European Neuropsychopharmacology最新文献

{"title":"EXPLORING THE MISSING GENETICS UNDERLYING NEUROPSYCHIATRIC DISORDERS WITH FUNCTIONAL GENOMICS","authors":"","doi":"10.1016/j.euroneuro.2024.08.057","DOIUrl":"10.1016/j.euroneuro.2024.08.057","url":null,"abstract":"","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442153","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":"PROGRESS OF AND CHALLENGES FACED BY THE ANTI-RACISM WORKING GROUP AT KING'S COLLEGE LONDON","authors":"","doi":"10.1016/j.euroneuro.2024.08.062","DOIUrl":"10.1016/j.euroneuro.2024.08.062","url":null,"abstract":"<div><div>The Anti-Racism Working Group (ARWG) of the Social, Genetic, Developmental Psychiatry (SGDP) Centre aims to help identify, propose, instigate, and support change consistent with an anti-racist agenda within the department. This talk will showcase the work done by the ARWG, the challenges we faced along the way, and where the team plans to go next. The ARWG was established in 2020 consists of three subgroups: (1) SGDP Centre Protocol, which aims to help develop and embed anti-racist procedures and practices within the department, (2) SGDP Centre Internal Events and Communication, which organises events on anti-racism for members of the department and the wider King's College London community, and (3) SGDP Centre External Events and Wider Opportunities, which aims to provide mentoring, allyship, training, and communication for people and organisations outside of King's College London. Since our inception, we have organised multiple events, including a talk from Dr Jedidiah Carlson titled ‘Disrupting the Weaponisation of Genetics Research by Extremists’, and have supervised multiple undergraduate projects with an anti-racism focus, for example, ‘Exploring anti-racist terminology and research practices for mental health researchers’. We also coordinate the annual faculty-wide outreach programme for London-based teenagers that aims to encourage continuation of science education to university level. To track and communicate perceptions and opinions about racism within the SGDP Centre, we distribute surveys and present the findings to the department, as well as deliver regular reports on our progress. A key challenge we encountered was fostering support and engagement from a wider audience. Building capacity across the university has been improved through collaboration with other departments and Culture, Equity, Diversity and Inclusion groups. Currently, the team is developing an anti-racist toolkit for use as an individual or within a team, guidelines on how to increase inclusivity of teaching, and a terminology guide for researchers measuring and reporting diversity. Moving forward, we hope to develop sustainable tools and initiatives that are embedded within departmental practice that promote diversity and equality of opportunity among students and staff across all levels of seniority.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442138","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":"THE CONTRIBUTION OF COPY NUMBER VARIANTS TO SCHIZOPHRENIA: FROM A GENOME-WIDE STUDY IN EAST ASIAN POPULATIONS","authors":"","doi":"10.1016/j.euroneuro.2024.08.069","DOIUrl":"10.1016/j.euroneuro.2024.08.069","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Here, we present a study on rare copy number variants (rCNVs) in schizophrenia, emphasizing the shift from traditional European (EUR) populations to a large East Asian (EAS) cohort, the largest to date, with 20,903 cases and 23,258 controls. The study confirms previous findings about the heightened genome-wide rCNV burden in schizophrenia patients within this EAS cohort. A combined meta-analysis of EAS and EUR cohorts, totaling 38,409 cases and 40,009 controls, identified 15 significant rCNV loci. Of these, five were novel, found at locations 1q21.2, 8p21.3, 11q13.1, 19p13.3, and 19q13.42. The comparison between EAS and EUR data suggested that differences in rCNV frequencies contribute to variability in discovery power across these populations rather than differences in genetic effect sizes.&lt;/div&gt;&lt;div&gt;Among the eight rCNV loci implicated in the PGC EUR study with genome-wide significance, seven had rCNVs captured in the EAS dataset, among which three achieved genome-wide significance (P&lt;6.88e-5, 22q11.21 deletion, 3q29 deletion, and 16p11.2 duplication) and an additional three reached nominal significance (P &lt; 0.05, 1q21.1 deletion, 16p11.2 deletion, and 7q11.23 duplication). None of these loci showed a significant difference in effect size between the two populations.