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Transdiagnostic subtypes link symptoms, behavior, function

Researchers developed a data-driven framework to identify transdiagnostic subtypes that suggest a meaningful correlation between symptoms, behavior, brain function and real-world function for patients with major depressive disorder, panic disorder and PTSD, according to recent findings.

For the cross-sectional study, researchers recruited 420 participants (mean age, 39.8; 61% female) through advertisement placed in outpatient and community health centers in proximity to the University of Sydney and the University of Adelaide, Australia between 2006 and 2010. Further data were collected from participants at Stanford University between 2013 and 2017. Analysis of data took place between October 2016 and October 2017.

Participants had a primary diagnosis of one of the following: major depressive disorder (MDD; n = 100), panic disorder (n = 53), PTSD (n = 47), or were healthy controls (n = 220). Some patients had comorbid mood and anxiety disorders.

Researchers used the Depression Anxiety and Stress Scale, version 21 (DASS-21) to evaluate participants for negative mood, and measured neurocognitive function with IntegNeuro, a standardized behavioral test battery. They also used electroencephalography to measure brain activation during resting conditions and during facial emotion-viewing paradigms. The Brief Risk Resilience Index for Screening was used to test daily functioning status.

The researchers used a data-driven approach to attain the study’s primary outcome, which was identification of transdiagnostic subtypes through machine learning with a hierarchical clustering algorithm. The researchers then evaluated the generalizability and strength of these subtypes in an independent sample. Next, they determined whether symptom subtypes were expressed at behavioral and physiological levels of functioning. Finally, they identified the clinically meaningful disparities in functional abilities of the subtypes.

The researchers included six specific subtypes in the final analysis, characterized by: tension (n = 81; 19%); anxious arousal (n = 55; 13%); general anxiety (n = 38; 9%) anhedonia (n = 29; 7%); melancholia (n = 37; 9%) and normative mood (n = 180; 43%). These subtypes were reproduced in an independent sample.

In a differential profile of behavioral performance on neurocognition tests, subtypes showed significant differences in their cognitive control (P < .001). The subtypes also showed disparities in working memory using the digit span test (P = .006).

In a differential profile of resting brain activation as evaluated by the neurophysiological measure EEG power, subtypes varied in power across the frontal area (P = .004) especially for the resting, eyes-open portion.

Differential profiles of self-reported functioning showed subtype differences in social skills as measured by the Brief Risk Resilience Index for Screening (P < .001) and also in emotional resilience (P < .001).

“We demonstrate a data-driven approach for identifying transdiagnostic subtypes that are distinct, reproducible, and expressed across domains of symptoms, neurocognitive functioning, brain activation and daily functioning,” the researchers wrote. “Because the symptom profiles map onto clinically relevant domains, they offer new targets for developing personalized treatment.” – by Jennifer Byrne

Disclosure: Dr. Williams has previously received consultant fees from Brain Resource and Humana and is currently on the Scientific Advisory Board for Psyberguide, a project of the One Mind Institute. Dr. Wang is an employee of Brain Resource.