Psychiatry and Clinical Neurosciences最新文献

{"title":"REIMAGINE: A central nervous system basket trial showing safety and efficacy of vafidemstat on aggression in different psychiatric disorders.","authors":"Marc Ferrer, Vanesa Richarte, Laura Gisbert, Jordi Xaus, Sonia Gutierrez, Maria Isabel Arevalo, Michael Ropacki, Roger Bullock, Carlos Buesa, Josep Antoni Ramos-Quiroga","doi":"10.1111/pcn.13800","DOIUrl":"10.1111/pcn.13800","url":null,"abstract":"<p><strong>Aim: </strong>Vafidemstat is a brain-penetrant, orally bioavailable, small molecule irreversible inhibitor of the histone lysine-specific demethylase KDM1A (also known as LSD1), which corrects memory deficits and behavior alterations including aggression and social interaction deficits in preclinical models.</p><p><strong>Methods: </strong>Here, we report the results of REIMAGINE, a phase IIa, single-center, open-label, one-arm basket trial that evaluated the safety and efficacy of vafidemstat on aggression in adult patients with borderline personality disorder (BPD), attention-deficit/hyperactivity disorder (ADHD), and autistic spectrum disorder (ASD). Participants received 1.2 mg/day of vafidemstat for 8 weeks.</p><p><strong>Results: </strong>Vafidemstat was shown to be safe and well tolerated, and no drug-related clinically significant adverse events were observed. Furthermore, all neuropsychiatric scales assessed showed notable efficacy signals, whether assessing agitation/aggression (Clinical Global Impression for Severity [CGI-S] and Clinical Global Impression for Improvement [CGI-I] and Neuropsychiatric Inventory [NPI] questionnaire for Agitation-Aggression [NPI-AA]), overall patient functioning (total NPI), or disease-specific features (Attention-Deficit/Hyperactivity Disorder Rating Scale [ADHD-RS] and Borderline Personality Disorder Checklist [BPDCL]). Statistically significant improvements were observed in the aggregated data (all participants) and for each of the three disease groups independently. Changes were evident within the first 2 weeks of treatment.</p><p><strong>Conclusion: </strong>In summary, the REIMAGINE study supports that vafidemstat is safe, well tolerated, and causes a significant and consistent reduction in agitation/aggression and nonaggression features in BPD, ADHD, and ASD. These data support continuing the development of vafidemstat as a new treatment option for these psychiatric disorders.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"257-265"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12047063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399824","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":"Towards a latent space cartography of subjective experience in mental health.","authors":"Shawn Manuel, Jean Gagnon, Frédéric Gosselin, Vincent Taschereau-Dumouchel","doi":"10.1111/pcn.13798","DOIUrl":"10.1111/pcn.13798","url":null,"abstract":"<p><strong>Aims: </strong>The way that individuals subjectively experience the world greatly influences their own mental well-being. However, it remains a considerable challenge to precisely characterize the breadth and depth of such experiences. One persistent problem is the lack of objective tools for directly quantifying and comparing narrative reports of subjective experiences. Here, we develop a new approach to map and compare reports of experience using the latent space of artificial neural networks.</p><p><strong>Methods: </strong>Using a series of 31 prompts, including 30 images and one open-ended question, we quantified how the verbal reports provided by participants (n = 210, 50% female) deviate from one another and how these variations are linked to subjective experience and mental health.</p><p><strong>Results: </strong>We found that latent space embeddings of experience can accurately predict subjective judgments of valence and arousal in a series of emotional pictures. Furthermore, we show that narrative reports to ambiguous images can accurately predict transdiagnostic factors of mental health. While distortions in the latent space of artificial neural networks are notoriously difficult to interpret, we propose a new approach to synthesize visual stimuli with generative artificial intelligence that can be used to explore semantic distortions in reported experiences.</p><p><strong>Conclusions: </strong>In sum, latent space cartography could offer a promising avenue for objectively quantifying distortions of subjective experience in mental health and could ultimately help identify new therapeutic targets for clinical interventions.