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Mapping relationships between ADHD genetic liability, stressful life events, and ADHD symptoms in healthy adults.

ABSTRACT: Attention-deficit/hyperactivity disorder (ADHD) symptoms are continuously distributed in the general population, where both genetic and environmental factors play roles. Stressful life events (SLEs) have been associated with ADHD diagnosis, but the relationship between ADHD genetic liability, SLEs, and ADHD symptoms in healthy individuals is less clear. Using a sample of 1,531 healthy adults (average age 26.9 years; 55.8% female), we investigated relationships between ADHD polygenic risk scores (ADHD-PRSs), SLEs, and ADHD symptoms in a general population sample. Confirming earlier findings in an overlapping sample, all SLE-measures assessed (lifetime SLEs, recent SLEs, and childhood trauma (CT)) were significantly correlated with total ADHD, inattention (IA), and hyperactivity-impulsivity (HI) scores (r² range = .08-.15; all p < .005). ADHD-PRSs was associated with HI (R² _best-fit = .37%), lifetime SLEs (R² _best-fit = .56%), and CT (R² _best-fit = .40%). Mediation analyses showed that lifetime SLEs partially mediated the association between ADHD-PRSs and HI (indirect effect: β = 68.6, bias corrected accelerated 95% confident interval (BCa95%CI) [11.9, 131.0], p = .016, proportion mediated (P_M ) =19.5%), with strongest effects contributed by CT (β = 34.4, BCa95%CI [0.4, 76.5], p = .040, P_M = 9.8%). On the other hand, HI partially mediated the association between the ADHD-PRSs and lifetime SLEs (β = 42.9, BCa95%CI [7.3, 83.9], p = .014, P_M = 18.8%). Our study observed a complex relationship of genetic and environmental risk factors contributing to ADHD symptoms in the healthy adult population.

SUBMITTER: Li T

PROVIDER: S-EPMC8359274 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Mapping relationships between ADHD genetic liability, stressful life events, and ADHD symptoms in healthy adults.

Li Ting T Franke Barbara B AriasVasquez Alejandro A Mota Nina Roth NR

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 20201215 4

Attention-deficit/hyperactivity disorder (ADHD) symptoms are continuously distributed in the general population, where both genetic and environmental factors play roles. Stressful life events (SLEs) have been associated with ADHD diagnosis, but the relationship between ADHD genetic liability, SLEs, and ADHD symptoms in healthy individuals is less clear. Using a sample of 1,531 healthy adults (average age 26.9 years; 55.8% female), we investigated relationships between ADHD polygenic risk scores ...[more]

PMID: 33319511

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Project description:ImportanceBoth adulthood stressful life events (SLEs) and liability for schizophrenia have been associated with poor mental and physical health in the general population, but their interaction remains to be elucidated to improve population-based health outcomes.ObjectiveTo test whether recent SLEs interact with genetic and environmental liability for schizophrenia in models of mental and physical health.Design, setting, and participantsThe Netherlands Mental Health Survey and Incidence Study-2 is a population-based prospective cohort study designed to investigate the prevalence, incidence, course, and consequences of mental disorders in the Dutch general population. Participants were enrolled from November 5, 2007, to July 31, 2009, and followed up with 3 assessments during 9 years. Follow-up was completed on June 19, 2018, and data were analyzed from September 1 to November 1, 2019.ExposuresRecent SLEs assessed at each wave and aggregate scores of genetic and environmental liability for schizophrenia: polygenic risk score for schizophrenia (PRS-SCZ) trained using the Psychiatric Genomics Consortium analysis results and exposome score for schizophrenia (ES-SCZ) trained using an independent data set.Main outcomes and measuresIndependent and interacting associations of SLEs with ES-SCZ and PRS-SCZ on mental and physical health assessed at each wave using regression coefficients.ResultsOf the 6646 participants included at baseline, the mean (SD) age was 44.26 (12.54) years, and 3672 (55.25%) were female. The SLEs were associated with poorer physical health (B = -3.22 [95% CI, -3.66 to -2.79]) and mental health (B = -3.68 [95% CI, -4.05 to -3.32]). Genetic and environmental liability for schizophrenia was associated with poorer mental health (ES-SCZ: B = -3.07 [95% CI, -3.35 to -2.79]; PRS-SCZ: B = -0.93 [95% CI, -1.31 to -0.54]). Environmental liability was also associated with poorer physical health (B = -3.19 [95% CI, -3.56 to -2.82]). The interaction model showed that ES-SCZ moderated the association of SLEs with mental (B = -1.08 [95% CI, -1.47 to -0.69]) and physical health (B = -0.64 [95% CI, -1.11 to -0.17]), whereas PRS-SCZ did not. Several sensitivity analyses confirmed these results.Conclusions and relevanceIn this study, schizophrenia liability was associated with broad mental health outcomes at the population level. Consistent with the diathesis-stress model, exposure to SLEs, particularly in individuals with high environmental liability for schizophrenia, was associated with poorer health. These findings underline the importance of modifiable environmental factors during the life span for population-based mental health outcomes.

Dataset Information

Mapping relationships between ADHD genetic liability, stressful life events, and ADHD symptoms in healthy adults.

Publications

Mapping relationships between ADHD genetic liability, stressful life events, and ADHD symptoms in healthy adults.

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