Transdiagnostic MRI-derived Features of Psychopathology Following Traumatic Brain Injury: A Systematic Review

The biological basis of psychopathology outcomes in moderate-severe traumatic brain injury (TBI) remains poorly understood. Previous reviews have found limited convergence in associations between brain regions or functions and specific psychopathology categories (e.g., anxiety, depression). The current systematic review aimed to evaluate MRI-derived features of psychopathology transdiagnostically across available diagnostic categories in moderate-severe TBI. Eligible studies investigated associations between MRI-derived features (macro-, micro-structure, function) and psychopathology in adults with closed-moderate-severe TBI. We searched English literature from Embase, PsycINFO, and MEDLINE via Ovid SP, and the review was last assessed as up to date on 2nd November 2023. Risk of bias was assessed using a customised tool based on the Joanna Brigg's Institute Critical Appraisal Tools. The total number of records screened was 7,777 articles, with 18 meeting eligibility criteria. Studies predominantly investigated hippocampal morphology (n = 7) and depression (n = 9). The average risk of bias fell within the "intermediate" range, associated with sampling, measurement, and statistical bias. Findings were heterogeneous and inconsistent within specific psychopathology categories, yet some morphological features converged transdiagnostically (e.g., hippocampus, thalamus, fronto-temporal regions). Notably, lower hippocampal volume was associated with higher depression (n = 2), anxiety (n = 1), apathy (n = 1), and psychosis (n = 1). No consistent microstructural and functional features converged across studies. This review provides a comprehensive evaluation of the current evidence regarding transdiagnostic MRI-derived features of psychopathology and critiques common limitations across the literature, including the focus on structural MRI, lack of appropriate comparators, and the narrow focus on specific psychopathology categories. We propose that transdiagnostic-dimensional frameworks may help address these gaps and advance the understanding of shared and distinct biological features of psychopathology in moderate-severe TBI.Review Registration: prospectively registered on 6/9/2022 in PROSPERO (CRD42022358358).