European Neuropsychopharmacology最新文献

{"title":"“The role of gut microbiota in adult attention deficit hyperactivity disorder: Insights and implications”","authors":"Muhammad Hussnain Sadiq, Ayesha Fatima","doi":"10.1016/j.euroneuro.2024.09.008","DOIUrl":"10.1016/j.euroneuro.2024.09.008","url":null,"abstract":"","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"90 ","pages":"Pages 58-59"},"PeriodicalIF":6.1,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142593627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lurasidone-related adverse events: A comprehensive analysis from the FAERs database in real-world settings","authors":"Jiannan Zhu , Lu Hou , Qin Zhou , Rongrong Lu , Zhiqiang Du , Ying Jiang , Haohao Zhu","doi":"10.1016/j.euroneuro.2024.10.010","DOIUrl":"10.1016/j.euroneuro.2024.10.010","url":null,"abstract":"","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"90 ","pages":"Pages 60-61"},"PeriodicalIF":6.1,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142593628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 profile of oral creatine monohydrate in add-on to cognitive-behavioural therapy in depression: An 8-week pilot, double-blind, randomised, placebo-controlled feasibility and exploratory trial in an under-resourced area","authors":"Nima Norbu Sherpa ,&nbsp;Riccardo De Giorgi ,&nbsp;Edoardo Giuseppe Ostinelli ,&nbsp;Amrita Choudhury ,&nbsp;Tenzin Dolma ,&nbsp;Sangila Dorjee","doi":"10.1016/j.euroneuro.2024.10.004","DOIUrl":"10.1016/j.euroneuro.2024.10.004","url":null,"abstract":"<div><div>Pre-clinical and clinical evidence proposes that creatine monohydrate, an affordable nutraceutical, could be a useful adjunct to conventional antidepressant treatments. In this pilot feasibility and exploratory study, we investigate the 8-week effects of creatine in addition to cognitive-behavioural therapy (CBT) versus placebo plus CBT in depression. For the primary efficacy outcome of change in Patient Health Questionnaire-9 depression score at study endpoint, we used mixed-model repeated measures analysis of covariance. Logistic regressions were employed to assess acceptability (any-cause dropouts), tolerability (dropouts for adverse events), and safety (patients experiencing one or more adverse events). We calculated effect sizes adjusted for age, sex, and baseline depression score. One-hundred participants (50 females, mean age= 30.4 ± 7.4 years) with depression (mean PHQ-9 = 17.6 ± 6.3) were randomised to either creatine+CBT (<em>N</em> = 50) or placebo+CBT (<em>N</em> = 50). At 8 weeks, PHQ-9 scores were lower in both study arms, but significantly more so in participants taking creatine (mean difference= -5.12). Treatment discontinuations due to any cause and to adverse events, and proportion of participants with at least one adverse event were comparable between study arms. This hypothesis-generating trial suggests that creatine could be a useful and safe supplement to CBT for depression. Longer and larger clinical trials are warranted.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"90 ","pages":"Pages 28-35"},"PeriodicalIF":6.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does 18 Hz deep TMS benefit a different subgroup of depressed patients relative to 10 Hz rTMS? The role of the individual alpha frequency","authors":"Helena Voetterl ,&nbsp;Uri Alyagon ,&nbsp;Victoria J. Middleton ,&nbsp;Jonathan Downar ,&nbsp;Abraham Zangen ,&nbsp;Alexander T. Sack ,&nbsp;Hanneke van Dijk ,&nbsp;Aimee Halloran ,&nbsp;Nancy Donachie ,&nbsp;Martijn Arns","doi":"10.1016/j.euroneuro.2024.09.007","DOIUrl":"10.1016/j.euroneuro.2024.09.007","url":null,"abstract":"<div><div>Both 10 Hz repetitive transcranial magnetic stimulation (rTMS) as well as 18 Hz deep TMS (dTMS) constitute effective, FDA-approved TMS treatment protocols for depression. However, not all patients experience sufficient symptom relief after either of these protocols. Biomarker-guided treatment stratification could aid in personalizing treatment and thereby enhancing improvement. An individual alpha frequency (iAF)-based EEG-biomarker, Brainmarker-I, can differentially stratify patients to depression treatments. For instance, an iAF close to 10 Hz was associated with better improvement to 10 Hz rTMS, possibly reflecting entrainment of endogenous oscillations to the stimulation frequency.</div><div>Accordingly, we examined whether 18 Hz dTMS would result in better improvement in individuals whose iAF lies around 9 Hz, a harmonic frequency of 18 Hz.