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. 2025 Jun 13:appineuropsych20240262.
doi: 10.1176/appi.neuropsych.20240262. Online ahead of print.

Depression Symptoms Associated With Clinical Symptoms, Disability, and Functional Connectivity After Traumatic Brain Injury

Joshitha Arora  1 , Alexandra Ossowski  1 , Abigail Patchell  1 , Keith W Jamison  1 , Amy Kuceyeski  1 , Jayden Singh  1 , Jacob Garetti  1 , Maddie Cappillo  1 , Lilah Hamill  1 , Emily Blunt  1 , Ulrike W Kaunzner  1 , Robert Winchell  1 , Stephanie Yee-Oleksy  1 , Shahenda Khedr  1 , Kristen Dams-O'Connor  1 , Nicholas D Schiff  1 , Conor Liston  1 , Sudhin Shah  1 , Abhishek Jaywant  1
Affiliations

Depression Symptoms Associated With Clinical Symptoms, Disability, and Functional Connectivity After Traumatic Brain Injury

Joshitha Arora et al. J Neuropsychiatry Clin Neurosci. .

Abstract

Objective: Depression is known to be highly heterogeneous, with distinct clusters of symptoms. Whether this heterogeneity exists after traumatic brain injury (TBI) and how clusters of depression symptoms after TBI may relate to clinical symptoms, functional outcomes, and underlying neurobiology are largely unknown.

Methods: The authors investigated depression symptom clusters after subacute TBI and evaluated their clinical, functional, and neural correlates. Community-dwelling participants with complicated mild, moderate, or severe TBI (N=53) were evaluated on average 5 months postinjury. Participants were administered the 17-item Hamilton Depression Rating Scale (HDRS), the Rivermead Post-Concussion Symptom Questionnaire, the Glasgow Outcome Scale-Extended, and a neuropsychological test battery. A subset of participants completed a resting-state functional MRI scan.

Results: Principal component analysis on the HDRS items yielded a two-component solution that accounted for 40% of the variance. Component 1 encompassed mood and affective symptoms as well as agitation and loss of libido, and component 2 encompassed anxiety, insomnia, and most somatic symptoms of the HDRS. Component 2 was associated with greater TBI symptom burden and disability and worse executive functions but not resting-state functional connectivity. Component 1 was not related to TBI symptom burden, neuropsychological function, or disability, but there was a trend-level association between higher negative affect scores and greater functional connectivity between the dorsal attention and default mode networks.

Conclusions: The findings suggest that depression after TBI may not be a unitary syndrome but rather may be composed of clusters of symptoms that have different associations with TBI symptom burden, disability, and brain connectivity.

Keywords: Depression; Functional outcome; Neuroimaging; Neuropsychiatry; Neuropsychology; Traumatic brain injury.

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Conflict of interest statement

Dr. Kaunzner reports receiving a grant from Genentech and speaker honoraria from EMd and Med Learn. Dr. Liston reports serving as a scientific adviser or consultant to Compass Pathways PLC, Delix Therapeutics, and Brainify.AI. Dr. Jaywant reports providing consulting services for Axem Neurotechnology Inc. and receiving royalties from Oxford University Press. The other authors report no financial relationships with commercial interests.

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