Acta Neuropsychiatrica最新文献

{"title":"Anxiolytic-like effects of acute serotonin-releasing agents in zebrafish models of anxiety: experimental study and systematic review.","authors":"Jakob Näslund, Jenny Landin, Fredrik Hieronymus, Rakesh Kumar Banote, Petronella Kettunen","doi":"10.1017/neu.2024.44","DOIUrl":"10.1017/neu.2024.44","url":null,"abstract":"<p><p>Though commonly used to model affective disorders, zebrafish display notable differences in terms of the structure and function of the brain serotonin system, including responses to pharmacological interventions, as compared to mammals. For example, elevation of brain serotonin following acute administration of serotonin reuptake inhibitors (SRIs) generally has anxiogenic effects, both in the clinical situation and in rodent models of anxiety, but previous research has indicated the opposite in zebrafish. However, several issues remain unresolved. We conducted a systematic review of SRI effects in zebrafish models of anxiety and, on the basis of these results, performed a series of experiments further investigating the influence of serotonin-releasing agents on anxiety-like behaviour in zebrafish, with sex-segregated wild-type animals being administered either escitalopram, or the serotonin releaser fenfluramine, in the light-dark test. In the systematic review, we find that the available literature indicates an anxiolytic-like effect of SRIs in the novel-tank diving test. Regarding the light-dark test, most studies reported no behavioural effects of SRIs, although the few that did generally saw anxiolytic-like responses. In the experimental studies, consistent anxiolytic-like effects were observed with neither sex nor habituation influencing treatment response. We find that the general effect of acute SRI administration in zebrafish indeed appears to be anxiolytic-like, indicating, at least partly, differences in the functioning of the serotonin system as compared to mammals and that caution is advised when using zebrafish to model affective disorders.</p>","PeriodicalId":48964,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"e35"},"PeriodicalIF":2.6,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the potential link between ΔFosB and <i>N</i>-acetylcysteine in craving/relapse dynamics: can <i>N</i>-acetylcysteine stand out as a possible treatment candidate?","authors":"Shokouh Arjmand, Mehran Ilaghi, Mohammad Shafie'ei, Pedro H Gobira, Rodrigo Grassi-Oliveira, Gregers Wegener","doi":"10.1017/neu.2024.38","DOIUrl":"10.1017/neu.2024.38","url":null,"abstract":"<p><p>From a neuroscientific point of view, one of the unique archetypes of substance use disorders is its road to relapse, in which the reward system plays a crucial role. Studies on the neurobiology of substance use disorders have highlighted the central role of a protein belonging to the Fos family of transcription factors, ΔFosB. Relying on the roles ΔFosB plays in the pathophysiology of substance use disorders, we endeavour to present some evidence demonstrating that <i>N</i>-acetylcysteine, a low-cost and well-tolerated over-the-counter medicine, may influence the downstream pathway of ΔFosB, thereby serving as a treatment strategy to mitigate the risk of relapse in cases of substance use.</p>","PeriodicalId":48964,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"e31"},"PeriodicalIF":2.6,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene expression of kynurenine pathway enzymes in depression and following electroconvulsive therapy.","authors":"Karen M Ryan, Myles Corrigan, Therese M Murphy, Declan M McLoughlin, Andrew Harkin","doi":"10.1017/neu.2024.34","DOIUrl":"10.1017/neu.2024.34","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate changes in mRNA expression of the kynurenine pathway (KP) enzymes <i>tryptophan 2, 3-dioxygenase</i> (<i>TDO</i>), <i>indoleamine 2, 3-dioxygenase 1</i> and 2 (<i>IDO1</i>, <i>IDO2</i>), <i>kynurenine aminotransferase 1</i> and 2 (<i>KAT1, KAT2</i>), <i>kynurenine monooxygenase</i> (<i>KMO</i>) and <i>kynureninase</i> (<i>KYNU</i>) in medicated patients with depression (<i>n</i> = 74) compared to age- and sex-matched healthy controls (<i>n</i> = 55) and in patients with depression after electroconvulsive therapy (ECT). Associations with mood score (24-item Hamilton Depression Rating Scale, HAM-D24), plasma KP metabolites and selected glucocorticoid and inflammatory immune markers known to regulate KP enzyme expression were also explored.</p><p><strong>Methods: </strong>HAM-D24 was used to evaluate depression severity. Whole blood mRNA expression was assessed using quantitative real-time polymerase chain reaction.