</div><div>Curve fitting and regression analyses were conducted to assess the relation between iAF and improvement. For treatment stratification purposes, correlations with iAF-distance to 10 Hz compared 18 Hz dTMS (<em>N</em> = 114) to 10 Hz rTMS (<em>N</em> = 72).</div><div>We found a robust quadratic effect, indicating that patients with an iAF around 9 Hz exhibited least symptom improvement (r²=0.126, <em>p</em>&lt;.001). Improvement correlated positively with iAF-distance to 10 Hz (<em>p</em>=.003). A secondary analysis in 20 Hz figure-of-eight data confirmed this direction. A significant interaction of iAF-distance and stimulation frequency between 10 and 18 Hz datasets emerged (<em>p</em>=.026).</div><div>These results question entrainment of endogenous oscillations by their harmonic frequency for 18 Hz, and suggest that 10 Hz and 18 Hz TMS target different subgroups of depression patients. This study adds to iAF stratification, augmenting Brainmarker-I with alternative TMS protocols (18 Hz/20 Hz) for patients with a slower iAF, thereby broadening clinical applicability and relevance of the biomarker.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"89 ","pages":"Pages 73-81"},"PeriodicalIF":6.1,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142417138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COMBINING MENDELIAN RANDOMISATION WITH DEPRESSION TRAJECTORIES TO IDENTIFY DEVELOPMENTALLY SPECIFIC PREDICTORS OF CHANGE IN DEPRESSIVE SYMPTOMS","authors":"Robyn Wootton ,&nbsp;Richard Parker ,&nbsp;Michael Lawton ,&nbsp;Kate Tilling","doi":"10.1016/j.euroneuro.2024.08.092","DOIUrl":"10.1016/j.euroneuro.2024.08.092","url":null,"abstract":"<div><div>Prevalence of depression is increasing, especially amongst adolescents and young adults, representing a key risk period where intervention is critical. When using Mendelian randomisation (MR) to identify causal risk factors for depression, estimates are limited to average lifetime effects, rather than being specific to developmental stages.</div><div><strong>Methods.</strong> We have combined trajectories of depressive symptoms with MR to identify developmentally specific risk factors. We used repeated measures of depressive symptoms (short Moods and Feelings Questionnaire) in the ALSPAC cohort, with 11 repeated assessments covering ages 9 to 27 years. First, we used a repeated measures multi-level model (MLM) to describe the average trajectory of depressive symptoms. Linear splines split by knot points were used to explain the non-linear pattern of growth. Second, we used latent class analysis to explore heterogeneity in depression trajectories. Third, we combined both trajectory models with genetic instruments for depression (positive control) and with modifiable risk factors for depression.</div><div>Our models included 44,611 repeated assessments of sMFQ from 6,422 unique individuals. Our best fitting MLM trajectory had three linear splines corresponding to puberty (9-14.5 years), adolescence (14.5-21 years) and early adulthood (21-27 years). Latent classes were stable low, decreasing, transient, increasing and stable high. Positive control genetic instrument for MDD predicted trajectories, most strongly membership into the increasing and stable high class. Genetic instruments for BMI and educational attainment were not associated with change in population average depressive symptoms at any of the different developmental stages nor with class membership. This could suggest no causal effects of these risk factors at these developmental stages, or low power.</div><div>We are continuing to develop our methods, test power and incorporate additional risk factors. We believe that combining outcome trajectories with MR analyses has wide ranging application to improve specificity of causal effects and recommendations for intervention development.