Social Safety Theory: A Biologically Based Evolutionary Perspective on Life Stress, Health, and Behavior

“One perspective, described by Holmes & Rahe (1967), argues that stressors can be ranked by the degree of change or upheaval that they typically cause, with greater change or upheaval in turn requiring greater adaptation.”

“…reviewed data from 148 studies and 308,849 participants who were followed for an average of 7.5 years, for example, being socially well integrated was associated with a 91% increase in odds of survival [odds ratio (OR) = 1.91; 95% confidence interval (CI) [1.63, 2.23]] (Holt-Lunstad et al. 2010).”

“…loneliness (OR = 1.26; 95% CI [1.04, 1.53]), 29% for social isolation (OR = 1.29; 95% CI [1.06, 1.56]), and 32% for living alone (OR = 1.32; 95% CI [1.14, 1.53]) in adjusted models that control for relevant demographic and clinical risk factors (Holt-Lunstad et al. 2015, Stringhini et al. 2017).”

“Otherwise, the response can heighten a person’s risk for viral infections and numerous inflammation-related conditions including anxiety, depression, asthma, heart disease, stroke, and cancer, as well as several metabolic, autoimmune, and neurodegenerative disorders (Furman et al. 2019).”

“First, it motivates individuals to foster social safety by developing and maintaining social bonds with people who are friendly, helpful, predictable, dependable, sincere, and trustworthy (Fiske et al. 2007).”

“First, for example, past adversity can cause epigenetic modification of the glucocorticoid receptor gene in the neural transcriptome, especially in the hypothalamus and amygdala, thereby degrading HPA axis regulation of the inflammatory response (McGowan et al. 2009).”

“…impact on stress research, as most articles published over the past century subsequently conceptualized life stress as a single, unitary construct, with little attention paid to how different stressors might have varying consequences for health (Hammen 2005, Monroe 2008, Slavich et al. 2010a).”

“The primary goal of the immune system, in turn, is to keep the body biologically safe and protected from these foreign invaders and from physical injuries that could cause illness or death if left unaddressed (Slavich & Irwin 2014).”

“…factors NF-κB, ATF2–c-Jun, interferon-regulatory factor 3, and interferon-regulatory factor 7, which induce antiviral immune response genes, particularly type I interferon genes, leading to the production of the inflammatory cytokines interferon-β and interferon-α (Kawai & Akira 2006).”

“Then, during the twentieth century, Walter Cannon (1929) discussed for the first time how emotions have specific physiologic consequences that help the body maintain homeostasis during different social-environmental situations.”

“5related risk of death that was three times greater than that of the overall population (Di et al. 2017).”

“…perceived social threat can also reduce www.annualreviews.org • Social Safety Theory 277 Human social genomics: the study of how social processes affect the human genome, which in turn shapes health and behavior prosocial behaviors, including helping, donating, and cooperating (Twenge et al. 2007).”

“NSSI may thus represent a behavioral trigger that induces neuroinflammation, which exacerbates a person’s perceptions of social conflict, criticism, or exclusion, in turn leading to heightened emotional distress and an even greater propensity to engage in NSSI (e.g., NSSI → inflammation → social threat → NSSI).”

“Social safety is also related to practicing better health behaviors, which in turn predicts numerous behavioral and health-related outcomes including longevity (Umberson et al. 2010).”

“…severing of relational ties often strongest for social integration and belonging but also extend to other indicators of social safety including socioeconomic status and subjective social status, which are strong predictors of all-cause mortality (see Adler & Rehkopf 2008, Muscatell et al. 2018).”

“…conditions, obesity shifts this immunologic stance toward a type 1 or T helper 1 state in which proinflammatory (i.e., M1-polarized) macrophages accumulate and secrete large amounts of different cytokines, including IL-1β and TNF-α, under conditions of psychological stress (Reilly & Saltiel 2017).”

