Childhood traumatic events and the dopaminergic theory of psychosis: A mini-review of studies investigating gene – environment interactions

There is great body of evidence showing a relationship between childhood adversity and psychosis onset. Genetic factors moderate the association between childhood adversity and psychosis risk potentially by influencing biological and/or psychological reaction following exposure to adversity. In this review, we discuss studies identifying the specific genetic variants known to affect dopamine levels involved in this interaction. Our review shows that the catechol-O-methyltransferase (COMT), dopamine D2 receptor (DRD2), AKT1 gene play a key role in mediating the relationship between childhood adversity and development of psychosis. We have also found conflicting findings on the impact of dopamine genes on the relationship between childhood adversity and development of psychosis, suggesting that other genetic and environmental factors should be taken into account. We here discuss the implications of our findings and future directions.

The Association Between Affective Temperament Traits and Dopamine Genes in Obese Population

Studies indicate the heritable nature of affective temperament, which shows personality traits predisposing to the development of mental disorders. Dopaminergic gene polymorphisms such as DRD4, COMTVal158Met, and DAT1 have been linked to affective disorders in obesity. Due to possible correlation between the aforementioned polymorphisms and the affective temperament, the aim of our research was to investigate this connection in an obese population. The study enrolled 245 obese patients (178 females; 67 males). The affective temperament was assessed using the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego autoquestionnaire (TEMPS-A). Genetic polymorphisms of DAT1, COMTVal158Met and DRD4 were collected from peripheral blood sample and determined using a polymerase chain reaction (PCR). Only in COMT polymorphisms, the cyclothymic and irritable dimensions were significantly associated with Met/Val carriers (p = 0.04; p = 0.01). Another interesting finding was the correlation between the affective temperament and age in men and women. We assume that dopamine transmission in heterozygotes of COMT may determine the role of the affective temperament in obese persons. Dopaminergic transmission modulated by COMT may be responsible for a greater temperament expression in obese individuals. To our knowledge, this is the first study describing the role of affective temperament in the obese population, but more research is needed in this regard.

Using a Systems-Based Risk Score Approach to Examine Genetic Predisposition to Novelty Seeking

Previous research is mixed regarding the relation between dopamine and Novelty Seeking. The goals of the current study were to support the hypotheses that Novelty Seeking is associated with dopamine genes and that modeling genetic risk score increases the utility of genetic information in hypothesis-driven research. The results showed that higher hypodopaminergic genetic risk score positively predicted higher Novelty Seeking score, F(1, 115) = 5.76, p < .01, R2 = 0.06. The findings support study hypotheses and, in combination with previous studies, show the utility of empirically validated system-based risk scores as a means of modeling genetic predisposition in neurobiological systems. This approach provides a mechanism for incorporating genetic predisposition into theory-driven multivariate etiological models of psychological constructs such as personality and mental illness.

The Interaction of Dopamine Genes and Financial Stressors to Predict Adulthood Intimate Partner Violence Perpetration

Three dopamine genes (DAT1, DRD2, and DRD4) have been associated with interpersonal delinquency, aggression, and violence when individuals experience adverse environmental exposures. Guided by the catalyst model of aggression, risk alleles identified in previous studies were hypothesized to be associated with intimate partner violence (IPV) perpetration in the presence of financial stressors, a possible environmental trigger. This hypothesis was tested using weighted, clustered logistic regression with data from the National Longitudinal Study of Adolescent to Adult Health. The direct effects DAT1, DRD2, and DRD4 on IPV perpetration, and the interaction of DAT1, DRD2, and DRD4 and financial stressors on IPV perpetration were assessed. Due to cell size, only White men and women were included in this analysis. Increasing number of financial stressors was associated with increased odds of IPV perpetration, regardless of DAT1, DRD2, and DRD4 alleles. As predicted, increasing number of financial stressors was more strongly associated with IPV perpetration among individuals with high-risk DAT1 alleles, than individuals with low-risk alleles. However, this relationship was inverted for DRD2. Although there was still a significant interaction between DRD2 and financial stressors, individuals with low-risk alleles had higher odds of IPV perpetration in the presence of financial stressors. A similar, nonsignificant relationship was found for DRD4. These findings indicate that these genes may interact differently with environmental exposures and types of violent behavior. In addition, the findings may, if replicated, suggest dopamine plays a different role in IPV perpetration compared with other forms of aggression and violence.