Familial clustering of latent class and DSM-IV defined attention-deficit/hyperactivity disorder (ADHD) substypes

Background: Findings from family and twin-based studies of Attention Deficit/Hyperactivity Disorder (ADHD) have indicated that inattentive and combined subtypes cluster together among sibling pairs who both express ADHD symptoms. The current report examines the familial clustering of ADHD subtypes, defined according to latent class and DSM-IV criteria, in a general population sample of 2,848 Australian twins, 1,013 of their non-twin siblings and 4,036 female twins from Missouri, USA. Significant clustering of DSM-IV inattentive and combined subtypes, and significant clustering of the same latent classes among siblings was predicted. Method: Logistic regression was used to assess 1) the clustering of same and different subtype combinations among twin and twin-sibling pairs and 2) whether genetic influences contribute significantly to the observed patterns of subtype combinations among siblings. Results: With the exception of the DSM-IV hyperactive-impulsive subtype and the severe hyperactive-impulsive latent class, all other sibling DSM-IV and latent class ADHD subtypes consistently exhibited significant same-subtype clustering with MZ probands, DZ probands and their siblings in both samples. Furthermore, a significant genetic influence contributing to subtype concordance was detected for every DSM-IV subtype excluding hyperactive-impulsive, and for all eight latent classes. While some instances of significant different-subtype clustering among siblings was observed across both classification systems and samples, the particular subtype combinations involved were largely inconsistent across samples and no significant genetic influences contributing towards these discordant subtype combinations were detected. Conclusions: For both DSM-IV and latent class subtypes, the overall pattern of findings in both samples indicated significant familial clustering of same-subtype combinations and significant genetic influences contributing to these patterns of subtype concordance, despite important sample differences. These findings further extend previous work and are most consistent with the presence of multiple independent forms of ADHD.