“Sleep disturbance (e.g., difficulty falling or staying asleep, nonrestorative sleep, early-morning awakening) is a strong predictor of both inflammation-related disease risk and all-cause mortality (Irwin 2019).”

“These regions in turn project to the brainstem nuclei, hypothalamus, and forebrain,which integrate visceral sensory information and coordinate autonomic and behavioral responses (Pavlov & Tracey 2012).”

“A second perspective, advanced by Maier & Seligman (2016) and Weiss & Simson (1985), focuses on the extent to which stressors are controllable or escapable.”

“…inhibiting the proinflammatory function of NF-κB, increasing the expression of the inhibitor of NF-κB (IκB), and antagonizing proinflammatory gene transcription via protein–protein interactions between the glucocorticoid receptor and NF-κB in the nucleus of immune cells (Irwin & Cole 2011).”

“The neural mentalizing network and neuropeptide oxytocin played particularly important roles in generating prosocial behavior, as they enabled humans to experience compassionate feelings and empathy toward others (Carter 2014, Kennedy & Adolphs 2012).”

“As bad as these dynamics are for social safety, countervailing effects are also present, driven by improvements in public health and hygiene, living standards, vaccine availability, and likelihood of exposure to inflammation-promoting pathogens (Finch & Crimmins 2004).”

“Over the course of history, humans were exposed to a plethora of healthy microbes from other people, animals, feces, and soil, which helped educate the immune system and strengthen its regulatory capacity (Rook 2013).”

“The neural mentalizing network and neuropeptide oxytocin played particularly important roles in generating prosocial behavior, as they enabled humans to experience compassionate feelings and empathy toward others (Carter 2014, Kennedy & Adolphs 2012).”

“Indeed, cytokine receptors are present on virtually all neural cell types, and recent animal model work has shown that they play a critical mechanistic role in linking neuronal connectivity, immunity, and social behavior (Filiano et al. 2016).”

“…myocardial infarction (Mookadam & Arthur 2004), amputation (Hawkins et al. 2016), acquired brain injury ( Jones et al. 2011), substance dependence treatment (Haslam et al. 2019),HIV/AIDS (van Luenen et al. 2018), stroke (Haslam et al. 2008), and heart disease and cancer (Valtorta et al. 2016).”

“It outputs to several organs including the heart, liver, gastrointestinal tract, intestine, and (possibly) the spleen, where it downregulates the production of the inflammatory cytokines IL-1β, IL-18, and TNF-α via alpha7 nicotinic receptors that inhibit NF-κB activity (Thayer & Sternberg 2010).”

“Once they receive word of a threat, they leave their barracks and enter the “boulevards” (i.e., the bloodstream) and migrate to the “battlefield” (i.e., the site of tissue damage or infection), which could be anywhere in the body (Dhabhar et al. 2012).”

“…bacteria to cross the epithelial barrier and activate a mucosal immune response that changes the microbiome, upregulates HPA axis and inflammatory activity, and heightens experiences of social threat (e.g., social threat → gut permeability → inflammation → social threat) (Dinan & Cryan 2012).”

“Finally, the mirror neuron system enables individuals to simulate others’ behavior to better understand their goals, emotions, and actions and includes the dorsal and ventral premotor cortex, inferior frontal gyrus, and inferior and superior parietal lobule (Rizzolatti & Sinigaglia 2016).”

“Several reviews have also explained how threats to social standing can affect health (Dickerson 2008, Kemeny 2009) and why social rejection and exclusion may be particularly potent in this regard (Allen & Badcock 2003, Williams 2007).”

“From this viewpoint, getting fired would be a severe stressor if (for example) a person worked for a company for a long time, had several coworkers as confidants, or had few other financial resources or job prospects (Brown & Harris 1978).”

