Peripheral inflammatory cytokines are associated with the microstructural characteristics of the corpus callosum and prefrontal cortex as detected by magnetic resonance T1/T2 mapping in the CUMS rat model.

Background: Several clinical neuroimaging studies have reported structural and functional brain abnormalities associated with peripheral inflammatory cytokines or kynurenine pathway metabolites in patients with depression. However, it is not clear whether the abnormal findings are changes that are intrinsic to depression or whether they are caused by confounding factors such as age, illness duration, or medication.

Methods: To exclude confounding factors, we used chronic unpredictable mild stress (CUMS) rat model and magnetic resonance T1/T2 mapping to investigate the microstructural characteristics of the prefrontal cortex (PFC), hippocampus and corpus callosum and further explored the association between peripheral blood depression-related indicators and microstructural characteristics.

Results: The results revealed that the T2 relaxation time of the corpus callosum was significantly decreased in the CUMS model compared to the control group. Additionally, positive correlations were found between the levels of inflammatory cytokines (interleukin (IL)-1 and IL-6) and the T1 relaxation time of the corpus callosum and between the level of IL-6 and the T1 relaxation time of the PFC.

Conclusion: Our study demonstrates that the microstructural abnormality of the corpus callosum is an intrinsic change that accompanies depression and also provides robust evidence that the microstructural characteristics of the corpus callosum and PFC associated with inflammatory cytokines in peripheral blood play an important role in the fundamental pathophysiological mechanism of depression.