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Mol Psychiatry. 2019 Dec;24(12):1856-1867. doi: 10.1038/s41380-018-0273-4. Epub 2018 Oct 19.

Clinical, cortical thickness and neural activity predictors of future affective lability in youth at risk for bipolar disorder: initial discovery and independent sample replication.

Author information

1
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA. bertoccima@upmc.edu.
2
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA.
3
Department of Statistics, University of Pittsburgh, Pittsburgh, PA, USA.
4
Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
5
Department of Child and Adolescent Psychiatry, New York University School of Medicine, New York, NY, USA.
6
Department of Psychiatry, Ohio State University, Columbus, OH, USA.
7
Nationwide Children's Hospital Columbus Ohio, Columbus, OH, USA.
8
Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
9
Department of Psychiatry, Johns Hopkins University, Baltimore, MD, USA.

Abstract

We aimed to identify markers of future affective lability in youth at bipolar disorder risk from the Pittsburgh Bipolar Offspring Study (BIOS) (n = 41, age = 14, SD = 2.30), and validate these predictors in an independent sample from the Longitudinal Assessment of Manic Symptoms study (LAMS) (n = 55, age = 13.7, SD = 1.9). We included factors of mixed/mania, irritability, and anxiety/depression (29 months post MRI scan) in regularized regression models. Clinical and demographic variables, along with neural activity during reward and emotion processing and gray matter structure in all cortical regions at baseline, were used to predict future affective lability factor scores, using regularized regression. Future affective lability factor scores were predicted in both samples by unique combinations of baseline neural structure, function, and clinical characteristics. Lower bilateral parietal cortical thickness, greater left ventrolateral prefrontal cortex thickness, lower right transverse temporal cortex thickness, greater self-reported depression, mania severity, and age at scan predicted greater future mixed/mania factor score. Lower bilateral parietal cortical thickness, greater right entorhinal cortical thickness, greater right fusiform gyral activity during emotional face processing, diagnosis of major depressive disorder, and greater self-reported depression severity predicted greater irritability factor score. Greater self-reported depression severity predicted greater anxiety/depression factor score. Elucidating unique clinical and neural predictors of future-specific affective lability factors is a step toward identifying objective markers of bipolar disorder risk, to provide neural targets to better guide and monitor early interventions in bipolar disorder at-risk youth.

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