The Creative Mind: Blending Oxytocinergic, Dopaminergic and Personality

In a fast-changing world, creative thinking (CT) is an extraordinary currency. Oxytocin (OT) is associated with CT and release of OT depends on ADP ribosyl-cyclases ( CD38 and CD157 ). Moreover, CT as well as OT’s mechanism of action are mediated via central dopaminergic pathways. Consequently, we evaluate the roles of CD38 , CD157 , dopamine receptor D2 ( DRD2 ) and catechol-O-methyltransferase ( COMT ) peripheral gene expression in CT. Two principal domains of CT, divergent thinking and insight solving problems, were assessed using validated behavioral assessments. To facilitate discriminant validity, two established correlates of CT, trait Openness and fluid intelligence as well as age and sex were included in the regression model. In women, significant main effects (p<0.01) were positively associated with the expression CD38 , CD15 , and their interaction CD38 x CD157 controlling for Openness, fluid intelligence and age. Subsequent analysis on the subscale-level revealed significant main effects for CD157 and CD38 x CD157 in men specifically for divergent thinking. In women, significant (p<0.01) results are also observed for dopaminergic expression ( DRD2 , COMT , DRD2 x COMT ). The full model (oxytocinergic and dopaminergic gene expressions, Openness, and fluid intelligence) explains a sizable 39% of the variance in females. Significant main effects are observed for CD38 , CD157 , DRD2 and COMT as well as their interactions ( CD38 x CD157 and DRD2 x COMT ). In conclusion, we show that oxytocinergic and dopaminergic gene expression contribute significantly to the complex CT phenotype suggesting the notion that the perspective gained from examining the peripheral transcriptome meaningfully adds to understanding the landscape of creative thinking. Significance Statement Creative thinking (CT) is a powerful driving force galvanizing progress and civilization. Towards better understanding the neurobiology of CT, we implement a gene expression strategy that is considered to capture not only genomic elements but also environmental signatures. We employ laboratory measures of CT (alternative uses test and insight problem solving), controlling for fluid intelligence and the personality trait of Openness. We focus on oxytocinergic and dopaminergic genes that contribute to the molecular architecture of CT. Oxytocinergic and dopaminergic gene expression significantly explains a robust 39% of the variance in CT. Notably, this study demonstrates the potential of the peripheral transcriptome towards tracing gene pathways underlying some complex cognitive behaviors such as creative thinking.