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Toward the Definition of a Bipolar Prodrome: Dimensional Predictors of Bipolar SpectrumDisorder in At-Risk Youth
Hafeman DM, Merranko J, Axelson D, Goldstein BI, Goldstein T, Monk K, Hickey MB, Sakolsky D, Rasim  R, Iyengar S, Brent DA, Kupfer DJ and Birmaher B
American Journal of Psychiatry, Published Online, 2016

A team of Department of Psychiatry investigators led by Drs. Danella Hafeman and Boris Birmaher have identified strong dimensional predictors of new-onset bipolar spectrum disorder in youth at familial risk of bipolar disorder. 

These findings emerge from the Pittsburgh Bipolar Offspring Study (BIOS), which has been following offspring of parents with bipolar disorder (and offspring of community controls) for an average of eight years. The BIOS team recruited offspring aged 6-18 of parents with bipolar-I/II disorder (n=391) and offspring of community controls (n=248); the latter were recruited without regard to non-bipolar psychopathology. At baseline, 8.4% of offspring of bipolar parents had bipolar spectrum; 14.7% of offspring with follow-up developed new-onset bipolar spectrum (15 with bipolar-I/II) over eight years. Scales collected at baseline and follow-up were reduced using factor analyses; factors (both at baseline and visit proximal to conversion or last contact) were then assessed as predictors of new-onset bipolar spectrum.

Relative to community control offspring, the investigators, led by Dr. Hafeman and Dr. Birmaher, found that at-risk and bipolar offspring had higher baseline levels of anxiety/depression, inattention/disinhibition, externalizing, subsydromal manic, and affective lability symptoms. The strongest predictors of new-onset bipolar spectrum were: baseline anxiety/depression, baseline and proximal affective lability, and proximal subsyndromal manic symptoms. While affective lability and anxiety/depression were elevated throughout follow-up in those who later developed bipolar spectrum, manic symptoms increased up to the point of conversion. A path analysis supported the hypothesized model that affective lability at baseline predicted new-onset bipolar spectrum, in part, through increased manic symptoms at the visit prior to conversion; earlier parental age of mood disorder onset also significantly increased risk of conversion. While youth without anxiety/depression, affective lability, and mania (and with a parent with older age of mood disorder onset) had a 2% predicted chance of conversion to bipolar spectrum, those with all risk factors had a 49% predicted chance of conversion.

Findings from this study are the first step to identifying a group of children and adolescents who are at ultra-high risk for converting to bipolar disorder, similar to what has been established in the psychosis literature. For clinicians, this risk profile can help to identify those patients who might require increased monitoring and/or early intervention. From a research perspective, this risk profile will facilitate studies to assess the neural underpinnings of risk in these youth, and to evaluate the efficacy of early interventions.

Contributors:
Danella M. Hafeman, MD, PhD, John Merranko, MS, Tina Goldstein, PhD, Kelly Monk, RN, Mary Beth Hickey, BA, Dara Sakolsky, MD, PhD, Rasim Diler, MD, David Brent, MD,MPH, David Kupfer, MD and Boris Birmaher, MD (Department of Psychiatry, University of Pittsburgh School of Medicine)

Satish Iyengar, PhD (Department of Statistics, University of Pittsburgh Kenneth P. Dietrich School of Arts and Sciences)

David Axelson, MD (Department of Psychiatry, Ohio State University)

Benjamin I. Goldstein, MD, PhD (Department of Psychiatry, University of Toronto)

This article appears in the American Journal of Psychiatry.  Click here to view the abstract.