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Childhood trauma, life-time self-harm, and suicidal behaviour and ideation are associated with polygenic scores for autism.

ABSTRACT: Autistic individuals experience significantly elevated rates of childhood trauma, self-harm and suicidal behaviour and ideation (SSBI). Is this purely the result of negative environmental experiences, or does this interact with genetic predisposition? In this study we investigated if a genetic predisposition for autism is associated with childhood trauma using polygenic scores (PGS) and genetic correlations in the UK Biobank (105,222 < N < 105,638), and tested potential mediators and moderators of the association between autism, childhood trauma and SSBI. Autism PGS were significantly associated with childhood trauma (max R² = 0.096%, P < 2 × 10^-16), self-harm ideation (max R² = 0.108%, P < 2 × 10^-16), and self-harm (max R² = 0.13%, P < 2 × 10^-16). Supporting this, we identified significant genetic correlations between autism and childhood trauma (r_g = 0.36 ± 0.05, P = 8.13 × 10^-11), self-harm ideation (r_g = 0.49 ± 0.05, P = 4.17 × 10^-21) and self-harm (r_g = 0.48 ± 0.05, P = 4.58 × 10^-21), and an over-transmission of PGS for the two SSBI phenotypes from parents to autistic probands. Male sex negatively moderated the effect of autism PGS on childhood trauma (β = -0.023 ± 0.005, P = 6.74 × 10^-5). Further, childhood trauma positively moderated the effect of autism PGS on self-harm score (β = 8.37 × 10^-3 ± 2.76 × 10^-3, P = 2.42 × 10^-3) and self-harm ideation (β = 7.47 × 10^-3 ± 2.76 × 10^-3, P = 6.71 × 10^-3). Finally, depressive symptoms, quality and frequency of social interactions, and educational attainment were significant mediators of the effect of autism PGS on SSBI, with the proportion of effect mediated ranging from 0.23 (95% CI: 0.09-0.32) for depression to 0.008 (95% CI: 0.004-0.01) for educational attainment. Our findings identify that a genetic predisposition for autism is associated with adverse life-time outcomes, which represent complex gene-environment interactions, and prioritizes potential mediators and moderators of this shared biology. It is important to identify sources of trauma for autistic individuals in order to reduce their occurrence and impact.

SUBMITTER: Warrier V

PROVIDER: S-EPMC8159746 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundChildhood adversity predicts adolescent suicidal ideation but there are few studies examining whether the risk of childhood adversity extends to suicidal ideation in midlife. We hypothesized that childhood adversity predicts midlife suicidal ideation and this is partially mediated by adolescent internalizing disorders, externalizing disorders and adult exposure to life events and interpersonal difficulties.MethodAt 45 years, 9377 women and men from the UK 1958 British Birth Cohort Study participated in a clinical survey. Childhood adversity was prospectively assessed at the ages of 7, 11 and 16 years. Suicidal ideation at midlife was assessed by the depressive ideas subscale of the Revised Clinical Interview Schedule. Internalizing and externalizing disorders were measured by the Rutter scales at 16 years. Life events, periods of unemployment, partnership separations and alcohol dependence were measured through adulthood.ResultsIllness in the household, paternal absence, institutional care, parental divorce and retrospective reports of parental physical and sexual abuse predicted suicidal ideation at 45 years. Three or more childhood adversities were associated with suicidal ideation at 45 years [odds ratio (OR) 4.31, 95% confidence interval (CI) 2.67-6.94]. Psychological distress at 16 years partially mediated the associations of physical abuse (OR 3.41, 95% CI 2.29-5.75), sexual abuse (OR 4.99, 95% CI 2.90-11.16) with suicidal ideation. Adult life events partially mediated the association of parental divorce (OR 6.34, 95% CI -7.16 to 36.75) and physical (OR 9.59, 95% CI 4.97-27.88) and sexual abuse (OR 6.59, 95% CI 2.40-38.36) with suicidal ideation at 45 years.ConclusionsAdversity in childhood predicts suicidal ideation in midlife, partially mediated by adolescent internalizing and externalizing disorders, adult life events and interpersonal difficulties. Understanding the pathways from adversity to suicidal ideation can inform suicide prevention and the targeting of preventive interventions.

