Abstract
There is a growing body of evidence to support the involvement of proinflammatory cytokines in the pathophysiology of depression; however, no previous studies have examined the relationship between cytokines and the brain morphology of patients with major depressive disorder (MDD). We therefore evaluated the relationship between serum cytokine levels and cortical thinning during the first depressive episode in drug-naïve patients with MDD. We measured the serum cytokine levels (IL-1β, IL-6, IFN-γ, and TNFα), and whole-brain cortical thickness and hippocampal subfield volumes on brain magnetic resonance imaging (MRI) using surface-based morphometry in 40 patients with MDD and 47 healthy volunteers (controls). Only the serum IL-6 level was significantly higher in patients with MDD than in controls. The prefrontal cortex (PFC) thickness was significantly reduced in patients with MDD, and showed a significant inverse correlation with the serum IL-6 level. Although high serum IL-6 levels were correlated with reduced left subiculum and right CA1, CA3, CA4, GC-DG, subiculum, and whole hippocampus volumes, the presence or absence of MDD had no effect on the volume of any hippocampal subfields. Our results suggest that IL-6 may play a key role in the morphological changes in the PFC during the early stage of MDD.
Highlights
There have many theories proposed regarding the cause of major depressive disorder (MDD), the pathogenesis is only partly understood; genes, the environment, and endocrine dysfunction are all considered to be factors influencing MDD1
We found that the cortical thicknesses in most regions of the superior frontal and medial orbitofrontal cortices were significantly negatively correlated with the serum IL-6 level
The thickness of the superior frontal and medial orbitofrontal cortices in MDD patients was significantly decreased in Cortical regions Thinner in MDD patientsa Left hemisphere inferior parietal and lateral occipital cortices superior frontal, medial orbitofrontal cortices caudal middle frontal cortices Right hemisphere superior frontal and medial orbitofrontal cortices precentral cortex inferior parietal and supra-marginal cortices lateral occipital cortex Correlation with serum IL-6 level in MDD patientsa Left hemisphere triangularis superior frontal, medial orbitofrontal, and paracentral cortices parahippocampal cortex rostral middle frontal cortex middle temporal cortex Right hemisphere caudal middle frontal cortex, insula, and opercularis superior and middle temporal cortices superior frontal, medial orbitofrontal, and cingulate cortices parahippocampal cortex
Summary
There have many theories proposed regarding the cause of major depressive disorder (MDD), the pathogenesis is only partly understood; genes, the environment, and endocrine dysfunction are all considered to be factors influencing MDD1. Several studies have shown that—in addition to the hippocampus—neuroinflammation was present in various brain regions of patients with MDD12– 14 This evidence led us to wonder whether elevated cytokine levels might be associated with a reduced cortical volume of the hippocampus, and extend into other brain regions in patients with MDD. To test this possibility, we employed a surface-based morphology (SBM) analysis, which has been proposed to identify the differences in the thickness of gray matter on the brain’s surface[16], as a whole-brain voxel based-morphometry (VBM) analysis procedure. The purpose of the current study was to investigate the relationship between the brain morphology (brain cortical thinning and hippocampal subfield volumes) and the serum cytokine levels during the first depressive episode in drug-naïve patients with MDD using a whole-brain SBM analysis
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