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Parsing Heterogeneity in the Brain Connectivity of Depressed and Healthy Adults during Positive Mood
Price RB, Lane S, Gates K, Kraynak TE, Horner MS, Thase ME and Siegle GJ
Biological Psychiatry, Published online, 2016

Psychiatric diagnoses exhibit significant heterogeneity in symptom presentation. Major depression, for example, has 16,400 possible combinations of symptoms contained within the nine DSM-5 criteria. This heterogeneity in depression may extend to positive affect. Using data-driven parsing of neural connectivity, Dr. Rebecca Price and her colleagues in the University of Pittsburgh Department of Psychiatry revealed subgroups present across depressed and healthy individuals during positive processing, informing targets for mechanistic intervention. The results of this study were published in Biological Psychiatry.

For this experiment, 92 individuals completed a sustained positive mood induction task during functional magnetic resonance imaging. Directed functional connectivity paths within a depression-relevant network were characterized using Group Iterative Multiple Model Estimation (GIMME), a method shown to accurately recover the direction and presence of connectivity paths in individual participants. Using this method, two connectivity-based subgroups emerged. One group had overall weaker connectivity, and another group exhibited hyperconnectivity. Patients in the second group had higher self-reported symptoms, lower sustained positive mood during the induction, and higher negative bias on a reaction-time task. 

In addition to the presence of two subtypes within the population at large, the study demonstrates that depression is more highly represented in the hyperconnectivity subtype?particularly, a form of depression characterized by higher severity of self-reported symptoms, moment-to-moment positive affect disruption, and negative information processing patterns. This line of inquiry can benefit intervention development by seeking to address diverse pathways to depression through a precision medicine approach and identifying compensatory mechanisms present in resilient individuals who remain depression-free in spite of sharing concurrent biological features with patients.

Contributors:
Rebecca Price, PhD, Thomas Kraynak, BA, and Greg Siegle, PhD (Department of Psychiatry, University of Pittsburgh)

Stephanie Lane, BA and Kathleen Gates, PhD (Department of Psychology, University of North Carolina at Chapel Hill).

Michelle Horner, DO (Department of Psychiatry and Behavioral Sciences, Johns Hopkins University)

Michael Thase, MD (Perelman School of Medicine, University of Pennsylvania)

The results of this investigation were published in Biological Psychiatry.  Click here for a link to the abstract.