Central and Peripheral Inflammation Link Metabolic Syndrome and Major Depressive Disorder

Abstract

Metabolic syndrome and major depression are two of the most common and debilitating disorders worldwide, occurring with significant rates of comorbidity. Recent studies have uncovered that each of these conditions is associated with chronic, low-grade inflammation. This is characterized by increased circulating pro-inflammatory cytokines, altered leukocyte population frequencies in blood, accumulation of immune cells in tissues including the brain, and activation of these immune cells. Cytokines that become elevated during obesity can contribute to the progression of metabolic syndrome by directly causing insulin resistance. During chronic stress, there is evidence that these cytokines promote depression-like behavior by disrupting neurotransmitter synthesis and signal transduction. Animal models of obesity and depression have revealed a bi-directional relationship whereby high-fat feeding and chronic stress synergize and exacerbate metabolic dysregulation and behavioral abnormalities. Although far from conclusive, emerging evidence suggests that inflammation in the central and peripheral immune system may link metabolic syndrome to major depressive disorder. In this review, we will synthesize available data supporting this view and identify critical areas for future investigation.

Depression is associated with non‐alcoholic fatty liver disease among adults in the United States

“…10,40,41 A recent study suggests that inflammation in the central and peripheral immune system may relate metabolic abnormalities to major depression. Increase in overall body stress due to underlying obesity, diabetes and/or metabolic syndrome leads chronic inflammatory state resulting from the increased production of pro-inflammatory cytokines, cortisol and epinephrine with further amplification by depression and increased predisposition to the pathogenesis of NAFLD.…”

“…Increase in overall body stress due to underlying obesity, diabetes and/or metabolic syndrome leads chronic inflammatory state resulting from the increased production of pro-inflammatory cytokines, cortisol and epinephrine with further amplification by depression and increased predisposition to the pathogenesis of NAFLD. 10,40,41 A recent study suggests that inflammation in the central and peripheral immune system may relate metabolic abnormalities to major depression. 41 Pathophysiological factors associated with depression, such as increased monoamine oxidase-A enzyme activity, might enhance cellular oxidative stress and thus adversely impact NAFLD.…”

“…10,40,41 A recent study suggests that inflammation in the central and peripheral immune system may relate metabolic abnormalities to major depression. 41 Pathophysiological factors associated with depression, such as increased monoamine oxidase-A enzyme activity, might enhance cellular oxidative stress and thus adversely impact NAFLD. 17 Chronic inflammation and oxidative stress lead to NAFLD.…”

Si-Ni-San Prevents Reserpine-Induced Depression by Inhibiting Inflammation and Regulating CYP450 Enzymatic Activity

“…Recently, clinical and preclinical evidence have suggested that i n fl a m m a t i o n i s a s s o c i a t e d w i t h t h e c o m p l i c a t e d pathophysiology of depression (Kaufmann et al, 2017;Pfau et al, 2018;Chan et al, 2019). Patients with depression exhibited an upregulation of proinflammatory cytokines, including interleukin-1b (IL-1b), IL-6, and tumor necrosis factor-a (TNF-a) (Kennedy et al, 2009).…”

Advances in understanding addiction treatment and recovery

“…Currently, we lack sufficient knowledge of the following relationships that challenge the development of successful treatment strategies: (i) mechanisms underlying the interactions among the affected neural circuits, molecular mechanisms, synaptic plasticity, and their relation to the functioning of the rest of the CNS and behavioral changes; (ii) causal relationships between neurobiological changes in the brain and their effects on the peripheral systems and vice versa (e.g., the interaction between the hormone ghrelin release in the gastrointestinal system and its effect on the CNS in alcohol craving and between the peripheral and central inflammatory systems in depression and addiction) (12)(13)(14)(15); and (iii) the extent to which social connections and environmental factors alter neurobiological mechanisms in brain circuitries in patients with SUDs. These challenges are fundamental knowledge gaps that require continued funding for relevant interdisciplinary research that can foster innovative approaches and discoveries by the engaged scientific communities.…”