Diagnostic Precursors to Bipolar Disorder in Offspring of Parents With Bipolar Disorder: A Longitudinal Study.
OBJECTIVE
The authors sought to identify diagnostic risk factors of manic, mixed, or hypomanic episodes in the offspring of parents with bipolar disorder ("high-risk offspring").


METHODS
High-risk offspring 6-18 years old (N=391) and demographically matched offspring (N=248) of community parents without bipolar disorder were assessed longitudinally with standardized diagnostic instruments by staff blind to parental diagnoses. Follow-up assessments were completed in 91% of the offspring (mean follow-up interval, 2.5 years; mean follow-up duration, 6.8 years).


RESULTS
Compared with community offspring, high-risk offspring had significantly higher rates of subthreshold mania or hypomania (13.3% compared with 1.2%), manic, mixed, or hypomanic episodes (9.2% compared with 0.8%), and major depressive episodes (32.0% compared with 14.9%). They also had higher rates of attention deficit hyperactivity disorder (30.7% compared with 18.1%), disruptive behavior disorders (27.4% compared with 15.3%), anxiety disorders (39.9% compared with 21.8%), and substance use disorders (19.9% compared with 10.1%), but not unipolar major depressive disorder (major depression with no bipolarity; 18.9% compared with 13.7%). Multivariate Cox regressions showed that in the high-risk offspring, subthreshold manic or hypomanic episodes (hazard ratio=2.29), major depressive episodes (hazard ratio=1.99), and disruptive behavior disorders (hazard ratio=2.12) were associated with subsequent manic, mixed, or hypomanic episodes. Only subthreshold manic or hypomanic episodes (hazard ratio=7.57) were associated when analyses were restricted to prospective data.


CONCLUSIONS
Subthreshold manic or hypomanic episodes were a diagnostic risk factor for the development of manic, mixed, or hypomanic episodes in the offspring of parents with bipolar disorder and should be a target for clinical assessment and treatment research. Major depressive episodes and disruptive behavior disorders are also indications for close clinical monitoring of emergent bipolarity in high-risk offspring.
From the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University College of Medicine, Columbus; the Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto Medical Center, Toronto; and Western Psychiatric Institute and Clinic and Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh.
David
D
Axelson
From the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University College of Medicine, Columbus; the Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto Medical Center, Toronto; and Western Psychiatric Institute and Clinic and Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh.
Benjamin
B
Goldstein
From the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University College of Medicine, Columbus; the Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto Medical Center, Toronto; and Western Psychiatric Institute and Clinic and Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh.
Tina
T
Goldstein
From the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University College of Medicine, Columbus; the Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto Medical Center, Toronto; and Western Psychiatric Institute and Clinic and Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh.
Kelly
K
Monk
From the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University College of Medicine, Columbus; the Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto Medical Center, Toronto; and Western Psychiatric Institute and Clinic and Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh.
Haifeng
H
Yu
From the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University College of Medicine, Columbus; the Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto Medical Center, Toronto; and Western Psychiatric Institute and Clinic and Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh.
Mary Beth
MB
Hickey
From the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University College of Medicine, Columbus; the Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto Medical Center, Toronto; and Western Psychiatric Institute and Clinic and Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh.
Dara
D
Sakolsky
From the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University College of Medicine, Columbus; the Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto Medical Center, Toronto; and Western Psychiatric Institute and Clinic and Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh.
Rasim
R
Diler
From the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University College of Medicine, Columbus; the Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto Medical Center, Toronto; and Western Psychiatric Institute and Clinic and Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh.
Danella
D
Hafeman
From the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University College of Medicine, Columbus; the Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto Medical Center, Toronto; and Western Psychiatric Institute and Clinic and Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh.
John
J
Merranko
From the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University College of Medicine, Columbus; the Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto Medical Center, Toronto; and Western Psychiatric Institute and Clinic and Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh.
Satish
S
Iyengar
From the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University College of Medicine, Columbus; the Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto Medical Center, Toronto; and Western Psychiatric Institute and Clinic and Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh.
David
D
Brent
From the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University College of Medicine, Columbus; the Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto Medical Center, Toronto; and Western Psychiatric Institute and Clinic and Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh.
David
D
Kupfer
From the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University College of Medicine, Columbus; the Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto Medical Center, Toronto; and Western Psychiatric Institute and Clinic and Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh.
Boris
B
Birmaher
D000293:Adolescent; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000235:genetics* / Q000523:psychology; D002648:Child; D016241:Child of Impaired Parents / Q000523:psychology*; D015897:Comorbidity; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D001523:Mental Disorders / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D010414:Pennsylvania; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors