Psychiatry and Clinical Neurosciences最新文献

{"title":"Copy number variations in RNF216 and postsynaptic membrane-associated genes are associated with bipolar disorder: a case-control study in the Japanese population.","authors":"Masahiro Nakatochi, Itaru Kushima, Branko Aleksic, Hiroki Kimura, Hidekazu Kato, Toshiya Inada, Youta Torii, Nagahide Takahashi, Maeri Yamamoto, Kunihiro Iwamoto, Yoshihiro Nawa, Shuji Iritani, Nakao Iwata, Takeo Saito, Kohei Ninomiya, Tomo Okochi, Ryota Hashimoto, Hidenaga Yamamori, Yuka Yasuda, Michiko Fujimoto, Kenichiro Miura, Kazutaka Ohi, Toshiki Shioiri, Kiyoyuki Kitaichi, Masanari Itokawa, Makoto Arai, Mitsuhiro Miyashita, Kazuya Toriumi, Tsutomu Takahashi, Michio Suzuki, Takahiro A Kato, Shigenobu Kanba, Hideki Horikawa, Kiyoto Kasai, Tempei Ikegame, Seiichiro Jinde, Tadafumi Kato, Chihiro Kakiuchi, Bun Yamagata, Shintaro Nio, Yasuto Kunii, Hirooki Yabe, Yasunobu Okamura, Shu Tadaka, Ueno Fumihiko, Taku Obara, Yasuyuki Yamamoto, Yuko Arioka, Daisuke Mori, Masashi Ikeda, Norio Ozaki","doi":"10.1111/pcn.13752","DOIUrl":"10.1111/pcn.13752","url":null,"abstract":"<p><strong>Aim: </strong>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.</p><p><strong>Methods: </strong>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%.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"12-20"},"PeriodicalIF":5.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AST-001 versus placebo for social communication in children with autism spectrum disorder: A randomized clinical trial.","authors":"Hyo-Won Kim, Ji-Hoon Kim, Un Sun Chung, Johanna Inhyang Kim, Se-Hoon Shim, Tae Won Park, Moon-Soo Lee, Jun-Won Hwang, Eun-Jin Park, Su-Kyeong Hwang, Yoo-Sook Joung","doi":"10.1111/pcn.13757","DOIUrl":"10.1111/pcn.13757","url":null,"abstract":"<p><strong>Aim: </strong>This study examined the efficacy of AST-001 for the core symptoms of autism spectrum disorder (ASD) in children.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>Our results provide preliminary evidence for the efficacy of AST-001 for the core symptoms of ASD.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"21-28"},"PeriodicalIF":5.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of subsequent Parkinson's disease among patients with bipolar disorder or major depression: A nationwide longitudinal study in Taiwan.","authors":"Mao-Hsuan Huang, Chih-Ming Cheng, Ju-Wei Hsu, Ya-Mei Bai, Tung-Ping Su, Cheng-Ta Li, Shih-Jen Tsai, Yee-Lam E Chan, Mu-Hong Chen","doi":"10.1111/pcn.13759","DOIUrl":"10.1111/pcn.13759","url":null,"abstract":"<p><strong>Aim: </strong>Bipolar disorder (BD) and major depression have been associated with an increased risk of developing Parkinson's disease (PD); however, few studies have directly compared the risk of PD development between patients with BD and major depression while considering relevant risk factors and psychotropic medications.</p><p><strong>Methods: </strong>Using the Taiwan National Health Insurance Research Database, 21,186 patients with BD, 21,188 patients with major depression, and 42,374 controls were enrolled between 2001 and 2009, and followed until the end of 2011. Individuals who developed PD during the follow-up period were identified. Cox regression models were used to analyze the hazard ratio (HR) of developing PD, adjusting for demographic factors, comorbidities, and psychotropic medication usage.</p><p><strong>Results: </strong>Both patients with BD [HR 8.63, 95% confidence interval (CI) 6.35-11.72] and those with major depression (HR 5.68, 95% CI 4.15-7.78) had an elevated risk of subsequent PD compared to the controls. Patients with BD were associated with a 51% increased risk of subsequent PD compared with patients with major depression. Long-term treatment with antiepileptic mood stabilizers was associated with increased PD risk among patients with late-onset BD and high Charlson comorbidity index scores. Lithium was not associated with an increased PD risk.</p><p><strong>Conclusions: </strong>The study highlights an elevated PD risk in patients with BD and major depression compared to the controls, with BD patients at highest risk. Further research is needed to elucidate the complex interplay between psychotropic medications and neurodegenerative processes in BD, aiming to optimize therapeutic strategies and improve patient outcomes.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"29-36"},"PeriodicalIF":5.