Beyond Dopamine: Possible Neurochemical Bases of Openness To Experience and Intellect
Beyond Dopamine: Possible Neurochemical Bases of Openness To Experience and Intellect
In recent years, efforts have been made to understand how individual differences & personality traits relate to neurotransmitter systems, such as dopamine and serotonin (e.g., Alkalay et al. 2022). To my knowledge however, research on the neurobiology of openness is limited, and almost all focuses on dopamine. However, dopamine is linked to both openness and extraversion, though are thought to be related to separate parts of the dopamine system (DeYoung 2013), leaving openness independent from extraversion or openness with low extraversion unexplained in regards to neurochemical influences. Understanding the neurobiology of openness beyond dopamine may be beneficial to treatment of disorders such as autism and schizophrenia, as persons with schizophrenia spectrum disorders tend to have high openness but low extraversion, and antipsychotics may worsen extraversion-linked symptoms, and autism is linked to low openness primarily in the aesthetics/imagination aspect. Additionally, the lower level aspects of openness - openness and intellect have not been characterized individually as to their biological bases. In this post I review evidence for links between openness and neurotransmitter systems beyond dopamine, as well as neurotransmitters specifically related to the intellect or openness facets. Openness as a whole, in addition to dopamine may be associated with acetylcholine, and negatively associated with serotonin and the 5-HT3 receptor. The openness/imagination aspect of openness may be positively related to oxytocin and endocannabinoids and negatively to testosterone, with intellect being positively related to testosterone and negatively to oxytocin and endocannabinoids.
Serotonin
Serotonin has been hypothesized to relate to personality traits in multiple models (e.g., Peirson et al. 1999; Fisher et al. 2015; Allen & DeYoung 2017), though to my knowledge openness has not been one of these traits. Serotonin appears to be associated with conformity, cautiousness, self restraint, and persistence (Fisher et al. 2015)(Allen & DeYoung 2017), which are characteristic of high conscientiousness and low openness. Expectedly, the serotonin scale of the Fisher Temperament Inventory, which has been validated to correlate with serotonin activity, most strongly correlates with high conscientiousness and low openness (Fisher et al. 2015). Serotonin is associated with disgust (Rubio-Godoy et al. 2007), and disgust sensitivity is reduced in individuals with high openness (Druschel & Sherman 1999). Serotonin also reduces emotionality (Kanen et al. 2021), and intensity and awareness of emotions is associated with high openness (DeYoung et al. 2012). Serotonin also appears to be increased in autism (Crespi 2011) and reduced in schizotypal personality disorder (Cloudfindings 2023c) which are associated with low and high openness respectively (Del Giudice 2018)(DeYoung et al. 2012)(Rogers et al. 2023)(Cloudfindings 2023a,c). Serotonin activity has an inverse genetic association with drug use and sensation seeking (Covault et al. 2007)(Gerra et al. 2005), and openness predicts strongly drug use (Dash et al. 2023)(Kang 2022) and sensation seeking (Del Giudice et al. 2014). Finally, serotonin has inhibitory effects on dopamine (Kapur & Remington 1996) and dopamine is positively associated with openness (DeYoung 2013). More evidence is needed to reveal what, if any relationship serotonin has with openness, however current evidence suggests serotonin may have a negative relationship with openness.
5-HT3 Receptor
The 5-HT3 receptor is a subtype of serotonin receptor. While there is limited research on the relationship between 5-HT3 and personality, there is some evidence to suggest that 5-HT3 activity in particular may be inversely related to openness. Ginger, which contains antagonists of 5-HT3 that are responsible for its antiemetic effects (Dai et al. 2022), is shown to reduce disgust sensitivity and lead to less harsh moral judgements, particularly to disgust and purity related moral violations (Tracy et al. 2019), as is characteristic of high openness (Cloudfindings 2023b)(Druschel & Sherman 1999). 5-HT3 activity seems to be inversely associated with cognitive ability, with 5-HT3 antagonists leading to enhancements in cognitive function (Mohammadi et al. 2010)(Arnsten et al. 1997), and cognitive ability is considered to be included within openness and is associated with openness over other personality traits (DeYoung et al. 2012). 5-HT3 antagonists also are shown to increase exploratory behavior in animals (Sawyer et al. 2012), exploratory behavior being linked to openness (DeYoung 2013). One study found that a polymorphism in the 5-HT3 receptor gene was associated with reduced novelty seeking, and increased intolerance of uncertainty (Melke et al. 2003), in opposition to openness which is associated with increased novelty seeking and reduced uncertainty intolerance (Cappana et al. 2012)(Jong et al. 2006). Overall, the existing evidence suggests the 5-HT3 receptor may influence openness, however more research is needed to verify this.