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"248-256"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12047060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374556","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":"Focused ultrasound as an emerging therapy for neuropsychiatric disease: Historical perspectives and a review of current clinical data.","authors":"Daniel N de Souza, Andreas Seas, Kathryn Blethen, Jacob Feigal, Bhavya R Shah, Gerald A Grant, Stephen C Harward","doi":"10.1111/pcn.13799","DOIUrl":"10.1111/pcn.13799","url":null,"abstract":"<p><p>Psychiatric disorders are a common source of disease morbidity with high rates of refractoriness to first-line treatments. As such, many have investigated the utility of neurosurgical interventions for treatment-resistant forms of these conditions. More recently among these, functional neurosurgical techniques using high- and low-intensity focused ultrasound (FUS) have emerged as promising options in this arena, largely due to their minimally-invasive nature and encouraging early safety and efficacy data. Existing clinical data have thus far demonstrated FUS to be a potentially useful intervention for treatment-refractory forms of obsessive-compulsive disorder, major depressive disorder, various anxiety disorders, substance-use disorder, and schizophrenia. This report presents a comprehensive review of existing clinical trial data, summarizing key findings, study specifications, and providing critical analysis. In addition to giving the most complete summary of modern clinical research on this topic to date, this report characterizes the current state of this body of literature using bibliometric analysis, succinctly highlighting the most investigated topics and the most promising areas of modern investigation. Based on our review of the literature, current work on this topic is highly heterogeneous with regard to specific treatment protocols and anatomic targets for FUS - targeting multiple nuclei at a wide variety of intensities. We recommend that future studies aim to clarify more precise therapeutic targets and specific treatment protocols which optimize the efficacy of these techniques.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"215-228"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399823","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":"Increase in luteinizing hormone is linked to reduction in depression in patients with dementia: Secondary analysis of a randomized clinical trial of benzoate.","authors":"Chieh-Hsin Lin, Shi-Heng Wang, Hsien-Yuan Lane","doi":"10.1111/pcn.13805","DOIUrl":"10.1111/pcn.13805","url":null,"abstract":"","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"290-291"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468963","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":"Epigenetic age acceleration is related to cognitive decline in the elderly: Results of the Austrian Stroke Prevention Study.","authors":"Piyush Gampawar, Sai Pavan Kumar Veeranki, Katja-Elisabeth Petrovic, Reinhold Schmidt, Helena Schmidt","doi":"10.1111/pcn.13793","DOIUrl":"10.1111/pcn.13793","url":null,"abstract":"<p><strong>Aim: </strong>Epigenetic clocks, quantifying biological age through DNA methylation (DNAmAge), have emerged as potential indicators of brain aging. As the variety of DNAmAge algorithms grows, consensus on their efficacy in predicting age-related changes is lacking. This study aimed to explore the intricate relationship between diverse DNAmAge algorithms and structural and cognitive markers of brain aging.</p><p><strong>Methods: </strong>Within a cohort of 796 elderly patients (mean age, 65.8 ± 7.9 years), we scrutinized 11 DNAmAge algorithms, including Horvath, Hannum, Zhang's clocks, PhenoAge, GrimAge, DunedinPACE, and principal component (PC)-based PCHorvath, PCHannum, PCPhenoAge, and PCGrimAge. We evaluated their association with baseline cognition and cognitive decline, assessed through follow-up evaluations at three (T1) and six (T2) years postbaseline. Additionally, we examined their relationship with structural magnetic resonance imaging markers of brain aging, including white matter.</p><p><strong>Results: </strong>Zhang's clock was the best predictor of decline in memory (β = -0.04) and global cognition (β = -0.03), whereas PCGrimAge was the best predictor of speed decline (β = -0.17). The DNAmAge algorithms were the second-best predictors in explaining cognitive variability after education in memory and global cognition (R² _partial = 1.66% to 2.82%) and the best predictors for speed decline (R² _partial = 2.13%). PC-trained DNAmAge algorithms outperformed their respective original version.</p><p><strong>Conclusion: </strong>DNAmAge algorithms are strong and independent predictors of cognitive decline in the normal elderly population and explain additional variability in cognitive decline beyond that accounted for by conventional risk factors.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"229-238"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12047057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374542","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":"Understanding heterogeneity in psychiatric disorders: A method for identifying subtypes and parsing comorbidity.","authors":"Aidas Aglinskas, Alicia Bergeron, Stefano Anzellotti","doi":"10.1111/pcn.13829","DOIUrl":"https://doi.org/10.1111/pcn.13829","url":null,"abstract":"<p><strong>Aim: </strong>Most psychiatric and neurodevelopmental disorders are heterogeneous. Neural abnormalities in patients might differ in magnitude and kind, giving rise to distinct subtypes that can be partly overlapping (comorbidity). Identifying disorder-related individual differences is challenging due to the overwhelming presence of disorder-unrelated variation shared with healthy controls. Recently, Contrastive Variational Autoencoders (CVAEs) have been shown to separate disorder-related individual variation from disorder-unrelated variation. However, it is not known if CVAEs can also satisfy the other key desiderata for psychiatric research: capturing disease subtypes and disentangling comorbidity. In this paper, we compare CVAEs to other methods as a function of hyperparameters, such as model size and training data availability. We also introduce a new architecture for modeling comorbid disorders and test a novel training procedure for CVAEs that improves their reproducibility.