The Neuroendocrinology of Social Isolation

In the paper

“the brain is the key organ for forming, monitoring, maintaining, repairing, and replacing salutary connections with others”

• Also stated in: § SOCIAL ISOLATION: A SOCIAL NEUROSCIENCE PERSPECTIVE · plain

  “the brain is the key organ for forming, monitoring, maintaining, repairing, and replacing salutary connections with others as well as regulating physiological processes relevant to morbidity and mortality (Cacioppo & Berntson 1992).”

What the sources say

• Not checked yetcites Cacioppo & Berntson 1992

In the paper

“The HPA axis is sensitive to the interpretation by the brain of threats and stressors, and it influences a wide range of physiological, behavioral, and health outcomes (e.g., Charmandari et al. 2005, Hostinar et al. 2014, McEwen & Gianaros 2011, Sapolsky et al. 2000).”

What the sources say

• Not checked yetcites Charmandari et al. 2005
• Not checked yetcites Hostinar et al. 2014
• Not checked yetcites McEwen & Gianaros 2011

In the paper

“The prefrontal cortex modulates attention, working memory, conflicting inputs, and emotion regulation as well as integrates information from plans (e.g., goals) and prior knowledge, information from peripheral afferents, and information from the environment—including the social environment—to coordinate neural, hormonal, and behavioral responses (Hostinar et al. 2014, McEwen & Gianaros 2011).”

What the sources say

• Not checked yetcites Hostinar et al. 2014
• Not checked yetcites McEwen & Gianaros 2011

In the paper

“Using a similar methodology at four points in time across the day, Pressman et al. (2005) similarly found loneliness to be related to salivary cortisol levels, although this association reached statistical significance only for salivary cortisol levels measured an hour after awakening and at night.”

What the sources say

• Not checked yetcites Pressman et al. 2005

In the paper

“The amygdala appears to be especially important for rapid-onset, short-duration behaviors that occur in response to specific threats, whereas the BNST appears to mediate slower-onset, longer-lasting responses that frequently accompany sustained threats (or the surveillance for threats) and that may persist even after threat termination (Walker et al. 2003).”

What the sources say

• Not checked yetcites Walker et al. 2003

In the paper

“Subsequent investigations suggest that loneliness is typically associated with higher levels of HPA activation, although the strength of the association may vary depending on the chronicity of loneliness, the specific tissue assayed, the parameter used to gauge HPA activity, the time of day of the measurements, and the reliability (e.g., number) of the measurements.”

In the paper

“trait loneliness was associated with a flattening of the diurnal cortisol rhythm”

What the sources say

• Not checked yetcites Doane & Adam 2010

In the paper

“Genome-wide microarray analyses revealed a reduction in the expression of genes bearing glucocorticoid receptor response elements, an upregulation of proinflammatory gene transcripts”

• Also stated in: § NEUROENDOCRINE ACTIVITY AND PERCEIVED SOCIAL ISOLATION (LONELINESS) · plain

  “in middle- and older-age adults who are high in loneliness compared with those low in loneliness (Cole et al. 2007, 2011).”

What the sources say

• Not checked yetcites Cole et al. 2007
• Not checked yetcites Cole et al. 2011

In the paper

“Results indicated that loneliness was positively correlated with salivary cortisol levels, but this association reached statistical significance only for chronic loneliness.”

What the sources say

• Not checked yetcites Cacioppo et al. 2000

In the paper

“Some data also suggest an association between perceived social isolation and increased circulating levels of catecholamines, although the SAM findings are less numerous and consistent (e.g., Edwards et al. 2010, Hawkley et al. 2006) and may be attributable at least in part to differences in perceived stress rather than perceived isolation per se (Hawkley et al. 2006).”

What the sources say

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

In the paper

“Several studies now suggest that social threat in general, and loneliness in particular, is associated with glucocorticoid resistance and a complementary increase in proinflammatory gene expression that may contribute to some of the adverse health outcomes associated with perceived social isolation.”

In the paper

“Glucocorticoids (e.g., cortisol) influence a wide range of physiological functions that include glucose regulation, metabolism, inflammatory control, cardiovascular activity (e.g., endothelial function, atherosclerosis), cellular and humoral immunity, reproductive processes, and neurodegeneration and apoptosis.”

What the sources say

• Not checked yetcites Borski 2000
• Not checked yetcites Chrousos 2009
• Not checked yetcites Hawkley et al. 2012

In the paper

“most are mediated by slower-acting genomic effects, where up to 20% of the expressed genome in a tissue is susceptible to the direct and indirect influences of glucocorticoids, estrogens, and androgens (Chrousos 2009, Hawkley et al. 2012).”