</p><p><strong>Results: </strong><i>KAT1, KYNU</i> and <i>IDO2</i> were significantly reduced in patient samples compared to control samples, though results did not survive statistical adjustment for covariates or multiple comparisons. ECT did not alter KP enzyme mRNA expression. Changes in <i>IDO1</i> and <i>KMO</i> and change in HAM-D24 score post-ECT were negatively correlated in subgroups of patients with unipolar depression (<i>IDO1</i> only), psychotic depression and ECT responders and remitters. Further exploratory correlative analyses revealed altered association patterns between KP enzyme expression, KP metabolites, <i>NR3C1</i> and <i>IL-6</i> in depressed patients pre- and post-ECT.</p><p><strong>Conclusion: </strong>Further studies are warranted to determine if KP measures have sufficient sensitivity, specificity and predictive value to be integrated into stress and immune associated biomarker panels to aid patient stratification at diagnosis and in predicting treatment response to antidepressant therapy.</p>","PeriodicalId":48964,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"e34"},"PeriodicalIF":2.6,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision psychiatry needs causal inference.","authors":"Martin Bernstorff, Oskar Hougaard Jefsen","doi":"10.1017/neu.2024.29","DOIUrl":"10.1017/neu.2024.29","url":null,"abstract":"<p><strong>Objective: </strong>Psychiatric research applies statistical methods that can be divided in two frameworks: causal inference and prediction. Recent proposals suggest a down-prioritisation of causal inference and argue that prediction paves the road to 'precision psychiatry' (i.e., individualised treatment). In this perspective, we critically appraise these proposals.</p><p><strong>Methods: </strong>We outline strengths and weaknesses of causal inference and prediction frameworks and describe the link between clinical decision-making and counterfactual predictions (i.e., causality). We describe three key causal structures that, if not handled correctly, may cause erroneous interpretations, and three pitfalls in prediction research.</p><p><strong>Results: </strong>Prediction and causal inference are both needed in psychiatric research and their relative importance is context-dependent. When individualised treatment decisions are needed, causal inference is necessary.</p><p><strong>Conclusion: </strong>This perspective defends the importance of causal inference for precision psychiatry.</p>","PeriodicalId":48964,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"e32"},"PeriodicalIF":2.6,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A double-blind, placebo-controlled, randomised withdrawal study of adjunctive brexpiprazole maintenance treatment for major depressive disorder.","authors":"Roger S McIntyre, Kripa Sundararajan, Saloni Behl, Nanco Hefting, Na Jin, Claudette Brewer, Mary Hobart, Michael E Thase","doi":"10.1017/neu.2024.32","DOIUrl":"10.1017/neu.2024.32","url":null,"abstract":"<p><strong>Objective: </strong>To compare time to relapse in patients with major depressive disorder (MDD) stabilised on antidepressant treatment (ADT) + brexpiprazole who were randomised to continued adjunctive brexpiprazole or brexpiprazole withdrawal (switch to placebo).</p><p><strong>Methods: </strong>This Phase 3, multicentre, double-blind, placebo-controlled, parallel-arm, randomised withdrawal study enrolled adults with MDD and inadequate response to 2–3 ADTs. All patients started on adjunctive brexpiprazole 2–3 mg/day (Phase A, 6–8 weeks). Patients whose symptoms stabilised (Phase B, 12 weeks) were randomised 1:1 to adjunctive brexpiprazole or adjunctive placebo (Phase C, 26 weeks). The primary endpoint was time to relapse in Phase C. Depression rating scale score changes were secondary endpoints.</p><p><strong>Results: </strong>1149 patients were enrolled and 489 patients were randomised (ADT + brexpiprazole <i>n</i> = 240; ADT + placebo <i>n</i> = 249). Median time to relapse was 63 days from randomisation in both treatment groups for patients who received ≥1 dose. Relapse criteria were met by 22.5% of patients (54/240) on ADT + brexpiprazole and 20.6% (51/248) on ADT + placebo (hazard ratio, 1.14; 95% confidence interval, 0.78–1.67; <i>p</i> = 0.51, log-rank test). Depression scale scores improved during Phases A–B and were maintained in Phase C. Mean weight increased by 2.2 kg in Phases A–B and stabilised in Phase C.</p><p><strong>Conclusion: </strong>Time to relapse was similar between continued adjunctive brexpiprazole and brexpiprazole withdrawal; in both groups, ∼80% of stabilised patients remained relapse free at their last visit. Adjunctive brexpiprazole therapy was generally well tolerated over up to 46 weeks, with minimal adverse effects following brexpiprazole withdrawal.ClinicalTrials.gov identifier: NCT03538691. Funding: Otsuka, Lundbeck.