&lt;/div&gt;&lt;div&gt;rCNVs, particularly, are significant as they have a pronounced potential to disrupt neuronal development and synaptic connectivity. The discovery of novel rCNV loci in the EAS population enriches our understanding of the genetic architecture of schizophrenia and underscores the potential influence of rCNVs on neurodevelopmental processes. Comparing rCNV profiles between EAS and EUR cohorts illuminates how population-specific genomic structures can influence the prevalence and impact of these genetic variations.&lt;/div&gt;&lt;div&gt;The current findings underscore the variability in genetic factors influencing schizophrenia across different populations and highlight the necessity of expanding genetic studies to include diverse populations beyond those of European descent. Identifying novel loci in the EAS population not only enriches our understanding of the genetic architecture of schizophrenia but also suggests that population-specific genetic variations could be crucial for tailoring more effective diagnostics and treatments.&lt;/div&gt;&lt;div&gt;Furthermore, this study enhances our understanding of the genetic diversity and complexity of schizophrenia, contributing valuable insights into how different populations may exhibit unique genetic profiles that influence the disease. By exploring these distinctions, the research advocates for a more inclusive approach to genetic research, which is essential for developing global health strategies and interventions sensitive to genetic diversity. This aligns with the conference theme by emphasizing the importance of including diverse genetic backgrounds to achieve a more comprehensive understanding of psychiatric disorders.&lt;/div&gt;&lt;/di","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442045","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":"INNOVATING KNOWLEDGE DISSEMINATION FOR CULTURAL RELEVANCE AND ACCESSIBILITY","authors":"","doi":"10.1016/j.euroneuro.2024.08.104","DOIUrl":"10.1016/j.euroneuro.2024.08.104","url":null,"abstract":"<div><div>We are all embedded within societies, communities, families, and institutions. But how do we ensure our research, methodologies, findings, and implications are accessible and meaningful for those who need the knowledge? As a Māori (Indigenous) researcher from New Zealand and a researcher within the NIH-funded International Eating Disorder Genetics Initiative (EDGI) study led by Professor Cynthia Bulik, I am acutely aware of the pivotal role language plays in bridging the gap between scientific communication and societal understanding.</div><div>My symposia presentation delves into the importance of a researcher's role as a knowledge creator to craft accessible and culturally sensitive narratives from complex scientific concepts. Researchers are responsible for spreading the knowledge of genetic findings beyond the confines of scholarly journals so that our work reaches and resonates with communities far and wide. It is imperative to embrace diverse modalities of dissemination and recognise that peer-reviewed articles are but one conduit through which knowledge can flow. I will cover opportunities for various dissemination modalities, including the use wānanga by our Māori communities in New Zealand. Wānanga (forum or seminar) is a way of sharing knowledge, discussing, exploring and making meaning of the content, and using the associated concepts can present new opportunities for knowledge dissemination in various contexts.</div><div>Ultimately, my presentation serves as a call to action for researchers and communicators alike. The true measure of research impact lies not solely in scholarly publications but in the tangible difference we make in the lives of people and communities through accessible, inclusive, and culturally resonant knowledge dissemination practices.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442222","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":"LATEST INSIGHTS FROM MULTI-ANCESTRY FINE-MAPPING IN PSYCHIATRIC DISORDERS","authors":"","doi":"10.1016/j.euroneuro.2024.08.033","DOIUrl":"10.1016/j.euroneuro.2024.08.033","url":null,"abstract":"<div><div>Genome-wide association studies (GWAS) identify associated variants but do not tell the whole story. The vast majority of target genes of these associations remain unknown. Without them it is impossible to fully reap the benefits of genetic research, such as better understanding of disease mechanisms and discovery of novel drug targets. Translating genome-wide significant (GWS) loci into causal genes and mechanisms is particularly challenging for psychiatric disorders (PD) due to linkage