</p><p><strong>Methods: </strong>We use synthetic neuroanatomical MRI data with known ground truth for shared and disorder-specific effects and study the performance of the CVAE and non-contrastive baseline models at detecting disorder-subtypes and disentangling comorbidity in brain images varying along shared and disorder-specific dimensions.</p><p><strong>Results: </strong>CVAE models consistently outperformed non-contrastive alternatives as measured by correlation with disorder-specific ground truth effects and accuracy of subtype discovery. The CVAE also successfully disentangled neuroanatomical loci of comorbid disorders, due to its novel architecture. Improved training procedure reduced variability in the results by up to 5.5×.</p><p><strong>Conclusion: </strong>The results showcase how the CVAE can be used as an overall framework in precision psychiatry studies, enabling reliable detection of interpretable neuromarkers, discovering disorder subtypes and disentangling comorbidity.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991149","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":"Response to [Reevaluating Antipsychotic Polypharmacy in Schizophrenia: A Broader Perspective on Social Recovery].","authors":"Yuhei Mori, Risa Shishido, Mizuki Hino, Akiko Sato, Atsuko Nagaoka, Hiroshi Hoshino, Masataka Hatano, Yuto Hosogai, Itaru Miura, Yasuto Kunii","doi":"10.1111/pcn.13834","DOIUrl":"https://doi.org/10.1111/pcn.13834","url":null,"abstract":"","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050871","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":"Corrigendum to \"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":"","doi":"10.1111/pcn.13832","DOIUrl":"https://doi.org/10.1111/pcn.13832","url":null,"abstract":"","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144008913","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":"Reevaluating antipsychotic polypharmacy in schizophrenia: A broader perspective on social recovery.","authors":"Mohsin Raza, Javed Iqbal, Muna A Al-Maslamani","doi":"10.1111/pcn.13826","DOIUrl":"https://doi.org/10.1111/pcn.13826","url":null,"abstract":"","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034643","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":"Genome-wide DNA methylation profiles in the raphe nuclei of patients with autism spectrum disorder.","authors":"Keiko Iwata, Kazuhiko Nakabayashi, Keisuke Ishiwata, Kazuhiko Nakamura, Yosuke Kameno, Kenichiro Hata, Hideo Matsuzaki","doi":"10.1111/pcn.13830","DOIUrl":"https://doi.org/10.1111/pcn.13830","url":null,"abstract":"<p><strong>Aim: </strong>Autism spectrum disorder (ASD) has a strong genetic basis, yet its genetic complexities remain elusive. Current research highlights environmental factors and epigenetic processes, such as DNA methylation, as crucial in ASD development. This exploratory study addresses a gap in understanding epigenetic regulation in the dorsal raphe (DR)-a region regulating multiple neurotransmitters and implicated in ASD-by examining DNA methylation profiles in postmortem ASD and control brains.</p><p><strong>Methods: </strong>We comprehensively analyzed genome-wide DNA methylation profiles in the DR brain region (seven controls and five ASD) using the Infinium HumanMethylation450 BeadChip (Illumina). Additionally, quantitative polymerase chain reaction was used to measure messenger RNA levels of differentially methylated genes in ASD (11 controls and six ASD).</p><p><strong>Results: </strong>We identified differentially methylated regions (DMRs) between ASD and controls. These DMRs were located among various genomic regions, including promoters, gene bodies, and intergenic regions. Notably, we found hypermethylation in genes related to olfaction (e.g. OR2C3), which is regulated by serotonin. Additionally, we observed that the hypomethylation of promoter-associated CpG islands in RABGGTB, a gene related to autophagy and synaptic function, corresponded with its increased expression.</p><p><strong>Conclusions: </strong>Our findings reveal extensive DNA methylation changes in critical genomic regions, shedding light on potential mechanisms underlying ASD. The identification of RABGGTB as a novel candidate gene, not listed in the SFARI database, underscores its significance and warrants further research to explore its role in ASD diagnosis. This study enhances our understanding of the epigenetic landscape in ASD, emphasizing the interplay between genetic and environmental factors in its pathophysiology.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064448","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}