Parsing the Comorbidity Between Bipolar Disorder and Anxiety Disorders: A Familial Risk Analysis

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Abstract
Background: A growing literature suggests that anxiety disorders (ANX) co-occur with bipolar disorder (BPD), but the nature of this overlap is unknown. Thus, we investigated the familial association between BPD and ANX among the first-degree relatives of children with BPD with and without comorbid ANX. Methods: We compared relatives of four proband groups defined by the presence or absence of BPD and ANX in the proband: (1) BPD + ANX (n = 23 probands, 74 relatives), (2) BPD without ANX (n = 11 probands, 38 relatives), (3) ANX without BPD (n = 48 probands, 167 relatives), and (4) controls without BPD or ANX (n = 118 probands, 385 relatives). All subjects were evaluated with structured diagnostic interviews. Diagnoses of relatives were made blind to the diagnoses of probands. Results: The results show high rates of both BPD and ANX in relatives of children with BPD + ANX. Moreover, BPD and ANX cosegregated among the relatives of children with BPD + ANX. Although relatives of both ANX proband groups (with and without BPD) had high rates of ANX, and relatives of both BPD proband groups (with and without ANX) had high rates of BPD, the combined condition BPD + ANX was the predominant form of BPD among relatives of probands with BPD + ANX. Conclusions: These family-genetic findings suggest that the comorbid condition BPD+ANX may be a distinct clinical entity. More work is needed to evaluate whether the presence of comorbid ANX may be a marker of very early onset BPD.