The Neuroendocrinology of Social Isolation

In the paper

“Functional magnetic resonance imaging research also indicates that loneliness is associated with greater activation of the visual cortex in response to negative social images in contrast to negative nonsocial images (Cacioppo et al. 2009)”

What the sources say

• Not checked yetcites Cacioppo et al. 2009

In the paper

“population-based longitudinal research indicates that perceived social isolation (loneliness) is a risk factor for morbidity and mortality independent of objective social isolation and health behavior.”

What the sources say

• Not checked yetcites Luo et al. 2012
• Not checked yetcites Luo & Waite 2014
• Not checked yetcites Hawkley et al. 2009

In the paper

“whether measured in a hospital laboratory (Cacioppo et al. 2002b) or over the course of a normal day using ambulatory procedures (Hawkley et al. 2003), loneliness is associated with elevated tonic vascular resistance—a marker of threat surveillance (Mendes et al. 2002).”

What the sources say

• Not checked yetcites Cacioppo et al. 2002b
• Not checked yetcites Hawkley et al. 2003
• Not checked yetcites Mendes et al. 2002

In the paper

“growing evidence indicates that loneliness increases attention to negative social stimuli (e.g., social threats, rejection, exclusion).”

What the sources say

• Not checked yetcites Cacioppo & Hawkley 2009
• Not checked yetcites Jones et al. 1981
• Not checked yetcites Cacioppo et al. 2006

In the paper

“Accordingly, the association between indices of perceived and objective social isolation is mediated by the perceived quality of social relationships”

In the paper

“The effects of loneliness on attention to potential social threats appear to be largely implicit.”

In the paper

“Human and animal investigations of neuroendocrine stress mechanisms that may be involved suggest that (a) chronic social isolation increases the activation of the hypothalamic pituitary adrenocortical axis”

In the paper

“Social isolation has been recognized as a major risk factor for morbidity and mortality in humans for more than a quarter of a century.”

• Also stated in: § INTRODUCTION · plain

  “Chronic social isolation has long been recognized as a risk factor for broad-based morbidity and mortality.”

What the sources say

• Not checked yetcites House et al. 1988

In the paper

“these effects are more dependent on the disruption of a social bond between a significant pair than objective isolation per se.”

In the paper

“These behavioral results suggest a more general principle, specifically, that perceived social isolation activates neural, neuroendocrine, and behavioral responses that promote short-term self-preservation.”

In the paper

“Stroop interference is used to gauge the implicit processing of stimuli, so these results suggest that loneliness is associated with a heightened accessibility of negative social information.”

In the paper

“In a modified emotional Stroop task, lonely participants relative to nonlonely participants show greater Stroop interference for negative social compared to negative nonsocial words (see review by Cacioppo & Hawkley 2009).”

What the sources say

• Not checked yetcites Cacioppo & Hawkley 2009

In the paper

“cross-sectional and longitudinal research showing that loneliness predicts more fragmented sleep (Cacioppo et al. 2002a, Kurina et al. 2011).”

What the sources say

• Not checked yetcites Cacioppo et al. 2002a
• Not checked yetcites Kurina et al. 2011

In the paper

“Specifically, the hippocampus, through inhibitory projections to the paraventricular nucleus in the hypothalamus, contributes to the maintenance of cortisol concentrations within bounds by inhibiting the secretion of CRH from the hypothalamus as well as the production of ACTH in the pituitary gland (Chrousos 2009, Hawkley et al. 2012, Hostinar et al. 2014).”

What the sources say

• Not checked yetcites Chrousos 2009
• Not checked yetcites Hawkley et al. 2012
• Not checked yetcites Hostinar et al. 2014

In the paper

“Yamada & Decety (2009) investigated the effects of subliminal priming on the detection of painful facial expressions and found that lonely individuals are more sensitive to the presence of pain in dislikable faces than are nonlonely individuals.”

What the sources say

• Not checked yetcites Yamada & Decety 2009

In the paper

“Interestingly, the percent of time spent alone was not associated with salivary cortisol levels.”

What the sources say

• Not checked yetcites Cacioppo et al. 2000

In the paper

“These longitudinal results were replicated in a study of high school students (Doane & Adam 2010)”

What the sources say

• Not checked yetcites Doane & Adam 2010

In the paper

“Subsequent work has confirmed that the association between loneliness and overall salivary cortisol levels is generally positive but small (Edwards et al. 2010, Hawkley et al. 2006, Steptoe et al. 2004).”