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perceived threat of potential military conflicts between Taiwan and China and psychological distress among Taiwanese individuals: A population-based study.","authors":"Cheng-Fang Yen, Ray C Hsiao, Yu-Hsuan Lin","doi":"10.1111/pcn.13747","DOIUrl":"10.1111/pcn.13747","url":null,"abstract":"","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"826-827"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Naproxen adjunct to fluoxetine for moderate-to-severe obsessive-compulsive disorder: A randomized, double-blind, placebo-controlled trial.","authors":"Ahmad Shamabadi, Zahra Motavalian, Yalda Farahmand, Kimia Farahmand, Razman Arabzadeh Bahri, Sanaz Askari, Sahar Ansari, Mohammadali Fallahzadeh, Mohammdreza Shalbafan, Shahin Akhondzadeh","doi":"10.1111/pcn.13748","DOIUrl":"10.1111/pcn.13748","url":null,"abstract":"<p><strong>Aim: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 ( <math> <mrow><msubsup><mi>η</mi> <mi>P</mi> <mn>2</mn></msubsup> </mrow> </math>  = 0.055) and total ( <math> <mrow><msubsup><mi>η</mi> <mi>P</mi> <mn>2</mn></msubsup> </mrow> </math>  = 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.</p><p><strong>Conclusion: </strong>Naproxen, adjunct to fluoxetine, outperformed adjunctive placebo in treating obsession and total symptoms of OCD patients in a safe and tolerable manner.</p><p><strong>Clinical trial registration: </strong>The study protocol was registered and published in the Iranian Registry of Clinical Trials (http://www.irct.ir; registration number IRCT20090117001556N139).</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"810-817"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of intravenous ketamine treatment in Japanese patients with treatment-resistant depression: A double-blind, randomized, placebo-controlled trial.","authors":"Yohei Ohtani, Hideaki Tani, Kie Nomoto-Takahashi, Taisuke Yatomi, Kengo Yonezawa, Sota Tomiyama, Nobuhiro Nagai, Keisuke Kusudo, Shiori Honda, Sotaro Moriyama, Shinichiro Nakajima, Takashige Yamada, Hiroshi Morisaki, Yu Iwabuchi, Masahiro Jinzaki, Kimio Yoshimura, Tsuyoshi Eiro, Sakiko Tsugawa, Sadamitsu Ichijo, Yu Fujimoto, Tomoyuki Miyazaki, Takuya Takahashi, Hiroyuki Uchida","doi":"10.1111/pcn.13734","DOIUrl":"10.1111/pcn.13734","url":null,"abstract":"<p><strong>Aim: </strong>Although the antidepressant effect of ketamine on treatment-resistant depression (TRD) has been frequently reported in North American and European countries, evidence is scarce among the Asian population. We aimed to evaluate the efficacy and safety of intravenous ketamine in Japanese patients with TRD.</p><p><strong>Methods: </strong>In this double-blind randomized placebo-controlled trial, 34 Japanese patients with TRD were randomized to receive either intravenous ketamine (0.5 mg/kg) or placebo, administered over 40 min, twice a week, for 2 weeks. The primary outcome was the change in the Montgomery Åsberg Depression Rating Scale (MADRS) total score from baseline to post-treatment. Secondary outcomes included changes in other depressive symptomatology scores and remission, response, and partial response rates. We also examined the association between baseline clinical demographic characteristics and changes in the MADRS total score.</p><p><strong>Results: </strong>Intention-to-treat analysis indicated no significant difference in the decrease in MADRS total score between the groups (-8.1 ± 10.0 vs -2.5 ± 5.2, t[32] = 2.02, P = 0.052), whereas per-protocol analysis showed a significant reduction in the ketamine group compared to the placebo group (-9.1 ± 10.2 vs -2.7 ± 5.3, t[29] = 2.22, P = 0.034). No significant group differences were observed in other outcomes. Adverse events were more frequent in the ketamine group than in the placebo group, and no serious adverse events were reported. A higher baseline MADRS total score and body mass index were associated with a greater reduction in the MADRS total score.</p><p><strong>Conclusion: </strong>Intravenous ketamine outperformed placebo in Japanese patients with TRD who completed the study, suggesting that ketamine could alleviate depressive symptoms of TRD across diverse ethnic populations.