Abstract
Many psychiatric disorders show gender differences in prevalence. Recent studies suggest that female patients diagnosed with anxiety and depression carry more genetic risks related to attention-deficit hyperactivity disorder (ADHD) compared with affected males. In this register-based study, we aimed to test whether female patients who received clinical diagnoses of anxiety, depressive, bipolar and eating disorders are at higher familial risk for ADHD and other neurodevelopmental disorders, compared with diagnosed male patients. We analysed data from a record-linkage of several Swedish national registers, including 151 025 sibling pairs from 103 941 unique index individuals diagnosed with anxiety, depressive, bipolar or eating disorders, as well as data from 646 948 cousin pairs. We compared the likelihood of having a relative diagnosed with ADHD/neurodevelopmental disorders in index males and females. Female patients with anxiety disorders were more likely than affected males to have a brother with ADHD (odd ratio (OR) = 1.13, 95% CI 1.05-1.22). Results for broader neurodevelopmental disorders were similar and were driven by ADHD diagnoses. Follow-up analyses revealed similar point estimates for several categories of anxiety disorders, with the strongest effect observed for agoraphobia (OR = 1.64, 95% CI 1.12-2.39). No significant associations were found in individuals with depressive, bipolar or eating disorders, or in cousins. These results provide modest support for the possibility that familial/genetic risks for ADHD may show gender-specific phenotypic expression. Alternatively, there could be gender-specific biases in diagnoses of anxiety and ADHD. These factors could play a small role in the observed gender differences in prevalence of ADHD and anxiety.
Highlights
Many psychiatric disorders show gender differences in prevalence
Female patients with anxiety disorders were more likely than affected males to have a brother with attention-deficit hyperactivity disorder (ADHD) (odd ratio (OR) = 1.13, 95% CI 1.05–1.22)
There could be genderspecific biases in diagnoses of anxiety and ADHD. These factors could play a small role in the observed gender differences in prevalence of ADHD and anxiety
Summary
Many psychiatric disorders show gender differences in prevalence. Recent studies suggest that female patients diagnosed with anxiety and depression carry more genetic risks related to attention-deficit hyperactivity disorder (ADHD) compared with affected males. In children diagnosed with anxiety or depression (both female-biased disorders), girls have on average a higher burden of common (i.e. polygenic risk) and rare (i.e. copy number variant) genetic risks implicated in ADHD (a male-biased disorder).[10,11] These findings support the possibility of gender-specific manifestation of biological risk, where the same risk variants are associated with different psychiatric disorders in males (for example ADHD) and females (for example anxiety/depression) These studies included fewer than 400 affected children, many of whom were young, not having passed through the risk period for depression, which limited the generalisability of the results to early-onset anxiety and depression
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