What the sources say

• Not checked yetcites Edwards et al. 2010
• Not checked yetcites Hawkley et al. 2006
• Not checked yetcites Steptoe et al. 2004

In the paper

“However, the HPA axis in adults remains responsive to metabolic needs, physiological inputs, and psychogenic stressors including social-evaluative threats (Dickerson & Kemeny 2004)”

What the sources say

• Not checked yetcites Dickerson & Kemeny 2004

In the paper

“Importantly, the prefrontal cortex has extensive neuroanatomical and functional connectivity with the limbic system, which in turn permits the modulation of HPA activity by the resulting environmental appraisals, including appraisals of the quality of companionship and mutual assistance available in the social environment—a strong determinant of perceived social isolation (Hawkley et al. 2008).”

What the sources say

• Not checked yetcites Hawkley et al. 2008

In the paper

“both the amygdala and the BNST project to hypothalamic and brain stem areas that mediate autonomic, neuroendocrine, and behavioral responses to aversive or threatening stimuli (Walker & Davis 2008).”

What the sources say

• Not checked yetcites Walker & Davis 2008

In the paper

“whereas the cortisol awakening response did not predict the subsequent levels of loneliness”

What the sources say

• Not checked yetcites Adam et al. 2006

In the paper

“Results averaged across the three days replicated those of Steptoe et al. (2004), showing that loneliness was related to larger cortisol awakening responses.”

What the sources say

• Not checked yetcites Adam et al. 2006
• Not checked yetcites Steptoe et al. 2004

In the paper

“Mechanistic studies have shown that the effects of social threat on glucocorticoid resistance are mediated in part by sympathetically induced alterations in immune cell production (hematopoiesis) (Hanke et al. 2012, Powell et al. 2013).”

What the sources say

• Not checked yetcites Hanke et al. 2012
• Not checked yetcites Powell et al. 2013

In the paper

“Cole (2008) found that loneliness was associated with smaller neutrophil:lymphocyte and neutrophil:monocyte ratios, consistent with leukocyte glucocorticoid resistance.”

What the sources say

• Not checked yetcites Cole 2008

In the paper

“loneliness predicted the size of the cortisol awakening response the following day independent of other variables such as demographic factors, nervousness, or perceived stress”

What the sources say

• Not checked yetcites Adam et al. 2006

In the paper

“In an early set of studies of medical students, loneliness was found to be associated with poorer cellular immune competence, as indexed by significantly higher Epstein-Barr virus antibody titers (Glaser et al. 1985) and natural killer cell activity (Kiecolt-Glaser et al. 1984a).”

What the sources say

• Not checked yetcites Glaser et al. 1985
• Not checked yetcites Kiecolt-Glaser et al. 1984a

In the paper

“alterations of the activity of the adult HPA axis are associated with numerous deleterious psychological and physical health outcomes (Chrousos 2009, Fries et al. 2009, Gunnar & Vazquez 2001)”

What the sources say

• Not checked yetcites Chrousos 2009
• Not checked yetcites Fries et al. 2009
• Not checked yetcites Gunnar & Vazquez 2001

In the paper

“A reduction in glucocorticoid receptor signaling has a permissive effect on NF-κB activation (Almawi & Melemedjian 2002)”

What the sources say

• Not checked yetcites Almawi & Melemedjian 2002

In the paper

“The extant human research suggests that perceived social isolation (loneliness) and social threats are associated most consistently with activity of the HPA axis (cf. Dickerson et al. 2011, Hawkley et al. 2012).”

What the sources say

• Not checked yetcites Dickerson et al. 2011
• Not checked yetcites Hawkley et al. 2012

In the paper

“Steptoe et al. (2004) reported that differences in loneliness across respondents, controlling for waking salivary cortisol value, gender, socioeconomic status, smoking, time of waking, and body mass, were associated with the cortisol awakening response, with higher levels of loneliness associated with larger cortisol increases.”

What the sources say

• Not checked yetcites Steptoe et al. 2004

In the paper

“momentary and daily assessments of loneliness were associated with momentary salivary cortisol levels”

What the sources say

• Not checked yetcites Doane & Adam 2010

In the paper

“chronic social isolation in rodents relative to control animals has been shown to increase catecholamine (Dronjak et al. 2004; cf. Dronjak & Gavrilovic 2006) and corticosterone responses to acute stressors (Dronjak et al. 2004, Ferland & Schrader 2011, Grippo et al. 2007b).”

What the sources say

• Not checked yetcites Dronjak et al. 2004
• Not checked yetcites Ferland & Schrader 2011
• Not checked yetcites Grippo et al. 2007b

In the paper

“so the impaired transcription of glucocorticoid receptor–regulated genes may also indicate an upstream activation of proinflammatory transcription factors that could contribute to the increased risk of inflammatory disease in chronically lonely individuals.”

What the sources say

• Not checked yetcites Almawi & Melemedjian 2002

In the paper

“Mechanistic animal studies therefore may provide a more direct test of the causal effects of a member of a social species being deprived of companionship and mutual assistance.”

