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Falling in Love Is Associated with Immune System Gene Regulation T ⁎ ⁎⁎ Damian R

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Falling in Love Is Associated with Immune System Gene Regulation T ⁎ ⁎⁎ Damian R Psychoneuroendocrinology 100 (2019) 120–126 Contents lists available at ScienceDirect Psychoneuroendocrinology journal homepage: www.elsevier.com/locate/psyneuen Falling in love is associated with immune system gene regulation T ⁎ ⁎⁎ Damian R. Murraya, , Martie G. Haseltonb,c, , Melissa Falesb, Steven W. Coled,e a Department of Psychology, Tulane University, New Orleans, LA 70118, United States b Department of Psychology, University of California, Los Angeles, Los Angeles, CA 90095, United States c Department of Communication Studies, University of California, Los Angeles, Los Angeles, CA 90095, United States d Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, CA 90095, United States e Norman Cousins Center, University of California, Los Angeles School of Medicine, Los Angeles, CA 90095, United States ARTICLE INFO ABSTRACT Keywords: Although falling in love is one of the most important and psychologically potent events in human life, the Romantic love somatic implications of new romantic love remain poorly understood. Psychological, immunological, and re- Social genomics productive perspectives offer competing predictions of the specific transcriptional regulatory shifts thatmight Immune system regulation accompany the experience of falling in love. To characterize the impact of romantic love on human genome Health function, we conducted genome-wide transcriptome profiling of 115 circulating immune cell samples collected from 47 young women over the course of a 2-year longitudinal study. Analyses revealed a selective alteration in immune cell gene regulation characterized by up-regulation of Type I interferon response genes associated with CD1C+/BDCA-1+ dendritic cells (DCs) and CLEC4C+/BDCA-2+ DCs, and a reciprocal down-regulation of α- defensin-related transcripts associated with neutrophil granulocytes. These effects emerged above and beyond the effects of changes in illness, perceived social isolation, and sexual contact. These findings are consistent with a selective up-regulation of innate immune responses to viral infections (e.g., Type I interferons and DC) and with DC facilitation of sexual reproduction, and provide insight into the immunoregulatory correlates of one of the keystone experiences in human life. 1. Introduction differences between groups in other neurotrophin levels were detected; Emanuele et al., 2006). Follow-up samples revealed that those new-love Falling in love is one of the most psychologically potent experiences participants who remained in the same relationship had NGF levels at in human life (Aron et al., 2005; Hatfield, 1987; Jankowiak and Fischer, (12–24 month follow-up) that were indistinguishable from other 1992; Leckman and Mayes, 1999). New romantic love is accompanied groups. Marazziti and Canale (2004) found elevated levels of cortisol in not only by psychological changes, but physiological changes as well both men and women who had recently fallen in love, and reduced (e.g., Marazziti and Canale, 2004; Schneiderman et al., 2011; Ulmer- testosterone and follicle-stimulating hormone in men, but increased Yaniv et al., 2016). However, the somatic impact of falling in love re- testosterone in women (these differences were eliminated at 12–24 mains poorly understood. Here, we investigate the impact of new ro- month follow-up). Other work has found that new romantic love is mantic love on immune-related gene regulation. associated with lower densities of specific serotonin transporter binding Several studies have begun to map the multiple neurobiological sites—densities that were equivalent to those found in individuals implications of new romantic love. Research investigating the en- suffering from obsessive-compulsive disorder (Marazziti et al., 1999). docrinological correlates of love suggest that circulating oxytocin is Another growing body of work has begun to illuminate the distinct higher in people in new romantic relationships compared to other neural and central nervous system (CNS) alterations associated with groups (such as new parents and single individuals; Schneiderman new romantic love. Some work suggests that new romantic love is as- et al., 2012; Ulmer-Yaniv et al., 2016). Work investigating circulating sociated with lowered autonomic reactivity to emotions (Schneiderman levels of neurotrophins has found elevated plasma levels of Nerve et al., 2011). The early stage of new romantic relationships has been Growth Factor in participants who had recently fallen in love relative to associated with greater neural activity in both the left posterior cin- single participants or participants in long term relationships (no gulate cortex and