European Neuropsychopharmacology最新文献

{"title":"WHEN YOU ASSUME: RESULTS AND REFLECTIONS FROM STUDIES ON PUBLIC UNDERSTANDING OF GENETICS","authors":"José J. Morosoli , Lucia Colodro-Conde , Fiona K. Barlow , Sarah E. Medland","doi":"10.1016/j.euroneuro.2024.08.102","DOIUrl":"10.1016/j.euroneuro.2024.08.102","url":null,"abstract":"<div><div>From my perspective, science communication goes beyond the mere transmission of information from experts to non-experts. Science communication is dynamic and influenced by personal characteristics and sociopolitical context. As scientists, we not only need to know our audience but also understand ourselves better. The main topics of this presentation are (i) literacy and the use of jargon when talking about genetics; and (ii) specific cognitive biases in how we process information about genetics, including how personal values and experiences can influence how we understand scientific information.</div><div>The talk will be structured in two sections: The first section synthesises our previous work on public understanding of genetics. First, I will discuss a survey study on genetic literacy and public attitudes towards genetic testing in mental health. In this study, we surveyed families that had previously participated in genetic research studies at QIMR Berghofer, Australia (N=3,974), and the general population from the U.K. (N=501) and the U.S. (N=500). Results showed a high interest in psychiatric genetic testing, but the potential for negative impact of such information is also high, with more than a third of the participants showing serious concerns relating to learning about personal genetic predisposition. Concerns were mitigated by higher levels of genetic literacy, leading to less worry about coping with learning about a high genetic predisposition for several mental health problems and less prejudice against people with a high genetic predisposition. Second, I will discuss our recent review on online media articles covering genome-wide association studies (GWAS). We show that we might be missing a major opportunity for increasing general knowledge about genetic findings. Indeed, ∼95% of the news sites and blogs on GWAS used a language too complex to be understood by most adults. Most news articles used the terms ‘RNA’, ‘risk’, ‘gene’, ‘genome’, and ‘DNA’, while the terms ‘marker, ‘polymorphism’, or ‘allele’, rarely appeared. To contextualise these results, I will present new data from our survey showing the results from a modified version of the Rapid Estimate of Adult Literacy in Genetics (REAL-G), which evaluates how familiar the public is with the terms ‘genetics’, ‘chromosome’, ‘susceptibility’, ‘mutation’, ‘genetic variant’, ‘heredity’, and ‘polygenic’. I will briefly touch on the concept of ‘framing’, or how interpretation of information can be influenced by the presence or absence of certain words or images. For example, media on GWAS tends to focus on ‘risk’ (mentioned in 63.7% of articles) versus ‘susceptibility’ (12.2%) or ‘protect’ (11.3%) – the stem of words such as ‘protective’.</div><div>In the second section, I will discuss previous research on genetic determinism as a cognitive bias, as well as the role of motivated cognition. That is, we are not passive or even objective recipients of scientific information, b","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"87 ","pages":"Pages 41-42"},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442315","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":"INTRODUCING MIND: THE METHYLATION, IMAGING AND NEURODEVELOPMENT CONSORTIUM","authors":"Isabel Schuurmans ,&nbsp;Esther Walton ,&nbsp;Charlotte Cecil ,&nbsp;MIND Consortium","doi":"10.1016/j.euroneuro.2024.08.088","DOIUrl":"10.1016/j.euroneuro.2024.08.088","url":null,"abstract":"<div><div>Epigenetic processes, such as DNA methylation (DNAm), show potential as biological markers and mechanisms underlying gene-environment interplay in the prediction of psychiatric and other brain-based phenotypes. However, we still know surprisingly little about how peripheral epigenetic patterns relate to individual differences in the brain itself. An increasingly popular approach to address this is by combining epigenetic and neuroimaging data; yet, research is almost entirely comprised of cross-sectional studies in adults, with modest sample sizes (median N = 80) and a lack of replication.</div><div>To bridge this gap, we present here the new Methylation, Imaging and NeuroDevelopment (MIND) Consortium. MIND aims to bring a developmental focus to the emerging field of Neuroimaging Epigenetics by (i) promoting collaborative, adequately powered developmental research via multi-cohort analyses; (ii) increasing scientific rigor through the establishment of shared pipelines and open science practices; and (iii) advancing our understanding of DNA methylation-brain dynamics at different developmental periods (from birth to emerging adulthood), by leveraging data from prospective, longitudinal pediatric studies.