Baseline and follow-up activity and functional connectivity in reward neural circuitries in offspring at risk for bipolar disorder


Bipolar disorder (BD) is a serious psychiatric illness with demonstrated abnormalities in reward processing circuitry. Examining this circuitry in youth at familial risk for BD may provide further insight into the underlying mechanisms of BD development. In this study, we compared offspring of bipolar parents (OBP, n = 32), offspring of comparison parents with non-BD psychopathology (OCP, n = 36), and offspring of healthy parents (OHP, n = 39) during a functional magnetic resonance imaging reward processing task. Elastic net regression analyses identified 26 activity, functional connectivity (FC), and demographic variables that explained 34.24% of the variance in group (λ = 0.224). ANOVA and post-hoc analyses revealed that OBP had significantly lower right ventral striatum–left caudal anterior cingulate FC to loss (OBP versus OCP: p = 0.028, OBP versus OHP: p = 0.015) and greater right pars orbitalis-left (OBP versus OCP: p = 0.003, OBP versus OHP: p = 0.036) and -right (OBP versus OCP: p = 0.001, OBP versus OHP: p = 0.038) orbitofrontal cortex FC to reward versus OCP and OHP, respectively. These findings were not affected by non-BD psychopathology, psychotropic medication use, or symptomatology. There were no changes in, or relationships between, neuroimaging or symptom measures at follow-up (mean(SD) = 2.70(1.22) year inter-scan interval) in a subset of youth with follow-up data (OBP, n = 14; OCP, n = 8; OHP, n = 19). These findings suggest that lower right ventral striatum–left caudal anterior cingulate FC to loss and greater right pars orbitalis–orbitofrontal cortex FC to reward may be trait-level neural markers that may reflect risk for BD in at-risk youth. These findings comprise important steps toward identifying neural markers of BD risk, which may enhance early identification and guide interventions for youth at familial risk for BD.

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The authors would like to acknowledge the participants and their families for their contributions to this study. The authors would also like to acknowledge the individuals involved in The Longitudinal Assessment of Manic Symptoms (LAMS) Study: Department of Psychiatry, Ohio State University, Columbus, OH: L. Eugene Arnold, Mary A. Fristad. Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA: Genna Bebko, Mary Kay Gill, Claudiu Schirda, Michael Travis. Department of Psychiatry and Behavioral Neuroscience, Wayne State University, Detroit, MI: Vaibhav A. Diwadkar. Department of Psychiatry, Johns Hopkins University, Baltimore, MD: Robert L. Findling. Department of Radiology, University Hospitals Case Medical Center/Case Western Reserve University, Cleveland, OH: Scott K. Holland. Department of Child and Adolescent Psychiatry, New York University School of Medicine, New York City, NY: Sarah M. Horwitz. Research Institute at Nationwide Children’s Hospital, Columbus, OH: Robert A. Kowatch. University Hospitals Case Medical Center/Case Western Reserve University, Cleveland, OH: Jeffrey L. Sunshine. Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC: Eric A. Youngstrom.

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Acuff, H.E., Versace, A., Bertocci, M.A. et al. Baseline and follow-up activity and functional connectivity in reward neural circuitries in offspring at risk for bipolar disorder. Neuropsychopharmacol. 44, 1570–1578 (2019) doi:10.1038/s41386-019-0339-2

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