Skip to main content
. Author manuscript; available in PMC: 2016 Nov 30.
Published in final edited form as: Annu Rev Psychol. 2014 Aug 22;66:733–767. doi: 10.1146/annurev-psych-010814-015240

Table 1.

Effect of social isolation across phylogeny

References
(alphabetical
order)		 Species Age at
testing		 Social isolation
duration		 Sample size
(per gender)
of the social
isolation
group* 		Socially
isolated from		 Sample size (per
gender) of the
comparison
group(s)		 Primary
dependent
variable(s)		 Primary effect(s) of social
isolation
Voles
Bosch et al. (2009) Prairie voles (Microtus ochrogaster) 70–100 days 5 days Males Female partner or male sibling Paired with either unfamiliar female or male siblings for a total of 10 days Plasma adrenocorticotropic hormone (ACTH) and corticosterone levels + corticotropin-releasing hormone (CRH) mRNA in the medial bed nucleus of the stria terminalis (mBNST) Corticosterone levels
 Social isolation from a female partner increases basal corticosterone levels

  • Basal plasma corticosterone levels significantly differ among groups (partner type × separation condition interaction)

  • Males separated from a female partner have higher corticosterone levels than do males that remained with the female partner

  • No changes for males paired/ separated with/from a sibling

  • No significant differences for ACTH

CRH mRNA expression in the mBNST
 Pairing with a female increases CRH mRNA

  • Main effect of partner type, such that males paired with a female or isolated from a female show significantly higher CRH mRNA grain counts in the mBNST relative to males paired or isolated from a sibling
Grippo et al. (2007b) Prairie voles (Microtus ochrogaster) 60–90 days 4 weeks Experiment 1: 8 females and 8 males Same-sex sibling Experiment 1: 8 females and 8 males pair housed with a same-sex sibling Experiment 1: plasma levels of oxytocin, ACTH, and CRH and corticosterone levels + c-Fos expression in hypothalamic paraventricular nucleus (PVN) Corticosterone levels

  • No significant effect of social isolation on corticosterone levels in either sex

ACTH levels

  • No significant effect of social isolation on ACTH levels in either sex

Oxytocin levels and immunoreactivity

  • Social isolation (compared to pair housing) increases basal levels of oxytocin in females but not in males

  • In comparison to paired animals, socially isolated female (but not male) prairie voles significantly increase oxytocin immunoreactive cell density in the PVN

CRH immunoreactivity

  • No significant effect of social isolation on CRH immunoreactive cell density in the PVN for either sex
Klein et al. (1997) Meadow voles (Microtus pennsylvanicus) and prairie voles (Microtus ochrogaster) 90–120 days 28 days Experiment 2: prairie voles: 6 males, 6 females; meadow voles: 6 males, 6 females Same-sex littermates Experiment 2: pair housed with same-sex conspecific (6–10 per group), or pair housed with opposite-sex conspecific (6–7 per group), or group housed with four per cage with same-sex conspecific (12 per group) or opposite-sex conspecifics (2 males, 2 females per cage; 6–8 per group) Experiment 2: corticosterone levels Corticosterone levels

  • Prairie voles have higher serum corticosterone concentrations than do meadow voles among socially isolated animals

  • Socially isolated female prairie voles have higher serum corticosterone concentrations than do socially isolated male prairie voles

  • No other gender differences among male and female prairie voles from other groups

  • Serum corticosterone concentrations of socially isolated female meadow voles are higher than those of socially isolated male meadow voles; concentrations are also higher than in same-sex pairs, mixed-sex pairs, same-sex groups, and mixed-sex groups

  • No corticosterone differences between prairie and meadow voles housed in same-sex pairs or in mixed-sex groups
McNeal et al. (2014) Prairie voles (Microtus ochrogaster) 60–90 days 5 days Experiment 1: 9 males
Experiment 2: 10 males, 10 females		 Experiment 1: female partner
Experiment 2: partner		 Experiment 1: pair-housed controls (8 males, 8 females)
Experiment 2: pair-housed controls (10 males, 10 females)		 Experiment 1: resting cardiac parameters + autonomic nervous system
Experiment 2: plasma ACTH and corticosterone levels		 Resting cardiac parameters (experiment 1)

  • Significant heart rate increase in isolated males compared to pair-housed animals

  • Significant heart rate increase and heart rate variability decrease in isolated males compared to preisolation baseline

Autonomic nervous system

  • Social isolation results in increased sympathetic and decreased parasympathetic drive to the heart compared to paired animals

ACTH and corticosterone levels (experiment 2)