</div><div>MIND currently brings together 14 cohorts worldwide, comprising samples from North and South America, Europe, Africa and Australia, with (repeated) measures of DNAm in peripheral tissues (blood, buccal cells, and saliva) and neuroimaging by magnetic resonance imaging (MRI) across up to five time points across development (Npooled DNAm = 11,791; Npooled neuroimaging = 9,350; Npooled combined = 5,249). The MIND Consortium operates as an open network, welcoming researchers who have access to neuroimaging and epigenetic data (collected at 1+ time points before 18 years) to join.</div><div>In this talk, we introduce the consortium, presenting key characteristics of the samples and data types included. We discuss main considerations, challenges and opportunities in collaborative research on developmental neuroimaging epigenetics, including: (i) separating developmental from technical variability, (ii) modeling time-varying DNAm-brain associations in multi-cohort analyses, and (iii) addressing the dimensionality of neuroimaging epigenetic data. We conclude with key priorities for the consortium, current plans and future directions.</div><div>By triangulating associations across multiple developmental time points and study types, we aim to generate new insights about the dynamic relationship between peripheral DNA methylation and the brain, and to improve understanding of how these ultimately relate to neurodevelopmental and psychiatric phenotypes.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"87 ","pages":"Pages 35-36"},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442150","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":"ADVANCING SUICIDE GENOMICS USING GWAS, 'OMICS AND ELECTRONIC HEALTH RECORDS","authors":"Niamh Mullins (Chair) ,&nbsp;Anna Docherty (Co-chair) ,&nbsp;Brenda Cabrera-Mendoza (Discussant)","doi":"10.1016/j.euroneuro.2024.08.048","DOIUrl":"10.1016/j.euroneuro.2024.08.048","url":null,"abstract":"<div><div>Suicide accounts for more than 700,000 preventable deaths worldwide per year, and suicide attempts (SAs) - defined as non-fatal self-injurious behaviors with intent to die - are up to 25 times more common. SAs are associated with disability, poor quality of life, and social and economic burden, and are the single strongest predictor of future suicide deaths (SDs). Suicidal ideation (SI), the contemplation of taking one's own life, occurs at even higher rates, with a cross-national lifetime prevalence of &gt; 9%. Currently, effective treatment options for alleviating suicidality in diverse populations are lacking, and the ability to predict risk remains poor.</div><div>Heritability estimates for SI, SA and SD are in the range of 30-55%, and recent large-scale genome-wide association studies (GWAS) have yielded the first replicable genome-wide significant (GWS) loci, and novel insights into the underlying biology. For example, GWAS by the Psychiatric Genomics Consortium Suicide Working Group (PGC SUI) of up to 43,871 SA cases, have identified 12 GWS loci, including an intergenic risk locus on chromosome 7, which remained GWS after conditioning on psychiatric disorders, and replicated in an independent cohort. The study also demonstrated a genetic liability to SA that is not mediated by associated psychiatric disorders, as well as pleiotropy between SA and psychiatric disorders, particularly major depression, and risk factors such as pain, smoking, risk-taking behavior, sleep disturbances, and poorer general health.</div><div>In this symposium, we will showcase recent highlights in suicide genomics research, covering the spectrum of suicide phenotypes, common genetic variation, diverse ancestry studies, a variety of ‘omics data and electronic health records. Sarah Colbert, PhD student, will present new unpublished GWAS by PGC SUI comprising &gt;259,000 SI cases, &gt; 73,000 SA cases and &gt; 6,000 SD cases from 46 cohorts of diverse genetic ancestries. Gustavo Turecki, MD PhD will share a detailed investigation of the intergenic chromosome 7 locus specific to SA, using a suite of ‘omics data, to uncover relevant genes and molecular mechanisms. Chittaranjan Behera, MD will discuss the first population-based collection of postmortem blood and brain tissue from non-European ancestry suicide decedents in India. Hilary Coon, PhD will present an analysis of the clinical and genetic profiles of SD cases with and without prior SA, through linking the Utah Suicide Mortality Risk Study with electronic health records and leveraging natural language processing of clinical notes. Finally, our Discussant Brenda Cabrera-Mendoza, MD, PhD will summarize the current state of the field of suicide genomics and provide perspectives on future research and the necessary next steps to translate findings to clinical prediction, treatment, and prevention.