Parent-of-origin effects in attention-deficit hyperactivity disorder

The goal of the present study was to investigate parent-of-origin effects in attention-deficit hyperactivity disorder (ADHD). Parent-of-origin effects in ADHD may be due to differences in the relative quantity of risk factors transmitted by each parent. Alternatively, parent-of-origin effects may be produced by qualitative differences in the risks transmitted, such as those carried on the sex chromosomes or regulated by genomic imprinting. 60 children with maternal-only history of ADHD and 131 children with paternal-only history of ADHD were compared on three domains for which prior evidence suggested parent-of-origin effects may exist: core symptoms, disruptive behaviours and depression. Dependent variables were derived from previously validated, age-appropriate and standardized parent and teacher interviews and questionnaires. Depression levels were rated using the Child Depression Inventory. Consistent with previous research and the predictions derived from threshold models of ADHD etiology, the maternal history group received higher ratings of behavioural disorder (ADHD, conduct disorder and oppositional symptoms) than the paternal history group. Parent-of-origin effects were also observed for depression, with the paternal history group rating themselves as significantly more depressed than children in the maternal history group, particularly girls. Heightened paternal transmission relative to maternal is suggestive of genomic imprinting, and the interaction with proband sex indicates the involvement of the sex chromosomes or sex-specific physiological or hormonal factors. Interpretations of these data in terms of environmental and genetic factors, including epigenetic and sex-linked hypotheses, are explored.