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Altered Functioning of Reward Circuitry in Youth Offspring of Parents with Bipolar Disorder
Manelis A, Ladouceur CD, Graur S, Monk K, Bonar LK, Hickey MB, Dwojak AC, Axelson D, Goldstein B, Goldstein TR, Bebko G, Bertocci MA, Gill MK, Birmaher B and Phillips ML.
Psychological Medicine, 46:197-208, 2016

Offspring of parents with bipolar disorder (BDO) are at higher risk of bipolar disorder than offspring of parents with non-bipolar disorder psychopathology (NBDO), although both groups are at higher risk than offspring of psychiatrically healthy parents (PHP) for other affective and psychiatric disorders. Abnormal functioning in reward circuitry has been demonstrated previously in individuals with bipolar disorder. In a study recently published by Dr. Anna Manelis and colleagues, investigators aimed to determine whether activation and functional connectivity in this circuitry during decision-making differentiated BDO, NBDO and PHP.

BDO (n = 29; mean age = 13.8 years), NBDO (n = 28; mean age = 13.9 years) and PHP (n = 23; mean age = 13.7 years) were scanned while performing a number-guessing reward task. Of the participants, 11 BDO and 12 NBDO had current non-BD psychopathology; five BDO and four NBDO were taking psychotropic medications.

Using a 3 (group) × 2 (conditions: win-control/loss-control) analysis of variance, investigators found a main effect of group on right frontal pole activation: BDO showed significantly greater activation than HP. There was a significant main effect of group on functional connectivity between the bilateral ventral striatum and the right ventrolateral prefrontal cortex (Z > 3.09, cluster-p < 0.05): BDO showed significantly greater negative functional connectivity than other participants. These between-group differences remained after removing youth with psychiatric disorders and psychotropic medications from analyses.

This is the first study to demonstrate that reward circuitry activation and functional connectivity distinguish BDO from NBDO and PHP. The fact that the pattern of findings remained when comparing healthy BDO vs. healthy NBDO vs. PHP suggests that these neuroimaging measures may represent trait-level neurobiological markers conferring either risk for, or protection against, bipolar disorder in youth.

Contributors:
Anna Manelis, PhD, Cecile D. Ladouceur, PhD, Simona Graur, MSW, Kelly Monk, RN, Lisa K. Bonar, BS, Mary Beth Hickey, BA, Amanda C. Dwojak, BA, Tina R. Goldstein, PhD, Genna Bebko, PhD, Michele A. Bertocci, PhD,  Mary Kay Gill RN, MSN, Boris Birmaher, MD and Mary L. Phillips, MD, MD (Cantab) (Department of Psychiatry, University of Pittsburgh School of Medicine)

David Axelson, MD (Department of Psychiatry, The Ohio State College of Medicine)

Benjamin Goldstein, MD (Department of Psychiatry, University of Toronto School of Medicine)

This article appears in the journal Psychological Medicine.  Click here to view the abstract.