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"87 ","pages":"Pages 17-18"},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442216","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":"GENOME-WIDE ASSOCIATION STUDY OF ADOLESCENT-ONSET DEPRESSION","authors":"Poppy Grimes ,&nbsp;Mark Adams ,&nbsp;Anita Thapar ,&nbsp;Christel M. Middeldorp ,&nbsp;Andrew McIntosh ,&nbsp;Heather Whalley ,&nbsp;Alex S.F. Kwong","doi":"10.1016/j.euroneuro.2024.08.091","DOIUrl":"10.1016/j.euroneuro.2024.08.091","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Depression is a complex trait disease which emerges most often and most severely during adolescence. Early-onset depression correlates with late-onset depression and has a three-fold higher single nucleotide polymorphism (SNP)-heritability. Early or adolescent depression is also well-predicted by polygenic risk scores (PRS) of adult major depressive disorder (MDD). Though genetic signal likely exists, attempts to determine variants associated with adolescent depression have been unfruitful due to phenotype heterogeneity and the lack of power available in prospective adolescent cohort sample sizes. To overcome the power problem whilst maintaining a stable phenotype, our study proposes to, i) leverage genetic data from both prospective and retrospective cohorts and, ii) restrict the phenotype to self-report symptoms only.&lt;/div&gt;&lt;div&gt;We perform a Genome-Wide Association Study (GWAS) of adolescent-onset depression leveraging approximately 180,000 individuals from over 20 cohorts in the Psychiatric Genomics Consortium (PGC) and Early Genetics and Lifecourse Epidemiology (EAGLE) consortium. Cohorts span 10 countries with diverse ancestries (including African, American-admixed, East Asian, European, Middle Eastern, and South Asian). We first analyse prospective and retrospective cohorts independently before combining all cohorts in a meta-analysis. We perform tissue expression analysis and compare results with findings in the GWAS catalogue.&lt;/div&gt;&lt;div&gt;Current results from 107,721 individuals (14 891 cases and 92 830 controls) have revealed 7 novel independent genome-wide significant SNPs in European ancestry. We determined a SNP-heritability (SE) of 0.053 (0.006). Genetic correlation (SE) between meta-analysed cohorts with the latest MDD GWAS summary statistics was 0.79 (0.04) and between prospective and retrospective cohorts was 0.52 (0.05). Gene-expression analysis determined tissue enrichment in the cortex, cerebellum and hippocampus. Leading SNPs of the association with adolescent-onset depression overlapped with results from previous GWASs of depression, neuroticism and wellbeing in adults.&lt;/div&gt;&lt;div&gt;Association analyses from the remaining contributing cohorts are ongoing. Current results already provide novel genetic associations, and we expect the addition of approximately 70,000 more individuals to further increase power and discovery across ancestries. Once all samples are received, we will derive PRS for out-of-sample prediction across ancestries, test genetic correlation with other traits, use genomic structural equation modelling to investigate shared architecture, run colocalization for shared trait variants and perform Mendelian randomisation to identify causality. We expect that biological insights, potentially hidden within the larger and more heterogeneous adult population, could be uncovered in the more genetically heritable adolescent-onset group. Investigating the genetic architecture of the adolescent-onset depression subty","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"87 ","pages":"Page 37"},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442228","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":"FAMILY-BASED WHOLE EXOME SEQUENCING IN MULTIPLEX PEDIGREES WITH SCHIZOPHRENIA AND BIPOLAR DISORDER FROM INDIA: FROM VARIANT HITS TO DISEASE MECHANISMS","authors":"","doi":"10.1016/j.euroneuro.2024.08.083","DOIUrl":"10.1016/j.euroneuro.2024.08.083","url":null,"abstract":"","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"87 ","pages":"Page 33"},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442141","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 UPDATE FROM THE PGC PEDIGREE SEQUENCING WORKING GROUP: RESULTS AND NOVEL METHODOLOGIES","authors":"Cathal Ormond ,&nbsp;Niamh Ryan ,&nbsp;William Byerley ,&nbsp;Elizabeth Heron ,&nbsp;Aiden Corvin","doi":"10.1016/j.euroneuro.2024.08.081","DOIUrl":"10.1016/j.euroneuro.2024.08.081","url":null,"abstract":"&lt;div&gt;&lt;div&gt;&lt;strong&gt;Background:&lt;/strong&gt; Examining rare variants in multiplex pedigrees offers a complementary approach to the case-control study design to identify genes robustly associated with psychiatric disorders. Affected individuals within a pedigree are likely influenced by the same rare variant(s), which can simplify the disease-gene discovery process. Also, pedigrees are less sensitive to confounding from population stratification or environmental effects compared to unrelated cohorts. The goal of the Pedigree Sequencing Working Group of the Psychiatric Genomics Consortium (PGC) is to evaluate the contribution of rare variants from whole genome sequencing (WGS) in densely affected pedigrees. To date, we have collated WGS data from 310 individuals in 50 pedigrees across a range of psychiatric diagnoses. Here we give a progress update of the working group as well as describing novel methodologies developed for analysing pedigree-based WGS data.