Health Questionnaire 9 [PHQ-9]: depressive symptoms, and Generalized Anxiety Disorder 7 [GAD-7]: anxiety symptoms), lifestyle factors, and sleep-related factors.

Results: Data from 1899 high school students were analyzed. The prevalence of depressive and anxiety symptoms was 17.3% and 19.0%, respectively. A commuting time of ≥1 h was significantly associated with depressive symptoms (adjusted odds ratio: 1.60 [95% confidence interval]: 1.14-2.24) and anxiety symptoms (adjusted odds ratio: 1.51 [95% confidence interval]: 1.09-2.10). Sex, grade, use of ≥8 h/day of electronic devices, and chronotype were significantly associated with depressive symptoms, while sex, grade, use of ≥8 h/day of electronic devices, and insomnia were significantly associated with anxiety symptoms.

Conclusion: It is suggested that long commuting times are associated with poor mental health in high school students. Parents and schools should consider commuting time when advising students on school selection to maintain their mental health.

Aim: Cerebello-cortical functional dysconnectivity plays a key role in the pathology of schizophrenia (SZ). We aimed to investigate the changes in cerebello-cortical directional connectivity in patients with SZ.

Methods: A total of 180 drug-naïve patients with first-episode SZ (54 reassessed after 1 year of treatment) and 166 healthy controls (HCs) were included. Resting-state functional magnetic resonance imaging was used to perform Granger causal analysis, in which each of the nine cerebellar functional systems was defined as a seed. The observed effective connectivity (EC) alterations at baseline were further assessed at follow-up and were associated with changes in psychotic symptom.

Results: We observed increased bottom-up EC in first-episode SZ from the cerebellum to the cerebrum (e.g. from the cerebellar attention and cingulo-opercular systems to the bilateral angular gyri, and from the cerebellar cingulo-opercular system to the right inferior frontal gyrus). In contrast, decreased top-down EC in the first-episode SZ was mainly from the cerebrum to the cerebellum (e.g. from the right inferior temporal gyrus, left middle temporal gyrus, left putamen, and right angular gyrus to the cerebellar language system). After 1 year of antipsychotic treatment, information projections from the cerebrum to the cerebellum were partly restored and positively related to symptom remission.

Conclusion: These findings suggest that decreased top-down EC during the acute phase of SZ may be a state-dependent alteration related to symptoms and medication. However, increased bottom-up EC may reflect a persistent pathological trait.

Aim: This study evaluated the effectiveness of high-dose vitamin D supplementation in alleviating fatigue and neuropsychiatric symptoms in post-COVID syndrome.

Methods: In an 8-week, double-blind, randomized, placebo-controlled trial, 80 patients with post-COVID fatigue or neuropsychiatric symptoms were enrolled. Participants were randomly assigned to receive either 60,000 IU of vitamin D weekly (n = 40) or a placebo (n = 40) for 8 weeks. Clinical outcomes were assessed using the 11-item Chalder Fatigue Scale (CFQ-11); 21-item Depression, Anxiety, and Stress Scale (DASS-21); Pittsburgh Sleep Quality Index (PSQI); Addenbrooke's Cognitive Examination III (ACE); and Trail Making Test A and B (TMT-A and TMT-B). Baseline and 8-week measurements of inflammatory markers, including interleukin 6 (IL-6) and C-reactive protein (CRP), were also collected.

Results: Significant improvements were found in the vitamin D group for CFQ (coefficient -3.5, P = 0.024), DASS-anxiety (-2.0, P = 0.011), and ACE (2.1, P = 0.012). No significant differences were observed in PSQI, DASS-depression, TMT, IL-6, or CRP levels. The incidence of adverse events was comparable between groups, with no serious adverse events reported.

Conclusion: High-dose vitamin D supplementation may benefit patients with post-COVID syndrome by reducing fatigue, alleviating anxiety, and improving cognitive symptoms, with minimal side effects.

Aim: Adverse childhood experiences are potentially traumatic events with long-lasting effects on the health and well-being of patients with autism spectrum disorder (ASD). It is important to clarify which types of long-lasting autism-related symptoms are influenced by childhood experiences to design future intervention studies. However, few studies have examined the association between childhood experiences and autistic symptoms in large samples of adults with ASD and individuals with typical development (TD). In this study, we evaluate the effects of adverse childhood experiences on multiple ASD phenotypes among both individuals with ASD and those with TD.

Method: We combined questionnaire evaluations; Childhood Abuse and Trauma Scale, the Japanese version of the Autism-Spectrum Quotient, Conners' Adult ADHD Rating Scale, the Japanese version of the Impact of Event Scale-Revised, and the Japanese version of the Adolescent/Adult Sensory Profile.

Results: Individuals with ASD and those with TD (n = 205 and 104, respectively) were included. There were significant correlations between the extent of adverse childhood experiences and severity of attention-deficit/hyperactivity disorder symptoms, posttraumatic stress disorder symptoms, and hypersensitivity in both participants with ASD and those with TD. By contrast, ASD core symptoms showed no significant correlation with adverse childhood experiences in either group. These results remained consistent after adjusting for age, sex, and the estimated intelligence quotient.

Conclusion: These findings suggest the need for a detailed disentanglement of ASD-related core and peripheral symptoms of adverse childhood experiences, which may help to appropriately set outcomes for future early interventions for the childhood experiences of individuals with ASD.