Testosterone
Testosterone is hypothesized to be related to an “analytical/tough-minded” temperament (Fisher et al. 2015), as well as being linked to higher spatial cognitive abilities, but lower imagination and cognitive empathy (Crespi 2015). The analytical/tough-minded temperament scale correlates highly with openness (Fisher et al. 2015), however measured testosterone levels do not correlate with openness to experience (Sundin et al. 2021). A possible explanation for this is that testosterone increases the intellect aspect of openness, but decreases the openness (aesthetics/imagination) aspect of openness. In support of this hypothesis, men and women do not differ in overall openness to experience on average, however men score higher on intellect, and women score higher on openness (Weisberg et al. 2011). Testosterone correlates with higher visual-spatial abilities (Crespi 2015), which are specifically linked to the intellect aspect of openness (Nusbaum & Silvia 2011). Testosterone is linked to autism and autistic traits, and autism is linked to reduced imagination and creativity, but increased spatial abilities (Crespi 2015), with autism being negatively related to the openness aspect of openness to experience (Del Giudice 2018). To my knowledge, no study has investigated the influence of testosterone specifically on intellect and openness, however the current evidence suggests that testosterone may be associated with higher intellect and lower openness.
Oxytocin
Oxytocin is mainly discussed in relation to agreeableness, however there is some evidence that oxytocin may be positively related to openness, specifically the openness/aesthetics aspect of openness rather than the intellect aspect, and may possibly have a negative relationship with intellect. Plasma oxytocin concentration has been found to predict novelty seeking, a trait associated with openness (De Dreu et al. 2014). The same authors also found oxytocin to be genetically associated with creative ideation, and intranasally administered oxytocin increases holistic processing, divergent thinking, and creative performance, all of which are associated with openness, and also decreases analytical reasoning, a trait associated with the intellect aspect of openness (De Dreu et al. 2014). Oxytocin is also associated with lower scores on the imagination scale (measuring reduced imagination - lower score = better imagination) of the autism quotient (De Dreu et al. 2015), imagination being closely linked to openness, and autism being negatively related to openness (Del Giudice 2018). Oxytocin is also associated with positive schizotypy (Crespi & Summers 2014), which is related to the openness aspect of openness to experience (DeYoung et al. 2012). Oxytocin enhances cognitive empathy (Crespi 2015), which is consistently associated with openness phenotypically and genetically (Warrier et al. 2018)(Melchers et al. 2016)(Koivisto et al. 2021). The prosocial/empathetic scale of the Fisher Temperament Inventory which intends to measure oxytocin also correlates positively with openness (Fisher et al. 2015). One study which investigated the relationships between plasma oxytocin and personality found a weak, insignificant positive correlation with openness (r=0.12) (De Dreu et al. 2015), the insignificance possibly contradicting this hypothesis, however the weak relationship may be due to oxytocin increasing the openness aspect but decreasing intellect, which has yet to be investigated. Overall, the evidence supports the hypothesis that oxytocin is positively related to openness but negatively related to intellect.
Cannabinoids
There is virtually no research on the relationship between the endogenous cannabinoid system and personality or cognitive abilities relevant to openness, however there is some evidence suggesting that cannabinoid activity may be positively related to openness, and possibly low intellect. Cannabis and its main active component, THC, are often used and reported to enhance creativity (Wheal & Kotler 2017)(Uebersax 2021). Kowal et al. (2015) found that low doses of THC insignificantly increase divergent thinking compared to placebo, though high doses impaired divergent thinking, possibly due to the cognitive impairing effects of cannabis. Heng et al. (2022) found that cannabis increased self-rated creativity, but did not increase evaluated creative performance. Cannabis produces other effects resembling openness as well as schizotypy which is linked with openness (DeYoung et al. 2012), which include reflection and introspection, increased appreciation of art and aesthetics, spiritual experiences, perceptual distortions, increased awareness of and intensity of emotionality, and enhancement of imagination (Uebersax 2021), all which are associated with openness (DeYoung et al. 2012). Cannabinoids enhance activity of 5-HT2A receptors, and agonists of 5-HT2A receptors increase openness (Nour et al. 2017)(Erritzoe et al. 2019) - studies on 5-HT2A receptor function and genetics have not found evidence of an association with openness however (Ni et al. 2006)(Kusumi et al. 2002)(Moresco et al. 2002). Hyperfunction and hypofunction of endogenous cannabinoids is associated with psychosis and autism respectively (Crespi 2019), psychosis and autism also being associated with high and low openness respectively (Del Giudice 2018)(DeYoung et al. 2012)(Rogers et al. 2023)(Cloudfindings 2023a). Given that cannabinoids are known to impair aspects of cognitive function, it seems likely that cannabinoid function would be associated with higher openness and lower intellect.
Acetylcholine
Acetylcholine is a neurotransmitter mainly studied in relation to cognition as an enhancer of cognitive abilities, with acetylcholine function being inversely associated with cognitive deficits and diseases such as dementia (e.g., Jia et al. 2004). Given that intelligence is part of openness (DeYoung et al. 2012), this suggests that acetylcholine, as well as other cognitive enhancing neurochemicals are associated with openness. There is some evidence that genetic variations in some acetylcholine receptors are associated with openness (Grazioplene et al. 2013). Enhancing acetylcholine function in rats is shown to increase exploratory behavior (Nagy & Aubert 2013), and exploration leads to increases in acetylcholine (Giovannini et al. 2001). Increasing acetylcholine reduces cognitive rigidity and improves social cognition in a mouse model of autism (Karvat & Kimchi 2014), these aspects of autism being negatively linked with openness (Cloudfindings 2023a)(Rogers et al. 2023). Overall, there is some evidence to suggest a possible association of acetylcholine with openness, though more research is needed to reveal whether there is an association.
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