Increased Rates of Comorbid Psychopathology in Preschool-Aged Females with Autism Spectrum Disorder
Objectives: We evaluated sex differences in comorbid psychopathology in preschool-aged females and males with ASD. Age-matched typically developing (TD) controls were included to investigate whether differences related to ASD varied between males and females.
Methods: Participants include 229 children with ASD (76 females, 153 males) and 131 age-matched TD controls (54 females, 77 males), mean age of 36.2 (sd 7.2) months. ASD diagnoses were confirmed using ADOS and ADI-R. Psychopathology was evaluated using the DSM-oriented scales for affective, anxiety, attention deficit/hyperactivity (ADHD), and oppositional defiant problems from the Child Behavior Checklist. Sex by diagnosis interactions were examined with negative binomial regression models using T-scores from each scale. For scales with significant interactions, the proportion of males and females with ASD who scored in the clinical range (>69) was compared using chi-square tests. As a secondary analysis to explore generalized psychopathology within the ASD sample, t-scores for each DSM-oriented scale were categorized as clinical (>69), borderline clinical (65-69), and normal (< 65), and a data-driven latent class analysis (LCA) was utilized to identify subgroups with higher rates of psychopathology across DSM-oriented scales. The proportion of females and males in each of the derived subgroups was compared.
Results: Sex by diagnosis interactions were identified for ADHD (p = .01 corrected for multiple comparisons) and affective problems (p = .06 corrected). Pairwise comparisons revealed a greater difference between ASD and TD within females than males on both ADHD [Female ASD vs TD: estimate 5.7 (SE 1.2), Male ASD vs TD: estimate 2.7 (SE 0.4)] and affective scales [Female ASD vs TD: estimate 5.5 (SE 1.1), Male ASD vs TD: estimate 2.3 (SE 0.5)]. A higher proportion of females with ASD than males with ASD scored within the clinical range on both the ADHD and affective scales (ADHD: 20% females vs. 9% males, p = .04; affective: 37% females vs 22% of males, p = .03). Within the ASD group, LCA of clinical, borderline, and normal scores across DSM-oriented scales revealed three subgroups: elevated scores across all measures (35%), low scores on all measures (25%), and a group in the middle (40%). A higher proportion of females were in the group with elevated scores than males (43% vs. 31%, p = .03), suggesting a higher overall rate of psychopathology in females.
Conclusions: Comorbid psychopathology occurs at a higher rate in girls with ASD than in boys, even at the young ages tested in this study. This difference is not mirrored in typical development. Specifically, preschool-aged females exhibited higher rates of clinically significant ADHD and affective problems, suggesting a need for closer evaluation and earlier interventions to potentially improve outcomes for females with ASD.