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Genetic Underpinnings of Neuroticism: A Replication Study

Lily R Aleksandrova, Renan P. Souza, R. Michael Bagby, David M. Casey, David C. Hodgins, Garry J. Smith, Rob J. Williams, Don P. Schopflocher, Rob T. Wood, Nady el-Guebaly, James L. Kennedy, Daniela S S Lobo

Background: Neuroticism, as defined and measured by the NEO Personality Inventory (Neuroticism Extraversion and Openness Personality Inventory), is a core personality trait reflecting an individual’s emotional reactivity. High neuroticism is thought to be an important vulnerability factor for various psychiatric disorders in the general population, including substance abuse, depression, anxiety, and psychosis. Recent findings support the hypothesis that genetic factors underlying the neuroticism trait could increase the susceptibility to psychiatric disorders. The current study aimed to replicate genetic associations with high neuroticism previously reported in the literature.
Methods: We genotyped four polymorphisms: CNR1 (rs7766029), GABRA2 (rs9291283), GABRA6 (rs3219151) and MAMDC1 (rs7151262) in 215 healthy Caucasian subjects, who completed a short version of the NEO-PI. NEO neuroticism scores of the three genotype groups were compared using ANCOVA, with age as a covariate.
Results: All four genetic polymorphisms were found to be significantly associated with NEO neuroticism scores (p < 0.0025), but not with any other NEO personality domain. Conclusion: Our results corroborate other studies proposing a role for the GABAergic and cannabinoid systems in the modulation of affective states and stress responses, as measured through neuroticism scores. It is important to replicate the genetic findings of neuroticism, in order to gain a better understanding of this personality domain that has been reported as an important risk factor for mood and anxiety disorders and substance addiction.