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Abstract
Cumulative exposure to psychosocial adversity at an early age has been shown to be a risk factor for attention-deficit hyperactivity disorder (ADHD) and autism that often co-occur. However, it is not clear if this association reflects a causal effect or familial confounding. We aimed to assess whether cumulative psychosocial adversity in the family increases the risk for ADHD and autism in offspring while accounting for unmeasured familial confounding. We used a population-based cohort of 1,877,901 individuals born in Sweden between 1990 and 2009. Participants were followed from the age of 3 until 2013, with a median follow up time of 13.8 years. We created a cumulative index based on 7 psychosocial adversity factors. We used Cox regression to estimate the hazard ratios (HRs) relating neurodevelopmental conditions to cumulative psychosocial adversity. To address familial confounding, the analyses were repeated in groups of relatives of different kinship: siblings and half-siblings and cousins. A dose-response relationship was observed between cumulative exposure to psychosocial adversity and ADHD at a general population level (covariate adjusted HRs (aHRs) with 95% confidence intervals ranged from 1.55 [one adversity; 1.53–1.58] to 2.65 [ ≥ 4 adversities; 1.98–3.54]). No clear dose-response relation was seen for autism (aHRs ranged from 1.04 [.59–1.84] to 1.37 [1.30–1.45]). HRs of ADHD and autism decreased with increasing level of kinship in the analysis of relatives. Cumulative exposure to psychosocial adversity was associated with both ADHD and autism in the general population, these associations were partly explained by unmeasured familial confounding between relatives. This highlights the need for using family-based designs in studies of psychosocial adversity and ADHD and autism.
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1 Karolinska Institutet, Department of Medical Epidemiology & Biostatistics, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626)
2 Karolinska Institutet, Department of Medical Epidemiology & Biostatistics, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626); Örebro University, School of medical sciences, Örebro, Sweden (GRID:grid.15895.30) (ISNI:0000 0001 0738 8966)
3 Karolinska Institutet, Department of Medical Epidemiology & Biostatistics, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626); University of Oslo, Institute of Clinical Medicine, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921); Akershus University Hospital, Division of Mental Health Services, Lørenskog, Norway (GRID:grid.411279.8) (ISNI:0000 0000 9637 455X); Medical University of Lodz, Department of Biostatistics and Translational Medicine, Lodz, Poland (GRID:grid.8267.b) (ISNI:0000 0001 2165 3025)
4 Karolinska Institutet, Department of Medical Epidemiology & Biostatistics, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626); Indiana University, Department of Psychological and Brain Sciences, Bloomington, USA (GRID:grid.411377.7) (ISNI:0000 0001 0790 959X)