Impaired Executive Function Mediates the Association between Maternal Pre-Pregnancy Body Mass Index and Child ADHD Symptoms

Increasing evidence suggests exposure to adverse conditions in intrauterine life may increase the risk of developing attention-deficit/hyperactivity disorder (ADHD) in childhood. High maternal pre-pregnancy body mass index (BMI) has been shown to predict child ADHD symptoms, however the neurocognitive processes underlying this relationship are not known. The aim of the present study was to test the hypothesis that this association is mediated by alterations in child executive function.A population-based cohort of 174 children (mean age = 7.3 ± 0.9 (SD) yrs, 55% girls) was evaluated for ADHD symptoms using the Child Behavior Checklist, and for neurocognitive function using the Go/No-go task. This cohort had been followed prospectively from early gestation and birth through infancy and childhood with serial measures of maternal and child prenatal and postnatal factors. Maternal pre-pregnancy BMI was a significant predictor of child ADHD symptoms (F((1,158)) = 4.80, p = 0.03) and of child performance on the Go/No-go task (F((1,157)) = 8.37, p = 0.004) after controlling for key potential confounding variables. A test of the mediation model revealed that the association between higher maternal pre-pregnancy BMI and child ADHD symptoms was mediated by impaired executive function (inefficient/less attentive processing; Sobel Test: t = 2.39 (± 0.002, SEM), p = 0.02).To the best of our knowledge this is the first study to report that maternal pre-pregnancy BMI-related alterations in child neurocognitive function may mediate its effects on ADHD risk. The finding is clinically significant and may extrapolate to an approximately 2.8-fold increase in the prevalence of ADHD among children of obese compared to those of non-obese mothers. These results add further evidence to the growing awareness that neurodevelopmental disorders such as ADHD may have their foundations very early in life

The CRF system, stress, depression and anxiety – insights from human genetic studies

A concatenation of findings from preclinical and clinical studies support a preeminent role for the corticotropin-releasing factor (CRF) system in mediating the physiological response to external stressors and in the pathophysiology of anxiety and depression. Recently, human genetic studies have provided considerable support to several long-standing hypotheses of mood and anxiety disorders, including the CRF hypothesis. These data, reviewed in this report, are congruent with the hypothesis that this system is of paramount importance in mediating stress-related psychopathology. More specifically variants in the gene encoding the CRF 1 receptor interact with adverse environmental factors to predict risk for stress-related psychiatric disorders. In depth characterization of these variants will likely be important in furthering our understanding of the long term consequences of adverse experience