Delineating the impact of childhood traumatic brain injury (TBI) on long-term depressive symptom severity: Does sub-acute brain morphometry prospectively predict 2-year outcome?

Despite evidence of a link between childhood TBI and heightened risk for depressive symptoms, very few studies have examined early risk factors that predict the presence and severity of post-injury depression beyond 1-year post injury. This longitudinal prospective study examined the effect of mild-severe childhood TBI on depressive symptom severity at 2-years post-injury. It also evaluated the potential role of sub-acute brain morphometry and executive function (EF) in prospectively predicting these long-term outcomes. The study involved 81 children and adolescents with TBI, and 40 age-and-sex matched typically developing (TD) controls. Participants underwent high-resolution structural magnetic resonance imaging (MRI) sub-acutely at five weeks post-injury (M = 5.55; SD = 3.05 weeks) and EF assessments were completed at 6-months post-injury. Compared to TD controls, the TBI group had significantly higher overall internalizing symptoms and were significantly more likely to exhibit clinically significant depressive symptoms at 2-year follow-up. The TBI group also displayed significantly lower EF and altered sub-acute brain morphometry in EF-related brain networks, including the default-mode network (DMN), salience network (SN) and central executive network (CEN). Mediation analyses revealed significant indirect effects of CEN morphometry on depression symptom severity, such that lower EF mediated the prospective association between altered CEN morphometry and higher depression symptoms in the TBI group. Parallel mediation analyses including grey matter morphometry of a non-EF brain network (i.e., the mentalising network) were not statistically significant, suggesting some model specificity. The findings indicate that screening for early neurostructural and neurocognitive risk factors may help identify children at elevated risk of depressive symptoms following TBI. For instance, children at greatest risk of post-injury depression symptoms could be identified based in part on neuroimaging of networks implicated in EF and post-acute assessments of executive function, which could support more effective allocation of limited intervention resources.