disequilibrium (LD) between risk variants, incomplete understanding of the non-coding regulatory mechanisms in the brain, and the highly polygenic architecture of most PDs. Therefore, a systematic analysis that applies fine mapping to jointly identify and validate a credible set of causal variants and genes for PDs using relevant tissues and cell types is critical. However, most fine-mapping studies have focused on individuals of genetically determined European (EUR) ancestries; with the functional impact of most identified causal variants, especially the non-coding variants, remaining unclear. A crucial progression is inclusion of diverse populations in PD GWAS and utilize the characteristics of diverse ancestral groups the to empower identification of target genes and mechanisms.</div><div>In this symposium, we will demonstrate how we can integrate data from diverse ancestries and cutting-edge statistical genetics techniques to improve the fine-mapping resolution and prioritize high confidence causal variants and genes for PDs. Specifically, we will showcase innovations and insights from four different perspectives: (i) results from the first large-scale fine-mapping and gene prioritization study of major depressive disorder (MDD) in an ancestrally diverse sample, including individuals of African, East Asian and South Asian ancestry, and Hispanic/Latin American samples (Prof Karoline Kuchenbaecker), (ii) integration of a suite of fine-mapping methods and novel single nuclei gene expression data to unravel the genetic etiology of complex disorders such as bipolar disorder (BD) (Dr Maria Koromina), (iii) latest insights from multi-ancestry fine-mapping in schizophrenia (SCZ) using advanced statistical genetics techniques such as implementation of the Polygenic Priority Score (PoPS) and machine-learning models (Dr Karl Heilborn), (iv) leveraging a new method for polygenic risk scoring which incorporates functional genomics annotations (SBayesRC) to improve fine-mapping of complex traits including PDs (Dr Jian Zeng). Finally, Prof. Naomi Wray will summarize the state of the field with regards to multi-ancestry and multi-omics aided fine-mapping and provide perspectives on future research and the crucial next steps to translate results to clinical prediction, treatment, and prevention.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442309","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":"GENETIC DETERMINANTS OF BRAIN AGING ACROSS CULTURES","authors":"","doi":"10.1016/j.euroneuro.2024.08.087","DOIUrl":"10.1016/j.euroneuro.2024.08.087","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Deviations from a typical ageing trajectory are an important risk factor for poor health outcomes. The difference between chronological and brain-predicted age (i.e., brain-predicted age difference [PAD]) is one such measure of deviation from healthy ageing. Brain-PAD has been linked to over 40 traits and is generally thought to be heritable. However, specific genetic loci that influence brain-PAD are still largely unknown. Three recent genome-wide association studies (GWASs) on brain-PAD in the UK Biobank (n up to 28,104; age range: 40 to 84) identified a small number of associated genetic variants. This small number might be explained by the narrow age range and moderate sample size used in these studies. Larger samples covering the complete adult lifespan are needed to elucidate the genes implicated in brain-PAD, their impact on other biological systems in the brain and peripheral tissues, and the causal relationship between PAD and mental health.&lt;/div&gt;&lt;div&gt;Brain-PAD was derived using a ridge regression model with 77 FreeSurfer-derived structural brain imaging features of surface area, cortical thickness and subcortical volume as an input in a total of n=47,167 participants from 28 datasets within the ENIGMA consortium. For a subset of these (n=34,112), we carried out a genome-wide association meta-analysis (GWAS) of brain-PAD. Additive effects of genetic variants on brain-PAD were tested, adjusting for age, age2, sex, total intracranial volume, genetic ancestry, imaging covariates (e.g. multiple scanners) and disease status (for case-control studies). We applied linear (mixed) models using BOLT-LMM, RareMetalWorker or PLINK2. Preliminary results were meta-analysed in METAL, weighing each cohort according to sample size. Ancestry-specific analyses were performed to disentangle universal versus population-specific genetic influences.