Involvement of inflammatory responses in the brain to the onset of major depressive disorder due to stress exposure

Abstract

Major depressive disorder (MDD) is a multifactorial disease affected by several environmental factors. Although several potential onset hypotheses have been identified, the molecular mechanisms underlying the pathogenesis of this disorder remain unclear. Several recent studies have suggested that among many environmental factors, inflammation and immune abnormalities in the brain or the peripheral tissues are associated with the onset of MDDs. Furthermore, several stress-related hypotheses have been proposed to explain the onset of MDDs. Thus, inflammation or immune abnormalities can be considered stress responses that occur within the brain or other tissues and are regarded as one of the mechanisms underlying the stress hypothesis of MDDs. Therefore, we introduce several current advances in inflammation studies in the brain that might be related to the pathophysiology of MDD due to stress exposure in this review.

Serum Protein Profiling Reveals a Decrease in Apolipoprotein A-IV During a Clinical Depressive Mood State

“…It has been reported that inflammatory and immune responses cause neurological changes and that neurological changes are followed by psychological symptoms. 12 , 15 Activation of the inflammatory response in patients with depressive mood states, including MDD and BD, does not result from the depressive mood itself; rather, it triggers the depressive mood and subsequent neurological changes and results in psychological symptoms. 12 , 15 Apolipoprotein A-IV cannot cross the blood–brain barrier.…”

“… 12 , 15 Activation of the inflammatory response in patients with depressive mood states, including MDD and BD, does not result from the depressive mood itself; rather, it triggers the depressive mood and subsequent neurological changes and results in psychological symptoms. 12 , 15 Apolipoprotein A-IV cannot cross the blood–brain barrier. 14 Therefore, it could be inferred that the depressive mood state occurs due to neurological changes in the brain initiated by the deactivation of an apolipoprotein A-IV-mediated anti-inflammatory response in the blood.…”

Efficacy, Tolerability, and Safety of Toludesvenlafaxine for the Treatment of Major Depressive Disorder—A Narrative Review

“…The importance of TRI investigation is derived from theoretical and pragmatic reasons. As previously mentioned, the monoamine hypothesis is under extensive scrutiny for its clinical limitations, and new theoretical frameworks for MDD have been formulated, based on other neurotransmitters’ dysfunction, gut microbiome alterations, inflammatory factors, immune or hypothalamic–pituitary–adrenal axis dysregulation, and neurogenesis or cholesterol biosynthesis pathway impairments [ 29 , 67 , 68 , 69 , 70 , 71 ]. Still, the monoaminergic system is considered a central element in the pathogenesis of MDD, although multiple interactions with other CNS pathways are also important for the understanding of this disorder [ 72 , 73 ].…”

Two possible mechanisms of ganciclovir for treatment of major depressive disorder

“…MDD is considered to be a multifactorial disorder caused by both environmental and genetic factors, but the mechanism underlying its pathogenesis is not fully understood (6). It is likely that there are multiple underlying mechanisms of pathogenesis (2,6), given the existence of multiple patient subgroups with different characteristics. Current treatments for MDD, including pharmacotherapy, have not yet achieved satisfactory results (7)(8)(9).…”

“…Furthermore, the prevalence of psychiatric disorders, including MDD, has increased during the COVID-19 pandemic ( 5 ). MDD is considered to be a multifactorial disorder caused by both environmental and genetic factors, but the mechanism underlying its pathogenesis is not fully understood ( 6 ). It is likely that there are multiple underlying mechanisms of pathogenesis ( 2 , 6 ), given the existence of multiple patient subgroups with different characteristics.…”