Molecular Changes Associated with Suicide

Abstract

Suicide is a serious global public health problem, with a worrying recent increase in suicide rates in both adolescent and adult populations. However, it is essential to recognize that suicide is preventable. A myriad of factors contributes to an individual's vulnerability to suicide. These factors include various potential causes, from psychiatric disorders to genetic and epigenetic alterations. These changes can induce dysfunctions in crucial systems such as the serotonergic, cannabinoid, and hypothalamic-pituitary-adrenal axes. In addition, early life experiences of abuse can profoundly impact an individual's ability to cope with stress, ultimately leading to changes in the inflammatory system, which is a significant risk factor for suicidal behavior. Thus, it is clear that suicidal behavior may result from a confluence of multiple factors. This review examines the primary risk factors associated with suicidal behavior, including psychiatric disorders, early life adversities, and epigenetic modifications. Our goal is to elucidate the molecular changes at the genetic, epigenetic, and molecular levels in the brains of individuals who have taken their own lives and in the plasma and peripheral mononuclear cells of suicide attempters and how these changes may serve as predisposing factors for suicidal tendencies.

Keywords: epigenetic change; gene; molecular alteration; risk factor; suicide.

Figure 1

Molecular changes found in the brains of suicide victims with psychiatric disorders. In BP, alterations in the serotonergic system, the HPA-axis in the GABAergic system, and BDNF reduction have been found. In MDD, alterations in the HPA-axis, GABAergic-Glutamatergic system, BDNF reduction, and increased proinflammatory cytokines were detected. Increased proinflammatory cytokines and changes in the HPA-axis were found in AD. In schizophrenia, alterations in the serotonergic system, the HPA- axis, and the glutamatergic system were reported. In BPD, the changes found are associated with comorbidity with other disorders. Finally, alterations in the ECS have been found in the brains of alcoholics who committed suicide. AD: anxiety disorder, BD: bipolar disorder, BDNF: brain-derived neurotrophic factor, BPD: borderline personality disorder, ECS: endocannabinoid system, MDD: major depression disorders, SUD: substance use disorder.

Figure 2

Flowchart linking early life adversity and suicidal behavior. up arrow: increase; down arrow: decrease.

Figure 3

Main epigenetic changes in suicide behavior. The figure represents the main DNA methylation changes observed in peripheral blood cells and brain areas of patients with suicide behavior and in those who died by suicide, respectively. HPA axis: hypothalamus–pituitary–adrenal axis, NR3C1: gene encoding glucocorticoid receptor, FKBP5: the gene encoding the FK506-binding protein 5, CRHBP: the gene encoding the corticotropin-releasing hormone binding protein, SKA2: gene encoding spindle and kinetochore associated complex subunit 2, BDNF: the gene encoding the brain-derived neurotrophic factor, HTR1A: the gene encoding serotonin receptor 1 A, MAOA: the gene encoding monoamine oxidase A, SCL6A4: serotonin transporter gene, TPH2: gene encoding tryptophan hydroxylase 2, NRTK2: the gene encoding neurotrophic receptor tyrosine kinase 2; GABRA1: the gene encoding the alpha-1 subunit of the GABAA receptor protein.