Elsevier

Psychoneuroendocrinology

Volume 100, February 2019, Pages 120-126
Psychoneuroendocrinology

Falling in love is associated with immune system gene regulation

https://doi.org/10.1016/j.psyneuen.2018.09.043Get rights and content

Highlights

  • Falling in love is associated with up-regulation of Type I interferon response genes.

  • Falling in love is associated with a reciprocal down-regulation of α-defensin-related transcripts.

  • These changes are independent of changes in physical illness or sexual contact.

  • Changes are consistent with selective up-regulation of innate immune responses to viral infections.

  • Changes also consistent with dendritic cell facilitation of sexual reproduction.

Abstract

Although falling in love is one of the most important and psychologically potent events in human life, the somatic implications of new romantic love remain poorly understood. Psychological, immunological, and reproductive perspectives offer competing predictions of the specific transcriptional regulatory shifts that might accompany the experience of falling in love. To characterize the impact of romantic love on human genome 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.

Introduction

Falling in love is one of the most psychologically potent experiences in human life (Aron et al., 2005; Hatfield, 1987; Jankowiak and Fischer, 1992; Leckman and Mayes, 1999). New romantic love is accompanied not only by psychological changes, but physiological changes as well (e.g., Marazziti and Canale, 2004; Schneiderman et al., 2011; Ulmer-Yaniv et al., 2016). However, the somatic impact of falling in love remains poorly understood. Here, we investigate the impact of new romantic love on immune-related gene regulation.

Several studies have begun to map the multiple neurobiological implications of new romantic love. Research investigating the endocrinological correlates of love suggest that circulating oxytocin is higher in people in new romantic relationships compared to other groups (such as new parents and single individuals; Schneiderman et al., 2012; Ulmer-Yaniv et al., 2016). Work investigating circulating levels of neurotrophins has found elevated plasma levels of Nerve Growth Factor in participants who had recently fallen in love relative to single participants or participants in long term relationships (no differences between groups in other neurotrophin levels were detected; Emanuele et al., 2006). Follow-up samples revealed that those new-love participants who remained in the same relationship had NGF levels at (12–24 month follow-up) that were indistinguishable from other groups. Marazziti and Canale (2004) found elevated levels of cortisol in both men and women who had recently fallen in love, and reduced testosterone and follicle-stimulating hormone in men, but increased testosterone in women (these differences were eliminated at 12–24 month follow-up). Other work has found that new romantic love is associated with lower densities of specific serotonin transporter binding sites—densities that were equivalent to those found in individuals suffering from obsessive-compulsive disorder (Marazziti et al., 1999).

Another growing body of work has begun to illuminate the distinct neural and central nervous system (CNS) alterations associated with new romantic love. Some work suggests that new romantic love is associated with lowered autonomic reactivity to emotions (Schneiderman et al., 2011). The early stage of new romantic relationships has been associated with greater neural activity in both the left posterior cingulate cortex and caudate regions relative to later stages of these relationships (e.g., Aron et al., 2005; Bartels and Zeki, 2000, 2004; Kim et al., 2009). This pattern of neural activity parallels in some respects the pattern associated with new maternal love (Bartels and Zeki, 2004), and these brain areas are also associated with high concentrations of reward-based neuromodulators (e.g., oxytocin, vasopressin, and dopamine; see Zeki, 2007). Animal models also attest to the role of oxytocin, alterations in CNS processes, and accompanying changes in HPA axis activity in pair-ponding (for reviews see de Boer et al., 2012; Carter, 1998).

While each of the above studies provides evidence for specific neurobiological changes associated with new romantic love, the broader somatic impact of falling in love remains poorly understood. The development of mating bonds has complex consequences for human physiology, and at least three different perspectives offer competing theories of what the somatic implications of falling in love might be. Theories focusing on the psychological experience of deep interpersonal connection, for example, might predict a reduction in stress-related physiological processes associated with social isolation (Cacioppo and Hawkley, 2009), such as activation of the hypothalamic-pituitary-adrenal (HPA)-axis and sympathetic nervous system (SNS; Cacioppo et al., 2015), or expression of the leukocyte conserved transcriptional response to adversity (CTRA) by CD16- “classical” monocytes (Cole et al., 2015). In contrast, an immunologic life history perspective derived from evolutionary biology (McDade, 2003) might predict an alternative regulatory shift toward generalized immune activation as the body adapts to a new microbial symbiosis, which would be characterized by up-regulating both inflammatory and antiviral gene modules in granulocytes and dendritic cells (DCs; Amit et al., 2009). Finally, a third perspective from reproductive life history theory (Abrams and Miller, 2011; Lorenz et al., 2015) implies a distinct set of gene regulatory responses that prepare the body for sexual reproduction (e.g., by down-regulating systemic inflammation and up-regulating natural killer cells and DCs to facilitate pregnancy; Lorenz et al., 2015; Mor et al., 2011; Plaks et al., 2008). Although psychological, immunologic, and reproductive perspectives imply distinct patterns of biological adaptation to new love, little is known about which pattern prevails; to date, no studies have comprehensively examined the gene regulatory impact of new romantic love.

To characterize the impact of romantic love on human genome function, we conducted a two-year longitudinal study of young women in new romantic relationships. We performed genome-wide transcriptome profiling of 115 circulating immune cell samples collected from 47 young women at three different relationship stages (which varied within individuals over time): not in love (but in a new romantic relationship), newly in love, and out-of-love. Analyses involved both unbiased characterization of the empirical transcriptome alterations associated with falling in love and targeted tests of specific competing hypotheses derived from psychological, immunological, and reproductive life history theories. Analyses focused in particular on gene-regulatory dynamics occurring in myeloid lineage immune cells (monocytes, granulocytes, and DCs), which have previously been found to show distinct profiles of transcriptional regulation in response to microbial exposures (i.e., immunologic activation, pro-inflammatory gene expression, and activation of Type I interferon-related antiviral genes; Amit et al., 2009), deep social connection (i.e., reductions in the CTRA profile of up-regulated inflammation and down-regulated Type I interferon activity; Cole et al., 2015), and pregnancy (i.e., down-regulated inflammation and granulocyte function and up-regulated monocyte and DC function; Mor et al., 2011).