  • Social isolation results in increased ACTH and corticosterone levels in both isolated males and females compared to paired animals
Pournajafi-Nazarloo & Partoo (2011) Prairie voles (Microtus ochrogaster) 2 months 1 hour total (single social isolation), or 1 hour every day for 4 weeks (repeated social isolation), or 4 continuous weeks (chronic social isolation) Males and females; 8 per group Same-sex sibling Handling without isolation (HAN group) or pair housed with a same-sex sibling partner; 8 per group Plasma levels of corticosterone levels + CRH, type 1 CRH receptor (CRH-R1 mRNA) + type 2 CRH receptor (CRH-R2 mRNA) expression in the hypothalamus, hippocampus, and pituitary gland Corticosterone levels

  • No significant differences between HAN and paired groups on plasma corticosterone levels

  • Compared to HAN group, single or repeated social isolation is followed by an increase in plasma corticosterone levels in both females and males

  • Compared to HAN group, chronic social isolation is not followed by different plasma corticosterone levels

CRH, CRH-R1, and CRH-R2 mRNA expression in the hypothalamus

  • Single or repeated social isolation increases hypothalamic CRH mRNA expression in both females and males when compared to HAN group

  • No significant differences in hypothalamic CRH-R1 mRNA expression for single, repeated, or chronic social isolation

  • Single or repeated social isolation decreases hypothalamus CRH-R2 mRNA expression when compared to HAN group

  • Chronic social isolation shows no effect on hypothalamic CRH mRNAs in female or male animals

  • Chronic social isolation reduces hypothalamic CRH-R2 mRNA when compared to paired group

CRH, CRH-R1, and CRH-R2 mRNA expression in the hippocampus

  • Single or repeated social isolation increases hippocampal CRH mRNA expression when compared to HAN group

  • No effect of single or repeated social isolation on hippocampal CRH-R1 and CRH-R2 when compared to HAN group and paired group

  • Chronic social isolation does not modulate hippocampal CRH or CRH-R1 mRNA

  • Chronic social isolation increases hippocampal CRH-R2 mRNA expression when compared to paired group

CRH, CRH-R1, and CRH-R2 mRNA expression in the pituitary gland

  • Single or repeated social isolation, but not chronic social isolation, significantly increases CRH-R1 mRNA in the pituitary gland compared to HAN group

  • Single or repeated social isolation decreases CRH-R2 mRNA in the pituitary gland compared to HAN group

  • No effect on CRH mRNA in the pituitary gland after chronic social isolation
Stowe et al. (2005) Experiment 1: prairie voles (Microtus ochrogaster) and meadow voles 3–4 months 24 hours or 2 weeks Experiment 1: males (9 prairie, 6 meadow for the 24-hour group; 9 prairie, 6 meadow for the 2-week group) Same-sex sibling Experiment 1: a no-social-isolation group (no-isolation group; 9 prairie, 8 meadow) in which subjects were housed with a same-sex sibling and transferred to the testing room for 24 hours prior to being tested + a group of animals serving as controls for handling (control group; 8 prairie voles, 6 meadow voles) Levels of plasma corticosterone + c-Fos-labeled cells were examined in brain areas involved in anxiety and social behaviors, i.e., the medial (MeA), anterior cortical (ACo), and central (CeA) subnuclei of the amygdala (AMYG); BNST (including the anterior dorsal and anterior ventral parts); lateral septum (LS) (intermediate); paraventricular nucleus (PVN); ventromedial hypothalamus (VMH); medial preoptic area (MPOA); anterior hypothalamus (aHYP); and prefrontal cortex (PFC) Corticosterone levels

  • A 24-hour or a 2-week period of social isolation did not alter plasma corticosterone levels in either species 2 hours post-elevated plus maze (EPM) test
Experiment 3: prairie voles (Microtus ochrogaster) 3–4 months 24 hours or 2 weeks Experiment 3: males (8 for the 24-hour group, 8 for the 2-week group) Same-sex sibling Experiment 3: control animals were housed with a male cage mate (n = 8) Levels of Fos-immunoreactivity (Fos-ir) expression

  • In comparison to control animals that were housed in pairs, increased Fos-ir staining is observed in several brain regions of male prairie voles following 24 hours or 2 weeks of social isolation in the absence of the elevated plus maze test

  • Animals that experienced 24 hours of social isolation have higher basal levels of Fos-ir expression in the MPOA, VMH, and aHYP relative to controls and to those animals isolated for 2 weeks

  • In addition, animals that experienced 2 weeks of social isolation have fewer Fos-ir cells in LS compared to control animals and animals isolated for 24 hours

