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. Author manuscript; available in PMC: 2017 Mar 1.
Published in final edited form as: Schizophr Res. 2016 Jan 21;171(0):1–15. doi: 10.1016/j.schres.2016.01.020

Figure 2.

Figure 2

A hypothetical model illustrating the central role of nAChRs and trait impulsivity in increasing the risk of schizophrenia in adolescent nicotine users. Susceptibility mechanisms such as a defective nAChR system (e.g. CHRNA7, CHRNA5/A3/B4 polymorphism) or D2/D3 receptor hypofunction may make adolescents more impulsive and engage in smoking initiation. Nicotine use by itself may aggravate impulsivity by upregulating the high-affinity α4β2 nAChRs leading to smoking maintenance. Sustained nicotine use initiates a vicious cycle in schizophrenia-susceptible adolescents that involves tolerance to the behavioral effects of nicotine, maladaptive circuit and neurochemical changes, enhanced sensitivity to withdrawal-related worsening of the cognitive and affective symptoms and higher relapse rates. Thus, nicotine use maintained in adolescent smokers may eventually put them at higher risk of developing schizophrenia.