Depressive and PTSD symptoms are associated with regional differences in light-evoked brain responses in chronic...

Chronic ocular pain (COP) often co-occurs with depression or post-traumatic stress disorder (PTSD), but whether these comorbidities confer a distinct biological signature is unknown. Thus, we compared light-evoked blood oxygen level-dependent (BOLD) responses in individuals with COP, stratified by the presence or absence of clinically relevant depressive and/or PTSD symptoms.

43 individuals with COP (pain intensity ≥ 1/10 for ≥ 3 months) underwent event-related functional magnetic resonance imaging using bright-light. Thirty participants were classified as COP with mental health comorbidity (COP + MHC+) based on a Patient Health Questionnaire-9 (PHQ-9) score ≥ 5 and/or a PTSD Checklist-Military Version (PCL-M) ≥ 33; 13 were classified as COP without MHC (COP + MHC-). BOLD responses exceeding an exploratory voxelwise threshold of Z > 2.3 were compared within predefined bilateral regions of interest (ROIs) comprising the anterior cingulate cortex (ACC), anterior mid-cingulate cortex (aMCC), anterior insula, and amygdala. Regional parameter estimates were correlated with clinical symptoms. Result Demographics were similar between groups. Participants with COP + MHC+ reported greater dry-eye symptom burden and non-ocular pain, whereas measured ocular surface signs and in-scanner eye-pain and unpleasantness ratings did not differ significantly between groups. In exploratory ROI analyses, COP + MHC+ participants demonstrated greater light-evoked BOLD responses in the right ACC and caudal right aMCC, whereas COP + MHC- participants demonstrated greater responses in the rostral right aMCC and right anterior insula. Conclusions These findings suggest that depressive and PTSD symptoms may contribute to heterogeneity in central pain processing among individuals with COP. If confirmed, such differences could help refine COP phenotyping and inform more targeted, mechanism-based treatment strategies.