Insights into the neurobiology of suicidality: explicating the role of glutamatergic systems through the lens of ketamine

Abstract

Suicidality is a prevalent mental health condition, and managing suicidal patients is one of the most challenging tasks for health care professionals due to the lack of rapid-acting, effective psychopharmacological treatment options. According to the literature, suicide has neurobiological underpinnings that are not fully understood, and current treatments for suicidal tendencies have considerable limitations. To treat suicidality and prevent suicide, new treatments are required; to achieve this, the neurobiological processes underlying suicidal behavior must be thoroughly investigated. Although multiple neurotransmitter systems, particularly serotonergic systems, have been studied in the past, less has been reported in relation to disruptions in glutamatergic neurotransmission, neuronal plasticity, and neurogenesis that result from stress-related abnormalities of the hypothalamic–pituitary–adrenal system. Informed by the literature, which reports robust antisuicidal and antidepressive properties of subanaesthetic doses of ketamine, this review aims to provide an examination of the neurobiology of suicidality (and relevant mood disorders) with implications of pertinent animal, clinical, and postmortem studies. We discuss dysfunctions in the glutamatergic system, which may play a role in the neuropathology of suicidality and the role of ketamine in restoring synaptic connectivity at the molecular levels.