  • No group differences found in any other brain areas
Hamsters
Castro & Matt (1997) Siberian dwarf hamster (Phodopus sungorus) 3 months 4 weeks 15 males Female partner after 3 weeks of pair bonding 13 pairs of mate-housed animals Plasma cortisol and catecholamine levels Cortisol levels

  • Social isolation from a female partner significantly increases resting plasma cortisol levels in separated males compared to controls

Catecholamine levels

  • Mean resting plasma catecholamine levels are lower in isolated compared to paired animals, but this is significant only for norepinephrine (not for epinephrine)
Rats
Djordjevic et al. (2010) Wistar rats 3 months 21 days Males 3 other same-sex rats A group of unstressed animals (control group) + a group of rats exposed to an acute stress (i.e., 30-minute immobilization period) + a group exposed to a combined stress (i.e., a 21-day social isolation period followed by a 30-minute immobilization period). In each comparison group, rats were housed 4 per cage Corticosterone and catecholamine levels + glucocorticoid receptor (GR) and nuclear factor kappa B (NF-κB) protein and mRNA expression, neural cell adhesion molecule (NCAM) mRNA, polysialylated (PSA)-NCAM protein, protein expression of Bax and Bcl-2, and DNA defragmentation in the PFC Corticosterone levels

  • Chronic social isolation decreases corticosterone serum levels (These corticosterone serum levels then increase when the chronically socially isolated animals are subjected to acute immobilization after social isolation)

Catecholamine levels

  • No effect of social isolation on epinephrine and norepinephrine serum levels

GR expression in the PFC

  • GR gene expression in the PFC is downregulated only after social isolation

  • The nuclear GR protein is slightly elevated in socially isolated animals

NF-κB (p65) protein and mRNA expression in the PFC

  • NF-κB protein levels are increased after social isolation and decreased in the nucleus under acute and combined stress

  • NF-κB mRNA levels remain unchanged under all three types of stress

NCAM mRNA and PSA-NCAM protein in the PFC

  • No effect of social isolation on NCAM mRNA expression in the PFC

  • Levels of PSA-NCAM protein are decreased under all three types of stress

Protein expression of Bax and Bcl-2 in PFC

  • Mitochondrial Bax is significantly increased only by combined stress of social isolation and immobilization

  • Decreased Bax/Bcl2 ratio in the cytoplasm under all stresses

  • Prevalence of proapoptotic Bax protein in mitochondria under chronic social isolation and combined stress

DNA fragmentation in PFC

  • Both social isolation and social isolation + stress result in an increase in DNA fragmentation(fragments seen after DNA cleavage associated with apoptosis) in the PFC
Dronjak & Gavrilovic (2006) Wistar rats 3 months 21 days Males 3 other same-sex rats A control group of 4 animals in a cage Plasma catecholamine levels Catecholamine levels

  • No effect of social isolation on epinephrine and norepinephrine levels in adrenal glands or in heart auricle norepinephrine levels
Dronjak et al. (2004) Wistar rats Adult 21 days 6 males 5 other rats A control group of 6 animals in a cage + a group of 12 animals housed per cage (crowding group) Changes in plasma levels of ACTH, CORT, and catecholamine as well as in cytosol GR and heat shock protein 70 (Hsp70) in hippocampus Corticosterone levels

  • Chronic social isolation increases basal levels of CORT and ACTH (Immobilization also increases plasma CORT and ACTH. Exposure to cold in chronically socially isolated group and long-term crowding group increases plasma CORT and ACTH compared to the basal level. Long-term isolation of rats exposed to 2 hours of immobilization or cold increases CORT in comparison with controls.)

Catecholamine levels

  • No effect of social isolation or social crowding on epinephrine and norepinephrine levels

GR and Hsp70 concentrations in the hippocampus

  • Chronic social isolation decreases both cytosolic GR and Hsp70 concentrations in hippocampus compared to that resulting from long-term exposure to crowding (However, acute exposure to cold stress leads to the most pronounced decrease of both hippocampal GR and Hsp70 concentration in controls.)
Ferland & Schrader (2011) Wistar rats 56 days Overnight social isolation for 14 days Males Cage mate One group of paired rats assigned to overnight social crowding (social crowding group: 6 rats per cage) and one group of paired rats assigned to a nonstressed (control group) condition CORT levels at 0-, 5-, 15-, 30-, or 90-minute intervals after separation from cage mate Corticosterone levels

  • No CORT difference between isolates and controls at 0 minutes

  • Social isolation increases levels of CORT at the 5-minute interval, peaks at the 15-minute interval, and remains elevated through the 30-minute interval

  • CORT levels return to baseline after 90 minutes of social isolation
Garrido et al. (2012) Wistar rats 3 months 12 weeks Males 9–11 other male rats A group of male rats housed together (10–12 animals per cage) with two running wheels, tunnels, and different objects Corticosterone and the mRNA levels of GRs in the PFC Corticosterone levels