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"87 ","pages":"Page 38"},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DRUG REPOSITIONING ANALYSIS IDENTIFIED HUNDREDS OF NOVEL COMPOUNDS ASSOCIATED WITH TOBACCO USE DISORDER","authors":"","doi":"10.1016/j.euroneuro.2024.08.097","DOIUrl":"10.1016/j.euroneuro.2024.08.097","url":null,"abstract":"","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"87 ","pages":"Page 39"},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRACKING THE LONGITUDINAL COURSE IN YOUNG PEOPLE AT HIGH RISK OF BIPOLAR DISORDER","authors":"Philip Mitchell ,&nbsp;Gloria Roberts ,&nbsp;Janice Fullerton ,&nbsp;Michael Breakspear ,&nbsp;Neve Thompson","doi":"10.1016/j.euroneuro.2024.08.019","DOIUrl":"10.1016/j.euroneuro.2024.08.019","url":null,"abstract":"<div><div>Young people with a first-degree relative with bipolar disorder (BD) have a 10-15% risk of developing this illness, but currently we have little understanding of the specific clinical and/or biological features which predict such an outcome. Our group in Sydney established the Bipolar Disorder Kids and Sibs high-risk cohort over a decade ago (with 170 high risk young people, 130 controls and 65 who had already developed BD) and have collaborated closely with the US multi-site consortium led by John Nurnberger. We have followed this Australian sample regularly over time, with particular interest in neuroimaging, genetic (including epigenetic), neuropsychological and clinical findings. We have scanned subjects on 3 occasions (baseline, 2 and 10 years), having already published on changes over the first two years. We reported significant weakening in the high-risk subjects of structural connectivity in a network encompassing the left inferior and middle frontal areas, left striatal and thalamic structures, the left fusiform, and right parietal and occipital regions. These findings were more pronounced in those who had developed a first episode of hypo(mania) over those two years. We have also explored for clinical predictors of hypo(mania) onset, finding particular depressive features to be a strong predictor of this outcome. We will present clinical and biological findings of our 10-year follow-up. More studies of long-term biological and clinical changes over time, and predictors of the onset of hypo(mania) are needed to enable rational development of early intervention studies in those at increased familial risk of BD.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"87 ","pages":"Pages 5-6"},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YOUTH AT RISK OF BIPOLAR DISORDER: TRACKING TRAJECTORIES, OUTCOMES AND BIOMARKERS USING NEUROIMAGING, GENOMICS AND EPIGENOMICS","authors":"Janice Fullerton ,&nbsp;Bronwyn Overs ,&nbsp;Gloria Roberts ,&nbsp;Sonia Hesam-Shariati ,&nbsp;Kate Ridgeway ,&nbsp;Tayla Williams ,&nbsp;Neve Thomson ,&nbsp;Kerrie Pierce ,&nbsp;Howard Edenberg ,&nbsp;Holly Wilcox ,&nbsp;Emma Stapp ,&nbsp;Melvin McInnis ,&nbsp;Leslie Hulvershorn ,&nbsp;John Nurnberger ,&nbsp;Philip Mitchell","doi":"10.1016/j.euroneuro.2024.08.021","DOIUrl":"10.1016/j.euroneuro.2024.08.021","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Longitudinal prospective studies in high-risk populations are key for identifying pre-morbid risk factors for the development of psychopathology. The Australia-US collaborative Bipolar high-risk study comprises 3 groups of participants aged 12-30 years: ‘high-risk’ (with a sibling or parent with bipolar-I or -II), controls with no family history, and an unrelated group of BD-probands; with clinical, demographic and biological data. Familial risk is sometimes considered a surrogate for genetic risk (that is indexed via inherited DNA variants), but we know that this is a simplification of the ‘heritable’ component, which might comprise both direct and indirect genetic effects as well as the impact of family environment. We have used multiple analytic approaches to define and characterize features of disease risk, using neuroimaging, genomics and epigenomics. Analysis of magnetic resonance imaging (MRI) data from 217 unrelated Australian ‘Bipolar Kids and Sibs study’ participants (baseline n=217, follow-up n=152) finds accelerated cortical thinning over time (two scans, 2 years apart) in high-risk subjects (n=105) compared to controls (n=112), suggesting an early brain over-growth followed by normalisation towards the typical age of BD onset. Accelerated thickness and volume reductions over time were observed in ‘high-risk’ individuals across multiple cortical regions, relative to controls, including right lateral orbitofrontal thickness (β=.033, p &lt; .001) and inferior frontal volume (β=.021, p &lt; .001). We also find that bipolar polygenic risk (PsychArray) interacts with stress to increase suicide risk. We examined polygenic risk for both suicide attempt and risky behaviour on structural variance in cortical