What the sources say

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

In the paper

“Analyses indicated that inpatients in the high lonely group had significantly higher levels of urinary cortisol than inpatients in the low lonely group, whereas the inpatients grouped in terms of high or low levels of recent stressful life events did not differ in urinary cortisol levels.”

What the sources say

• Not checked yetcites Kiecolt-Glaser et al. 1984b

In the paper

“animal models of social disruption suggest that social factors can lead to glucocorticoid resistance in which the glucocorticoid receptor becomes less efficient in transducing endogenous glucocorticoid signals (e.g., Cole et al. 2009, Hanke et al. 2012, Pace et al. 2007, Powell et al. 2013), thereby increasing an inflammatory biology that can contribute to the development of diseases ranging from”

What the sources say

• Not checked yetcites Cole et al. 2009
• Not checked yetcites Hanke et al. 2012
• Not checked yetcites Pace et al. 2007

In the paper

“Experimentally imposed social isolation thus can have different effects in various animal models; this may be due to species- and sex-related differences in the natural social conditions of the animal populations studied and resulting differences in the contrast condition created by experimental social isolation”

In the paper

“chronic social isolation from same-sex peers in rats elevates nuclear glucocorticoid protein in prefrontal cortex (Djordjevic et al. 2010), downregulates glucocorticoid receptor expression in the prefrontal cortex (Djordjevic et al. 2010), and decreases cytosolic glucocorticoid receptors in the hippocampus (Dronjak et al. 2004).”

What the sources say

• Not checked yetcites Djordjevic et al. 2010 source
• Not checked yetcites Dronjak et al. 2004

In the paper

“Studies in monogamous prairie voles, for instance, show that a single acute (e.g., one hour) or repeated acute (e.g., one hour per day for four weeks) social isolation from a group or from a same-sex sibling increases corticosterone levels (e.g., Pournajafi-Nazarloo & Partoo 2011).”

What the sources say

• Not checked yetcites Pournajafi-Nazarloo & Partoo 2011

In the paper

“Following one hour of social isolation from their pair mates, the normally monogamous titi monkeys (for whom partner preference is high) showed a significant increase in plasma cortisol, whereas the normally polygynous squirrel monkeys (for whom partner preference is relatively low) did not (Mendoza & Mason 1986a).”

What the sources say

• Not checked yetcites Mendoza & Mason 1986a

In the paper

“In contrast, the HPA axis in the squirrel monkeys is unresponsive to isolation from polygamous partners or adult peers (Hennessy 1986, Mendoza et al. 1992), but the separation of squirrel monkey mothers from their infant produces significant increases in plasma cortisol levels in both the mother and the infant (Coe et al. 1978, Mendoza et al. 1978, Vogt & Levine 1980).”

What the sources say

• Not checked yetcites Hennessy 1986
• Not checked yetcites Mendoza et al. 1992 source
• Not checked yetcites Coe et al. 1978

In the paper

“The isolated males showed elevated plasma cortisol levels but similar levels of epinephrine and testosterone (and lower levels of norepinephrine) compared to pair-housed males.”

What the sources say

• Not checked yetcites Castro & Matt 1997

In the paper

“Studies in rats similarly suggest that chronic social isolation increases corticosterone levels when experimental animals are socially isolated from a group of same-sex rats (Djordjevic et al. 2010; Dronjak et al. 2004; Garrido et al. 2012; Zlatković & Filipović 2012, 2013), but inconsistencies have also been observed (cf. Pournajafi-Nazarloo & Partoo 2011).”

What the sources say

• Not checked yetcites Djordjevic et al. 2010 source
• Not checked yetcites Dronjak et al. 2004
• Not checked yetcites Garrido et al. 2012

In the paper

“The titi monkeys show elevated HPA activity when isolated from their monogamous partner, but they do not show HPA activation when separated from their infant (Mendoza & Mason 1986b).”

What the sources say

• Not checked yetcites Mendoza & Mason 1986b

In the paper

“As Button et al. (2013) detail, a small sample size reduces the likelihood of detecting a true effect (due to low statistical power), increases the likelihood that the effect size of a true effect is overestimated”

What the sources say

• Not checked yetcites Button et al. 2013

In the paper

“the nature of the relationship that is disrupted by isolating an animal and the duration of isolation are important influences on the neuroendocrine response to social isolation.”