&lt;/div&gt;&lt;div&gt;A total of n=47,167 participants were included in the phenotypic analysis (age range 18-75 years; 52.8% females). Brain age was predicted with mean absolute error of 9.58 years (range 4.67-21.29). For the subset of datasets included in the GWAS, the mean absolute error was slightly larger (14.25 years; range 6.30-21.29; age-bias corrected=9.08). Fixed effect meta-analysis using METAL identified 66 genome-wide significant variants associated with brain-PAD at P=5 × 10. Three of these variants (on chromosomes 2, 15 and 16) were independent using r=0.1 and 500 kb window size. Two out of three variants identified had been previously implicated in brain-related phenotypes. SNP-based heritability was estimated at 0.1923 (SE=0.0167).&lt;/div&gt;&lt;div&gt;Our findings indicate that brain age deviations in adulthood might be moderately heritable. Genetic loci overlapped partially with previous studies using overlapping data (e.g., UK Biobank), but different brain age estimation methods, suggesting a degree of consistency across methods. Identifying the underlying genetic loci can help to shed light on the causal ri","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442149","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":"SYSTEMS BIOLOGY OF PTSD REVEALS MECHANISMS OF RISK AND DISEASE PROCESSES AT BRAIN MULTI-OMIC, BRAIN CELL TYPE, AND BLOOD LEVELS","authors":"","doi":"10.1016/j.euroneuro.2024.08.015","DOIUrl":"10.1016/j.euroneuro.2024.08.015","url":null,"abstract":"<div><div>Stress-related disorders stem from the interplay of genetic susceptibility and stress exposure, shaping gene and protein expression through epigenetic modifications across the lifespan. Studies on postmortem brains of PTSD and MDD patients, compared to neurotypical controls, reveal genetic overlaps, sex disparities, and immune and interneuron signaling involvement, yet lack integrative analyses. To address this gap, we established a brain multi-omic, multi-region database comprising individuals with PTSD, MDD, and NCs (77/group, n = 231). We analyzed molecular changes across the central nucleus of the amygdala (CeA), medial prefrontal cortex (mPFC), and hippocampal dentate gyrus (DG) at transcriptomic, methylomic, and proteomic levels. Our approach is supplemented by single-nucleus RNA sequencing (snRNA-seq), genetics, and blood proteomics, aiming for a comprehensive systems perspective. Our findings highlight predominant molecular</div><div>changes in the mPFC, with differentially expressed genes (DEGs) and exons carrying disease signals. Notably, methylation alterations were concentrated in the DG for PTSD and CeA for MDD. Findings supported by replication analyses across two cohorts (n = 114). We observed a moderate overlap between disorders, with childhood trauma and suicide driving molecular variations, and sex-specificity was more notable in MDD. Pathway analyses link disease-associated molecular signatures to immune mechanisms, metabolism, mitochondria function, and stress hormone signaling, albeit with low concordance across omics. Top upstream regulators include IL1B, GR, STAT3, and TNF. Multi-omic factor and gene network analyses suggest latent factors and modules related to aging, inflammation, vascular processes, and stress.</div><div>Complementing multi-omics, our snRNA-seq in the dorsolateral PFC reveals dysregulated pathways and upstream regulators in neuronal and non-neuronal cell types, including stress-related genes. Examining brain multi-omics with blood proteins in the large UK Biobank cohort shows significant correlation, overlap, and directional similarity, implying potential blood-based biomarkers. Fine-mapping of PTSD and MDD genome-wide association study results reveals limited overlap between risk and disease processes at the gene and pathway level.</div><div>Ultimately, prioritized genes with multi-omic, multi-region, or multi-trait associations are implicated in pathways/networks, exhibit cell-type specificity, demonstrate blood biomarker potential, or are linked to genetic risk for PTSD and MDD.</div><div>In conclusion, our study unveils shared and unique brain multi-omic molecular dysregulations in PTSD and MDD, elucidating distinct cell-type involvement and paving the way for blood-based biomarker development. These insights not only implicate established stress-related pathways but also offer potential therapeutic avenues.