Personality traits, immune function, and health are related: Inflammatory processes may be the mechanistic driver in these relationships; personality traits predict both in vivo and in vitro measures of inflammation

Exploring the links between personality and immune function. Summer Mengelkoch, Jeff Gassen, Emily K. Corrigan, Sarah E. Hill. Personality and Individual Differences, Volume 184, January 2022, 111179. https://doi.org/10.1016/j.paid.2021.111179

Highlights

• Personality traits, immune function, and health are related.

• Inflammatory processes may be the mechanistic driver in these relationships.

• Genetic polymorphisms known to impact cytokine release predict personality traits.

• Personality traits predict both in vivo and in vitro measures of inflammation.

• Relationships between personality and inflammation are sex and cytokine specific.

Abstract: Decades of research finds associations between personality traits and health. In recent years, it has become clear that the activities of the immune system play a key role in linking these variables. In the current work, we add to this research by exploring the relationship between Big Five personality traits and (Study 1) polymorphisms known to impact cytokine release and (Study 2) immunological parameters measured in vivo (differential white blood cell counts, plasma proinflammatory cytokine levels) and in vitro (proinflammatory cytokine release by peripheral blood mononuclear cells, S. aureus growth in plasma). Results provide insights into potential mechanistic drivers of the links between personality and immune function and the possibility that, in some cases, relationships between personality and immune function may be sex differentiated.

Keywords: PersonalityCytokinesInflammationExtraversionNeuroticismOpenness to experienceAgreeablenessConscientiousness

4. General discussion

Results of the current research provide continued support for links between personality traits and immune function (e.g., Allen & Laborde, 2017; Armon et al., 2013; D'Acquisto, 2017; Lopes, 2017; Segerstrom, 2000), some of which differed by sex. For example, results of Study 1 revealed that high TNF-α producers were more extraverted than low-producers and that men who were high IL-6 producers were less extraverted than low-producers, suggesting that the links between health-relevant variables and personality may be sex-, context-, and cytokine-dependent. Study 1 also revealed that high IL-10 producers were more open to experience than low-producers. This is consistent with animal research that finds IL-10 may have anxiolytic properties (Martinez et al., 2018; Mesquita et al., 2008; Munshi et al., 2019; Nava et al., 1997).

One particularly striking result from Study 1 was the regularity with which intermediate IFN-γ producers were found to differ from high- and low-producers across personality traits. Intermediate-producers, overall, reported being less agreeable, more neurotic, and, compared low-producers only, less conscientiousness and less extraverted. While we did not predict these results a priori, it is possible that this relationship could have emerged in response to these individuals' heightened risk for infectious disease. Researchers find that intermediate IFN-γ producers have an increased risk of certain infectious diseases relative to high- or low-producers (e.g., leishmaniasis: Kalani et al., 2019; tuberculosis: Amim et al., 2008). Accordingly, although the participants in the current study are unlikely to have come into contact with these infectious agents, it is possible that genetic predisposition to disease risk influences the development of personality traits (e.g., Bilbo & Schwarz, 2009). Additionally, separate research suggests that women with metabolic syndrome who are intermediate-producers of IFN-γ exhibit altered tryptophan metabolism compared to high- or low-producers (Szkup et al., 2019), which may influence personality traits. Although these interpretations are speculative, they raise interesting possibilities for future research.

Study 2 revealed additional associations between personality and immune measures. For example, higher extraversion was related to greater LPS-induced proinflammatory cytokine release by PBMCs in vitro, while higher conscientiousness was associated with lower levels of plasma IL-6, a result that is consistent with the results of previous research (e.g., Sutin et al., 2010). While similar results were found for the effect of conscientiousness on the remaining measures of inflammation, these effects were sex-differentiated with higher conscientiousness predicting lower levels of plasma TNF-α and diminished proinflammatory cytokine release by PBMCs in men and women, respectively. Results also revealed that higher levels of extraversion were associated with lower numbers of eosinophils and basophils (the latter in women only), potentially suggesting a skew towards Th1 over Th2 immunity in individuals high on this trait (Sokol et al., 2009; Spencer & Weller, 2010). This possibility is further supported by the finding that men high in extraversion had higher counts of monocytes than did men low in extraversion. Th1 immunity is primarily involved in the body's response to intracellular pathogens, like viruses, while Th2-biased responses are typically observed during macroparasite infection, such as with helminths, and also play a role in allergies (Romagnani, 2000). Interestingly, due to growing population density and urbanization, most modern human populations are exposed to much higher numbers of viruses than parasitic worms (Amoroso & Nunn, 2021). Accordingly, the heightened sociality associated with high extraversion likely increases one's exposure to viruses, specifically, which may lead to a Th1 skew.

Additionally, high levels of extraversion, and for women, high levels of agreeableness, were found to predict increased S. aureus growth in plasma in vitro. Additional research is needed to determine the exact differences in plasma composition that contribute to differences in rates of S. aureus growth (e.g., minerals: Cross et al., 2015, complement proteins: Walport, 2001); however, previous research has found lower S. aureus growth in the plasma of individuals whose PBMCs exhibit greater proliferation in response to antigen stimulation (Gassen, Leyva, et al., 2019), suggesting that this measure is related to well-characterized immunological parameters.