“In a notable example of this, Gostic et al. (2016) analyzed epidemiologic data from six countries over nearly 100 years and showed that an abrupt worldwide change in human infections of avian influenza A/H5N1 and A/H7N9 around birth year 1968 could be attributed solely to the widespread use of a…”

“Ultimately, these abilities led to a strong preference for others who are friendly, emotionally warm, and socially safe (Hare 2017).”

“…differences in the availability of healthy foods during pregnancy (which is generally better during spring and summer months) and to differences in infants’ likelihood of exposure to inflammation-promoting pathogens (which is generally worse in autumn and winter months) (Doblhammer & Vaupel 2001).”

“The relevance of social safety for human health and behavior is thus difficult to overestimate (KiecoltGlaser & Wilson 2017, Pietromonaco & Collins 2017).”

“…activity by priming heightened inflammatory reactivity, stimulating immune cell trafficking, and promoting glucocorticoid insensitivity/resistance (Sorrells et al. 2009). www.annualreviews.org • Social Safety Theory 271 Social signal transduction: process by which neurocognitive representations…”

“…impact on stress research, as most articles published over the past century subsequently conceptualized life stress as a single, unitary construct, with little attention paid to how different stressors might have varying consequences for health (Hammen 2005, Monroe 2008, Slavich et al. 2010a).”

“…enable what we have previously referred to as social signal transduction—namely, the transmission of signals from the external social environment into the internal biological environment that shapes human health and behavior (Slavich & Cole 2013, Slavich & Irwin 2014, Slavich & Sacher 2019).”

“Adipocytes can also produce leptin, which can have proinflammatory effects by upregulating the secretion of TNF-α, IL-6, and IL-12 via IRS-1, PI3K/Akt, STAT-3, and NF-κB signaling (Iikuni et al. 2008).”

“…impact on stress research, as most articles published over the past century subsequently conceptualized life stress as a single, unitary construct, with little attention paid to how different stressors might have varying consequences for health (Hammen 2005, Monroe 2008, Slavich et al. 2010a).”

“…subsequent meta-analysis examined data from 41 studies and 73,037 participants and found that being socially well integrated was associated with lower levels of the inflammatory markers TNF-α, IL-6, C-reactive protein (CRP), and fibrinogen (Zr = −0.076; 95% CI [−0.11, −0.04]) (Uchino et al. 2018).”

“Such beneficial effects are evident in a diverse array of clinical contexts as well and are often independent of other risk factors affecting health (Vogt et al. 1992).”

“…effective interventions for producing social safety–related benefits will likely be those that target modifiable social cognitions and behaviors that increase perceptions of social safety and reduce perceptions of social threat (Black & Slavich 2016, O’Donovan et al. 2013, Slavich et al. 2010b).”

“…for example, cytokines can affect threat and pain sensitivity, exploratory and pleasure-seeking behavior, ingestive behavior, sleep, learning, attention, memory, impulsivity, temporal focus, emotion regulation, executive function, and cognitive control (Larson & Dunn 2001, Shields et al. 2017).”

“…severing of relational ties often strongest for social integration and belonging but also extend to other indicators of social safety including socioeconomic status and subjective social status, which are strong predictors of all-cause mortality (see Adler & Rehkopf 2008, Muscatell et al. 2018).”

“278 Slavich In another study, Cole et al. (2010) examined a functionally active regulatory SNP in the human IL6 promoter (-174G>C, rs1800795) that is known to affect inflammatory dynamics.”

“This process refines the functional capacity and regulation of each individual’s immune system and provides humans with a highly evolved biological defense network that is critical for survival (Rook et al. 2017).”

“Emerging from this large body of research is substantial evidence that exposure to life stress and adversity can negatively affect human functioning, disease risk, and longevity (Lupien et al. 2009, Shields & Slavich 2017).”