caudate regions relative to later stages of these ⁎ Corresponding author at; Department of Psychology, Tulane University, 2007 Percival Stern Hall, New Orleans, LA, 70118 United States. ⁎⁎ Corresponding author at: Department of Communication Studies, UCLA, 2303 Rolfe Hall, Los Angeles, CA 90095 United States. E-mail addresses: [email protected] (D.R. Murray), [email protected] (M.G. Haselton). https://doi.org/10.1016/j.psyneuen.2018.09.043 Received 28 June 2018; Received in revised form 3 August 2018; Accepted 30 September 2018 0306-4530/ © 2018 Elsevier Ltd. All rights reserved. D.R. Murray et al. Psychoneuroendocrinology 100 (2019) 120–126 relationships (e.g., Aron et al., 2005; Bartels and Zeki, 2000, 2004; Kim Table 1 et al., 2009). This pattern of neural activity parallels in some respects Participant demographics and baseline characteristics. the pattern associated with new maternal love (Bartels and Zeki, 2004), Age 20.5 years (SD = 2.6) and these brain areas are also associated with high concentrations of reward-based neuromodulators (e.g., oxytocin, vasopressin, and dopa- Ethnicity 36.2% White or Caucasian, mine; see Zeki, 2007). Animal models also attest to the role of oxytocin, 25.5% Asian 17.0% multi-racial alterations in CNS processes, and accompanying changes in HPA axis 12.8% Hispanic or Latino activity in pair-ponding (for reviews see de Boer et al., 2012; Carter, 6.4% Black or African American 1998). 2.1% American Indian 2 While each of the above studies provides evidence for specific BMI 22.1 kg/m (SD = 3.6) Cigarettes smoked (previous 2 wk) 0.0 (SD = 0) neurobiological changes associated with new romantic love, the Alcoholic beverages consumed (previous 2 7.0 (SD = 9.3; maximum = 35) broader somatic impact of falling in love remains poorly understood. wk) The development of mating bonds has complex consequences for Using hormonal contraceptive 40.4% human physiology, and at least three different perspectives offer com- * peting theories of what the somatic implications of falling in love might Data represent mean (standard deviation) of continuous variables or % of total be. Theories focusing on the psychological experience of deep inter- sample for categorical variables. personal connection, for example, might predict a reduction in stress- related physiological processes associated with social isolation study enrollment, all participants had recently begun a new (< 1 (Cacioppo and Hawkley, 2009), such as activation of the hypothalamic- month) exclusive romantic relationship and reported having not yet pituitary-adrenal (HPA)-axis and sympathetic nervous system (SNS; fallen in love with their partners (by answering “no” to the question, Cacioppo et al., 2015), or expression of the leukocyte conserved tran- “Would you consider yourself to have fallen in love with your partner?” scriptional response to adversity (CTRA) by CD16- “classical” mono- during prescreening via either telephone or email). Additional elig- cytes (Cole et al., 2015). In contrast, an immunologic life history per- ibility criteria assessed during prescreening included 1) being hetero- spective derived from evolutionary biology (McDade, 2003) might sexual, 2) not being pregnant or breastfeeding, 3) being a non-smoker, predict an alternative regulatory shift toward generalized immune ac- 4) having no immune, cardiovascular, or psychiatric medication, and 5) tivation as the body adapts to a new microbial symbiosis, which would planning to remain in the city for at least 6 months. Analyses utilized a be characterized by up-regulating both inflammatory and antiviral gene repeated measures design to relate intra-individual changes in immune modules in granulocytes and dendritic cells (DCs; Amit et al., 2009). cell gene expression profiles to intra-individual changes in in-love Finally, a third perspective from reproductive life history theory status (thereby controlling for baseline individual differences). Sixty- (Abrams and Miller, 2011; Lorenz et al., 2015) implies a distinct set of one eligible women enrolled and provided an online baseline ques- gene regulatory responses that prepare the body for sexual reproduc- tionnaire and blood sample; among those, 47 (77%) provided at least tion (e.g., by down-regulating systemic inflammation and up-regulating one follow-up blood sample (and accompanying online questionnaire) natural killer cells and DCs to facilitate pregnancy; Lorenz et al., 2015; and could thus be included in within-subject repeated measures ana- Mor et al., 2011; Plaks et al., 2008). Although psychological, im- lyses of transcriptome change over time. All procedures were approved munologic, and reproductive perspectives imply distinct patterns of by the UCLA Biomedical Institutional Review Board (#13-001122). biological adaptation to new love, little is known about which pattern Participants provided
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