Epigenetics and immunology: Under-recognized aspects of suicidality

Figure 1 Genetic, epigenetic and environmental factors influence the pathophysiology of suicidality. Brain areas most commonly examined in postmortem suicidality research are labeled in the center of the image. Some of the genes associated with suicidality via targeted and (epi)genome-wide approaches are listed in the boxes to the left and right of the center. In the upper part of the image, environmental influences that act distally or proximally to alter suicide risk are represented. The interaction between the environment, genetic predisposition and epigenetic mechanisms drives the development of molecular and functional alterations associated with suicidality, including the disruption of key neurobiological processes like neurotransmission, neurotrophin signaling, stress and inflammatory responses (presented in the bottom of the image). GWAS: Genome-wide association study; EWAS: Epigenome-wide association study; HPA: Hypothalamic-pituitary-adrenal; GR: Glucocorticoid receptor; TrkB: Tropomyosin receptor kinase B; BDNF: Brain-derived neurotrophic factor; IL-6: Interleukin 6; TNF-α: Tumor necrosis factor alpha; SLC6A4: Solute carrier family 6 member 4; SLC4A2: Solute carrier family 4 member 2; SLC6A9: Solute carrier family 6 member 9; TPH1/2: Tryptophan hydroxylase 1/2; SKA2: Spindle and kinetochore associated complex subunit 2; CX30/43: Connexin 30/43; MAOA: Monoamine oxidase A; HTR1A: Serotonin 1A receptor; HTR2C: Serotonin 2C receptor; DRD2: Dopamine receptor 2; FURIN: Paired basic amino acid cleaving enzyme; NLGN1: Neuroligin-1; SOX5: SRY-box transcription factor 5; PDE4B: Phosphodiesterase 4B; CACNG2: Calcium voltage-gated channel auxiliary subunit gamma 2; CDK5: Cyclin-dependent kinase 5; PDE3A: Phosphodiesterase 3A; RARRES3: Retinoic acid receptor responder 3; PSORS1C: Psoriasis susceptibility 1 candidate 1. Created in BioRender. Šmon J. (2025) https://BioRender.com/kzls5et.