Page 55 - The prevalence of the Val66Met polymorphism in musicians: Possible evidence for compensatory neuroplasticity from a pilot study

S. Si et al. NeuroImage 213 (2020) 116681
genotypes might moderate how individuals experience environment polymorphism parenting style interactions to be investigated are in-
instead of having a direct effect on creativity. For example, potential role clined to have small effects (Kendler, 2005; Duncan and Keller, 2011),
in creativity is suggested for the serotoninergic genes (Bachner-Melman such that roles of many functional variants with minor effects cannot be
et al., 2005; Volf et al., 2009). Among them, the tryptophan hydroxylase detected.
1 gene (TPH1) is the most extensively studied. However, previous studies Fortunately, recent researchers have found that investigating the role
examining the association of TPH1 and creativity yielded incompatible of multiple genetic polymorphisms using a cumulative genetic score
results (Reuter et al., 2006; Runco et al., 2011; Zhang and Zhang, 2017). (CGS) approach may be a way to address these concerns (e.g., Dobewall
Researchers argued that the effect of genetics may only become apparent et al., 2018; Mehta et al., 2016; Mitchell et al., 2011). A CGS models
if certain environmental factors are present (Rutter, 2006). Recent cumulative genetic influences and combines the susceptibility conferred
research on gene environment interaction (G E) highlights that the by two or more polymorphisms into a single score. Use of a CGS provides
negative effect of parental authoritarianism on creativity is only promi- several notable advantages, including increased power, as compared
nent in individuals with TPH1 rs1799913 CC genotype (Zhang et al., with the small effect sizes of individual polymorphisms and the ability to
2018). This suggests that some individuals are more susceptible to model more variability in the dopamine system. For the present study, we
environment than others because of different genetic background. Thus are using a CGS approach to determine whether the CGS of COMT and
understanding the genetic factors that influence individual sensitivity to DRD2 influences the relationship between parenting style and creativity.
environment is critical for a better understanding the effect of parenting These two genes, and the dopaminergic functions that they influence,
style on creativity. appear to interact in prefrontal and striatum brain regions (Zhang et al ,
Besides TPH1, two other genes (DRD2 and COMT) have also been 2014b). This finding suggests that the DRD2.
implicated in creativity. The DRD2 gene encodes a G protein-coupled And COMT may be biologically and behaviorally linked. Hence,
receptor that plays an important role in mediating synaptic DA dopaminergic genes which strongly affect frontal and striatal activities
signaling in striatum. The COMT gene encodes the key metabolic enzyme may tend to jointly influence creativity. This has been further elucidated
responsible for the degradation of catecholamines (including dopamine by a recent study which found creativity can also be predicted from in-
and norepinephrine). Extensive molecular genetic studies of creativity teractions between genetic polymorphisms related to frontal (COMT) and
have shown that variations of DRD2 and COMT as well as the interactions striatal (DAT) DA pathways (Zabelina et al., 2016).
between these variations were closely related to individual differences in To explain why the effect of rearing experience is more pronounced in
creativity (e.g., Murphy et al., 2013; Reuter et al., 2006; Runco et al., some individuals with particular genetic make-up, two competing
2011; Zhang et al , 2014a; Jiang et al., 2015; Zhang et al, 2014b; Han models of G E interactions: diathesis-stress and differential suscepti-
et al., 2018), suggesting the importance of dopamine and bility have been formulated. The traditional diathesis-stress model was
norepinephrine-related genes (as well as the potential interactions be- first put forward which suggest that individuals who are “vulnerable”
tween dopamine and norepinephrine-related genes) in creativity genetically are worse off in unfavorable environments (Monroe and Si-
(Beversdorf, 2018). mons, 1991). As the dysfunctional “vulnerable alleles” were found to
Single variations in dopaminergic genes do not work independently, provide advantages over other genotypes, at least in certain contexts,
but might interact with environment to influence creativity. For example, researchers recently proposed the differential susceptibility model, sug-
in previous work, a study has shown a gene by environment interaction gesting individuals with certain alleles may be not only adversely
between family stress and a variation in the DRD2 on cognitive functions affected by negative environments, but also benefit the most from posi-
(Berman and Noble, 1997). It was found that the family stress score tive environmental factors (Belsky and Pluess, 2009). This model is
negatively associated with cognitive abilities only in individuals with considered to be much more consistent with recent G E data results.
þ
A1 allele (rs1800497). Besides, there was also a study demonstrating a Therefore, it would seem more appropriate to speak of “plasticity genes”
significant DRD2 (rs1800497) strict maternal disciplinary style inter- rather than “vulnerability genes” (Belsky et al., 2009). More recently, a
action in predicting novelty seeking (Keltikangas-J€ arvinen et al., 2009). cumulative genetic plasticity model has been proposed, which predicts
With regard to COMT polymorphisms, G E interaction effects for many that more “plasticity” alleles individuals carry, the more susceptible they
cognitive abilities have been reported in previous studies. For example, will be to environmental influences (Belsky et al., 2007; Belsky et al.,
many researchers (e.g., Enoch et al., 2009; Goldberg et al., 2013; 2009; Belsky and Pluess, 2009). Several studies have provided support
O’Donnell et al., 2017) have investigated whether COMT variant rs4680 for this model (LeClair et al , 2014; Disner et al., 2014).
moderates the influence of adverse environments on creativity-related Considering that the relationship between parenting style and crea-
cognitive functions (e.g., working memory, decision making, atten- tivity has been closely associated with dopaminergic functioning, the
tion). Furthermore, a few studies did find rs4680 would interact with present study sets out to systematically identify how variants in DRD2
positive versus more adverse parenting on decision making and attention and COMT moderate this critical association. We first examined whether
(Voelker et al., 2009; He et al., 2012). Therefore, individuals might be each individual polymorphism interacts with parenting style to predict
differentially susceptible to parenting style due to their DRD2 and COMT individual differences in creativity. Then, we aggregated the contribution
genotype, potentially accounting for individual differences in creativity. of these polymorphisms in DRD2 and COMT into a CGS which combines
To further identify the genetic factors that moderate context sensi- the susceptibility conferred by two or more single nucleotide poly-
tivity which are likely to influence the relationship between parenting morphism (SNPs) into a single score. Finally, to further clarify the G E
style and creativity, it would be important to systematically investigate if interaction pattern for creativity as well as to better explain the potential
variations in DRD2 and COMT genes might interact with parenting style interaction of genetic profile (CGS) and parenting styles, the present
to predict creativity. Despite no study available to illustrate COMT study also examined whether the potential gene parenting interaction
polymorphisms moderating roles in the relationship between parenting would coincide with the diathesis-stress model or the differential sus-
style and creativity, a recent study showed gene by environment (G E) ceptibility model.
interaction between parenting style and a variation in DRD2 (Si et al.,
2018). As a preliminary result, this study does provide important insight 2. Materials and methods
into the role of dopamine-related single genes that influence individual
sensitivity to parenting style in a better understanding of individual 2.1. Participants and procedures
difference in creativity; however, it should also be noted that, one
polymorphism does not sufficiently explain the variation in gene func- The main characteristics of participants and study procedure have
tion, possibly limiting our range of understanding of biological suscep- been described previously (Si et al., 2018). Briefly, 427 Chinese under-
tibility to environmental influence. Besides, single genetic graduate students ages 18–22 (mean age ¼ 18.92, SD ¼ 0.84,

2