Section snippets

Participants and procedures

Participants were 47 young women (mean age = 20.5 yrs) who were attending a U.S. university (sample characteristics in Table 1). At study enrollment, all participants had recently begun a new (<1 month) exclusive romantic relationship and reported having not yet fallen in love with their partners (by answering “no” to the question, “Would you consider yourself to have fallen in love with your partner?” during prescreening via either telephone or email). Additional eligibility criteria assessed

Results

Preliminary analyses of intraindividual psychological change revealed that falling in love was associated with a nonsignificant decrease in self-reported stress (mean = 2.4 ± 0.16 SE in love vs. 2.6 ± 0.14 SE at baseline, p =  .21). Falling in love was similarly associated with a nonsignificant decrease in self-reported depressive symptoms (0.20 ± 0.036 SE in love vs. 0.25 ± 0.058 SE at baseline, p =  .29).

Discussion

These analyses mapped the human transcriptomic response to falling in love and identified a small but biologically coherent alteration in immune cell gene regulation characterized by up-regulation of Type I interferon response genes associated with CD1C+/BDCA-1+ DCs and CLEC4C+/BDCA-2+ DCs, and a reciprocal down-regulation of α-defensin-related transcripts associated with neutrophil granulocytes. These shifts in myeloid cell gene regulation occurred above and beyond the effects of changes in

Ethics statement

This research was approved by the UCLA Biomedical Institutional Review Board for research on human subjects (Approval #13-001122). Informed consent was obtained for all participants during each clinic visit.

Data

Data can be accessed at Gene Expression Omnibus as series GSE102689.

Funding

This research was supported by grants from the UCLA Norman Cousins Center for Psychoneuroimmunology (awarded to MH and SC) and NIHR01-AG043404, R01-AG033590, P30-AG017265, P30-CA016042, and P30-AI028697 (awarded to SC).

Conflict of interest

None.

References (37)

  • A. Ulmer-Yaniv et al.

    Affiliation, reward, and immune biomarkers coalesce to support social synchrony during periods of bond formation in humans

    Brain Behav. Immun.

    (2016)
  • S. Zeki

    The neurobiology of love

    FEBS Lett.

    (2007)
  • E.T. Abrams et al.

    The roles of the immune system in women’s reproduction: evolutionary constraints and life history trade-offs

    Am. J. Phys. Anthropol.

    (2011)
  • I. Amit

    Unbiased reconstruction of a mammalian transcriptional network mediating pathogen responses

    Science

    (2009)
  • A. Aron et al.

    Reward, motivation, and emotion systems associated with early-stage intense romantic love

    J. Neurophysiol.

    (2005)
  • A. Bartels et al.

    The neural basis of romantic love

    Neuroreport

    (2000)
  • J.T. Cacioppo et al.

    The neuroendocrinology of social isolation

    Annu. Rev. Psychol.

    (2015)
  • C.S. Carter

    Neuroendocrine perspectives on social attachment and love

    Psychoneuroendocrinology

    (1998)
  • Cited by (12)

    • The immunomodulatory effects of social isolation in mice are linked to temperature control

      2022, Brain, Behavior, and Immunity
      Citation Excerpt :

      These include classical challenges coming from pathogens, organ disfunction caused by tissue and cell damage, and any other changes that can occur ‘outside’ the physical body. These are both positive and negative conditions like fear (Segerstrom et al., 1999; Young et al., 2018), anger (Farnam et al., 2016; Pesce et al., 2013; Suinn, 2001), stress (Aubert, 2008; D'Acquisto, 2016; D'Acquisto, 2017; Solomon et al., 1974), a state of eudaemonia (Boyle et al., 2019; Cole et al., 2015; Fredrickson et al., 2015), falling in love (Murray et al., 2019) or general relaxation (Esch et al., 2003; Jasnoski and Kugler, 1987; Peavey et al., 1985; Winchell and Watts, 1988; Zachariae et al., 1994). Unlike the classical challenges described above, these external conditions modulate the immune response in ways that are far from being fully established.

    • Sex Bias and Autoimmune Diseases

      2022, Journal of Investigative Dermatology
      Citation Excerpt :

      Because males do not experience this selective pressure, it results in sex-specific differences in immunity (Natri et al., 2019). Preparation for an immunosuppressive fetus may begin even before pregnancy; a study utilizing genome-wide transcriptome profiling to follow the shifts in gene regulation of 47 women as they reported feeling new love for a romantic partner found an upregulation of genes involved in IFN-1 signaling and DC markers even when controlling for self-reported illness and sexual contact (Murray et al., 2019). The pattern of DC marker upregulation in particular is consistent with theories that postulate that psychological love regulates DC function to facilitate sexual reproduction (Murray et al., 2019).

    • Emotions relating to romantic love—further disruptors of adolescent sleep

      2020, Sleep Health
      Citation Excerpt :

      This is an especially important aspect in relation to mental well-being, as our study replicates previous findings5, which have suggested that romantic love may be associated with higher risks of experiencing anxiety and depressive symptoms in adolescents. A recent study also reported associations between romantic love and elective alteration in immune cell gene regulation, suggesting vital changes in somatic health and psychological well-being34. Future studies are needed to investigate what is sleep’s role in this finding.

    View all citing articles on Scopus
    View full text