Transdiagnostic MRI Markers of Psychopathology following Traumatic Brain Injury: A Systematic Review

Background: The neural underpinnings of psychopathology following moderate-severe traumatic brain injury (TBI) remain poorly understood. Previous reviews have found limited and inconsistent neural markers linked to specific categories psychopathology, such as anxiety and depression. In contrast with previous reviews, our review moves beyond traditional diagnostic categories, exploring how neural markers may be implicated across various forms of post-TBI psychopathology using a transdiagnostic approach. Objectives: The aim of this systematic review was to analyse MRI findings across a spectrum of psychopathologies in adults with closed- moderate-severe TBI by conducting a comprehensive analysis of neural markers across diverse diagnostic categories.Methods: Eligible studies investigated associations between MRI markers—including changes in brain macro- or micro-structure and functional activity—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. Findings from eligible studies were synthesised descriptively for each MRI technique (structural, diffusion, and functional MRI) across a range of psychopathology categories. Narrative synthesis was used to identify common MRI findings that were associated with at least two different psychopathology categories. Results: The total number of records screened was 7,777 articles, with 18 meeting eligibility criteria. The most investigated MRI marker was hippocampal morphology (n=7). Studies predominantly investigated psychopathology in isolation, particularly depression (n=6) and only three studies considered multiple forms of psychopathology. The overall risk of bias of studies reviewed fell within the “intermediate” range, on average, with significant risks of bias associated with sampling, measurement tools, and statistical power. Several structural and functional MRI markers were consistently associated with multiple categories of post-TBI psychopathology. Notably, reduced hippocampal volume was associated with higher depression (n=2), anxiety (n=1), apathy (n=1), and psychosis (n=1). Other MRI markers associated with more than one psychopathology included the frontal and temporal cortices, the thalamus, and altered substantia nigra-left angular gyrus connectivity, yet some results were impacted by risk of bias. Conclusions: Our review provides preliminary evidence that relationships between post-TBI neural markers and psychopathology may not align neatly with traditional diagnostic categories. On the basis of this review, we propose that adopting transdiagnostic and dimensional frameworks could provide a more comprehensive understanding of the neural mechanisms underlying post-TBI psychopathology. Moreover, the included studies were limited by their focus on regional neuroanatomical associations, lack of appropriate comparator groups, and focus on individual psychopathology categories, particularly depression. Therefore, future research should examine brain-network dynamics, include appropriate comparator groups, and explore a wider spectrum of psychopathologies.Review Registration PROSPERO (CRD42022358358)