The interactive effects of Catechol-O-methyltransferase (COMT), D-amino acid oxidase-activator (DAO-A) and stressful life events on neuroticism and depression in a healthy Caucasian population.

Abstract

Extensive research identified several vulnerability factors for psychiatric disorders, including personality traits, environmental stress and genetic risk. Relatively little is known about the interaction between environmental stressors and multiple genes. The present study investigates the (interactive) effects of dopaminergic gene COMT and glutamatergic gene DAO-A, as well as the (interactive) effects of early life stress and recent life stress on neuroticism and depression. The personality trait neuroticism is considered a predictor for numerous psychiatric disorders, including depression. It is expected that the considered high-risk carriers of a gene have increased neuroticism levels due to altered neurotransmitter availability. Also, increased experienced environmental stress – either in early life or in recent life – is expected to raise neuroticism. Besides main effects, it is expected that genetic risk can combine with environmental stressors in elevating neuroticism. Also, both environmental stress and genetic risk are expected to accumulate their adverse effects to further increase neuroticism. These hypotheses are tested in a healthy population with Caucasian background. For genetic analyses, only carriers of homozygote gene-variants are included. Gene groups are matched on social economic status, age and sex. Indeed, the risk-variant of COMT leads to higher neuroticism levels. However, DAO-A does not influence neuroticism. As expected, increases in experienced stress increase neuroticism and depression. In line with expectations, although not consistent in all genes, genetic and environmental influences can combine since COMT interacts with early life stress and recent life stress in increasing neuroticism. Environmental stress and genetic risk seem to be able to accumulate their adverse effects, but this effect is moderate and inconsistent. The findings of this study address the influences of genetic variation in its ability (by itself and in combination with environmental factors) to produce adverse psychological effects. Also, the impact of early life stress and recent life stress on psychological wellbeing is made clearer, even more because of the seemingly accumulating properties of stress.