Familial risk for mood disorder and the personality risk factor, neuroticism, interact in their association with frontolimbic serotonin 2A receptor binding

Abstract

Life stress is a robust risk factor for later development of mood disorders, particularly for individuals at familial risk. Likewise, scoring high on the personality trait neuroticism is associated with an increased risk for mood disorders. Neuroticism partly reflects stress vulnerability and is positively correlated to frontolimbic serotonin 2A (5-HT(2A)) receptor binding. Here, we investigate whether neuroticism interacts with familial risk in relation to frontolimbic 5-HT(2A) receptor binding. Twenty-one healthy twins with a co-twin history of mood disorder and 16 healthy twins without a co-twin history of mood disorder were included. They answered self-report personality questionnaires and underwent [(18)F]altanserin positron emission tomography. We found a significant interaction between neuroticism and familial risk in predicting the frontolimbic 5-HT(2A) receptor binding (p=0.026) in an analysis adjusting for age and body mass index. Within the high-risk group only, neuroticism and frontolimbic 5-HT(2A) receptor binding was positively associated (p=0.0037). In conclusion, our data indicate that familial risk and neuroticism interact in their relation to frontolimbic 5-HT(2A) receptor binding. These findings point at a plausible neurobiological link between genetic and personality risk factors and vulnerability to developing mood disorders. It contributes to our understanding of why some people at high risk develop mood disorders while others do not. We speculate that an increased stress reactivity in individuals at high familial risk for mood disorders might enhance the effect of neuroticism in shaping the impact of potential environmental stress and thereby influence serotonergic neurotransmission.

Figure 1

Effect of familial risk on the association between frontolimbic 5-HT_2A receptor BP_P and neuroticism, adjusted for BMI and age. In the high end of the neuroticism scale, the high-risk group showed an elevated BP_P, whereas in the low end, they showed a decreased BP_P as compared with the low-risk group. This reflects the stronger association between neuroticism and frontolimbic 5-HT_2A receptor binding in individuals at high familial risk of developing mood disorders (p=0.026). The high-risk group showed a significant positive association between neuroticism and frontolimbic 5-HT_2A receptor binding, whereas the low-risk group did not. Please see text for estimates. Point-wise 95% symmetric confidence bands of the regression lines are displayed. The regression lines represent the associations given a mean BMI and mean age.

Figure 2

Effect of zygosity and familial risk on the association between frontolimbic 5-HT_2A receptor binding and neuroticism, adjusting for BMI and age. Genetic risk load: (low-risk DZ and MZ < high-risk DZ < high-risk MZ). The high-risk MZ group shows the strongest association followed by the high-risk DZ group and the low-risk group. However, the differences in slopes between groups represented a trend only (p=0.12).