UCLA

Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent and costly mental health condition. Innovation in ADHD prevention requires elucidation of underlying causal processes to highlight precise targets for early interventions that promote resilience. However, although ADHD is sensitive to multiple risk factors, including considerable heritability as well as prenatal/perinatal influences (e.g., low birth weight, prenatal exposure to maternal metabolic conditions), the pathways mediating these associations are relatively unknown. This dissertation consists of three studies that address this important gap in knowledge directly.

Cognitive functioning domains including executive functioning (EF) and reasoning (e.g., cognitive flexibility, fluid reasoning) are biologically plausible pathways from genetic and prenatal/perinatal influences to individual differences in ADHD. However, to date, mediation has primarily been inferred rather than formally evaluated, and no study has concurrently tested parallel or overlapping ADHD risk processes in the same sample. Thus, Study 1 employed multiple mediation to test diverse EF and reasoning dimensions as collective and unique mediators of ADHD symptoms from both birth weight and replicated candidate genes in a sample of youth from multiplex families with ADHD. Extending this novel integration of perinatal and genetic influences, Study 2 used a genome-wide association approach in a large population-based sample to estimate if correlations among birth weight, EF, reasoning, and ADHD symptoms were sensitive to shared genetic influences.

Although exposure to adverse maternal health factors during pregnancy (e.g., inflammation, hyperglycemia) reliably predict child EF deficits, it is unclear which factors most compromise child cognitive development and when exposure to these factors is most consequential. To improve traction specifically on the development of child EF deficits from prenatal/perinatal influences, Study 3 employed a prospective, longitudinal sample of maternal health and child development to evaluate multiple maternal metabolic and pro-inflammatory factors (i.e., C-reactive protein, glycated hemoglobin, blood pressure) simultaneously as predictors of offspring EF and compare their relative temporal influence prior to and across pregnancy.

Collectively, results of the three studies partially support that specific prenatal/perinatal influences uniquely predict particular domains of child cognitive development. Results are discussed in the context of implications for future research and for optimizing prevention strategies to reduce the significant public health burden of ADHD.