Genetic Variations in the Human Cannabinoid Receptor Gene Are Associated with Happiness

Abstract

Happiness has been viewed as a temporary emotional state (e.g., pleasure) and a relatively stable state of being happy (subjective happiness level). As previous studies demonstrated that individuals with high subjective happiness level rated their current affective states more positively when they experience positive events, these two aspects of happiness are interrelated. According to a recent neuroimaging study, the cytosine to thymine single-nucleotide polymorphism of the human cannabinoid receptor 1 gene is associated with sensitivity to positive emotional stimuli. Thus, we hypothesized that our genetic traits, such as the human cannabinoid receptor 1 genotypes, are closely related to the two aspects of happiness. In Experiment 1, 198 healthy volunteers were used to compare the subjective happiness level between cytosine allele carriers and thymine-thymine carriers of the human cannabinoid receptor 1 gene. In Experiment 2, we used positron emission tomography with 20 healthy participants to compare the brain responses to positive emotional stimuli of cytosine allele carriers to that of thymine-thymine carriers. Compared to thymine-thymine carriers, cytosine allele carriers have a higher subjective happiness level. Regression analysis indicated that the cytosine allele is significantly associated with subjective happiness level. The positive mood after watching a positive film was significantly higher for the cytosine allele carriers compared to the thymine-thymine carriers. Positive emotion-related brain region such as the medial prefrontal cortex was significantly activated when the cytosine allele carriers watched the positive film compared to the thymine-thymine carriers. Thus, the human cannabinoid receptor 1 genotypes are closely related to two aspects of happiness. Compared to thymine-thymine carriers, the cytosine allele carriers of the human cannabinoid receptor 1 gene, who are sensitive to positive emotional stimuli, exhibited greater magnitude positive emotions when they experienced positive events and had a higher subjective happiness level.

Genetic correlations between wellbeing, depression and anxiety symptoms and behavioral responses to the emotional faces task in healthy twins

“…Chakrabarti & Baron-Cohen, 2011; Chakrabarti et al, 2006;Domschke et al, 2008; M A N U S C R I P T Matsunaga et al, 2014). Variation in this gene has been shown to modulate activity in the striatum which is central to reward processing, specifically in response to happy faces in both healthy (Chakrabarti & Baron-Cohen, 2011;Chakrabarti et al, 2006) and clinicallydepressed (Domschke et al, 2008) samples.…”

“…Variation in this gene has been shown to modulate activity in the striatum which is central to reward processing, specifically in response to happy faces in both healthy (Chakrabarti & Baron-Cohen, 2011;Chakrabarti et al, 2006) and clinicallydepressed (Domschke et al, 2008) samples. In healthy individuals, allelic variation in four single-nucleotide polymorphisms (SNPs) of the CNR1 gene (the C allele in rs806377; G in rs806380; G in rs6454674; C in rs1049353) have been associated with higher striatal activity, a sensitivity for positive stimuli (i.e., happy faces) and, in the case of rs806377, higher levels of happiness (Chakrabarti & Baron-Cohen, 2011;Chakrabarti et al, 2006;Matsunaga et al, 2014). In clinically depressed individuals, genetic variation in the opposing G allele for the CNR1 SNP rs1049353 has been shown to confer risk for anxiety and depression, and antidepressant treatment resistance (Domschke et al, 2008).…”

“…Evidence to date has so far shown a common genetic link between aspects of emotional function and depression and anxiety symptoms. Genetic variation has been shown to differentially impact the neural and behavioral processing of happy and sad faces (Chakrabarti, Kent, Suckling, Bullmore, & Baron-Cohen, 2006;Domschke et al, 2008;Matsunaga et al, 2014) in regions critical in reward processing, and which are associated with depression and anxiety symptoms (Dillon et al, 2014). In contrast, genetic influences for any common associations between emotion processing and wellbeing are unknown.…”

Culture and cannabinoid receptor gene polymorphism interact to influence the perception of happiness

“…The endocannabinoid system is a group of neuromodulatory lipids and their receptors [1]. The endocannabinoids, such as anandamide and 2-arachidonoyl glycerol [2–4], bind to brain cannabinoid receptors, which are involved in several physiological processes including appetite regulation, nociception, memory, and emotional processing [1–7]. Recent studies have indicated that a cytosine (C) to thymine (T) single nucleotide polymorphism (SNP) of the human cannabinoid receptor 1 ( CNR1 ) gene (dbSNP number rs806377) is associated with positive emotional processing [5–7].…”

“…The endocannabinoids, such as anandamide and 2-arachidonoyl glycerol [2–4], bind to brain cannabinoid receptors, which are involved in several physiological processes including appetite regulation, nociception, memory, and emotional processing [1–7]. Recent studies have indicated that a cytosine (C) to thymine (T) single nucleotide polymorphism (SNP) of the human cannabinoid receptor 1 ( CNR1 ) gene (dbSNP number rs806377) is associated with positive emotional processing [5–7]. Studies have shown that the activity of the striatum, which is a part of the brain reward system, is higher, and gaze duration for faces is longer in C allele carriers than in individuals with the TT genotype when they are presented with a happy face [5,6].…”