Role of Inflammation in Suicide: From Mechanisms to Treatment

Abstract

Suicidal behavior is complex and manifests because of a confluence of diverse factors. One such factor involves dysregulation of the immune system, which has been linked to the pathophysiology of suicidal behavior. This review will provide a brief description of suicidality and discuss the contribution of upstream and downstream factors in the etiology of suicidal behavior, within the contextual framework of inflammation. The contribution of inflammatory conditions such as traumatic brain injury, autoimmune disorders, and infections to neuropsychiatric symptoms and suicidality is only beginning to be explored. We will summarize studies of inflammation in the etiology of suicide, and provide a neurobiological basis for different mechanisms by which inflammation might contribute to the pathophysiology. Finally, we will review treatments that affect upstream and downstream pathways related to inflammation in suicidality.

Figure 1

Contributing factors to suicidal behavior etiology. Genetic factors can predispose individuals to behavioral traits that predispose them to exhibit suicidal behavior. Proximal factors with an underlying immune component can induce a sustained immune response, which, then, is known to modulate a variety of downstream effectors including modifying monoamine metabolism, increasing tryptophan metabolism via the kynurenine pathway, and dysregulating the hypothalamic–pituitary axis. KYN, kynurenine; KYNA, kynurenic acid; MS, multiple sclerosis; NE, norepinephrine; QUIN, quinolinic acid; SLE, systemic lupus erythematosus; 5-HT, serotonin.