Comorbid Mood and Anxiety Disorders in Autism Spectrum Disorder: A Longitudinal, Population-Based, Birth Cohort Study

Background: Increased risk of comorbid mood and anxiety disorders among individuals with autism spectrum disorder (ASD) has been reported in the literature; however, estimates of co-morbidities range widely. Diverse methodology and samples (e.g., inpatient unit, clinic-referred samples) have yielded discrepant findings about the risk of comorbidity. The few existing population-based studies have been cross-sectional, primarily examining medical or broad psychiatric categories, and have not yielded clear, generalizable findings about the risk of specific psychiatric concerns in this population.

Objectives: Since psychiatric symptoms are known to impact functioning in social, academic, and vocational environments, understanding the risk for mood and anxiety disorders is critical to improve long-term outcomes for individuals with ASD. The current study uses a large, longitudinal population-based birth cohort to examine the cumulative incidence of depression, anxiety, and bipolar disorders during childhood through early adulthood in individuals with ASD relative to controls.

Methods: Using symptoms uniformly abstracted from medical and educational records, 1,014 cases of ASD (73.7% male) were research-identified (ASD-R) from a population-based cohort of individuals born in Olmsted County, MN from 1976 to 2000 (N=31,220). For each ASD-R case, 2 age- and sex-matched controls (N=2,028) were identified from the birth cohort. Diagnoses of depression, anxiety, and bipolar disorder were electronically-obtained from diagnostic codes in medical records through December 2017. The cumulative incidences of mood and anxiety disorder diagnoses were estimated using the Kaplan-Meier method. Cox proportional hazards models were fit to estimate the association between ASD case status and each diagnosis.

Results: Among individuals with ASD-R, the estimates of cumulative incidence by age 35 years were 12.4% (95% CI=7.2-17.4%) for bipolar disorder, 58.3% (95% CI=53.2- 62.8%) for depression, and 56.7% (95% CI=51.8-61.1%) for anxiety. By comparison, the estimates of cumulative incidence by age 35 years for bipolar disorder, depression, and anxiety were 1.7% (95% CI=0-3.4%), 34.8% (95% CI=29.7-39.5%), and 32.3% (95% CI=27.0-37.2%), respectively, in the control group (Figure).

ASD-R individuals were significantly more likely to have comorbid bipolar disorder (HR=9.34; 95% CI=4.57-19.06), depression (HR=2.81; 95% CI=2.45-3.22), and anxiety (HR=3.56; 95% CI=3.06-4.13) compared to controls. Significant associations were observed separately among males and females, although the association between ASD-R status and depression was significantly higher (p=0.01) among males (HR=3.17; 95% CI=2.67-3.77) compared to females (HR=2.28; 95% CI=1.82-2.86).

Compared to controls, ASD-R individuals met criteria at a younger age for depression (median:18.1 vs 15.7 years, p<0.001) and anxiety (median:20.1 vs. 14.8 years, p<0.001).

Conclusions: This research demonstrates individuals with ASD are at increased risk for depression, anxiety, and bipolar disorder compared to controls. Over 50% of individuals with ASD are diagnosed with mood or anxiety disorders across their lifespan. While females in general are at greater risk for depression overall, a diagnosis of ASD more strongly increases the risk for depression among males. Additionally, individuals with ASD are more likely to be diagnosed at earlier ages. This highlights the importance of early, ongoing screening for psychiatric comorbidities across the lifespan and supports the need for targeted treatments to address the psychiatric needs of individuals with ASD.