&lt;/div&gt;&lt;div&gt;&lt;strong&gt;Methods:&lt;/strong&gt; As an example of the above, we evaluated WGS data from 61 samples across ten pedigrees recruited from Utah multiply affected with schizophrenia or bipolar disorder. For single nucleotide variants (SNVs) and indels, we applied a simple filtering approach to identify plausible causal variants within each pedigree. We prioritised variants with a full co-segregation pattern (carried by all affected samples in-family and absent from unaffected and marry-in samples) or a reduced co-segregation pattern (carried by all but one affected sample in-family and absent from unaffected and marry-in samples). In addition, we applied an in-house Bayesian methodology known as BICEP to further identify variants of interest that would have been lost to the strict filtering. For copy number variants (CNVs), we applied our pedigree-aware consensus framework known as PECAN to call variants from the WGS data. We then applied a simple filtering prioritisation as before.&lt;/div&gt;&lt;div&gt;&lt;strong&gt;Results:&lt;/strong&gt; For the SNV/indel analysis, our filtering approach identified an ultra-rare, deleterious variant in ATP2B2 that had a reduced co-segregation pattern with schizophrenia. Recently, this gene was reported as significantly associated with bipolar disorder from a large case-control analysis of ultra-rare variants. Additionally, BICEP identified an ultra-rare variant in TTBK1 that perfectly co-segregated with schizophrenia. De novo pathogenic variants in this gene have been reported for childhood-onset schizophrenia. Finally, PECAN identified a rare, exonic deletion that perfectly co-segregates with schizophrenia in one of the pedigrees. The CNV overlaps PITRM1, which has been implicated in a complex phenotype including ataxia, developmental delay, and schizophrenia-like episodes in affected adults.&lt;/div&gt;&lt;div&gt;&lt;strong&gt;Discussion:&lt;/strong&gt; Our results highlight how pedigree-based analyses can provide a useful orthogonal approach to case-control strategies in identifying plausible risk genes for r","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"87 ","pages":"Page 33"},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442144","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 GENOME-WIDE ASSOCIATION STUDY ENRICHMENT SHOWS PROMISE FOR FUTURE PSYCHOPHARMACEUTICAL DISCOVERIES","authors":"","doi":"10.1016/j.euroneuro.2024.08.096","DOIUrl":"10.1016/j.euroneuro.2024.08.096","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":"142442262","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 Discovery and the Genetic and Biological Underpinnings of Schizophrenia","authors":"David Collier","doi":"10.1016/j.euroneuro.2024.08.042","DOIUrl":"10.1016/j.euroneuro.2024.08.042","url":null,"abstract":"<div><div>Genome-wide association and the analysis of rare genetic variants has provided great insights into the genetic basis of schizophrenia, with over 250 variants now identified. Evidence suggests that genetic evidence for association between a gene and disease (even for low risk, common variants) increased the probability of success as a drug target by two-fold or more (Minikel et al., 2024). However, there are several barriers to drug development using this information, including variant-to-gene mapping, target prioritisation, the validity of disease models, target tractability and the development of a therapeutic hypothesis. On the plus side, mapping of the genes within these loci have identified the dopamine D2 receptor (DRD2) gene, a major target of typical antipsychotic drugs, as well as a number of other genes that produce druggable or potentially druggable proteins (Kraft et al., 2024). In this presentation, potential pathways to drug development and stratification using genetics and genomics will be explored.