Simplex and Multiplex Stratification in ASD and ADHD Families: A Promising Approach for Identifying Overlapping and Unique Underpinnings of ASD and ADHD?

Autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) are highly heterogeneous neuropsychiatric disorders, that frequently co-occur. This study examined whether stratification into single-incidence (SPX) and multi-incidence (MPX) is helpful in (a) parsing heterogeneity and (b) detecting overlapping and unique underpinnings of the disorders. ASD and ADHD traits were measured in 56 ASD/31 ADHD SPX families, 59 ASD/171 ADHD MPX families and 203 control families. In ASD but not ADHD, behavioral traits were less elevated in SPX than MPX unaffected relatives, suggesting that SPX-MPX stratification may thus help parse ASD, but not ADHD heterogeneity. Particularly unaffected relatives from MPX ASD/ADHD families displayed elevated trait levels of both disorders, indicating shared (multifactorial) underpinnings underlying ASD and ADHD in these families. Cross-disorder traits were highest in MPX ASD unaffected siblings