The effect of inflammation markers on cortical thinning in major depressive disorder: A possible mediator of depression and cortical changes

Background: Major depressive disorder (MDD) is a prevalent mental health condition with significant societal impact. Owing to the intricate biological diversity of MDD, treatment efficacy remains limited. Immune biomarkers have emerged as potential predictors of treatment response, underscoring the interaction between the immune system and the brain. This study investigated the relationship between cytokine levels and cortical thickness in patients with MDD, focusing on the corticolimbic circuit, to elucidate the influence of neuroinflammation on structural brain changes and contribute to a deeper understanding of the pathophysiology of MDD. Method: A total of 114 patients with MDD and 101 healthy controls (HC) matched for age, sex, and body mass index (BMI) were recruited. All participants were assessed for depression severity using the Hamilton Depression Rating Scale (HDRS), and 3.0 T T1 weighted brain MRI data were acquired. Additionally, cytokine levels were measured using a highly sensitive bead -based multiplex immunosorbent assay. Results: Patients diagnosed with MDD exhibited notably elevated levels of interleukin-6 (p = 0.005) and interleukin-8 (p = 0.005), alongside significant cortical thinning in the left anterior cingulate gyrus and left superior frontal gyrus, with these findings maintaining significance even after applying Bonferroni correction. Furthermore, increased interleukin-6 and interleukin-8 levels in patients with MDD are associated with alterations in the left frontomarginal gyrus and right anterior cingulate cortex (ACC). Conclusions: This suggests a potential influence of neuroinflammation on right ACC function in MDD patients, warranting longitudinal research to explore interleukin-6 and interleukin-8 mediated neurotoxicity in MDD vulnerability and brain morphology changes.