Nitric oxide synthase genetic variant is a risk factor for suicidal behaviour

The presence of a genetic variant of NOS3 is associated with early suicidal behaviour, risk of multiple attempts, and risk of violent suicide attempts. This genetic risk factor increased the suicide risk independently of other risk factors like childhood abuse.

Although many risk factors for suicidal behaviour are known, the prediction of suicide (attempts) at an individual level is almost impossible. Apart from environmental parameters, e.g. physical and/or emotional abuse in childhood and exposure to challenges during a lifetime, biological factors, e.g. genetics, are believed to play a role [1]. A potential genetic candidate involved in the risk of suicide is nitric oxidase synthase (NOS), a family of enzymes that synthesise endogenous nitric oxide (NO). NO is involved in many body functions and, in some studies, abnormal NO plasma levels were found in people who attempted suicide [2]. Dr Aiste Lengvenyte (CHU Montpellier, France) explored the role of NOS genetic polymorphisms as a risk factor for suicide attempts and their relation to environmental risk factors [3].

The researchers analysed genetic, clinical, and personal historical data from 414 people who attempted suicide. As could be expected, in this population, a history of emotional, physical, and/or sexual abuse was associated with an early-onset suicide attempt. In addition, the presence of a genetic variant of NOS3 (27 bp-VNTR b/b genotype) was associated with early suicidal behaviour, multiple attempts, and violent suicide attempts (see Figure). This genetic risk factor increased the suicide risk independently of other risk factors like childhood abuse. In addition, carriers of this NOS3 genotype were more likely to have their first suicide attempt at a younger age compared with non-carriers [4].

Figure: The presence of a NOS3 polymorphism increases suicide risk [3]



“Our data shows that genetic variants of the NO system might be involved in the vulnerability to early-onset suicidal behaviour,” Dr Lengvenyte concluded. “The additive –rather than interactive– association of the genetic status and childhood abuse with an early suicide attempt suggests that early suicidal behaviour is the result of both nature and nurture.”

Dr Lengvenyte remarked that limitations of the study are the small sample size (for a genetic study), the cross-sectional setting of the study, retrospective reporting, and survivorship bias. Moreover, suicidal behaviour is likely modulated by a large number of gene variants [5].

1. Lengvenyte A, et al. Eur J Neurosci. 2021;53:330–351.
2. Lee B-H, et al. Neuropsychobiology. 2006;53:127–132.
3. Lengvenyte A, et al. Implicating the nitric oxide system in the nurture-nature debate: nitric oxide synthase genetic variant, childhood maltreatment and onset of suicidal behaviours. Abstract S10.04, ECNP Congress 2022, 15–18 October, Vienna, Austria.
4. Lengvenyte A, et al. Prog Neuropsychopharmacol Biol Psychiatry. 2022;119:110617.
5. Mullins N, et al. Biol Psychiatry. 2022;91(3):313–327.

 

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Posted on 28 November 2022