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Emergent course of bipolar disorder among at-risk offspring develops over time

Observational study findings describing the emergent course of bipolar disorder in high-risk offspring of affected parents revealed that the course of bipolar disorder usually evolves in a progressive clinical sequence.

The results, published in the American Journal of Psychiatry, also showed important predictors of bipolar disorder included childhood sleep and anxiety disorders, clinically significant mood symptoms, and psychotic symptoms in depressive episodes.

“The accurate diagnosis of bipolar disorder in young people is a challenge, in part because acute symptoms are often nonspecific and overlap with other disorders, and the illness course appears to be influenced by both developmental and clinical stage,” Anne Duffy, MD, FRCPC, from the psychiatry department at Queens University, Ontario, and the Mood Disorders Centre of Ottawa, Canada, and colleagues wrote. “Delayed recognition and treatment of bipolar disorder contributes to the associated substantial burden and increased mortality.”

Duffy and colleagues analyzed the emergent clinical course of bipolar disorder over 1 to 21 years follow-up in 279 high-risk offspring of affected parents and 87 control patients.

Participants were blindly assessed annually based on semi-structured interviews using the Kiddie Schedule for Affective Disorders and Schizophrenia–Present and Lifetime version or the Schedule for Affective Disorders and Schizophrenia–Lifetime version. Researchers used mixed models to evaluate the link between parent and offspring course, and a multistate model to determine the clinical trajectory into bipolar disorder. Using lifetime syndrome- and symptom-level data, they established cumulative incidence and median age at onset.

The investigators found that the cumulative incidence of bipolar disorder was 24.5% and the median age at bipolar disorder onset was 20.7 years.

Bipolar disorder manifested only in high-risk offspring and not in controls. The clinical course of bipolar disorder in parents was linked to the course in offspring, according to the results. In addition, earlier age at onset in the bipolar parent was linked to earlier age at mood disorder onset in the child.

Among high-risk offspring, childhood sleep (HR = 1.63; P = .044) and anxiety (HR = 1.84; P = .002) disorders predicted increases in mood disorder risk, as did depressive (HR = 2.67; P < .001) and hypomanic symptoms (HRs = 2.34; P = .045). Major depressive disorder and sleep disorders were primarily observed in the high-risk offspring compared with those in the control groups (32.93% vs. 23.19% [P = .003] and 4.88% vs. 0% [P = .013]).

The results also showed that subthreshold sleep symptoms in high-risk offspring were significantly linked to transition from well to non-mood disorder, and psychotic symptoms in mood episodes were significantly linked to transition from unipolar to bipolar disorder.

“This study supports consistency in phenotype across generations, implicating shared underlying etiology and treatment response,” Duffy and colleagues wrote. “The findings emphasize the importance of antecedent anxiety and sleep disorders as well as major depression (especially with psychotic symptoms) in the emergent course of bipolar disorder in young people at confirmed familial risk — which can complicate early recognition and contribute to paradoxical or seemingly refractory response to antidepressant treatment.” – by Savannah Demko

Disclosure: The authors report no relevant financial disclosures.