Neurodevelopmental and genetic determinants of exposure to adversity among youth at risk for mental illness

Abstract

Background: Attention-deficit/hyperactivity disorder (ADHD) and lower cognitive ability have been linked with increased likelihood of exposure to adversity. We hypothesized that these associations may be partly due to genetic factors. Methods: We calculated polygenic scores for ADHD and intelligence and assessed psychopathology and general cognitive ability in a sample of 297 youth aged 5-27 years enriched for offspring of parents with mood and psychotic disorders. We calculated an adversity score as a mean of 10 indicators, including socio-economic disadvantage, childhood maltreatment and bullying. We tested the effects of polygenic scores, externalizing symptoms and IQ on adversity scores using mixed-effects linear regression. Results: Externalizing symptoms and general cognitive ability showed expected positive and negative relationships with adversity, respectively. Polygenic scores for intelligence were unrelated to adversity, but polygenic scores for ADHD were associated with adversity (b = 0.23, 95% CI 0.13 to 0.34, p < .0001). ADHD polygenic scores uniquely explained 4.0% of variance in adversity score. The relationship between polygenic scores for ADHD and adversity was independently significant among individuals with (b = 0.49, 95% CI 0.25 to 0.75, p < .0001) and without (b = 0.14, 95% CI 0.02 to 0.26, p = .022) ADHD. Conclusions: A genetic score indexing liability to ADHD was associated with exposure to adversity in early life. Previously observed associations between externalizing symptoms, lower cognitive ability and adversity may be partially attributed to genetic liability to ADHD.

Prevalence of attention‐deficit/hyperactivity disorder in people with mood disorders: A systematic review and meta‐analysis

“…28 In addition, genetic propensity to ADHD also increases the likelihood of multiple types of adversity, including maltreatment and bullying, which are known to increase the risk of major mood disorders. 29 The rates of ADHD were consistently higher among individuals with BD compared to those with MDD. This is in line with findings that ADHD is more common in offspring of parents with BD compared to offspring of parents with MDD.…”

“…For example, ADHD may contribute to lower self‐esteem, 27 which is a risk factor for mood disorders 28 . In addition, genetic propensity to ADHD also increases the likelihood of multiple types of adversity, including maltreatment and bullying, which are known to increase the risk of major mood disorders 29 …”

Reliability of multimodal MRI brain measures in youth at risk for mental illness

“…Socioeconomic status was captured as a composite variable (range 0–5) indexing: (i) maternal and (ii) paternal levels of education (iii) family household annual income, (iv) ownership of primary residence, and (v) ratio of bedrooms to residents in household, as previously described (MacKenzie et al, 2017; Zwicker et al, 2019). Higher numeric value reflects higher SES.…”

Editorial: Polygenic scores in child and adolescent psychiatry – strengths, weaknesses, opportunities and threats

“…Thus, we see that PGS research is advancing our understanding of nature–nurture interplay. In this issue of the Journal of Child Psychology and Psychiatry , a study shows that the current ADHD PGS predicts adversity in child offspring of parents with emotional and psychotic disorders (Zwicker et al, 2020), a new example of gene–environment correlation at work. Children’s environments are not random but to some degree correlated with genetic predisposition.…”

“…Most risk indicators are not 100% predictive, and we should not expect PGS to be either. PGS research, as shown in this issue, is already influencing child and adolescent psychiatry through innovative findings (Zwicker et al, 2020).…”