Abstract
Bipolar disorder is often comorbid with anxiety, which is itself associated with poorer clinical outcomes, including suicide. A better etiologic understanding of this comorbidity could inform diagnosis and treatment. The present study aims to test whether comorbid anxiety in bipolar disorder reflects shared genetic risk factors. We also sought to assess the contribution of genetic risk for anxiety to suicide attempts in bipolar disorder. Polygenic risk scores (PRS) were calculated from published genome-wide association studies of samples of controls and cases with anxiety (n = 83,566) or bipolar disorder (n = 51,710), then scored in independent target samples (total n = 3369) of individuals with bipolar disorder who reported or denied lifetime anxiety disorders or suicidal attempts in research interviews. Participants were recruited from clinical and nonclinical settings and genotyped for common genetic variants. The results show that polygenic risk for anxiety was associated with comorbid anxiety disorders and suicide attempts in bipolar disorder, while polygenic risk for bipolar disorder was not associated with any of these variables. Our findings point out that comorbid anxiety disorders in bipolar disorder reflect a dual burden of bipolar and anxiety-related genes; the latter may also contribute to suicide attempts. Clinical care that recognizes and addresses this dual burden may help improve outcomes in people living with comorbid bipolar and anxiety disorders.
Highlights
Anxiety and bipolar disorder (BP) are highly comorbid conditions[1,2], but the basis of this comorbidity is uncertain
The primary aim of the present study is to examine the genetic relationship between genetic risk for anxiety disorders and anxiety comorbidity in bipolar disorder
Sex was used as a covariate for anxiety comorbidity, since we observed an association between Anxiety and Sex in the target (p < 0.001) sample, consistent with previous findings[8,9]
Summary
Anxiety and bipolar disorder (BP) are highly comorbid conditions[1,2], but the basis of this comorbidity is uncertain. It is possible that both conditions share environmental risk factors but these do not appear to be much more common in people with comorbid anxiety and BP than in those with BP alone[1]. Comorbid anxiety has important clinical implications for people living with BP. Several studies have reported unfavorable outcomes in BP with comorbid anxiety, including more frequent mood episodes[5,6], more severe depressive episodes[7], higher rates of substance abuse[6], less favorable treatment response[6,8,9], and increased suicide attempts[10,11,12].
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