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441740","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":"GENETIC AND ENVIRONMENTAL PREDICTORS OF TREATMENT RESISTANT DEPRESSION","authors":"","doi":"10.1016/j.euroneuro.2024.08.067","DOIUrl":"10.1016/j.euroneuro.2024.08.067","url":null,"abstract":"&lt;div&gt;&lt;div&gt;A range of pharmacological and psychological treatments for depression exist. However, across these treatment types, outcomes are variable and many individuals do not experience any remission of symptoms. Approximately one third of individuals diagnosed with major depressive disorder (MDD) are refractory to treatment, often termed ‘treatment-resistant depression (TRD)’. The complex and heterogeneous features and pathophysiology of MDD, influenced by various environmental and biological factors, is likely a major contributor to the high rates of treatment failure. Consequently, identifying predictors associated with treatment-resistant depression may help optimize therapy and mitigate the risk of poor treatment outcomes for individuals with depression.&lt;/div&gt;&lt;div&gt;The Australian genetics of depression study (AGDS) comprises ∼16 000 genotyped participants that report a diagnosis of depression. Using AGDS data, we defined TRD cases using prescription record data according to the following criteria: i) at least three unique antidepressant medications; ii) each prescription was prescribed for a period of at least two months before switching medications; iii) the time between the prescriptions of two consecutive drugs was no longer than 14 weeks and iv) prescriptions did not overlap when switching medications. Controls were defined as i) individuals with two or less antidepressant prescriptions, prescribed at least twice (for 2 months or longer) and ii) if two antidepressant were prescribed, the time between the two antidepressant prescriptions was &gt; 14 weeks. This lead to a final sample size of 1,411 TRD cases and 8,711 controls. We used regression analysis to explore the association of TRD with biological predictors such a polygenic score (PGS) and CYP2C19 and CYP2D16 metaboliser profiles, measured personality traits, and environmental predictors such as social support and exposure to stressful life events. Lastly, we tested for any gene-environment interactions across our predictors.&lt;/div&gt;&lt;div&gt;Individuals with TRD were more likely to be male, have an earlier age of onset and report more lifetime depressive episodes in our cohort. Preliminary analyses show that PGS for depression, bipolar disorder, ADHD and PTSD were all significantly associated with TRD (p &lt; 0.001). CYP gene metaboliser profiles did not differ significantly between TRD and non-TRD groups. We found a nominally significant association between individuals with high levels of neuroticism and increased TRD risk. In line with previous studies, we show a significant interaction effect between depression PGS and stressful life event exposure on TRD risk as well as and interaction between bipolar disorder PGS and social support.&lt;/div&gt;&lt;div&gt;Given the limited resources available to the thousands of individuals seeking treatment for depression, there is a strong rationale to understand who is most likely to benefit from certain types of treatment. The incorporation of genetic infor","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442043","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":"PRENATAL AND PERINATAL RISK SUB TYPES ASSOCIATED WITH AUTISM AND BEHAVIOURAL PROFILES IN KENYA AND SOUTH AFRICA","authors":"","doi":"10.1016/j.euroneuro.2024.08.044","DOIUrl":"10.1016/j.euroneuro.2024.08.044","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Autism is a neurodevelopmental condition that has been reported to affect 1 in 100 children. Over 90% of children under the age of 5 years with neurodevelopmental disabilities (NDDs), such as autism, live in lower and middle-income countries. However, the majority of autism research is carried out in high-income countries. Prenatal and perinatal risk factors may give more insight into patterns of factors that may be shared or shared aetiology of autism and other neurodevelopmental conditions. Multipleprenatal risk factors have been put forward as being associated with an elevated risk of autism and other NDDs, endorsing the hypothesis that environmental and genetic factors contribute to autism. Pre-and-peri-natal events such as preeclampsia, alcohol exposure, prolonged labour, birth asphyxia, preterm birth and low birth weight are common in Africa. These environmental risk factors potentially increase the risk for autism; however, little is known from the Geographical South regarding unique risk factor clusters and their association with the clinical presentation of autism and co-occurring behavioural subtypes.