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"87 ","pages":"Page 14"},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442308","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":"WHAT DO WE KNOW ABOUT OFFSPRING AT RISK FOR BIPOLAR DISORDER AND WHAT REMAINS TO BE DISCOVERED","authors":"John Nurnberger ,&nbsp;Melvin McInnis ,&nbsp;Janice Fullerton ,&nbsp;Philip Mitchell ,&nbsp;Howard Edenberg ,&nbsp;Leslie Hulvershorn ,&nbsp;Emma Stapp ,&nbsp;Holly Wilcox ,&nbsp;Neera Ghaziuddin ,&nbsp;Masoud Kamali ,&nbsp;Gloria Roberts","doi":"10.1016/j.euroneuro.2024.08.020","DOIUrl":"10.1016/j.euroneuro.2024.08.020","url":null,"abstract":"&lt;div&gt;&lt;div&gt;The High Risk paradigm is inherently a genetic epidemiologic study, similar to twin studies, adoption studies, and family studies. The questions posed are: What does the disorder look like before its onset? and What determines the transition between the risk state and onset of illness? These questions relate to the developmental expression of the risk genotype and interactions between risk and resilience.&lt;/div&gt;&lt;div&gt;Many studies have been done using this paradigm in bipolar disorder (BD). The particular sample we have been following comprises 307 young people at risk (first-degree relative of a proband with BD) and 166 controls, followed over the past 15 years. Ascertainment sites in the US are Indiana University School of Medicine, Johns Hopkins University, the University of Michigan and Washington University in St. Louis. We have collaborated with the University of New South Wales in Sydney, Australia. Similar methods of assessment (KSADS-BP and DIGS) have been used in all sites, along with a battery of self-assessment instruments. All participants have provided blood for DNA. All have had GWAS completed and polygenic risk scores calculated and 103 have DNA methylation data. A series of follow-up assessments were carried out over 2007-2020.&lt;/div&gt;&lt;div&gt;Diagnostic outcome is related to polygenic risk (Fullerton et al, 2015 PMID &lt;span&gt;&lt;span&gt;26178159&lt;/span&gt;&lt;svg&gt;&lt;path&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;; Zwicker et al, 2023 PMID &lt;span&gt;&lt;span&gt;36856707&lt;/span&gt;&lt;svg&gt;&lt;path&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;, Freeman et al, unpublished). Polygenic risk interacts with history of trauma to increase the chances of attempted suicide in high-risk offspring (Wilcox et al, 2017 PMID &lt;span&gt;&lt;span&gt;29173741&lt;/span&gt;&lt;svg&gt;&lt;path&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;). Polygenic risk also interacts dramatically with perceived pattern of family interaction (Stapp et al, 2023 PMID &lt;span&gt;&lt;span&gt;37378048&lt;/span&gt;&lt;svg&gt;&lt;path&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;).&lt;/div&gt;&lt;div&gt;Different patterns of comorbidity predicted major mood disorder in high-risk offspring, including both internalizing and externalizing disorders during childhood and early adolescence. These patterns of comorbidity are related to distinct polygenic signatures (Fullerton et al, unpublished).&lt;/div&gt;&lt;div&gt;In the literature, studies focused specifically on the emergence of BD have implicated subthreshold hypomanic/manic symptomatology as a premorbid indicator of developing illness (Hafeman et al, 2017 PMID &lt;span&gt;&lt;span&gt;28678992&lt;/span&gt;&lt;svg&gt;&lt;path&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;). Study of early symptomatic indicators in high-risk offspring have also implicated sleep disorders (Duffy et al, 2019 PMID &lt;span&gt;&lt;span&gt;30525908&lt;/span&gt;&lt;svg&gt;&lt;path&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;) and this may relate to premorbid disruption of circadian rhythms.&lt;/div&gt;&lt;div&gt;Although BD presents clinically as a distinctive syndrome, the genetic predisposition and developmental course of the disorder is complex. Risk for BD may be expressed phenotypically as an internalizing disorder, an externalizing disorder, or a disruption of","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"87 ","pages":"Page 6"},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441625","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":"MENDELIAN RANDOMIZATION – WHAT ARE THE PROMISES?","authors":"Sibylle Schwab (Chair) ,&nbsp;Naomi Wray (Co-chair and Discussant)","doi":"10.1016/j.euroneuro.2024.08.028","DOIUrl":"10.1016/j.euroneuro.2024.08.028","url":null,"abstract":"<div><div>With the availability of sufficiently large data from genome wide association analyses for varied phenotypes, a technique, Mendelian Randomization, has become common when searching for causal factors. Essentially, this technique uses genetic factors as proxies for modifiable exposures to explore causal relationships. There are several conditions, which are required for a valid andimpactful Mendelian Randomization estimation. In this symposium, we explore these conditions in more detail, in addition to providing some examples for meaningful explorations in psychiatric genetics.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"87 ","pages":"Pages 9-10"},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441635","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}