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Bipolar disorder, which has peak onset in early adulthood, is often difficult to accurately diagnose due to misreporting mania/hypomania, even though mania/hypomania is a pathognomonic feature of the disorder. The misreporting of this feature frequently results in mistaking bipolar disorder for unipolar depression. To facilitate earlier and accurate bipolar disorder diagnoses, there is a vital need for objective markers distinguishing risk of mania/hypomania from risk of depression in young adulthood. 

To identify neural markers differentiating mania/hypomania from depression risk, Pitt Psychiatry investigators including Maya Schumer, PhD; Michele Bertocci, PhD (Assistant Professor of Psychiatry); Henry Chase, PhD (Research Assistant Professor of Psychiatry); and Mary Phillips, MD, MD (Cantab) (Distinguished Professor of Psychiatry, Clinical and Translational Science, and Bioengineering, and Pittsburgh Foundation-Emmerling Endowed Chair in Psychotic Disorders), conducted a cross-sectional study of three samples of 299 young adults (ages 18-30 years old) without bipolar disorder or active substance use disorder.

“This study was able to take advantage of the availability of three separate samples of young adults with neuroimaging and clinical data. We were excited to see that findings from the first sample replicated in each of the two other samples. This is very important, given the critical need to replicate neuroimaging findings in independent samples,” said Dr. Schumer, first author of the study recently published in JAMA Psychiatry.

Study participants completed the MOODS Spectrum Self-Report and underwent functional magnetic resonance imaging (fMRI) of the amygdala, prefrontal cortex, and caudate. Study results indicated that greater interamygdala functional connectivity was associated with greater risk of both mania/hypomania and depression. By contrast, greater functional connectivity between ventral attention/salience and central executive networks and greater caudate deactivation were reliably associated with greater risk of mania/hypomania and depression, respectively.

“These are the first findings to our knowledge distinguishing between neural marker predictors of future mania/hypomania and neural markers of future depression risk, and provide insights into neural mechanisms underlying risk for these symptoms. We are hopeful that these findings will aid efforts to use objective markers in early identification of bipolar disorder risk,” said Dr. Phillips, senior author of the study.

Patterns of Neural Network Functional Connectivity Associated with Mania/Hypomania and Depression Risk in 3 Independent Young Adult Samples
Schumer MC, Bertocci MA, Aslam HA, Graur S, Bebko G, Stiffler RS, Skeba AS, Brady TJ, Benjamin OE, Wang Y, Chase HW, Phillips ML.
JAMA Psychiatry. Published online November 01, 2023. doi:10.1001/jamapsychiatry.2023.4150