Understanding the predisposing risk factors of young suicide

Rashmi Wardhan, Padmshree Mudgal


Suicide is an unfortunate multifactorial problem impacting families and communities. Many young lives are lost every year due to suicide. There is an urgent need to understand the multifactorial risk factor mechanisms providing vulnerability to suicidal behavior for early detection of impending incidents, monitoring, and prevention. This review aims to give an insight into the various biochemical and genetic markers along with the associated socio-economic factors and mental disorders which contribute to increased suicide risk. The role of different neurotransmitter-associated pathways such as serotonin, gamma aminobutyric acid (GABA), and norepinephrine pathway, and pathways involving the hypothalamic-pituitary-adrenal (HPA) axis, lipid metabolism, and neuroinflammation in suicide ideation and risk have been explored. Understanding of these predisposing factors and associated pathways could help identify the risk and lead to the development of drugs/ treatment to prevent suicides.


Suicide, Risk factors, Biochemical markers, Genetic markers, Neuroinflammation, Socio-economic factors, Mental disorders, Substance abuse

Full Text:



O’Connor E, Gaynes B, Burda BU, Williams C, Whitlock EP. Screening for Suicide Risk in Primary Care: A Systematic Evidence Review for the U.S. Preventive Services Task Force. Rockville (MD): Agency for Healthcare Research and Quality (US). 2013; Report No:13-05188.

Suicide. World Health Organization. 2019. Available at: detail/suicide. Accessed on 30 September 2020.

WHO Mental Health Geneva. World Health Organisation. 2018. Available at: http://www.who. int/mental_health/en/. Accessed on 30 September 2020.

Bilsen J. Suicide and Youth: Risk Factors. Front psychiatry. 2018;9:540.

Pandey GN. Biological basis of suicide and suicidal behavior. Bipolar disord. 2013;15(5):524-41.

COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE). ArcGIS. Johns Hopkins University. 2020. Accessed on 30 September, 2020.

Sher L. The impact of the COVID-19 pandemic on suicide rates. An Int J Med. 2020;113(10):707-12.

Chadda RK, Gupta A. Looking into biological markers of suicidal behaviors. Indian J Med Res. 2019;150:328-31.

Oquendo MA, Sullivan GM, Sudol K, Baca-Garcia E, Stanley BH, Sublette ME, et al. Toward a bio-signature for suicide. Am J Psychiatry. 2014;171:1259-77.

Pandey GN. Biological basis of suicide and suicidal behavior. Bipolar Disord. 2013;15:524-41.

Underwood MD, Kassir SA, Bakalian MJ, Galfalvy H, Dwork AJ, Mann JJ et al. Serotonin receptors and suicide, major depression, alcohol use disorder and reported early life adversity. Transl Psychiatry. 2018;8(1):279.

Kovachich GB, Aronson CE, Brunswick DJ, Frazer A. Quantitative autoradiography of serotonin uptake sites in the rat brain using 3H-cyano imipramine. Brain Res. 1998;454:78-88.

Oquendo MA, Mann JJ. The biology of impulsivity and suicidality. Psychiat Clin N Am. 2000;23:11-25.

Kaschka WP, Rujescu D (eds). Biological Aspects of Suicidal Behavior. Adv Biol Psychiatry. Basel, Karger. 2016;30:37-50.

Gonda X, Sarginson J, Eszlari N. A new stress sensor and risk factor for suicide: the T allele of the functional genetic variant in the GABRA6 gene. Sci Rep. 2017;7:12887.

Dahlström A, Fuxe K. Localization of monoamines in the lower brain stem. Experientia. 1964;20(7):398-9.

Cooper JR, Bloom FE, Roth RH. The Biochemical Basis of Neuropharmacology. Oxford University Press. 2003:181-224.

Carballo JJ. Neurobiological underpinnings of suicidal behavior: Integrating data from clinical and biological studies. Eur J Psychiat. 2009;23:243-59.

Van Moffaert M, Dierick M. Noradrenaline (Norepinephrine) and Depression. Mol Diag Ther. 1999;12:293-305.

McEwen BS. Physiology and neurobiology of stress and adaptation: Central role of the brain. Physiol Rev. 2007;87:873-904.

Fudalej S, Kopera M, Woły ´nczyk-Gmaj, et al. Association between FKBP5 Functional Polymorphisms and Completed Suicide. Neuropsychobiol. 2015;72:126-131.

Coryell W, Schlesser M. The dexamethasone suppression test and suicide prediction. Am J Psychiatry. 2001;158:748-53.

Sublette ME. Lipids and Suicide Risk. In: Current Topics in Behavioral Neurosciences. Springer, Berlin, Heidelberg. 2020.

Wardhan R, Mudgal P. In: Membrane Biology. Springer Singapore. 2017.

De Berardis D, Marini S, Piersanti M, Cavuto M. The Relationships between Cholesterol and Suicide: An Update. ISRN Psychiatry. 2012;2012:387901.

Pompili M, Longo L, Dominici G, Serafini G, Lamis DA, Sarris J, et al. Polyunsaturated fatty acids and suicide risk in mood disorders: A systematic review. Prog Neuropsychopharmacol Biol Psychiatry. 2017;74:43-56.

