To Örebro University

Cumulative exposure to psychosocial adversity (PSA) at an early age is a risk factor for developing neuro developmental disorders(NDDs) such as attention-deficit hyperactivity disorder (ADHD) and autism. However, it is not clear if this statistical association reflects a true causal effect. We aimed to assess the degree to which cumulative PSA increases the risk for ADHD and autism while accounting for unmeasured familial confounding. We used a population-based cohort of 1,877,901 individuals born from 1990 to 2009 in Sweden who were followed from the age of 3. We created a cumulative index based on 7 PSA factors: large family size, parental bereavement, divorce, low income and education, crime conviction, psychiatric history. We used Cox regression to estimate hazard ratios (HRs) for cumulative PSA and ADHD/autism with 95% confidence intervals (CI) in the general population and among groups of relatives (siblings, half-siblings, and cousins) to address familial confounding. We observed a dose–response relationship between cumulative PSA and ADHD in the general population (adjusted HRs with 95% CI ranged from 1.55 [one adversity: 1.52–1.58] to 2.61 [C 4 adversities: 1.95–3.49]). No clear dose–response relation was seen for autism (adjusted HRs ranged from 1.06 [0.60–1.87] to 1.34 [1.30–1.38]). HRs of ADHD and autism decreased with increasing levels of kinship in the analyses of groups of relatives. These results suggest that familial confounding is an important factor to consider for the associations between cumulative PSA and ADHD/autism which hasn't been done in previous studies.