“For example, individuals with greater social safety exhibit better outcomes in the context of acute myocardial infarction (Mookadam & Arthur 2004), amputation (Hawkins et al. 2016), acquired brain injury ( Jones et al. 2011), substance dependence treatment (Haslam et al. 2019),HIV/AIDS (van Luenen…”

“It outputs to several organs including the heart, liver, gastrointestinal tract, intestine, and (possibly) the spleen, where it downregulates the production of the inflammatory cytokines IL-1β, IL-18, and TNF-α via alpha7 nicotinic receptors that inhibit NF-κB activity (Thayer & Sternberg 2010).”

“NSSI may thus represent a behavioral trigger that induces neuroinflammation, which exacerbates a person’s perceptions of social conflict, criticism, or exclusion, in turn leading to heightened emotional distress and an even greater propensity to engage in NSSI (e.g., NSSI → inflammation → social threat → NSSI).”

“In one study of 168 women with histologically confirmed epithelial ovarian cancer, for example, having a socially safe relationship characterized by a stable sense of emotional security was associated with a 34% lower hazard of death during the 7-year study period (Lutgendorf et al. 2012).”

“Consistent with Social Safety Theory, these so-called targeted rejection stressors hasten onset of depression (Slavich et al. 2009), promote suicidal ideation (Massing-Schaffer et al. 2019), upregulate molecular signaling pathways that increase inflammatory activity (Murphy et al. 2013), and…”

“It is well known that NSSI is more common in people who have experienced major threats to social safety, such as emotional, physical, or sexual abuse, thus making social threat a key risk factor for NSSI (Nock 2009, Stewart et al. 2019).”

“Second, adversity can lead to epigenetic reprogramming of innate immune cells (Crişan et al. 2016) and alter the hematopoietic output of these cells from the bone marrow (Hanke et al. 2012), skewing them toward amore proinflammatory state.”

“Several reviews have also explained how threats to social standing can affect health (Dickerson 2008, Kemeny 2009) and why social rejection and exclusion may be particularly potent in this regard (Allen & Badcock 2003, Williams 2007).”

“…myocardial infarction (Mookadam & Arthur 2004), amputation (Hawkins et al. 2016), acquired brain injury ( Jones et al. 2011), substance dependence treatment (Haslam et al. 2019),HIV/AIDS (van Luenen et al. 2018), stroke (Haslam et al. 2008), and heart disease and cancer (Valtorta et al. 2016).”

“…of the leukocyte basal transcriptome that is structured by the social signal transduction pathways described previously (i.e., NF-кB, AP-1, CREB, and the glucocorticoid receptor) (Thames et al. 2019), and accelerates biological aging as indexed by telomere length (Guarneri-White et al. 2018).”

“…for example, cytokines can affect threat and pain sensitivity, exploratory and pleasure-seeking behavior, ingestive behavior, sleep, learning, attention, memory, impulsivity, temporal focus, emotion regulation, executive function, and cognitive control (Larson & Dunn 2001, Shields et al. 2017).”

“…interactions that promote physiologic recursion and cause persistently heightened sensitivity to social adversity Adaptive Versus Maladaptive Responsivity The question of whether these responses are helpful versus harmful ultimately comes down to the issue of timing and regulation (Slavich 2015).”

“Second, adversity can lead to epigenetic reprogramming of innate immune cells (Crişan et al. 2016) and alter the hematopoietic output of these cells from the bone marrow (Hanke et al. 2012), skewing them toward amore proinflammatory state.”

“…are most deleterious and no consensus regarding the socialpsychological characteristics that make particular stressors stressful (Cohen et al. 2019, Epel et al. nology (Slavich 2019), some theorists have gone so far as to argue that the term stress should be abandoned altogether (see Kagan 2016).”

“…of depression (Slavich et al. 2009), promote suicidal ideation (Massing-Schaffer et al. 2019), upregulate molecular signaling pathways that increase inflammatory activity (Murphy et al. 2013), and downregulate molecular signaling pathways that reduce inflammatory activity (Murphy et al. 2015).”