Daray FM, Mann JJ, Sublette ME. How lipids may affect risk for suicidal behavior. J Psychiatr Res. 2018;104:16-23.

Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK et al. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010;67:446-57.

Brundin L, Bryleva EY, Thirtamara Rajamani K. Role of inflammation in suicide: From mechanisms to treatment. Neuropsychopharmacol. 2017;42:271-83.

Pandey GN, Rizavi HS, Ren X, Bhaumik R, Dwivedi Y. Toll-like receptors in the depressed and suicide brain. J Psychiatr Res. 2014;53:62-8.

Ganança L, Oquendo MA, Tyrka AR, Cisneros-Trujillo S, Mann JJ, Sublette ME. The role of cytokines in the pathophysiology of suicidal behavior. Psychoneuroendocrinol. 2016;63:296-310.

Erhardt S, Lim CK, Linderholm KR, Janelidze S. Connecting inflammation with glutamate agonism in suicidality. Neuropsychopharmacol. 2013;38:743-52.

Stone TW, Stoy N, Darlington LG. An expanding range of targets for kynurenine metabolites of tryptophan. Trends Pharmacol Sci. 2013;34:136-43.

Carlborg A, Jokinen J, Jonsson EG, Erhardt S, Nordstrom P. CSF kynurenic acid and suicide risk in schizophrenia spectrum psychosis. Psychiatry Res. 2013;205:165-7.

Bondy B, Buettner A, Zill P. Genetics of suicide. Mol Psychiatry. 2006;11:336-51.

Courtet P, Jollant F, Castelnau D, Buresi C, Malafosse A. Suicidal behavior: relationship between phenotype and serotonergic genotype. Am J Med Genet C Semin Med Genet. 2005;133:25-33.

Du L. Catechol-O-methyltransferase Val158Met polymorphism and altered COMT gene expression in the prefrontal cortex of suicide brains. Prog Neuropsychopharmacol Biol Psychiatry. 2014;50:178-83.

Mandelli L. Interaction between serotonin transporter gene, catechol-O-methyltransferase gene and stressful life events in mood disorders. Int J Neuropsychopharmacol. 2007;10(4):437-47.

Brådvik L. Suicide Risk and Mental Disorders. Int J Environ Res Public Health. 2018;15(9):20-28.

Holmstrand C, Bogren M, Mattisson C. Long-term suicide risk in no, one or more mental disorders: the Lundby Study 1947–1997. Acta Psychiatr Scand. 2015;132:459-69.

Roca M, del Amo AR, Riera-Serra P. Suicidal risk and executive functions in major depressive disorder: a study protocol. BMC Psychiatry. 2019;19:253.

Dome P, Rihmer Z, Gonda X. Suicide Risk in Bipolar Disorder: A Brief Review. Medicina (Kaunas). 2019;55(8):403.

Too LS, Spittal MJ, Bugeja L, Reifels L, Butterworth P, Pirkis J. The association between mental disorders and suicide: A systematic review and meta-analysis of record linkage studies. J Affect Disord. 2019;259:302-313.

Ventriglio A, Gentile A, Bonfitto I, Stella E, Mari M, Steardo L et al. Suicide in the Early Stage of Schizophrenia. Front Psychiatry. 2016;7:116.

Wang Q, Ren L, Wang W. The relationship between post-traumatic stress disorder and suicidal ideation among shidu parents: the role of stigma and social support. BMC Psychiatry. 2019;19:352.

Wilcox HC, Conner KR, Caine ED. Association of alcohol and drug use disorders and completed suicide: an empirical review of cohort studies. Drug Alcohol Depend. 2004 ;76:S11-9.

Tobore TO. On the Neurobiological Role of Oxidative Stress in Alcohol-Induced Impulsive, Aggressive and Suicidal Behavior. Subst Use Misuse. 2019;54 (14):2290-2303.

Haorah J, Ramirez SH, Floreani N, Gorantla S, Morsey B, Persidsky Y. Mechanism of alcohol-induced oxidative stress and neuronal injury. Free Radical Biol Med. 2008;45:1542-50.

WHO: Preventing suicide: a global imperative. World Health Organization, Geneva. 2014. Accessed on 30 September, 2020.

Lund C, Breen A, Flisher AJ, Kakuma R, Corrigall J, Joska JA et al. Poverty and common mental disorders in low and middle income countries: A systematic review. Soc Sci Med. 2010;71(3):517-528.

Arya V, Page A, River J, Armstrong G, Mayer P. Trends and socio-economic determinants of suicide in India: 2001-2013. Soc Psychiatry Psychiatr Epidemiol. 2018;53(3):269-78.

Srivastava K, Chaudhury S, Bhat PS, Prakash J. Occupation-related suicide. Ind Psychiatry J. 2019;28(1):1-3.

Kumar C. One every hour: At 10,335, last year saw most student suicides in 25 years. 2020. Available at Accessed on 3 September 2020.

Birla N. A student commits suicide in India every hour; how can our educational system prevent this? 2018. Available at: https://economictimes. Accessed on 3 September 2020.