In the paper

“the effect of social isolation on the HPA axis in animals may not be a general effect but may depend on the social structure and dynamics of the species—that is, the brain’s interpretation of the social environment.”

In the paper

“These results are consistent with the notion that it is not the objective presence of or absence of a conspecific that determines HPA activation but rather the brain’s interpretation of the presence or absence of the conspecific.”

In the paper

“The predictable outcome is a literature with somewhat inconsistent results.”

In the paper

“In the marmoset, acute and chronic isolation have been shown to increase levels of basal cortisol.”

What the sources say

• Not checked yetcites Cross et al. 2004
• Not checked yetcites Smith & French 1997
• Not checked yetcites Smith et al. 2011

In the paper

“there is evidence in the animal literature that the chronic social isolation of an adult animal from preferred partners enhances neuroendocrine responsiveness to acute stressors.”

What the sources say

• Not checked yetcites Dronjak et al. 2004
• Not checked yetcites Ferland & Schrader 2011
• Not checked yetcites Grippo et al. 2007b

In the paper

“The cumulative human and animal research suggests that perceived social isolation—that is, chronic isolation from a meaningful (e.g., pair-bonded) conspecific rather than isolation per se—is associated with increased HPA activity.”

In the paper

“This finding is in line with a large body of studies describing the separation of an animal from conspecifics as a stressor (Garrido et al. 2012; Zlatković & Filipović 2012, 2013).”

What the sources say

• Not checked yetcites Garrido et al. 2012
• Not checked yetcites Zlatković & Filipović 2012, 2013

In the paper

“Similar effects have been found in other monogamous species, such as Siberian dwarf hamsters (Castro & Matt 1997) and nonhuman primates (Mendoza & Mason 1986a,b; Smith & French 1997).”

What the sources say

• Not checked yetcites Castro & Matt 1997
• Not checked yetcites Mendoza & Mason 1986a,b
• Not checked yetcites Smith & French 1997

In the paper

“Although only suggestive, these results are consistent with the hypothesis that chronic social isolation contributes to glucocorticoid resistance and a corresponding reduction in the negative feedback that constrains HPA activation.”

In the paper

“Gavrilovic and colleagues (2010), in contrast, reported increased plasma levels of epinephrine and norepinephrine in adult male Wistar rats following 12 weeks of social isolation.”

What the sources say

• Not checked yetcites Gavrilovic et al. 2010

In the paper

“Prolonged social isolation (6–20 weeks) in adult Geoffroy marmosets prior to cohabitation with an opposite-sex partner, compared to the animals that had remained with their natal group prior to cohabitation, exhibited higher cortisol levels that remained elevated over the course of the 90-day cohabitation period (Smith et al. 2011).”

What the sources say

• Not checked yetcites Smith et al. 2011

In the paper

“Similar temporal dynamics in the effects of acute social isolation on cortisol also have been found in cows (Rushen et al. 1999) and sheep (Parrot et al. 1988)”

What the sources say

• Not checked yetcites Rushen et al. 1999
• Not checked yetcites Parrot et al. 1988

In the paper

“the causal role of social isolation is difficult to test conclusively in humans.”

In the paper

“As in the human literature, the effects of chronic social isolation on SAM activity and plasma catecholamine levels are less consistent across studies than are the effects of chronic isolation on HPA (see Table 1).”

What the sources say

• Not checked yetcites Table 1

In the paper

“Correlational research in adult baboons indicates that relative social isolation (i.e., negative deviations from median values on a composite measure of social connectedness) is associated with elevated levels of basal cortisol (Sapolsky et al. 1997)”

What the sources say

• Not checked yetcites Sapolsky et al. 1997

In the paper

“Research on acute social isolation shows it typically produces an acute neuroendocrine response.”

In the paper

“Adult marmosets exposed to a brief 15-minute period of social isolation (Cross et al. 2004) and to 11 hours of social isolation (Smith & French 1997), relative to normally housed animals, exhibited increased cortisol levels.”

What the sources say

• Not checked yetcites Cross et al. 2004
• Not checked yetcites Smith & French 1997

In the paper

“Studies examining systemic SAM catecholamine levels in parallel with localized SNS-derived catecholamines have found a surprising degree of discontinuity between the two (Lutgendorf et al. 2009, 2011)”

What the sources say

• Not checked yetcites Lutgendorf et al. 2009, 2011

In the paper

“Experimental molecular studies show that the proinflammatory gene-regulation dynamics observed in mouse paradigms involving repeated social threat derive in part from catecholamine-mediated alterations in immune cell development within the bone marrow, which generates a population of glucocorticoid-resistant monocytes that are primed for hyperinflammatory responses as they subsequently circulate”

What the sources say

• Not checked yetcites Hanke et al. 2012
• Not checked yetcites Powell et al. 2013

In the paper

“To the extent that human loneliness stems from a chronic sense of social threat and a diminished reward from social interactions (Cacioppo & Patrick 2008, Cacioppo et al. 2014), nonhuman primate models of repeated low-grade social threat may also help illuminate the neural and biological consequences of experienced isolation in humans.”

