Acta Neuropsychiatrica最新文献

{"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":"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":"Interplay between endocannabinoid and endovanilloid mechanisms in fear conditioning.","authors":"Rayssa C Briânis, Julia P Andreotti, Fabrício A Moreira, Lia P Iglesias","doi":"10.1017/neu.2023.54","DOIUrl":"10.1017/neu.2023.54","url":null,"abstract":"<p><strong>Objective: </strong>The transient receptor potential cation channel, subfamily V (vanilloid), member 1 (TRPV1) mediates pain perception to thermal and chemical stimuli in peripheral neurons. The cannabinoid receptor type 1 (CB₁), on the other hand, promotes analgesia in both the periphery and the brain. TRPV1 and CB₁ have also been implicated in learned fear, which involves the association of a previously neutral stimulus with an aversive event. In this review, we elaborate on the interplay between CB₁ receptors and TRPV1 channels in learned fear processing.</p><p><strong>Methods: </strong>We conducted a PubMed search for a narrative review on endocannabinoid and endovanilloid mechanisms on fear conditioning.</p><p><strong>Results: </strong>TRPV1 and CB₁ receptors are activated by a common endogenous agonist, arachidonoyl ethanolamide (anandamide), Moreover, they are expressed in common neuroanatomical structures and recruit converging cellular pathways, acting in concert to modulate fear learning. However, evidence suggests that TRPV1 exerts a facilitatory role, whereas CB₁ restrains fear responses.</p><p><strong>Conclusion: </strong>TRPV1 and CB₁ seem to mediate protective and aversive roles of anandamide, respectively. However, more research is needed to achieve a better understanding of how these receptors interact to modulate fear learning.</p>","PeriodicalId":48964,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"255-264"},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138048279","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":"Cannabidiol improves non-motor symptoms, attenuates neuroinflammation, and favours hippocampal newborn neuronal maturation in a rat model of Parkinsonism.","authors":"Bianca Andretto de Mattos, Jéssica Mendes Bonato, Maria Clara Splendor, Elaine Del Bel, Humberto Milani, Rúbia Maria Weffort de Oliveira","doi":"10.1017/neu.2024.15","DOIUrl":"10.1017/neu.2024.15","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the effects of cannabidiol (CBD) on emotional and cognitive symptoms in rats with intra-nigral 6-hydroxydopamine (6-OHDA) lesions.</p><p><strong>Methods: </strong>Adult male Wistar rats received bilateral intranigral 6-OHDA infusions and were tested in a battery of behavioural paradigms to evaluate non-motor symptoms. The brains were obtained to evaluate the effects of CBD on hippocampal neurogenesis.</p><p><strong>Results: </strong>6-OHDA-lesioned rats exhibited memory impairments and despair-like behaviour in the novelty-suppressed feeding test and forced swim test, respectively. The animals also exhibited dopaminergic neuronal loss in the substantia nigra pars compacta (SNpc), striatum, and ventral tegmental area and a reduction of hippocampal neurogenesis. CBD decreased dopaminergic neuronal loss in the SNpc, reduced the mortality rate and decreased neuroinflammation in 6-OHDA-lesioned rats. In parallel, CBD prevented memory impairments and attenuated despair-like behaviour that were induced by bilateral intranigral 6-OHDA lesions. Repeated treatment with CBD favoured the neuronal maturation of newborn neurons in the hippocampus in Parkinsonian rats.</p><p><strong>Conclusion: </strong>The present findings suggest a potential beneficial effect of CBD on non-motor symptoms induced by intra-nigral 6-OHDA infusion in rats.</p>","PeriodicalId":48964,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"307-319"},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141072183","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":"Effects of cannabidiol on reward contextual memories induced by cocaine in male and female mice.","authors":"Rayssa C Briânis, Lia P Iglesias, Lucas G Bedeschi, Fabrício A Moreira","doi":"10.1017/neu.2023.53","DOIUrl":"10.1017/neu.2023.53","url":null,"abstract":"<p><strong>Objective: </strong>Preclinical studies suggest that cannabidiol (CBD), a non-intoxicating phytocannabinoid, may reduce addiction-related behaviours for various drug classes in rodents, including ethanol, opiates, and psychostimulants. CBD modulates contextual memories and responses to reward stimuli. Nonetheless, research on the impact of CBD on cocaine addiction-like behaviors is limited and requires further clarification. This study tested the hypothesis that CBD administration inhibits the acquisition and retrieval of cocaine-induced conditioned place preference (CPP) in adult male and female C57BL6/J mice. We also ought to characterise a 5-day CPP protocol in these animals.</p><p><strong>Methods: </strong>Male and female C57BL/6J mice were administered CBD (3, 10, and 30 mg/kg) 30 minutes before cocaine (15 mg/kg) acquisition of expression of CPP.</p><p><strong>Results: </strong>Cocaine induces a CPP in both female and male mice in the 5-day CPP protocol. CBD failed to prevent the acquisition or retrieval of place preference induced by cocaine. CBD did not decrease the time spent on the side paired with cocaine at any of the doses tested in male and female mice, in either acquisition or expression of contextual memory.</p><p><strong>Conclusion: </strong>This study found no support for the hypothesis that CBD decreases reward memory involved in the formation of cocaine addiction. Further research is necessary to investigate the involvement of CBD in other behavioural responses to cocaine and other psychostimulant drugs. This study, however, characterised a 5-day CPP protocol for both female and male C57BL/6J mice.</p>","PeriodicalId":48964,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"299-306"},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134650254","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":"The therapeutic potential of cannabidiol in neuropsychiatric and neurodegenerative disorders.","authors":"Sâmia Joca, Francisco S Guimarães","doi":"10.1017/neu.2024.48","DOIUrl":"https://doi.org/10.1017/neu.2024.48","url":null,"abstract":"","PeriodicalId":48964,"journal":{"name":"Acta Neuropsychiatrica","volume":"36 5","pages":"253-254"},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511083","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}