“…social threat characterized by verbal attacks, social exclusion, devaluation, and aggression heightens inflammatory reactivity to social stress (Giletta et al. 2018), promotes an increased proinflammatory/reduced antiviral skewing of the leukocyte basal transcriptome that is structured by the…”

“…secreted more IL-6 in response to an inflammatory challenge (i.e., concanavalin A) in vitro, and PBMC secretion of the anti-inflammatory cytokine IL-10 was suppressed by two different inflammatory challenges (i.e., LPS and concanavalin A), but only for urban participants (Böbel et al. 2018).”

“Experiencing social threat in childhood therefore predicted greater inflammation in adulthood, but only for individuals born into a relatively hygienic microbial environment (McDade et al. 2013).”

“…life event was moderated by a functional single nucleotide polymorphism (SNP) in the μ-opioid receptor gene (OPRM1, rs1799971) that causes an amino acid change (N40D) that governs central OPRM1 expression, leading to differences in social and physical pain sensitivity (Slavich et al. 2014).”

“Several reviews have also explained how threats to social standing can affect health (Dickerson 2008, Kemeny 2009) and why social rejection and exclusion may be particularly potent in this regard (Allen & Badcock 2003, Williams 2007).”

“Although sleep disturbance is relatively common in general, with up to 48% of adults reporting at least some sleep complaints, it is especially prevalent among persons exposed to stressors that threaten social safety, such as interpersonal violence and aggression (Gallegos et al. 2019).”

“When these innate immune system defenses are insufficient for addressing a particular threat, the body engages the evolutionarily younger, 450-million-year-old adaptive immune system (Travis 2009).”

“…with Social Safety Theory, these so-called targeted rejection stressors hasten onset of depression (Slavich et al. 2009), promote suicidal ideation (Massing-Schaffer et al. 2019), upregulate molecular signaling pathways that increase inflammatory activity (Murphy et al. 2013), and downregulate…”

“Promoter-based bioinformatics analyses in turn indicated that these gene expression changes were structured by increased NF-κB activity (Chiang et al. 2019).”

“…of depression (Slavich et al. 2009), promote suicidal ideation (Massing-Schaffer et al. 2019), upregulate molecular signaling pathways that increase inflammatory activity (Murphy et al. 2013), and downregulate molecular signaling pathways that reduce inflammatory activity (Murphy et al. 2015).”

“…individuals with greater social safety exhibit better outcomes in the context of acute myocardial infarction (Mookadam & Arthur 2004), amputation (Hawkins et al. 2016), acquired brain injury ( Jones et al. 2011), substance dependence treatment (Haslam et al. 2019),HIV/AIDS (van Luenen et al.…”

“Moreover, these effects were specific to early-life stressors involving interpersonal conflict and did not extend to non-social-safety-related forms of stress (Reid et al. 2019).”

“…myocardial infarction (Mookadam & Arthur 2004), amputation (Hawkins et al. 2016), acquired brain injury ( Jones et al. 2011), substance dependence treatment (Haslam et al. 2019),HIV/AIDS (van Luenen et al. 2018), stroke (Haslam et al. 2008), and heart disease and cancer (Valtorta et al. 2016).”

“Life stress has been a notoriously messy construct with little agreement about what actually matters (Cohen et al. 2019, Malat et al. 2017, Monroe & Slavich 2020).”

“…of the leukocyte basal transcriptome that is structured by the social signal transduction pathways described previously (i.e., NF-кB, AP-1, CREB, and the glucocorticoid receptor) (Thames et al. 2019), and accelerates biological aging as indexed by telomere length (Guarneri-White et al. 2018).”

“In conclusion, a sense of belonging is a core part of what makes us human (Baumeister & Leary, 1995; Deci & Ryan, 2000; Slavich, 2020; Vaillant, 2012).”

“This possibility is also supported by contemporary models that articulate how stress affects psychological and biological systems associated with anxiety and depression (e.g., Slavich, 2020).”