Project description:IntroductionThere are few studies investigating genetic factors related to suicidal ideation or behavior in older adult populations. Our aim was to test associations between passive and active suicidal ideation and polygenic risk scores (PRSs) for suicidality and other traits of relevance for suicidality in old age (i.e. depression, neuroticism, loneliness, Alzheimer's disease, cognitive performance, educational attainment, and several specified vascular diseases) in a population-based sample aged 70 years and older.MethodsParticipants in the prospective H70 study in Gothenburg, Sweden, took part in a psychiatric examination that included the Paykel questions on active and passive suicidal ideation. Genotyping was performed with the Neurochip (Illumina). After quality control of the genetic data the sample included 3467 participants. PRSs for suicidality and other related traits were calculated based on summary statistics from recent GWASs of relevance. Exclusion of persons with dementia or incomplete data on suicidal ideation yielded 3019 participants, age range 70-101 years. Associations between past year suicidal ideation (any level) and selected PRSs were analysed using general estimation equation (GEE) models, adjusted for sex and age.ResultsWe observed associations between passive/active suicidal ideation and PRSs for depression (three versions), neuroticism, and general cognitive performance. After excluding individuals with current major depressive disorder (MDD), similar associations were seen with PRS for neuroticism, general cognitive performance and two PRSs for depression. No associations were found between suicidal ideation and PRSs for suicidality, loneliness, Alzheimer's disease, educational attainment, or vascular disease.DiscussionOur results could indicate which types of genetic susceptibility that are of importance for suicidality in old age, and these findings can help to shed light on potential mechanisms that may be involved in passive and active suicidal ideation in late-life, also in those with no current MDD. However, due to the limited sample size, the results need to be interpreted with caution until replicated in larger samples.

Project description:ObjectiveSuicidal ideation is a clinical exigency heightening the risk of suicide at different levels of suicidal behavior. This study sought to explore crucial correlates of this phenomenon with a structural equation modeling approach. Accordingly, the mediating role of depressive symptoms and difficulties in emotion regulation between childhood trauma and suicidal ideation were explored.MethodThe sample consisted of 372 university students (57.3% females, M = 20.75, SD = 2.25) who completed self-report measures examining experiences of childhood trauma, depressive symptoms, difficulties in emotion regulation, and suicidal ideation. Structural equation modeling was employed, and mediation analysis was conducted. Confirmatory factor analysis was used to test the measurement model of each construct before evaluating the conceptual mediated model.ResultsFindings indicate that depressive symptoms with difficulties in emotion regulation had the strongest association (r = 0.60, P = 0.001), then depressive symptoms and suicidal ideation (r = 0.58, P = 0.001), suicidal ideation with difficulties in emotion regulation (r = 0.45, P = 0.001) then suicidal ideation with childhood trauma (r = 0.39, P = 0.001), difficulties in emotion regulation with childhood trauma (r = 0.36 P = 0.001) and finally depressive symptoms and childhood trauma (r = 0.35, P = 0.001). Regarding indirect paths, difficulties in emotion regulation and depression function together (in a sequential path) to mediate the association between childhood trauma and suicidal ideation ( χ2(68) = 216.86, P < 0.01, CFI = 0.95, TLI = 0.93, RMSE = 0.077, CI [0.066 to 0.089], SRMR = 0.049).ConclusionResults demonstrate that childhood trauma, depressive symptoms, and difficulties in emotion regulation are linked to suicidal ideation, highlighting the necessity of recognizing and addressing suicidal ideation as well as the factors that contribute to suicidal ideation. Emotion regulation interventions can be effective in reducing the negative effects of childhood trauma and lowering the risk of suicide. These interventions can help in reducing depressive symptoms and improve overall mental well-being, leading to a lower risk of suicide.

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Childhood trauma, life-time self-harm, and suicidal behaviour and ideation are associated with polygenic scores for autism.

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