Relationship between interleukin (IL)-6 and brain morphology in drug-naïve, first-episode major depressive disorder using surface-based morphometry

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.

Brain Aging in Major Depressive Disorder: Results from the ENIGMA Major Depressive Disorder working group

“…49 Moreover, work by Kakeda and colleagues (2018) demonstrated a significant inverse relationship between IL-6 levels and surface-based cortical thickness and hippocampal subfields in medication-free, first-episode MDD patients. 50 This accords with the current observation of increased brain-PAD in medication-free and first-episode patients, compared to controls, perhaps suggesting that neuroimmune mechanisms may be chief candidates involved in the brain morphology alterations, also in the early stage of illness. Further, the age-related structural alterations in MDD may also be explained by shared underlying (epi)genetic mechanisms involved in brain development and plasticity (thereby influencing brain structure) and psychiatric illness.…”

Meta-analysis of cortical thickness abnormalities in medication-free patients with major depressive disorder

“…Some have reported increased cortical thickness in patients with MDD compared with healthy controls (HCs) in the orbitofrontal cortex (OFC) [7,8], rostral middle frontal gyrus [7], superior frontal gyrus [8], parietal cortex [9], temporal cortex [10,11], cingulate cortex [7,9], occipital cortex [12], and insula [11]. Other studies have reported decreased cortical thickness in MDD in the middle frontal gyrus as well as OFC [13,14], parietal cortex [15], temporal cortex [9,16], occipital cortex [13], insula [11], anterior cingulate cortex (ACC), and parahippocampus [17]; some studies have reported no cortical thickness differences in these regions [18,19]. These discrepancies may be explained by study differences in sample size, patient characteristics, clinical symptom severity, medication status, and image acquisition and processing protocols.…”

Role of Interleukin-6 in Depressive Disorder

“…They found that the prefrontal cortex thickness was significantly reduced in MDD patients, and showed a significant inverse correlation with the serum IL-6 level. High levels of serum IL-6 were associated with reduced left subiculum and right CA1, CA3, CA4, GC-DG, subiculum and whole hippocampus volumes in MDD patients [54].…”

“…IL-6 levels may be associated with the phenotypes of MDD. An interesting research done by Kakeda et al investigated the relationship between IL-6 levels and brain morphology in first-episode drug-naïve MDD patients [54]. They found that the prefrontal cortex thickness was significantly reduced in MDD patients, and showed a significant inverse correlation with the serum IL-6 level.…”