In the paper

“A major advantage of using animal models is the ability to experimentally manipulate social isolation from conspecifics, controlling for other aspects of the environment (e.g., amount of space available, complexity of the environment, thermoregulation), to investigate its effects on the SAM and HPA axes.”

In the paper

“Chronic social isolation increased basal levels of ACTH and corticosterone, whereas no effect of social isolation (or social crowding) was found for basal catecholamine levels.”

What the sources say

• Not checked yetcites Dronjak et al. 2004

In the paper

“studies in monogamous prairie voles show that animals that are chronically isolated from their pair-bonded partner show increased corticosterone levels (e.g., Bosch et al. 2009, McNeal et al. 2014) and higher corticosterone levels after a resident-intruder test (Grippo et al. 2007a), whereas prairie voles that are chronically isolated from a conspecific for whom partner preference is low (e.g.,”

What the sources say

• Not checked yetcites Bosch et al. 2009
• Not checked yetcites McNeal et al. 2014
• Not checked yetcites Grippo et al. 2007a

In the paper

“A study of neuroendocrine responses to acute isolation in adult female dairy goats also documented increased norepinephrine levels but no change in epinephrine or cortisol levels (Carbonaro et al. 1992).”

What the sources say

• Not checked yetcites Carbonaro et al. 1992

In the paper

“Studies in Wistar rats provide information about the temporal dynamics of the effect of repeated acute social isolation on levels of corticosterone: Levels peak at the 5- and 15-minute intervals, then plateau through the 30-minute interval, and finally return to baseline after 90 minutes of social isolation (Ferland & Schrader 2011).”

What the sources say

• Not checked yetcites Ferland & Schrader 2011

In the paper

“There is not an animal literature on loneliness per se, but there is a large literature in which social animals are randomly assigned either to normal social living conditions or to socially isolated living conditions.”

In the paper

“a functional magnetic resonance imaging study found that perceived isolation was associated with (a) stronger activity in the visual cortex in response to unpleasant social relative to unpleasant nonsocial visual stimuli and (b) weaker activity in the ventral striatal area in response to pleasant social compared to pleasant nonsocial visual stimuli (Cacioppo et al. 2009).”

What the sources say

• Not checked yetcites Cacioppo et al. 2009

In the paper

“Once reintroduced into social settings, isolated male rodents often display a greater propensity for dominant/aggressive behavior (Blanchard et al. 2001), which has parallels in the increased negativity/hostility profile observed in lonely individuals but possibly less so in the socially withdrawn/anxious/depressed profile observed in lonely humans (Cacioppo et al. 2006).”

What the sources say

• Not checked yetcites Blanchard et al. 2001
• Not checked yetcites Cacioppo et al. 2006

In the paper

“The animal research, for instance, suggests that chronic social isolation between meaningful pairs not only elevates basal levels of glucocorticoids (see Table 1) but also tends to enhance the neuroendocrine response to an acute stressor (i.e., stress reactivity)—an effect not typically observed in the human literature.”

What the sources say

• Not checked yetcites Table 1

In the paper

“the presence of others did not differentially affect the ratings of the severity of stressors for individuals who did and did not feel socially isolated; instead, social interactions, which themselves are a potential uplift and a source of pleasure for most individuals, were experienced less positively by individuals who felt socially isolated.”

What the sources say

• Not checked yetcites Hawkley et al. 2003

In the paper

“CRH is produced not only by neurons in the medial parvocellular region of the paraventricular nucleus of the hypothalamus but also by cells in the lateral central amygdala that release CRH into the lateral BNST (Walker & Davis 2008).”

What the sources say

• Not checked yetcites Walker & Davis 2008

In the paper

“This pattern is similar to the immunologic effects observed in lonely humans (Cole et al. 2007, 2011), but it is not observed in rodents subject to objective social isolation.”

What the sources say

• Not checked yetcites Cole et al. 2007
• Not checked yetcites Cole et al. 2011

In the paper

“Several studies in rhesus macaques have shown that unstable social conditions (experimentally preventing the development of a stable social hierarchy) confer risk for greater mortality due to viral infection (Capitanio et al. 1998, Capitanio & Lerche 1998) and induce both socially anxious behavior and immunoregulatory alterations that resemble those observed in lonely humans (Sloan et al. 2007).”

What the sources say

• Not checked yetcites Capitanio et al. 1998
• Not checked yetcites Capitanio & Lerche 1998
• Not checked yetcites Sloan et al. 2007

In the paper

“Analyses revealed two main effects—higher vascular resistance in lonely than nonlonely participants and higher vascular resistance during the stressors than during the baseline—whereas the interaction did not approach significance (Cacioppo et al. 2002b).”

