Parental psychopathology in families of children with attention-deficit/hyperactivity disorder and exposed to maternal smoking during pregnancy Sarojini M. Sengupta, 1,2 Marie-  Eve Fortier, 1,2 Geeta A. Thakur, 1,2 Venkat Bhat, 1,3 Natalie Grizenko, 1,2, * and Ridha Joober 1,2,3,4, * 1 Douglas Mental Health University Institute, Montreal, QC; 2 Department of Psychiatry, McGill University, Montreal, QC; 3 Department of Human Genetics, McGill University, Montreal, QC; 4 Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada Background: Both genetic and environmental factors have been implicated in the etiology of attention-deficit/ hyperactivity disorder (ADHD). We had previously suggested that exposure to maternal smoking during pregnancy (MSDP) may be a valid basis for delineating a distinct subtype of ADHD, where children exposed to MSDP present with a more severe clinical picture. Here, we examine the psychopathology of parents in this group, to better understand the etiology of ADHD. Methods: Using the Family Interview for Genetic Studies in a sample of 514 families of children with ADHD, we collected data pertaining to lifetime parental psychopathology. Families were stratified based on maternal smoking during the complete gestational period. The frequency of different disorders was compared using the v 2 statistic. Results: In the group where mothers smoked during pregnancy, both parents were significantly more likely to have antisocial personality disorder, and problems with alcohol and drug abuse. Mothers had a significantly higher frequency of major depressive disorder (MDD), while fathers showed a trend for both MDD and bipolar disorder. Conclusions: Based on the pattern of psychopathology in parents of children exposed to MSDP, as well as earlier reports of the severe clinical, behavioral, and cognitive phenotype in these children, combined with the large body of epidemiological evidence, we propose that these children present a distinct subtype of ADHD with comorbid conduct disorder. Furthermore, we propose that MSDP may be a proxy measure to help delineate this subtype. Keywords: Attention-deficit/hyperactivity disorder, behavior problems, comorbidity, family history, smoking. Introduction Attention-deficit/hyperactivity disorder (ADHD) is one of the most common early-onset neurobehavioral disorders, occurring in 8%–12% of the population (Faraone, Sergeant, Gillberg, & Biederman, 2003). ADHD is complex in its etiology, with genetic and environmental factors both implicated in the disorder (Biederman & Faraone, 2005). The average heritabil- ity of ADHD is estimated at 76% (Biederman & Faraone, 2005); both common DNA sequence variants (single nucleotide polymorphisms or SNPs) with small effect size and rare copy number variants having large effect size have been implicated in the disorder (Tha- par, Cooper, Eyre, & Langley, 2013). Several environ- mental factors have been associated with ADHD (Thapar et al., 2013), of which maternal smoking during pregnancy (MSDP) emerges as the most con- sistently associated risk factor (Linnet et al., 2003). Several studies have examined the familial aggre- gation of ADHD and related psychopathology (Bark- ley, Fischer, Edelbrock, & Smallish, 1991; Barkley, McMurray, Edelbrock, & Robbins, 1989; Befera & Barkley, 1985; Biederman et al., 1992; Chronis, Gamble, Roberts, & Pelham, 2006; Chronis et al., 2003; Epstein et al., 2000; Faraone & Biederman, 1997; Gadow et al., 2000; Ghanizadeh, Mohammadi, & Moini, 2008; Goldstein et al., 2007; Margari et al., 2013; Psychogiou, Daley, Thompson, & Sonu- ga-Barke, 2007; Scahill et al., 1999; Segenreich, Fortes, Coutinho, Pastura, & Mattos, 2009; Stein- hausen et al., 2013). Most studies, using either community-based or clinic-referred samples, have reported an elevated level of psychopathology in parents of children with ADHD. However, the nature of the psychopathology is not consistent among studies. In a review on psychological functioning in families of children with ADHD, the most important observation highlighted was the inconsistency between studies (Johnston & Mash, 2001). These differences arise not only because of the diversity in study design but also because of the inherent complexity and heterogeneity of the disorder. The diversity in results between studies is briefly illus- trated below. Biederman et al. (1992) compared first-degree relatives of children and adolescents (between 6 and 17 years) with ADHD (n = 140) and healthy controls (n = 120). Their results from both clinical and community-referred samples showed that relatives of individuals with ADHD were more likely to have ADHD, major depressive disorder (MDD), antisocial disorders, anxiety disorders, and *Contributed equally to the research design and collection of data. Conflict of interest statement: No conflicts declared. © 2014 The Authors. Journal of Child Psychology and Psychiatry. © 2014 Association for Child and Adolescent Mental Health. Published by John Wiley & Sons Ltd, 9600 Garsington Road, Oxford OX4 2DQ, UK and 350 Main St, Malden, MA 02148, USA Journal of Child Psychology and Psychiatry 56:2 (2015), pp 122–129 doi:10.1111/jcpp.12286