What the sources say

• Not checked yetcites Cacioppo & Patrick 2008
• Not checked yetcites Cacioppo et al. 2014

In the paper

“Moreover, the colocalization of CRHR2 and oxytocin in hypothalamic neurons and in axon terminals throughout the BNST suggests that the BNST is involved in a potential feedback loop between the hypothalamic oxytocin system and the forebrain CRH system (Dabrowska et al. 2011).”

What the sources say

• Not checked yetcites Dabrowska et al. 2011

In the paper

“Most quotidian stressors in industrialized societies are neither extreme nor life threatening.”

What the sources say

• Not checked yetcites Sapolsky 2001

In the paper

“The basal differences in vascular resistance between lonely and nonlonely participants were also apparent when participants performed postural adjustments (sitting, standing; Cacioppo et al. 2002b) and during rest whether in the laboratory or during the course of a normal day (Hawkley et al. 2003).”

What the sources say

• Not checked yetcites Cacioppo et al. 2002b
• Not checked yetcites Hawkley et al. 2003

In the paper

“the SAM neuroendocrine component of sympathetic activation (which does not seem to be consistently associated with loneliness or glucocorticoid resistance and other proinflammatory dynamics)”

What the sources say

• Not checked yetcites Lutgendorf et al. 2009, 2011
• Not checked yetcites Sloan et al. 2007, 2008

In the paper

“Moreover, longitudinal studies in humans and experimental studies in animals indicate that perceived isolation has a causal effect on the HPA axis.”

In the paper

“In small rodent models, repeated social threat from an aggressive conspecific may also model important aspects of the chronic sense of social threat and hostility seen in lonely humans.”

In the paper

“Their results indicated a reciprocal neuroanatomical relationship between CRH-containing neurons in the BNST and oxytocin-containing neurons in the hypothalamus.”

What the sources say

• Not checked yetcites Dabrowska et al. 2011

In the paper

“The most appropriate animal model for investigating the mechanisms underlying perceived isolation and mortality may depend not only on the nature of the relationship between conspecifics but also on the specific mechanism under scrutiny.”

In the paper

“Both the amygdala and the BNST are involved in HPA adjustments in conditions that permit anticipatory or preparatory responses to a potentially threatening situation.”

What the sources say

• Not checked yetcites Walker & Davis 2008

In the paper

“That is, there was no difference between these groups in stress reactivity.”

In the paper

“social buffering has not been a particularly robust finding in human studies of the effects of perceived social isolation on autonomic and neuroendocrine activity in adults.”

In the paper

“The difference in the effects of chronic social isolation on stress reactivity in the human and animal literatures, therefore, may be attributable to the use of relatively mild acute stressors in human studies.”

In the paper

“Rather than the social buffering of stressors, several studies suggest that perceived social isolation may diminish the generally salubrious effects of interacting with others.”

In the paper

“The BNST, through projections to the brain stem and paraventricular nucleus of the hypothalamus, produces neuroendocrine and autonomic responses that appear as changes in relatively tonic activity.”

What the sources say

• Not checked yetcites Walker & Davis 2008

In the paper

“The extant evidence indicates that the perception of social isolation (i.e., loneliness) is also a risk factor for broad-based morbidity (both physical and psychological) and mortality.”

In the paper

“social processes appear to be much more strongly related to the latter (as are immunobiological alterations in animal models; Sloan et al. 2007).”

What the sources say

• Not checked yetcites Sloan et al. 2007

In the paper

“The correspondence of the behavioral, neurobiological, and genomic effects of repeated social threat in animals and those of human loneliness”

In the paper

“The experimental research in adult animals further demonstrates that social isolation can have a causal effect on neuroendocrine functioning.”

In the paper

“Mechanistic animal studies provide a means to evaluate the effects of social isolation on the HPA axis, autonomic functioning, and SAM axis.”

In the paper

“(b) the effects of chronic social isolation appear to be more dependent on the disruption of a social bond between a significant social pair (e.g., as indexed by behavioral measures of partner preference in animals or rated quality of relationships in humans) than isolation from others per se.”

In the paper

“However, the causal role of loneliness on neural and neuroendocrine mechanisms is difficult to test conclusively in humans.”

In the paper

“Experimental animal models of repeated social threat (but not chronic social isolation) have been found to generate immunobiological dynamics that resemble those observed in lonely human beings”