Microglial Dysregulation and Suicidality: A Stress-Diathesis Perspective

Area of Science:

• Neuroscience
• Psychiatry
• Immunology

Background:

• The stress-diathesis model posits that suicidal behavior arises from the interplay between psychosocial stressors and inherent susceptibility.
• Emerging evidence implicates the over-activation of microglia, the brain's resident immune cells, in stress-induced suicidal behavior.
• The precise role of microglial dysregulation within clinical models of suicidal behavior requires further clarification.

Purpose of the Study:

• To review human post-mortem and neuroimaging studies linking microglial activation to suicidal behavior.
• To update the clinical model of suicidal behavior by integrating the function of microglia.

Main Methods:

• A systematic literature search was conducted across SCOPUS, PubMed, PsycINFO, and Embase.
• Studies reporting on microglial morphology and activation markers in individuals with suicidality were analyzed.

Main Results:

• Evidence indicates morphological changes in microglia and increased translocator protein density in the brains of individuals exhibiting suicidality.
• Microglial dysregulation is positively associated with suicidal behavior.
• Pathological pathways involving microglial dysregulation include altered tryptophan metabolism via the kynurenine pathway, increased N-methyl-D-aspartate signaling, neurotoxicity, and elevated interleukin-6 contributing to excitotoxicity.

Conclusions:

• Microglial dysregulation is a significant factor in suicidal behavior.
• The findings support the reconceptualization of the stress-diathesis theory to include the role of microglial activity in suicidal behavior.