The Massachusetts General Hospital studies of gender influences on attention-deficit/hyperactivity disorder in youth and relatives

With the single exception of SUDs, no statistically significant gender-by-ADHD interactions were identified in the multiple outcomes evaluated. These results suggest that with the exception of SUDs, ADHD expresses itself similarly in boys and girls relative to comparison subjects of the same gender, indicating that ADHD-associated impairments are correlates of ADHD in both genders. Gender differences, such as the higher prevalence of symptoms of inattention and lower rates of comorbidity with disruptive behavior disorders, major depression, and learning disability, were identified among the ADHD subjects. Because these differences were caused by the main effects of gender rather than effect modification of ADHD by gender, these findings indicate that girls were at the same relative risk for these adverse outcomes as boys, but that female gender resulted in a different clinical presentation than that affecting boys. The single statistically significant gender-by-ADHD interaction identified was the association between ADHD and SUDs (alcohol or drug abuse or dependence). ADHD in females was a more serious risk factor for SUDs than it was in males was an unanticipated and surprising finding. In light of ongoing concerns regarding ADHD as a putative risk factor of SUDs [12], this finding may indicate that girls are particularly at risk in early adolescence. Considering that the age of onset of ADHD and SUDs are separated by at least a decade [13,14], this finding would support targeting of substance abuse prevention programs to girls with ADHD. Furthermore, results show that although the combined type of ADHD was the predominant type in both genders, girls with ADHD were twice as likely as boys with ADHD to manifest the predominantly inattentive type of the disorder. Because symptoms of inattention are more covert than those of hyperactivity and impulsivity, their higher prevalence in girls with ADHD relative to boys also may explain partially the markedly higher male-to-female ratios in referred versus nonreferred samples of children with ADHD. This work also showed that the pattern of transmission of ADHD and comorbid disorders is not influenced by the proband's gender. This is true for the type of disorder transmitted and the degree of risk to relatives. The finding of no interactions between proband ADHD diagnosis and proband gender clearly rejects the idea that gender differences in comorbid disorders can be attributed to genes or other familial causes. Prior work had shown this to be true for the diagnosis of ADHD in relatives [15-20]. Thus, gender and ADHD appear to be independent risk factors for comorbid psychopathology and for the familial transmission of comorbid psychopathology. In summary, these results suggest that gender was a limited effect modifier of ADHD as a risk factor for ADHD-associated dysfunction in referred children and adolescents. Gender, however, did impact the clinical presentation of the disorder. This was largely because girls with ADHD were less likely than boys to have comorbid disruptive behavior problems and higher prevalence of symptoms of inattention. Because these features could result in gender-based referral bias unfavorable to girls, more work is needed in referred and nonreferred samples of youth with ADHD to more fully assess this issue. These results also showed similar patterns in the familial transmission of comorbid disorders in families of boys and girls with ADHD. Thus, although ADHD is associated with the familial transmission of comorbid disorders, the pattern of transmission is not influenced by the proband's gender. These similar patterns provide further evidence for the idea that, when ADHD is diagnosed in girls it corresponds to the same disorder diagnosed in boys.