Eley, T. C., Ball, D., Hill, L., Jolley, E., Freeman, B., Riemann, R., Spinath, F. M., Angleitner, A. & Plomin, R. (1998). Association study of extreme high and low
neuroticism with genetic markers for the dopaminergic system. American Journal of Medical Genetics, 81, 487.


There are now several reported associations between genetic markers for the dopaminergic neurotransmitter system and traits related to one of the "superfactors" of personality, extraversion (novelty-seeking, substance abuse, and hyperactivity). However, the role of the dopaminergic neurotransmitter system for the other major "superfactor", neuroticism, which is strongly associated with internalizing symptoms such as anxiety and depression, has been less thoroughly investigated. Neuroticism is a quantitatively distributed trait with a roughly normal distribution, and thus an ideal candidate for a selected extremes approach.
We explored the possible role of genes involved in the dopaminergic neurotransmitter system on neuroticism using a selected extremes design. From a sample of 2.085 individuals, each assessed for neuroticism by two independent peers, we selected 52 individuals from the top 5% of scores, and 54 individuals from the bottom 5%. Using selected extreme low subjects as the controls, rather than an unselected control group, gives roughly twice the power of a standard case-control design. No associations were found between neuroticism and polymorphismsin DRD1, DRD2, DRD3, DRD4, and DAT1, using either an allelic or genotypic approach. This suggests that the dopaminergic system may play a greater role in "externalizing" rather than "internalizing" behaviors and personality traits.


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