</p>","PeriodicalId":48964,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"e33"},"PeriodicalIF":2.6,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"International trends in male youth suicide and suicidal behaviour.","authors":"Timothy Rice, Anton Livshin, Zoltan Rihmer, Andreas Walther, Mohammed Bhuiyan, Adriana Bruges Boude, Ying-Yeh Chen, Xenia Gonda, Aliza Grossberg, Yonis Hassan, Ezequiel Lafont, Gianluca Serafini, Arthi Vickneswaramoorthy, Salonee Shah, Leo Sher","doi":"10.1017/neu.2024.37","DOIUrl":"https://doi.org/10.1017/neu.2024.37","url":null,"abstract":"<p><strong>Objective: </strong>Suicide and suicidal behaviour strongly contribute to overall male youth mortality. An understanding of worldwide data contextualises suicide and suicidal behaviour in young men within any given country.</p><p><strong>Method: </strong>Members and colleagues of the World Federation of Societies of Biological Psychiatry's Task Force on Men's Mental Health review the relevant data from several regions of the world. The review identifies notable findings across regions of relevance to researchers, policymakers, and clinicians.</p><p><strong>Results: </strong>Male suicide and suicidal behaviour in adolescence and emerging adulthood within North America, Latin America and the Caribbean, Europe, the Mediterranean and the Middle East, Continental Africa, South Asia, East Asia, China, and Oceania share similarities as well as significant points of divergence.</p><p><strong>Conclusions: </strong>International data provide an opportunity to obtain a superior understanding of suicide and suicidal behaviour amongst young men.</p>","PeriodicalId":48964,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"1-21"},"PeriodicalIF":2.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing psychiatric nosology through philosophical inquiry.","authors":"Shokouh Arjmand, Reza Saboori Amleshi, Francisco S Guimarães, Gregers Wegener","doi":"10.1017/neu.2024.21","DOIUrl":"https://doi.org/10.1017/neu.2024.21","url":null,"abstract":"<p><p>Here, we have utilised the concept of fuzzy logic and Karl Popper's notion of verisimilitude to advocate navigating the complexity of psychiatric nosology, emphasising that psychiatric disorders defy Boolean logic. We underscore the importance of embracing imprecision and collecting extensive data for a more nuanced understanding of psychiatric disorders, asserting that falsifiability is crucial for scientific progress. We encourage the advancement of personalised psychiatric taxonomy, urging the continual accumulation of data to inform emerging advancements like artificial intelligence in reshaping current psychiatric nosology.</p>","PeriodicalId":48964,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"1-4"},"PeriodicalIF":2.6,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obsessive-compulsive symptoms relating to psychosocial functioning for people with schizophrenia, schizoaffective disorder, or bipolar disorder.","authors":"Nina Grootendorst-van Mil, Chin-Kuo Chang, David Chandran, Frederike Schirmbeck, Nico van Beveren, Hitesh Shetty, Robert Stewart, Deborah Ahn-Robbins, Lieuwe de Haan, Richard D Hayes","doi":"10.1017/neu.2024.42","DOIUrl":"10.1017/neu.2024.42","url":null,"abstract":"<p><p>To assess the psychosocial functioning concerning obsessive-compulsive symptoms (OCS) and/or obsessive-compulsive disorder (OCD) comorbidity in people with schizophrenia, schizoaffective disorder, or bipolar disorder diagnosed in a large case register database in Southeast London. Data were retrieved from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) register using Clinical Record Interactive Search (CRIS) system, a platform allowing research on full but de-identified electronic health records for secondary and tertiary mental healthcare services. Information of schizophrenia, schizoaffective disorder, bipolar disorder diagnosis and OCS/OCD status was ascertained from structural or free-text fields through natural language processing (NLP) algorithms based on artificial intelligence techniques during the observation window of January 2007 to December 2016. Associations between comorbid OCS/OCD and recorded Health of the Nation Outcome Scales (HoNOS) for problems with activities of daily living (ADLs), living conditions, occupational and recreational activities, and relationships were estimated by logistic regression with socio-demographic confounders controlled. Of 15,412 subjects diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder, 2,358 (15.3%) experienced OCS without OCD, and 2,586 (16.8%) had OCD recorded. The presence of OCS/OCD was associated with more problems with relationships (adj.OR = 1.34, 95% CI: 1.25-1.44), ADLs (adj.OR = 1.31, 95%CI: 1.22-1.41), and living conditions (adj.OR = 1.31, 95% CI: 1.22-1.41). Sensitivity analysis revealed similar outcomes. Comorbid OCS/OCD was associated with poorer psychosocial functioning in people with schizophrenia, schizoaffective disorder, or bipolar disorder. This finding highlights the importance of identification and treatment of comorbid OCS among this vulnerable patient group.