Patterns of Psychiatric Comorbidity and Genetic Correlations Provide New Insights Into Differences Between Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder

Abstract

Background: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) share common genetic factors but seem to have specific patterns of psychiatric comorbidities. There are few systematic studies on adults; therefore, we compared psychiatric comorbidities in adults with these two neurodevelopmental disorders using population-based data and analyzed their genetic correlations to evaluate underlying factors.

Methods: Using data from Norwegian registries, we assessed patterns of psychiatric disorders in adults with ADHD (n = 38,636; 2.3%), ASD (n = 7528; 0.4%), and both diagnoses (n = 1467; 0.1%) compared with the remaining adult population (n = 1,653,575). We calculated their prevalence ratios (PRs) and differences using Poisson regression, also examining sex-specific relations. Genetic correlations (r_g) among ADHD, ASD, and the examined psychiatric disorders were calculated by linkage disequilibrium score regression, exploiting summary statistics from relevant genome-wide association studies.

Results: For all psychiatric comorbidities, PRs differed between ADHD and ASD. Associations were strongest in individuals with ADHD and ADHD+ASD for most comorbidities, in both men and women. The relative prevalence increase of substance use disorder was three times larger in ADHD than in ASD (PR_ADHD, 6.2; 95% confidence interval [CI], 6.1-6.4; PR_ASD, 1.9; 95% CI, 1.7-2.2; p < .001); however, the opposite was true for schizophrenia (PR_ASD, 13.9; 95% CI, 12.7-15.2; PR_ADHD, 4.4; 95% CI, 4.1-4.7; p < .001). Genetic correlations supported these patterns but were significantly different between ADHD and ASD only for the substance use disorder proxies and personality traits (p < .006 for all).

Conclusions: Adults with ADHD, ASD, or both ADHD and ASD have specific patterns of psychiatric comorbidities. This may partly be explained by differences in underlying genetic factors.

Keywords: ADHD; ASD; Genetics; Psychiatric comorbidity; SUD; Schizophrenia.

Figure 1.

Prevalence ratios of psychiatric disorders in adults with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), or ADHD+ASD relative to the remaining population, by sex. Log scale, 95% confidence interval, error bars. Adjusted for birth year (5-year groups, from 1967 to 1997, with 1967–1973 as the reference), maternal marital status (single, married/cohabiting [reference], other), maternal and paternal education (low [,10 years], middle [10–12 years] and high [.12 years] [reference]), maternal age (<20, 20–24, 25–29 [reference], 30–34, 35–39, 40+ years of age) and paternal age (<20, 20–24, 25–29, 30–34 [reference], 35–39, 40–44, 45–49, 50+ years of age) at delivery, gestational age (<28, 28–31, 32–34, 35–36, 37–41 [reference], 42+ weeks of age), gestational age- and sex-specific birth weight Z scores (< ‒2.0;‒2.0 to ‒0.51; ‒0.5 to 0.5 [reference]; 0.51 to 2.0; 2.01+), and maternal and paternal psychiatric disorders (yes/no). BD, bipolar disorder; MDD, major depressive disorder; PD, personality disorders; schizophrenia, schizophrenia spectrum disorder; SUD, substance use disorder.

Figure 2.

Prevalence difference of psychiatric disorders in adults with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), ADHD+ASD relative to the remaining population, by sex. Prevalence difference, 95% confidence interval, error bars, analog scale. Adjusted for birth year (5-year groups, from 1967 to 1997). BD, bipolar disorder; MDD, major depressive disorder; PD, personality disorders; schizophrenia, schizophrenia spectrum disorder; SUD, substance use disorder.

Figure 3.

(Left panel) The pattern of prevalence ratios of psychiatric comorbidity in adults with attention-deficit/hyperactivity disorder (ADHD) (n = 38,636) or autism spectrum disorder (ASD) (n = 7528) observed in this study and (right panel) genetic correlations (r_g) calculated from genome-wide association studies.(Left panel) Prevalence ratio, model II, log-scale, 95% confidence interval, error bars. Adjusted for birth year (5-year groups, from 1967 to 1997, with 1967–1973 as the reference), maternal marital status (single, married/cohabiting [reference], other), maternal and paternal education (low [< 10 years], middle [10–12 years] and high [> 12 years] [reference]), maternal age (,20, 20–24, 25–29 [reference], 30–34, 35–39, 401 years of age) and paternal age (< 20, 20–24, 25–29, 30–34 [reference], 35–39, 40–44, 45–49, 50+ years of age) at delivery, gestational age (< 28, 28–31, 32–34, 35–36, 37–41 [reference], 42+ weeks of age), gestational age- and sex-specific birth weight Z scores (<‒2.0; ‒2.0 to ‒0.51; ‒0.5 to 0.5 [reference]; 0.51 to 2.0; 2.01+), and maternal and paternal psychiatric disorders (yes/no). (Right panel) Genetic correlations, r_g, linear scale, SE bars, with “Ever vs Never Smoked” and “Alcohol Dependence” as proxies for substance use disorder, and “NEO–5–Personality Traits” as proxy for personality disorder.