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"765-775"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of psilocybin on cognitive function: A systematic review.","authors":"Shakila Meshkat, Triana Juliana Tello-Gerez, Fatemeh Gholaminezhad, Benjamin T Dunkley, Amy C Reichelt, David Erritzoe, Eric Vermetten, Yanbo Zhang, Andrew Greenshaw, Lisa Burback, Olga Winkler, Rakesh Jetly, Leah M Mayo, Venkat Bhat","doi":"10.1111/pcn.13741","DOIUrl":"10.1111/pcn.13741","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"744-764"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commentary on the article titled \"Human in vivo evidence of reduced astrocyte activation and neuroinflammation in patients with treatment-resistant depression following electroconvulsive therapy\" by Xu et al.","authors":"Alexander A Yakovlev","doi":"10.1111/pcn.13679","DOIUrl":"10.1111/pcn.13679","url":null,"abstract":"","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"828"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring possible causes of lower-than-expected suicide rates in Taiwan and South Korea during the 2020-2021 COVID-19 pandemic: a time trend analysis by sex, age, and method.","authors":"Chien-Yu Lin, Minjae Choi, Yo Han Lee, Myung Ki, Chia-Yueh Hsu, Shu-Sen Chang","doi":"10.1111/pcn.13746","DOIUrl":"10.1111/pcn.13746","url":null,"abstract":"<p><strong>Aims: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"800-809"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of novel genomic loci for anxiety symptoms and extensive genetic overlap with psychiatric disorders.","authors":"Markos Tesfaye, Piotr Jaholkowski, Alexey A Shadrin, Dennis van der Meer, Guy F L Hindley, Børge Holen, Nadine Parker, Pravesh Parekh, Viktoria Birkenæs, Zillur Rahman, Shahram Bahrami, Gleda Kutrolli, Oleksandr Frei, Srdjan Djurovic, Anders M Dale, Olav B Smeland, Kevin S O'Connell, Ole A Andreassen","doi":"10.1111/pcn.13742","DOIUrl":"10.1111/pcn.13742","url":null,"abstract":"<p><strong>Aims: </strong>Anxiety disorders are prevalent and anxiety symptoms (ANX) co-occur with many psychiatric disorders. We aimed to identify genomic loci associated with ANX, characterize its genetic architecture, and genetic overlap with psychiatric disorders.</p><p><strong>Methods: </strong>We included a genome-wide association study of ANX (meta-analysis of UK Biobank and Million Veterans Program, n = 301,732), schizophrenia (SCZ), bipolar disorder (BIP), major depression (MD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), and validated the findings in the Norwegian Mother, Father, and Child Cohort (n = 95,841). We employed the bivariate causal mixture model and local analysis of covariant association to characterize the genetic architecture including overlap between the phenotypes. Conditional and conjunctional false discovery rate analyses were performed to boost the identification of loci associated with anxiety and shared with psychiatric disorders.</p><p><strong>Results: </strong>Anxiety was polygenic with 12.9k genetic variants and overlapped extensively with psychiatric disorders (4.1k-11.4k variants) with predominantly positive genetic correlations between anxiety and psychiatric disorders. We identified 119 novel loci for anxiety by conditioning on the psychiatric disorders, and loci shared between anxiety and MD <math> <mrow> <mfenced><mrow><mi>n</mi> <mo>=</mo> <mn>47</mn></mrow> </mfenced> </mrow> </math> , BIP <math> <mrow> <mfenced><mrow><mi>n</mi> <mo>=</mo> <mn>33</mn></mrow> </mfenced> </mrow> </math> , SCZ <math> <mrow> <mfenced><mrow><mi>n</mi> <mo>=</mo> <mn>71</mn></mrow> </mfenced> </mrow> </math> , ADHD <math> <mrow> <mfenced><mrow><mi>n</mi> <mo>=</mo> <mn>20</mn></mrow> </mfenced> </mrow> </math> , and ASD <math> <mrow> <mfenced><mrow><mi>n</mi> <mo>=</mo> <mn>5</mn></mrow> </mfenced> </mrow> </math> . Genes annotated to anxiety loci exhibit enrichment for a broader range of biological pathways including cell adhesion and neurofibrillary tangle compared with genes annotated to the shared loci.</p><p><strong>Conclusions: </strong>Anxiety is highly polygenic phenotype with extensive genetic overlap with psychiatric disorders, and we identified novel loci for anxiety implicating new molecular pathways. The shared genetic architecture may underlie the extensive cross-disorder comorbidity of anxiety, and the identified molecular underpinnings may lead to potential drug targets.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"783-791"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}