The current research finds certain personality traits are more consistently related to aspects of immune function than others. Across studies, conscientiousness and extraversion appear to be reliably related to levels of inflammation (although the directions of these relationships sometimes differ, e.g., Allen & Laborde, 2017; Armon et al., 2013; Sutin et al., 2010), while agreeableness is not. For example, the current research finds conscientiousness to be negatively related to plasma IL-6 levels, a pattern which is also reliably observed in others' work (e.g., Chapman et al., 2011; Luchetti et al., 2014; Sutin et al., 2010). Repeated replication of this result suggests that these two variables are likely interconnected in a meaningful way. For example, one possibility is that those with low IL-6 levels tend to utilize behavioral strategies, such as avoiding individuals who may be sick, visiting the doctor regularly for check-ups, washing hands often, etc., to compensate for their low levels of inflammation by avoiding pathogens in their environments. In this way, aspects of conscientiousness may develop as a strategy for managing infectious disease risk in a state of low inflammation or lack of immunological preparedness. Alternatively, it is also possible that the relationship between inflammation and conscientiousness primarily operates in the other direction. That is, individuals high in conscientiousness (compared to those lower in conscientiousness) may be more careful with their health and avoid circumstances that elicit inflammatory responses, such as eating unhealthy food or engaging in unsafe sexual practices. Future research is needed to test these, as well as other, hypotheses about the causal links between these variables.

The consistent relationships observed between inflammation and extraversion, both in the current work and in the work of others, further underscore that individual differences in human tendencies for behavior may be shaped by one's immunological vulnerabilities. For example, over human history, levels of extraversion would have been reliably linked to exposure to infectious diseases. That is, because humans are vectors for transmissible disease, increased sociality would have increased one's likelihood of coming in to contact with pathogens; however, elevated inflammation could be protective, rather than reactive, in this context, preventing an individual from becoming ill after encountering pathogens. Based on the results of Study 1, in which extraversion was associated with being a high-producer of TNF-α, our results suggest that differences in extraversion may be borne out of different immunological profiles, rather than the differences in levels of inflammation being exclusively the result of greater contact with others. Future research should explore this possibility, along with the threshold of inflammatory levels extraverted individuals must experience before exhibiting social withdrawal, one facet of inflammation-induced sickness behavior (Dantzer, 2001; Dantzer & Kelley, 2007), in response to elevated inflammation. While the levels of elevated inflammation explored in the current work are likely lower than what would be necessary to induce intense sickness behavior, it is possible that those high in extraversion require a larger release of proinflammatory cytokines before exhibiting social avoidance in response to inflammation compared to those lower in extraversion, given the potential for generally elevated inflammation and heightened stimulated proinflammatory cytokine release to buffer those high in extraversion from the somatic costs of elevated sociality. Identifying these thresholds would yield novel insights into the dynamic relationship between cytokines and the motivation to socially engage and withdraw.

The current work makes an important contribution to the literature by taking a step towards disentangling the directionality relationships between personality and immune function (Study 1), examining relationships between personality and novel measures of immunological functioning (Study 2), and examining sex differences in these effects (Studies 1 & 2). While Study 1 was cross-sectional, preventing us from drawing strong conclusions regarding causal directions, it is far more likely that one's genotype would predict their personality than vice versa. Relationships observed between cytokine genotypes and personality therefore provide initial support for the idea that immunological variables may impact aspects of personality in addition to personality having an impact on immune function, specifically in the case of extraversion. Further, Study 2 assessed the relationship between personality measures and novel measures of immunological functioning, including bacterial growth in plasma and stimulated proinflammatory cytokine release in PBMCs, both of which measure immune responses in the face of an immunological challenge. A better understanding of how personality relates to immunological responses to overt challenges will be informative for understanding how personality relates to immune function in the context of disease. Finally, this work also stands out from existing studies examining links between personality and immune function by reporting sex differences in these relationships. Much of the extant personality and health literature has not investigated sex differences, which may be important to consider as men and women consistently exhibit differences in immune function (e.g., Fish, 2008; Klein et al., 2015) and personality (e.g., Schmitt et al., 2008). This study was the first – to our knowledge – to investigate sex differences in relationships between personality traits and a comprehensive set of immune measures (e.g., bacterial growth in plasma, stimulated cytokine release, WBC composition, etc.).

The current studies do, however, have limitations to consider. First, the sample of participants in Study 2 was relatively homogenous and small, limiting the generalization of these results to all populations. Additionally, the measure used to assess personality was brief, and while validated in previous research (Gosling et al., 2003), the TIPI is not the most comprehensive measure of personality available. In light of these limitations, further research should include larger, more diverse samples of participants and administer a more comprehensive personality questionnaire, while also including a wide variety of immune measures capturing facets of immunity not assayed in the current research (e.g., adaptive immunity). A larger sample size would also allow for greater power to test for interactions between personality traits, sex, and immune function.

Furthermore, despite the hypothesized bi-directional nature of relationships between personality and health, in Study 1, we utilized genomic measures, and as such, investigated the impact of TNF-α, IL-10, IL-6, and IFN-γ genotypes on personality traits. In Study 2, we limited our analyses to the impact of personality on immune function to preserve power and limit the number of analyses ran. While this allowed us to test for relationships in both directions, we are nevertheless limited in the causal claims that can be made about the relationships found. Future longitudinal or experimental studies are warranted to provide a stronger test of directionality in relationships between personality and immunity.

Despite limitations, the current studies provide important data bearing on relationships between personality and immune function. The present results lend support for the growing body of theory and research suggesting covariation between psychological traits, like personality, and immunity. This research lays the foundation for future work that may provide groundbreaking insights into complex relationships between health, immune function, and behavior.