Increased Rates of Comorbid Psychopathology in Preschool-Aged Females with Autism Spectrum Disorder

Background: There is some evidence that females with autism spectrum disorder (ASD) have higher rates of comorbid psychopathology, particularly anxiety and depression, in older childhood and adolescence than males with ASD. Studies utilizing large samples of females with ASD are lacking, and little is known about sex differences in comorbid psychopathology in very young children with ASD.

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.