Inflammation and depressive phenotypes: evidence from medical records from over 12 000 patients and brain morphology

Abstract

BackgroundPreclinical and human studies suggest an association between chronic inflammation and the development of depressive behaviors. This is proposed to occur through downstream effects of inflammatory cytokines on neuroplasticity, neurogenesis and neurotransmitter function, although the neural correlates remain poorly understood in humans.MethodsIn Study 1, structural magnetic resonance imaging and serum inflammatory cytokine data were analyzed from 53 psychiatrically healthy female participants. Correlational analyses were conducted between interleukin-6 (IL-6) and volume in a priori regions implicated in the pathophysiology of major depressive disorder (MDD). In Study 2, medical data [including serum inflammatory acute phase reactants (C-reactive protein)] were analyzed for 12 589 participants. Participants were classified as having (n = 2541) v. not having (n = 10 048) probable lifetime MDD using phenotypes derived using machine-learning approaches. Non-parametric analyses compared inflammation between groups, whereas regression analyses probed whether inflammation predicted probable MDD classification while accounting for other variables.ResultsIn Study 1, significant negative correlations emerged between IL-6 and hippocampal, caudate, putamen and amygdalar volume. In Study 2, the MDD group showed a higher probability of elevated inflammation than the non-MDD group. Moreover, elevated inflammation was a significant predictor of probable MDD classification.ConclusionsFindings indicate that inflammation is cross-sectionally related to reduced volume in brain regions implicated in MDD phenotypes among a sample of psychiatrically healthy women, and is associated with the presence of probable MDD in a large clinical dataset. Future investigations may identify specific inflammatory markers predicting first MDD onset.

Dihydrolipoic acid protects against lipopolysaccharide-induced behavioral deficits and neuroinflammation via regulation of Nrf2/HO-1/NLRP3 signaling in rat

“…In recent years, many studies have shown that the pathogenesis and progression of depression are related to the overreaction of inflammation and immune responses [4,44]. The inflammasome is an inducer of immune response with the function of identifying and targeting multiple pathogens [45].…”

“…Accumulating evidence revealed a close link between inflammation and major depression disorder [2,3]. The nod-like receptor pyrin-containing pyrin domain 3 (NLRP3) inflammasome is one of the most widely studied inflammasomes [4]. After NLRP3 inflammasome is assembled and activated, it activates caspase-1 by proteolytic cleavage, which in turn, converts pro-IL-1β into bioactive IL-1β, leading to inflammatory responses in bodies [5,6].…”

Dihydrolipoic acid protects against lipopolysaccharide-induced behavioral deficits and neuroinflammation via regulation of Nrf2/HO-1/ NLRP3 signaling in rat

“…In recent years, many studies have shown that the pathogenesis and progression of depression are related to the overreaction of inflammation and immune responses [4,39]. The inflammasome is an inducer of immune response with the function of identifying and targeting multiple pathogens [40].…”

Rapid anti‐depressant‐like effects of ketamine and other candidates: Molecular and cellular mechanisms

“…Depression is considered to be relevant with the activation of chronic, low‐grade inflammatory responses and cell‐mediated immunity 130,131 . Chronic inflammatory reactions cause neurons apoptosis in brain regions associated with emotion regulation such as hippocampus, 132,133 leading to impairment of synaptic plasticity. Ketamine could normalize abnormal neurobehaviours induced by neuroinflammation through regulating the interleukin (IL)‐1β, tumour necrosis factor (TNF)‐α and IL‐6 134 .…”