&lt;/div&gt;&lt;div&gt;The aim of this study is to measure how environmental risk factor variables and de novo variant burden interact to generate specific neurodevelopmental profiles, influencing autistic traits, ADHD traits, social communication traits, and internalising and externalising behaviours.&lt;/div&gt;&lt;div&gt;This study is nested within a larger case-control study referred to as the NeuroDev study, which aims to characterise the genetic and phenotypic architecture of neurodevelopmental conditions such as autism. Participants in this study included 273 children with autism and 248 children with other NDDs. Pre-and-peri-natal variables and socio-demographic factors were collected using a bespoke neuromedical questionnaire, an alcohol exposure questionnaire; asset index questionnaires that measure socio-economic status, and a demographics questionnaire. Genetic variants associated with an NDD diagnosis are also available. We will first describe the frequencies of the pre-and-peri-natal factors of interest between autistic children and children with other NDDs. We will thereafter use latent profile analysis to delineate the clusters of risk factors in the underlying data from Kenya and South Africa. With these emerging risk factor subtypes, we will test whether diagnostic categories of NDDs map onto these subtypes and explore the concordance between risk factor profiles and autism/NDD phenotypes. We will use the autism and neurodevelopmental symptom sub-domain scores and the total scores of behavioural tools such as the Developmental Diagnostic Dimensional Interview (3Di), the Child Behaviour Checklist (CBCL), Swanson Nolan and Pelham (SNAP)-ADHD questionnaire, and the Social Communications Disorder Checklist (SCDC). We hypothesise that there may be unique clusters of pre-and-peri-natal events that are associated with specific autism and co-oc","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442257","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":"PSYCHIATRIC GENETICS RESEARCH IN AFRICA – A CLINICIAN'S PERSPECTIVE","authors":"","doi":"10.1016/j.euroneuro.2024.08.060","DOIUrl":"10.1016/j.euroneuro.2024.08.060","url":null,"abstract":"<div><div>Psychiatric genetics may improve understanding of etiology, predicting susceptibility, and tailoring treatments for patients in African psychiatric clinics. However, its development and application in Africa and other low-and-middle-income settings presents unique challenges and opportunities. This presentation will review both the practice and promise of genetic research from a psychiatrist's perspective, sharing with attendees cultural attitudes for psychiatric research, barriers faced when conducting research and potential for local impact.</div><div>In African clinics, patients often seek explanations for their mental illness and their children's risk for acquiring the illnesses. However, a lack of concrete answers leaves them dissatisfied, leading many to rely on cultural explanations. A better understanding of psychiatric genetics in Africa could provide these answers and help retain patients in care. Also explaining complex genetic terms to patients is often challenging for clinicians since patients have varying education and health literacy levels. Simplifying and translating these terms is crucial.</div><div>There is still limited research on the genetic risks for mental disorders in Africa. &lt; 5% of psychiatric genetic samples worldwide are from people of African ancestry despite evidence of the high level of genetic diversity in comparison to other populations. Importantly, African clinicians have limited training in use of psychiatric genetics in the clinic. For example, only five out of eighty Ugandan psychiatrists have received training in psychiatric genetics through the Global Initiative for Neuropsychiatric Genetics Education and Research (GINGER). In addition, implementing genetic insights requires infrastructure, but few facilities offer services like genetic testing, and costs are prohibitive.</div><div>The ever-expanding field of psychiatric genetics research must include and cater to African clinicians. Involving clinicians in psychiatric genetic research is crucial as they play an important role integrating psychiatric genetics research into practice. It is imperative that stakeholders from participating African countries, including clinicians not directly involved in genetics research, are enlightened on the benefits of genetics research to patient care. These clinicians can further advocate for incorporating genetic research into national health policies to benefit the broader population.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442136","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}