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• While maternal smoking during pregnancy (MSDP) is established as a risk factor for ADHD, the mechanisms underlying this association are not well understood. • We investigated the effect of MSDP on cortical brain structures in children with ADHD. • A significant effect of MSDP on structural MRI parameters was detected when using an epigenetic signature instead of maternal recall. 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. [ABSTRACT FROM AUTHOR]

Highlights • There is evidence that neurodevelopmental disorders overlap. Yet it is unclear how etiological pathways intersect. • SNPs identified in non-ADHD GWAS showed association with multiple dimensions related to ADHD. • Here we attempt to tease apart the heterogeneity in the phenotype, and understand its genetic underpinnings. • Results are presented as preliminary findings as they provide insight into cross-disorder associations. Abstract Several epidemiological and genetic studies have provided evidence of an overlap between neurodevelopmental disorders. However, the details of the etiological pathways remain to be elucidated. In this study, we garnered the findings of previous GWAS, conducted with schizophrenia and bipolar disorder. We conducted an exploratory study to examine the association between these SNPs and quantitative clinical/ behavioural/ cognitive/ structural brain parameters, as well as response to treatment with a fixed dose of methylphenidate, in a relatively large sample of children with ADHD. Family-based association tests were conducted with nine tag SNPs with 602 nuclear families. In addition, structural magnetic resonance imaging (sMRI) was conducted in a subset of children with ADHD (n = 76). Of the 9 tag SNPs examined, rs1602565 showed a significant association with ADHD, several dimensional measures and response to treatment. An association was also observed between rs1006737 (CACNA1C) and performance IQ. In addition, significant reductions in cortical thickness measurements were observed with the risk allele in rs1006737. These results provide preliminary evidence for putative shared genetic vulnerability between childhood ADHD and other neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]

Maternal smoking during pregnancy is the most commonly cited risk factor for ADHD. While the causal relation between this factor and ADHD is debated, several lines of evidence suggest that it modulates the severity of ADHD, particularly through higher association with conduct disorder (CD). We hypothesized that maternal smoking during pregnancy may be associated with differential methylation in selected genes in children with ADHD. DNA extracted from peripheral blood was used to examine methylation between 25 children exposed, and 22 children not exposed to maternal smoking during pregnancy. Three genes ( AHRR , CYP1A1 , GFI 1) were selected based on previous results observed in the general population. Regression analysis was conducted between methylation levels in these candidate genes and: (a) total number of ADHD and CD symptoms; (b) birth weight. Significant differences in methylation were observed in each of the candidate genes between children exposed and not exposed to maternal smoking during pregnancy. Methylation at the selected sites showed significant association with specific phenotypes. Significant correlations were observed between methylation within AHRR and number of CD symptoms; GFI 1 and number of ADHD symptoms and GFI 1 and birth weight. These initial results may have important clinical implications if confirmed in a larger independent sample. [ABSTRACT FROM AUTHOR]