</p>","PeriodicalId":48964,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"e45"},"PeriodicalIF":2.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA m⁶A methyltransferase activator affects anxiety-related behaviours, monoamines and striatal gene expression in the rat.","authors":"Margus Kanarik, Kristi Liiver, Marianna Norden, Indrek Teino, Tõnis Org, Karita Laugus, Ruth Shimmo, Mati Karelson, Mart Saarma, Jaanus Harro","doi":"10.1017/neu.2024.36","DOIUrl":"10.1017/neu.2024.36","url":null,"abstract":"<p><p>Modification of mRNA by methylation is involved in post-transcriptional regulation of gene expression by affecting the splicing, transport, stability and translation of mRNA. Methylation of adenosine at N⁶ (m⁶A) is one of the most common and important cellular modification occurring in the mRNA of eukaryotes. Evidence that m⁶A mRNA methylation is involved in regulation of stress response and that its dysregulation may contribute to the pathogenesis of neuropsychiatric disorders is accumulating. We have examined the acute and subchronic (up to 18 days once per day intraperitoneally) effect of the first METTL3/METTL14 activator compound CHMA1004 (methyl-piperazine-2-carboxylate) at two doses (1 and 5 mg/kg) in male and female rats. CHMA1004 had a locomotor activating and anxiolytic-like profile in open field and elevated zero-maze tests. In female rats sucrose consumption and swimming in Porsolt's test were increased. Nevertheless, CHMA1004 did not exhibit strong psychostimulant-like properties: CHMA1004 had no effect on 50-kHz ultrasonic vocalizations except that it reduced the baseline difference between male and female animals, and acute drug treatment had no effect on extracellular dopamine levels in striatum. Subchronic CHMA1004 altered <i>ex vivo</i> catecholamine levels in several brain regions. RNA sequencing of female rat striata after subchronic CHMA1004 treatment revealed changes in the expression of a number of genes linked to dopamine neuron viability, neurodegeneration, depression, anxiety and stress response. Conclusively, the first-in-class METTL3/METTL14 activator compound CHMA1004 increased locomotor activity and elicited anxiolytic-like effects after systemic administration, demonstrating that pharmacological activation of RNA m⁶A methylation has potential for neuropsychiatric drug development.</p>","PeriodicalId":48964,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"e52"},"PeriodicalIF":2.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A meta-analysis of the prevalence of neuropsychiatric disorders and their association with disease onset in myotonic dystrophy.","authors":"Carlos Pascual-Morena, Vicente Martínez-Vizcaíno, Iván Cavero-Redondo, Celia Álvarez-Bueno, Maribel Lucerón-Lucas-Torres, Alicia Saz-Lara, Irene Martínez-García","doi":"10.1017/neu.2024.27","DOIUrl":"https://doi.org/10.1017/neu.2024.27","url":null,"abstract":"<p><p>There is a high prevalence of neuropsychiatric disorders in myotonic dystrophy types 1 and 2 (DM1 and DM2), including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) in DM1, and depression and anxiety in both DMs. The aim of this systematic review and meta-analysis was to estimate the prevalence of ASD, ADHD, depression and anxiety in the population with DM, and their association with disease onset. A systematic search of Medline, Scopus, Web of Science, and the Cochrane Library was conducted from inception to November 2023. Observational studies estimating the prevalence of these disorders in DM1 or DM2 were included. A meta-analysis of the prevalence of these disorders and an association study with disease onset by prevalence ratio meta-analysis were performed. Thirty-eight studies were included. In DM1, the prevalence of ASD was 14%, with congenital onset being 79% more common than juvenile onset, while the prevalence of ADHD was 21%, with no difference between congenital and juvenile onset, and the prevalence of depression and anxiety were 14% and 16%. Depression was more common in the adult onset. Finally, the prevalence of depression in DM2 was 16%. A higher prevalence of neuropsychiatric disorders is observed in individuals with DM1 and DM2 than in the general population. Therefore, actively screening for congenital and juvenile neurodevelopmental disorders in DM1 and emotional disorders in DM1 and DM2 may improve the quality of life of those affected.</p>","PeriodicalId":48964,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"1-12"},"PeriodicalIF":2.6,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}