Maternal smoking during pregnancy and cortical structure in children with attention-deficit/hyperactivity disorder.

Maternal smoking during pregnancy (MSDP) is considered a risk factor for ADHD. While the mechanisms underlying this association are not well understood, MSDP may impact the developing brain in ways that lead to ADHD. Here, we investigated the effect of prenatal smoking exposure on cortical brain structures in children with ADHD using two methods of assessing prenatal exposure: maternal recall and epigenetic typing. Exposure groups were defined according to: (1) maternal recall (+MSDP: n = 24; -MSDP: n = 85) and (2) epigenetic markers (EM) (+EM: n = 14 -EM: n = 21). CIVET-1.1.12 and RMINC were used to acquire cortical brain measurements and perform statistical analyses, respectively. The vertex with highest significance was tested for association with Continuous Performance Test (CPT) dimensions. While no differences of brain structures were identified between +MSDP and -MSDP, +EM children (n = 10) had significantly smaller surface area in the right orbitofrontal cortex (ROFc), middle temporal cortex (RTc) and parahippocampal gyrus (RPHg) (15% FDR) compared to -EM children (n = 20). Cortical surface area in the RPHg significantly correlated with CPT commission errors T-scores. This study suggests that molecular markers may better define exposure to environmental risks, as compared to human recall.

Cumulative exposure to ADHD medication is inversely related to hippocampus subregional volume in children.

BACKGROUND: Although there is some evidence for a normalization of brain structure following exposure to ADHD medication, literature on the effects of duration and dose of continued use on the brain is scarce. Here, we investigated the association between cumulative exposure to medication (range 1 week to 4.69 years) and cortical structures and subcortical volumes in a clinical sample of children with ADHD taking medication (n = 109). To the best of our knowledge, this is the first structural MRI study investigating the effects of cumulative exposure to medication on subregional volumes in children treated for ADHD. METHODS: Cumulative exposure to ADHD medication (CEM) was defined as the product of duration on medication (days) and dose (mg/day), yielding the area under the curve (total mg). Cortical thickness and surface area measurements (CIVET-1.1.12), and subcortical volumes in 51 regions (MAGeT-Brain) were analyzed using general linear modelling. RESULTS: Significant effects of CEM were found in two subregions of the left hippocampus, the CA1 (df = 95; q = 0.003) and the strata radiatum/lacunosum/moleculare (df = 95; q = 0.003). Specifically, higher CEM was associated with smaller volumes within these subregions. No effects of medication exposure were detected on cortical thickness or surface area. CONCLUSIONS: Although this study is cross-sectional, the results found within this sample of children show that prolonged ADHD medication use at higher doses is significantly associated with smaller hippocampus volumes in specific subregions. More research is required to determine whether these results are reproduced in other samples of children of ADHD, and further, whether these are beneficial or off-target effects of the medication.