parcellations that have previously shown replicable associations with suicide attempts, finding that structural differences in the anterior cingulate, parahippocampal, and cuneus warrant further investigation as potential biomarkers for suicide attempts, particularly within the context of BD. Examination of epigenetic markers (450k/EPIC array) shows that genome-wide methylation patterns are broadly impacted by polygenic risk; highlighting an important interplay between genomically inherited risk and the potential biological encoding of environmental exposures. We are now collecting a 3rd MRI scan to capture nonlinear cortical developmental trajectories, and a 2nd blood sample to extend our baseline epigenetic work, derive serum measures and examine mRNA transcription patterns as potential biomarkers of emergent psychopathology. Brain regions associated with both genetic and clinical measures of psychopathology may serve as viable biomarkers, with clinical utility for the identification of individuals who are at greatest risk of developing psychopathology or suicidal intent. Future work will enable integration of these features into a prediction model of disease, to identify biological subgroups on the trajectory towards mental il","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"87 ","pages":"Pages 6-7"},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LEVERAGING CONTEXT-SPECIFIC EPIGENOMIC REGULATORY NETWORKS (EPINETS) TO DISSECT THE GENETICS OF NEUROPSYCHIATRIC DISORDERS","authors":"Ting-Ting Fu,&nbsp;Bhavana Kapalli,&nbsp;Jawahar Mahendran,&nbsp;Neha Rao,&nbsp;Lei Hou","doi":"10.1016/j.euroneuro.2024.08.024","DOIUrl":"10.1016/j.euroneuro.2024.08.024","url":null,"abstract":"<div><div>Expression quantitative locus (eQTL) mapping provides deep insights into the function of disease-associated variants from Genome-wide association studies (GWAS). However, previous studies and our research reported misalignment between eQTLs and GWAS signals, likely due to bulk eQTLs mapped in non-pathology-relevant contexts and lack of cell-type resolution. Alternatively, unraveling the links between cis-regulatory elements (CREs) and genes in various cellular contexts offers an independent strategy to associate GWAS variants with their target genes beyond eQTL mapping. The state-of-the-art approaches, such as experimental assays (e.g., Promoter Capture Hi-C and macro-C) and computational models (e.g., ABC and EpiMap), provide linking resources based on different pieces of evidence, however, are each confined to limited brain cell types or cellular states.</div><div>Addressing this challenge, our study proposes a machine-learning approach to predict CRE-gene associations by combining protein-protein interactions and transcription factor (TF) binding predictions based on ATAC-seq, an assay measuring genomic accessibility. This computational approach facilitates the discovery of CRE-gene connections across different contexts (combinations of cell types and various conditions) whenever ATAC-seq data are available, enriching our understanding of the cis-regulatory networks between TF-CRE-gene.</div><div>We have amassed over 130 cell-sorted and single-cell ATAC-seq datasets encompassing a variety of brain cell types—excitatory neurons, inhibitory neurons, oligodendrocytes, oligodendrocyte progenitor cells (OPCs), astrocytes, microglia, immune cells, and brain vascular cells—under a range of conditions including chemical perturbations, genetic modifications, infections, and disease status. Utilizing this extensive data collection and our integrative pipeline, we have constructed an atlas of TF-CRE-gene linking, namely cEpiNets. We finally employ the atlas to evaluate the enrichment of GWAS signals in CRE modules under various cellular contexts and to prioritize target genes and key drivers across a spectrum of neuropsychiatric disorders.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"87 ","pages":"Page 8"},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LEVERAGING COMORBIDITY TO REFINE PTSD ASSOCIATIONS AND DISSECT GENETIC RISK","authors":"","doi":"10.1016/j.euroneuro.2024.08.014","DOIUrl":"10.1016/j.euroneuro.2024.08.014","url":null,"abstract":"<div><div>Leveraging comorbidity to refine PTSD associations and dissect genetic risk</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"87 ","pages":"Page 3"},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}