Psychological well-being and gene expression in Korean adults: The role of age

Highlights

• Higher eudaimonia links to reduced inflammatory gene expression, CTRA.

• Psychological well-being (PWB) is associated with reduced CTRA in Korean adults.

• Among subscales of PWB, autonomy showed the strongest inverse correlation with CTRA.

• The inverse association between PWB and CTRA is stronger for older participants.

Abstract

Background

Happiness has traditionally been thought to comprise two parts - pleasure (hedonia) and meaning (eudaimonia). Even though the two types of happiness are correlated, genomics studies have found distinct transcriptional correlates of hedonia and eudaimonia, particularly in the Conserved Transcriptional Response to Adversity (CTRA) marked by up-regulation of proinflammatory genes and down-regulation of interferon-related genes. Eudaimonia has been associated with reduced CTRA gene expression in several studies, whereas hedonia shows no consistent association with the CTRA. However, most of these social genomics studies have been conducted in Western cultures with Caucasian samples, so it is unclear if these findings extended to non-Western cultures with other ethnic groups. Moreover, it is unknown whether age might modify the association between CTRA gene expression and eudaimonia. To this end, we examined in a sample of Koreans the relationship between CTRA profiles and measures of hedonia and eudaimonia, as well as the role of age in modulating the strength of those relationships.

Methods

Blood samples were collected from 152 healthy Korean adults (mean age = 44.64; 50 % female). Well-being was measured using the Mental Health Continuum short form (MHC-SF), Ryff Scales of Psychological Well-being (PWB), and subjective well-being (SWB) scales. RNA transcriptome profiles were obtained by RNA sequencing. Mixed effect linear model analyses examined the association between CTRA gene expression and measures of MHC-SF, SWB, PWB (total scores and six subscales) and additional analyses examined a possible moderating role of age.

Results

CTRA gene expression was significantly downregulated in association with the MHC-SF eudaimonic scores as well as the PWB total scores. Among the six domains of PWB, autonomy showed the strongest inverse correlation with CTRA profiles. Moreover, the inverse association between CTRA and PWB was stronger for older participants.

Conclusion

Eudaimonia is associated with reduced CTRA gene expression in a Korean population, with particularly marked relationships for autonomy. Findings also suggest that aging with meaning may bring biological advantage in later life.

Introduction

Adverse environmental circumstances can trigger biological responses throughout the body, including changes in gene expression. One example of this is a gene regulatory response that occurs in white blood cells (leukocytes), known as the Conserved Transcriptional Response to Adversity (CTRA) (Cole, 2019). The CTRA is characterized by increased expression of genes involved in inflammation and decreased expression of genes involved in Type I interferon-mediated antiviral responses (Cole, 2013, 2014, 2018; Slavich and Cole, 2013). This pattern has been observed across different adverse social conditions such as loneliness, chronic stress, and post-traumatic stress disorder (Cole, 2010; Kohrt et al., 2016). The CTRA response results in part from a signaling pathway where the sympathetic nervous system activates gene regulatory transcription factors via beta-adrenergic receptors (Cole, 2014). This ‘social signal transduction’ pathway is hypothesized to be activated in the central nervous system in adverse environments such as poverty, trauma, and social instability, resulting in down-stream impacts on gene expression that may have been adaptive under ancestral conditions but now likely promote disease pathogenesis when activated by chronic stress (Cole, 2014).

Recent research has begun to explore various protective or resilience factors that might buffer the CTRA response. For example, a series of studies have linked pro-social behavior to reduced CTRA expression (Nelson-Coffey et al., 2017; Seeman, Merkin, Goldwater, & Cole, 2019); these finding revealed significant reductions in CTRA gene expression in people who performed kind acts for others over a 5-week period or participated in a 9-month pro-social intergenerational helping program. Furthermore, well-being practices such as mindfulness meditation, mind-body therapies such as Tai Chi, and stress management are also associated with reduced expression of inflammatory genes (Black et al., 2013; Boyle et al., 2019; Creswell et al., 2012, Irwin et al., 2014).

Recent studies also linked eudaimonic well-being to lower CTRA, whereas these studies have not found any reduction in CTRA related to hedonic well-being (Cole et al., 2015; Fredrickson et al., 2013, 2015). The two types of well-being are highly related but distinct in that hedonic well-being refers to the sum of an individuals’ pleasure and comfort over pain whereas eudaimonic well-being involves striving toward meaning and developing the best in oneself (Diener et al., 1999; Huta and Ryan, 2010; Ryff, 2014). This diverging pattern of CTRA associations for eudaimonic and hedonic well-being suggests that experiencing meaning and purpose in life may have different molecular correlates than experiencing pleasure, or feeling good. This CTRA down-regulation in association with eudaimonic well-being has been replicated in several American samples including older adults participating in the US Health and Retirement Study, young adult video gamers, middle aged breast cancer survivors, and older adults serving as mentors for disadvantaged students (Boyle et al., 2019; Cole et al., 2015; Fredrickson et al., 2013, 2015; Seeman et al., 2019; Snodgrass et al., 2019) as well as among male workers at a Japanese information technology firm (Kitayama et al., 2016). The finding that eudaimonic, not hedonic, well-being exclusively showed an inverse correlation with CTRA is important not only for social genomics research but also well-being research more broadly because it opened a new opportunity to answer a long-standing question regarding the distinctive aspects of hedonic vs eudaimonic well-being.

In spite of the replicated findings linking eudaimonic (but not hedonic) well-being to reduced CTRA gene expression, some have questioned the specific measure of eudaimonic well-being used in several of these studies - the Mental Health Continuum-Short Form (MHC-SF) (Keyes, 2002) – and in particular the combination of its social well-being and psychological well-being subscales into a single measure of eudaimonic well-being (Brown et al., 2014). In response to the criticism, one previous study did use an alternative measure of eudaimonic well-being, the Ryff Scales of Psychological Well-being (PWB) (Fredrickson et al., 2015). However, that study could not examine divergent effects of hedonic and eudaimonic well-being due to the absence of a hedonic well-being measure. Second, the evidence linking reductions in CTRA to eudaimonic well-being is almost exclusively derived from studies of Western, educated, industrialized populations (cf. Kitayama et al., 2016). Hence, the differential impact of hedonic versus eudaimonic well-being on CTRA found in previous studies warrants more replication, preferably with more diverse samples to validate its cultural generality. Finally, the association between eudaimonic well-being and CTRA has not been examined at different age groups. Previous research suggests that people tend to seek meaning in life when mortality is salient (Simon et al., 1998) suggesting that eudaimonic well-being may become more important among older adults. Moreover, growing evidence suggests that maintaining high level of eudaimonic well-being is beneficial among older adults, possibly by reducing age-related health risks (Kim et al., 2014; Ryff et al., 2016). Yet, little effort has been made to explore the moderating role of age on the strength of association between the eudaimonic well-being and health-related outcomes.

The present study was conducted to address the issues noted above by 1) using multiple well-being measures including the MHC-SF and two most commonly used measures of hedonic and eudaimonic well-being, the Subjective Well-being (SWB) Scale and Ryff Scales of Psychological Well-being (PWB), respectively; 2) examining a Korean population; and 3) exploring whether age might moderate the association of eudaimonic well-being with CTRA gene expression.