What the sources say

• Not checked yetcites Cacioppo et al. 2002b

In the paper

“There is now a sizable literature in humans and animals for social buffering, including an attenuation of the sympathetic and HPA response to a stressor (Cacioppo et al. 1998, Hostinar et al. 2014).”

What the sources say

• Not checked yetcites Cacioppo et al. 1998
• Not checked yetcites Hostinar et al. 2014

In the paper

“These differences raise the possibility that the BNST plays a key role in the effects of perceived social isolation from a significant conspecific on basal HPA functioning.”

In the paper

“The distinction between the effects of the amygdala versus the BNST on HPA activity may also be relevant to understanding how social isolation affects neuroendocrine activity and mortality in contemporary society.”

In the paper

“perceived social isolation has typically been associated with changes in tonic functioning such as basal differences in sympathetic vascular tonus (as gauged by vascular resistance), cortisol awakening responses, elevated evening cortisol levels, circulating glucocorticoid levels, and decreased glucocorticoid receptor sensitivity (e.g., Cacioppo et al. 2003, Hawkley et al. 2012).”

What the sources say

• Not checked yetcites Cacioppo et al. 2003
• Not checked yetcites Hawkley et al. 2012

In the paper

“These behavioral findings suggest that perceived social isolation may both increase surveillance for social threats and decrease the rewards that one derives from interpersonal relationships.”

In the paper

“In an experience sampling study, undergraduate students were just as likely to interact with other people whether or not they felt socially isolated. For those who felt isolated, the interactions were rated as being of poorer quality and as providing less support and comfort (Hawkley et al. 2003).”

What the sources say

• Not checked yetcites Hawkley et al. 2003

In the paper

“The animal model for repeated social threat activates neuroendocrine responses in both the HPA and SAM axes, and it also induces proinflammatory/glucocorticoid-resistant immune dynamics (Hanke et al. 2012, Powell et al. 2013) analogous to those observed in lonely humans (Cole 2008; Cole et al. 2007, 2011).”

What the sources say

• Not checked yetcites Hanke et al. 2012
• Not checked yetcites Powell et al. 2013
• Not checked yetcites Cole 2008

In the paper

“The HPA axis is also under the influence of oxytocin and vasopressin, and these hormones exert opposite effects on the HPA axis, with oxytocin decreasing and vasopressin increasing HPA axis activity (De Boer et al. 2012).”

What the sources say

• Not checked yetcites De Boer et al. 2012

In the paper

“In a similar study, Steptoe et al. (2004) reported the interaction to be significant, but it held only for women and only for diastolic blood pressure, not systolic blood pressure or heart rate.”

What the sources say

• Not checked yetcites Steptoe et al. 2004

In the paper

“the acute stressors used commonly in human studies are relatively mild (e.g., public speaking, serial subtraction) models of the stressors encountered in modern societies. In contrast, the acute stressors used in animal studies are relatively severe (e.g., two hours of immobilization simulating the collapse of a burrow, two hours in a 4°C chamber).”

In the paper

“The amygdala is especially important for rapid-onset, short-duration behaviors that occur in response to specific threats, whereas the BNST appears to mediate slower-onset, longer-lasting responses that frequently accompany sustained threats and that may persist even after threat termination (Walker & Davis 2008).”

What the sources say

• Not checked yetcites Walker & Davis 2008

In the paper

“social isolation of male adult rodents is generally associated with a substantial reduction in physical activity (and attending decreases in activity-related SNS activity) and a notable decrease in fighting and other overtly aggressive behavior.”

In the paper

“Experimentally imposed social instability also induces SNS innervation of the lymph node tissues in which immune cells coordinate responses to tissue injury and infection (Sloan et al. 2007, 2008) even though social instability does not appear to alter circulating SAM catecholamine levels.”

What the sources say

• Not checked yetcites Sloan et al. 2007
• Not checked yetcites Sloan et al. 2008

In the paper

“Such observations suggest that nonhuman primate models may provide an ethologically valid context for analyzing the effects of perceived social isolation and may play an important role in identifying the most appropriate small rodent models for mechanistic investigations.”

In the paper

“To date it is clear that a full understanding of the core psychological and biological features of human loneliness requires a consideration of the brain’s interpretation of the social environment.”

In the paper

“(a) chronic social isolation is associated with relatively consistent increases in HPA axis activity but little alteration in SAM catecholamine activity”