Contributions of Dopamine-Related Genes and Environmental Factors to Highly Sensitive Personality: A Multi-Step Neuronal System-Level Approach

Abstract

Traditional behavioral genetic studies (e.g., twin, adoption studies) have shown that human personality has moderate to high heritability, but recent molecular behavioral genetic studies have failed to identify quantitative trait loci (QTL) with consistent effects. The current study adopted a multi-step approach (ANOVA followed by multiple regression and permutation) to assess the cumulative effects of multiple QTLs. Using a system-level (dopamine system) genetic approach, we investigated a personality trait deeply rooted in the nervous system (the Highly Sensitive Personality, HSP). 480 healthy Chinese college students were given the HSP scale and genotyped for 98 representative polymorphisms in all major dopamine neurotransmitter genes. In addition, two environment factors (stressful life events and parental warmth) that have been implicated for their contributions to personality development were included to investigate their relative contributions as compared to genetic factors. In Step 1, using ANOVA, we identified 10 polymorphisms that made statistically significant contributions to HSP. In Step 2, these polymorphism's main effects and interactions were assessed using multiple regression. This model accounted for 15% of the variance of HSP (p<0.001). Recent stressful life events accounted for an additional 2% of the variance. Finally, permutation analyses ascertained the probability of obtaining these findings by chance to be very low, p ranging from 0.001 to 0.006. Dividing these loci by the subsystems of dopamine synthesis, degradation/transport, receptor and modulation, we found that the modulation and receptor subsystems made the most significant contribution to HSP. The results of this study demonstrate the utility of a multi-step neuronal system-level approach in assessing genetic contributions to individual differences in human behavior. It can potentially bridge the gap between the high heritability estimates based on traditional behavioral genetics and the lack of reproducible genetic effects observed currently from molecular genetic studies.

The Dopamine D2 Receptor Polymorphism (DRD2 TaqIA) Interacts with Maternal Parenting in Predicting Early Adolescent Depressive Symptoms: Evidence of Differential Susceptibility and Age Differences

“…That is, adolescents with the A1 allele appeared to be more differentially susceptible to the effects of both high and low risk environments during early adolescence, lending support for the differential susceptibility hypothesis (Belsky et al 2007). Prior evidence suggests that the DRD2 gene may be associated with greater environmental sensitivity in personality generally (Chen et al 2011), and the A1 allele of the DRD2 TaqIA polymorphism may be linked with reward sensitivity specifically (Lee et al 2007).…”

“…This polymorphism site commonly includes three genotypes: A1A1 homozygotes, A2A2 homozygotes, and A1A2 heterozygotes. Compared with A2A2 homozygotes, A1A1 homozygotes and A1A2 heterozygotes tend to have lower density of the D2 dopamine receptor in striatum and nucleus accumbens (Noble et al 1991;Pohjalainen et al 1998), and reduced glucose metabolism in striatum (Chen et al 2011;Noble et al 1997). These functional correlations between TaqIA polymorphism and dopamine functioning in the ventral striatum region suggest an important role of TaqIA polymorphism in depressive symptoms.…”

Influence of Catechol-O-methyltransferase on Executive Functioning Longitudinally After Early Childhood Traumatic Brain Injury

“…47 Specifically, dopamine receptor and dopamine pathway, serotonin transporter, and COMT genetic variants interact with environmental factors to influence cognitive and behavioral functioning in various childhood populations. 18,48-58 Although the higher activity enzyme genotype (GG) is generally associated with a reduction in executive cognition, it is also associated with better stress resiliency, indicating that stressful environmental factors may overwhelm the direct effects the COMT genotype has on cognition 59 Because a TBI often leads to increased family burden 42,60,61 , the potential stress resiliency effects of the high activity genotype (GG) may outweigh the effects on executive cognition. Future studies should evaluate the interaction of genetics and environmental and other factors on recovery.…”

Web-based cognitive bias modification for problem drinkers: protocol of a randomised controlled trial with a 2x2x2 factorial design

“…Symptoms of depression and anxiety are measured with the Beck Depression Inventory-II (BDI-II [39]), and the Spielberger State-Trait Anxiety Inventory (STAI [40]), respectively. High trait sensitivity, which is correlated with genes related to susceptibility to both positive and negative environmental influences [41,42], is measured as a possible predictor of the changeability of automatic biases (using a short version of the High Sensitive Personality Child Questionnaire (HSC [43]).…”