Investigating gender-specific effects of familial risk for attention-deficit hyperactivity disorder and other neurodevelopmental disorders in the Swedish population

Abstract

Background 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. Aims 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. Method 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. Results 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. Conclusions 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.

Examining sex differences in neurodevelopmental and psychiatric genetic risk in anxiety and depression

“…The finding that females are more likely to report a family history of neurodevelopmental and psychiatric disorders is consistent with the Swedish register-based study of children and adults, which reported a higher rate of having a sibling diagnosed with ADHD in females with anxiety disorders, although the same sex difference in having a sibling with ADHD was not found for depression (20). However, the results of our study may stem from factors independent of genetic burden.…”

“…Depression also shows important developmental differences in aetiology and treatment (21) and no sex differences have been observed in the association between ADHD polygenic risk and anxiety or depression in older adults in the UK Biobank (22), suggesting that age at assessment may influence whether sex differences in liability to ADHD are observed in individuals with these disorders. Additionally, the Swedish register-based population study mentioned above found no sex difference in the rates of ADHD in the siblings of individuals with depression (20). Taken together, the evidence for sex-specific manifestation of neurodevelopmental genetic risks comes from studies using register-based clinical diagnoses in children, with less consistent evidence in adults or using other methods of assessment of anxiety and depression.…”

“…Third, in children with anxiety or depression diagnoses, girls have a higher polygenic burden of common risk alleles for ADHD, compared to boys (19). Finally, according to a Swedish register-based population study of children and adults, females with anxiety disorders are more likely to have a brother diagnosed with ADHD, compared to males with anxiety disorders (20).…”

Examining sex differences in neurodevelopmental and psychiatric genetic risk in anxiety and depression

“…Third, in children with anxiety or depression diagnoses, girls have a higher polygenic burden of common risk alleles for ADHD, compared to boys [ 21 ]. Finally, according to a Swedish register-based population study of children and adults, females with anxiety disorders are more likely to have a brother diagnosed with ADHD, compared to males with anxiety disorders [ 22 ].…”

“…Depression also shows important developmental differences in aetiology and treatment [ 23 ] and no sex differences have been observed in the association between ADHD polygenic risk and anxiety or depression in older adults in the UK Biobank [ 24 ], suggesting that age at assessment may influence whether sex differences in liability to ADHD are observed in individuals with these disorders. Additionally, the Swedish register-based population study mentioned above found no sex difference in the rates of ADHD in the siblings of individuals with depression [ 22 ]. Taken together, the evidence for sex-specific manifestation of neurodevelopmental genetic risks comes from studies using register-based clinical diagnoses in children, with less consistent evidence in adults or using other methods of assessment of anxiety and depression.…”