Early-onset use of psychoactive substances, such as tobacco, may have neurotoxic and neuromodulatory effects, which can be related also with SRB. Especially, the age of smoking initiation may be an important determinant for risk of various somatic and mental adverse health outcomes (DeBry & Tiffany., 2008). Part of the association between tobacco use and SRB may be explained by the confounding effects of these well-known risk factors, such as depression or abuse of other addictive substances. However, another part of the association may be the result of the effect of tobacco use itself, especially cigarette smoking that may increase the risk of SRB through a biological pathway. Cigarette smoking has been suggested to have implications also for brain neurobiology. For example, smoking can significantly decrease the activity of the serotonergic system of the human hippocampus and may reduce brain serotonin function which is negatively related to risk of suicide. Furthermore, nicotine, the addictive substance in all kinds of tobacco products, is a potent activator of the hypothalamic-pituitary-adrenal (HPA) axis and is able to activate the attenuated responsiveness of the HPA
