Mohammad Azizur Rahman1*, Md Imran Mia1, Md Rezowan Islam Badhon1, Fahmida Rahman1, Md. Touhidul Islam2
Abstract
Suicide is a complex and grave mental illness sprouted from polygenic factors that disrupt normal neurobiology, physiology and psychology of the affected person manifesting behavioral alterations termed as suicidal behavior (SB). SB owes about 50% liability towards genetic discrepancy leaving the rest for environment or other issues. About 3000 genes have been linked with SB, of which 50 are associated with cell cycle and DNA repair events. Mostly noted genes linked with suicide and suicidal ideation have been highlighted below:
Glutamatergic signaling pathway
In suicidal patients, the glutamatergic signaling pathway becomes disrupted. It is the main excitatory neurotransmission system in the brain, regulated by the sex hormones, that controls cell proliferation and survival and calcium signaling [1,2]. In the central nervous system (CNS), leucine rich repeat transmembrane neuronal 4 gene (LRRTM4), a promoter of glutamatergic synapse development, have been found to associated with SB. Another signaling cascade co-linked with SB is the cardiac-B-adrenergic signaling pathway E. Brain of the suicide attempters also showed elevated expression of the genes—SH3 And SYLF Domain Containing 1 (SH3YL1), Acid Phosphatase 1 (ACPI) and ALK And LTK Ligand 1 (ALKALI) [1,2].
Glial genes
Differential expression of glial genes have been observed in the suicide attempters compared with those of the controls and the persons suffering from suicidal ideation (SI) [1,2]. Cerebral levels of tumor necrosis factor - alpha (TNF-α) and interleukin1-beta (IL1-β) raises in the suicide attempters. Cannabinoid receptors (CBr2) and non-cannabinoid receptors (GPR55) have profound effect on anxiety, depression, mental illnesses, suicidal ideation and suicide [1,2]. Altered expression of both the cannabinoid receptors (CBr2) and non-cannabinoid receptors (GPR55) have been observed in the suicide attempters [1,2].
Serotonin
Serotonergic system ranks the topmost among the disrupted systems linked with suicide and suicidal behavior. Thus, the genes related to serotonin synthesis, transport and metabolism have received much attention. Variability in the genes for tryptophan hydroxylase 1 and 2, serotonin receptors 1A, 1B, 2A, and the SLC6A4 transporter have been correlated with suicide [1,2].
Polymorphism in the intron 7 of the tryptophan hydroxylase gene had been associated with suicidal behavior in the alcohol offenders [1,2]. Aggressive behavior-led suicidal attempts have also been observed in case of genes for 5-hydroxy tryptamine (5-HT2A, 5-HT1B) gene and receptor for 5-HT2A and 5-HT1B as well as for monoamine oxygenase (MAO) gene [1,2]. Case control association study correlated genetic variants in tyrosine hydroxylase and tryptophan hydroxylase with attempted suicide among the 13-29 years old Indian adolescents and young adults [3].
According to the world health organization (WHO), suicide is the third leading cause of death globally [4]. Global suicidal death toll exceeds 720 000 per annum, majority of which are the youngsters (15-29 years old) [4]. Time is up to take proper care and measures to hold the rein of suicide and suicidal ideation. Otherwise, mankind would fall a grave danger soon.
References
[1] Abou Chahla, M.N., Khalil, M.I., Comai, S., Brundin, L., Erhardt, S. and Guillemin, G.J. (2023) Biological Factors Underpinning Suicidal Behaviour: An Update. Brain Sciences, 13, 505.
[2] Constanza-Cañón, S., García-Restrepo, N., María Aluma-Betancourt, L., Botero-Peláez, D., Devia-Cabrera, M., Rojas-Vargas, E., Manuela Sánchez-Pinto, L., Piedrahita Muñoz, S., Hurtado-Salazar, V. and Manuela Rodríguez-Gutiérrez, M. (2024) Description of Genetic Factors Associated with Suicidal Behavior and Suicide: A Topical Review. Revista de la Facultad de Medicina Humana, 24, 106.
[3] Mathew, A., Alex, A.M., Shafeeque, C.M., Muthubeevi, S.B., Krishnapillai, V. and Banerjee, M. (2025) Genetic Predictors of Attempted Suicide among South Indian Adolescents and Young Adults: A Case-Control Study. Biomarkers in Neuropsychiatry, 12, 100126.
[4] https://www.who.int/news-room/fact-sheets/detail/suicide
Citation: Rahman, M. A., Mia, M. I., Badhon, M. R. I., Rahman, F., & Islam, M. T. (2026). Genes Responsible for Causing Suicide. J. Psychol. Neurosci. Res. Learn.