Effects of low birth weight, maternal smoking in pregnancy and social class on the phenotypic manifestation of Attention Deficit Hyperactivity Disorder and associated Antisocial behaviour: Investigation in a clinical sample Authors:

Background: Attention Deficit Hyperactivity Disorder (ADHD) is a genetically influenced condition although indicators of environmental risk including maternal smoking during pregnancy, low birth weight and low social class have also been found to be associated with the disorder. ADHD is a phenotypically heterogeneous disorder in terms of the predominant symptom types (inattention, hyperactive-impulsivity), their severity and comorbidity, notably Conduct Disorder. It is possible that these different clinical manifestations of the disorder may arise because of the differing effects of the environmental indicators of environmental risk. We set out to test this hypothesis. Methods: In a sample of 356 children diagnosed with ADHD, we sought to investigate possible effects of three indicators of environmental risk – maternal smoking during pregnancy, birth weight and social class – on comorbid Conduct Disorder, conduct disorder symptoms and inattentive and hyperactive-impulsive symptom severity. Results: Multiple regression analysis revealed that, after controlling for significant covariates, greater hyperactive-impulsive symptom severity was significantly associated with maternal smoking during pregnancy (r 2 =0.02, Beta=0.11, t=1.96, p=0.05) and social class (r 2 =0.02, Beta=0.12, t=2.19, p=0.03) whilst none of the environmental risk indicators significantly predicted number of inattentive symptoms. Conduct Disorder symptoms were positively predicted by maternal smoking in pregnancy (r 2 =0.04, Beta=0.18, t=3.34, p=0.001) whilst both maternal smoking during pregnancy and social class significantly predicted a diagnosis of Conduct Disorder (OR=3.14, 95% CI: 1.54, 6.41, Wald=9.95, p=0.002) and (OR=1.95 95% CI: 1.18, 3.23 Wald=6.78, p=0.009) respectively. Conclusions: These findings suggest that indicators of environmental risk, in this instance maternal smoking in pregnancy and environmental adversity indexed by lower social class, independently influence the clinical presentation of the ADHD phenotype. Other types of study design are needed to investigate whether these associations between indicators of environmental risk factors and ADHD clinical heterogeneity are attributable to causal risk effects and to further establish the magnitude of these effects. These findings have implications, not only for our understanding of the aetiology of ADHD, but may also be of clinical value, enabling the identification of individuals who are at higher risk of problematic behaviours in ADHD, notably conduct disorder, to enable earlier, targeted risk reduction strategies.