| 1. |
- Mullins, Niamh, et al.
(author)
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Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
- 2022
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In: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
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Journal article (peer-reviewed)abstract
- BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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| 2. |
- Docherty, Anna R, et al.
(author)
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GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
- 2023
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In: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
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Journal article (peer-reviewed)abstract
- Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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| 3. |
- Denyer, Hayley, et al.
(author)
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ADHD Remote Technology study of cardiometabolic risk factors and medication adherence (ART-CARMA) : a multi-centre prospective cohort study protocol
- 2022
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In: BMC Psychiatry. - : BioMed Central (BMC). - 1471-244X. ; 22:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Emerging evidence points at substantial comorbidity between adult attention deficit hyperactivity disorder (ADHD) and cardiometabolic diseases, but our understanding of the comorbidity and how to manage cardiometabolic disease in adults with ADHD is limited. The ADHD Remote Technology study of cardiometabolic risk factors and medication adherence (ART-CARMA) project uses remote measurement technology to obtain real-world data from daily life to assess the extent to which ADHD medication treatment and physical activity, individually and jointly, may influence cardiometabolic risks in adults with ADHD. Our second main aim is to obtain valuable real-world data on adherence to pharmacological treatment and its predictors and correlates during daily life from adults with ADHD.METHODS: ART-CARMA is a multi-site prospective cohort study within the EU-funded collaboration 'TIMESPAN' (Management of chronic cardiometabolic disease and treatment discontinuity in adult ADHD patients) that will recruit 300 adults from adult ADHD waiting lists. The participants will be monitored remotely over a period of 12 months that starts from pre-treatment initiation. Passive monitoring, which involves the participants wearing a wrist-worn device (EmbracePlus) and downloading the RADAR-base Passive App and the Empatica Care App on their smartphone, provides ongoing data collection on a wide range of variables, such as physical activity, sleep, pulse rate (PR) and pulse rate variability (PRV), systolic peaks, electrodermal activity (EDA), oxygen saturation (SpO2), peripheral temperature, smartphone usage including social connectivity, and the environment (e.g. ambient noise, light levels, relative location). By combining data across these variables measured, processes such as physical activity, sleep, autonomic arousal, and indicators of cardiovascular health can be captured. Active remote monitoring involves the participant completing tasks using a smartphone app (such as completing clinical questionnaires or speech tasks), measuring their blood pressure and weight, or using a PC/laptop (cognitive tasks). The ART system is built on the RADAR-base mobile-health platform.DISCUSSION: The long-term goal is to use these data to improve the management of cardiometabolic disease in adults with ADHD, and to improve ADHD medication treatment adherence and the personalisation of treatment.
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| 4. |
- Franke, Barbara, et al.
(author)
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Live fast, die young? A review on the developmental trajectories of ADHD across the lifespan
- 2018
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In: European Neuropsychopharmacology. - : Elsevier. - 0924-977X .- 1873-7862. ; 28:10, s. 1059-1088
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Research review (peer-reviewed)abstract
- Attention-deficit/hyperactivity disorder (ADHD) is highly heritable and the most common neurodevelopmental disorder in childhood. In recent decades, it has been appreciated that in a substantial number of cases the disorder does not remit in puberty, but persists into adulthood. Both in childhood and adulthood, ADHD is characterised by substantial comorbidity including substance use, depression, anxiety, and accidents. However, course and symptoms of the disorder and the comorbidities may fluctuate and change over time, and even age of onset in childhood has recently been questioned. Available evidence to date is poor and largely inconsistent with regard to the predictors of persistence versus remittance. Likewise, the development of comorbid disorders cannot be foreseen early on, hampering preventive measures. These facts call for a lifespan perspective on ADHD from childhood to old age. In this selective review, we summarise current knowledge of the long-term course of ADHD, with an emphasis on clinical symptom and cognitive trajectories, treatment effects over the lifespan, and the development of comorbidities. Also, we summarise current knowledge and important unresolved issues on biological factors underlying different ADHD trajectories. We conclude that a severe lack of knowledge on lifespan aspects in ADHD still exists for nearly every aspect reviewed. We encourage large-scale research efforts to overcome those knowledge gaps through appropriately granular longitudinal studies.
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| 5. |
- Kittel-Schneider, Sarah, et al.
(author)
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Non-mental diseases associated with ADHD across the lifespan : Fidgety Philipp and Pippi Longstocking at risk of multimorbidity?
- 2022
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In: Neuroscience and Biobehavioral Reviews. - : Pergamon Press. - 0149-7634 .- 1873-7528. ; 132, s. 1157-1180
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Research review (peer-reviewed)abstract
- Several non-mental diseases seem to be associated with an increased risk of ADHD and ADHD seems to be associated with increased risk for non-mental diseases. The underlying trajectories leading to such brain-body co-occurrences are often unclear - are there direct causal relationships from one disorder to the other, or does the sharing of genetic and/or environmental risk factors lead to their occurring together more frequently or both? Our goal with this narrative review was to provide a conceptual synthesis of the associations between ADHD and non-mental disease across the lifespan. We discuss potential shared pathologic mechanisms and genetic background and treatments in co-occurring diseases. For those co-occurrences for which published studies with sufficient sample sizes exist, meta-analyses have been published by others and we discuss those in detail. We conclude that non-mental diseases are common in ADHD and vice versa and add to the disease burden of the patient across the lifespan. Insufficient attention to such co-occurring conditions may result in missed diagnoses and suboptimal treatment in the affected individuals.
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| 6. |
- Li, Lin, et al.
(author)
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Attention-deficit/hyperactivity disorder is associated with increased risk of cardiovascular diseases : A systematic review and meta-analysis
- 2023
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In: JCPP Advances. - : John Wiley & Sons. - 2692-9384. ; 3:3
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Research review (peer-reviewed)abstract
- Attention-deficit/hyperactivity disorder (ADHD) often co-occurs with other psychiatric and physical diseases. However, available evidence on associations between ADHD and cardiovascular diseases (CVDs) is mixed. To systematically review, quantitatively synthesize, and appraise available evidence on the link between ADHD with CVDs, we searched relevant articles in PubMed, Embase, PsycINFO, and Web of Science from inception to May 1, 2022. Study quality was assessed by using the Newcastle-Ottawa Scale, and random-effects model meta-analyses were performed. A total of 18,391,169 (ADHD: n = 421,224) individuals from 11 studies were included in our systematic review and 8,196,648 (ADHD = 332,619) individuals from five studies were included in the main meta-analysis of adjusted estimates. Pooled estimates showed that ADHD was significantly associated with an increased risk of CVDs in analyses based on adjusted effect size (odds ratio (OR) = 1.96; 95% confidence interval (CI) = 1.19-2.23, Q = 140.74, P Q < 0.001, I 2 = 97.2%). When restricted among adults, the heterogeneity declined to null (OR = 1.73; 95% CI = 1.14-2.62, Q = 6.28, P Q = 0.10, I 2 = 6.28%), suggesting age might be the main source of heterogeneity. In subgroup analyses, we found increased risk of CVDs associated with ADHD across age groups, type of CVDs, and data sources. This systematic review and meta-analyses indicate that ADHD is associated with increased risk for CVDs, but further studies with various study designs are warranted to advance the understanding of the underlying mechanisms for the observed association between ADHD and CVDs. Additional research is also needed to resolve the role of ADHD medications which remains unclear due to the limited number of primary studies exploring this issue.
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