  • Social isolation increases corticosterone levels in the PFC in response to acute restraint stress (20 minutes) compared to control group

GR mRNA level in the PFC

  • Nonsignificant effect on GR mRNA levels in PFC
Gavrilovic et al. (2010) Wistar rats 11 weeks 12 weeks Males 3 other male rats Group-housed rats Plasma epinephrine and norepinephrine Catecholamine levels

  • Social isolation increases plasma levels of epinephrine and norepinephrine
Zlatković & Filipović (2012) Wistar rats 2–3 months 21 days Males 3 other male rats A group of unstressed rats + a group of rats submitted to an acute stressor (2 hours of immobilization or cold) + a group subjected to a combined stressor (social isolation followed by acute stressor) Serum corticosterone levels; ratio of proapoptotic to antiapoptotic proteins (e.g., Bax protein/Bcl-2) and cytosolic/ mitochondrial levels in relation to cytosolic (NO) metabolites (nitrates and nitrites) and p53 protein redistribution between cytosolic and mitochondrial compartments in the PFC and hippocampus (HIPP) Corticosterone levels

  • Chronic social isolation alone results in CORT levels similar to basal values [Acute stressors (either alone or combined with social isolation) elevate CORT levels. However, repeated acute stressors do not elevate CORT levels.]

NO metabolites in PFC and HIPP

  • Chronic social isolation (and/or acute stress) increases NO metabolites in HIPP compared to controls, whereas it remains unchanged in PFC (Combined stressors increase NO levels in both PFC and HIPP)

Mitochondrial p53 protein levels in PFC and HIPP

  • Combined stressors increase p53 levels in PFC compared to control group and to acute stressor alone

  • No effect on p53 immunoreactivity in HIPP, except for the effect of acute immobilization compared to the control group

Protein expression of Bax, Bcl-2 in PFC and HIPP

  • Chronic social isolation and combined stress increase cystolic Bcl-2 in PFC

  • Chronic social isolation and combined stress increase mitochondrial Bax and Bcl-2 in the HIPP

  • With regard to the cystolic fraction of the PFC, acute and chronic social isolation decrease cystolic Bax

  • Regarding cystolic fraction of the HIPP, main effect of acute stress alone on Bcl-2 (Acute cold stress and combined stress increase mitochondrial Bax levels. Compared to acute stress alone, combined stressors decrease mitochondrial Bcl-2.)

Bax:Bcl-2 ratio

  • The Bax:Bcl-2 ratio in the PFC is significantly increased following chronic social isolation and remains elevated after combined stressors (Acute stressors do not change the Bax:Bcl-2 ratio in either brain region. No ratio change in HIPP.)
Zlatković & Filipović (2013) Wistar rats 2–3 months 21 days 6 males 3 other male rats A group of unstressed rats (n = 6) + a group of rats submitted to an acute stressor (2 hours of immobilization or cold, n = 6 per stressor) + a group subjected to a combined stressor (social isolation followed by acute stressor, n = 6 per stressor) Serum corticosterone levels; Hsp70 concentrations; cytosolic and neuronal distributions of NF-κB as a transcriptional factor for inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS) synthesis in PFC; protein expression of cytosolic Hsp70i as a suppressor of NF-κB activation Corticosterone levels

  • Chronic social isolation alone results in CORT levels similar to control values [Acute stressors (either alone or combined with social isolation) increase CORT levels. However, repeated acute stressors do not elevate CORT levels.]

Hsp70 concentrations

  • Chronic social isolation and combined stressors decrease cytosolic Hsp70 concentrations

NF-κB activation

  • Chronic social isolation and combined stress increase NF-κB nuclear fraction of the PFC

nNOS and iNOS protein expression

  • All types of stress (chronic social isolation, combined stress, and acute stress) increase nNOS protein levels in cytosolic fractions of the PFC

  • Only chronic social isolation and combined stress increase iNOS protein levels in cytosolic fractions of PFC
Nonhuman primates
Cross et al. (2004) Marmosets (Callithrix jacchus) 5–9 years 15 minutes 4 males and 4 females A group of 20 other marmosets Relative to their preisolation cortisol levels Salivary cortisol levels Cortisol levels

  • Cortisol levels at acute social isolation onset (t = 0 minutes) and 5 minutes after social isolation onset (t = 5 minutes) are increased compared to presocial isolation levels
Mendoza & Mason (1986a) Squirrel monkeys (Saimiri) and titi monkeys (Callicebus) Adult 1 hour in home cage 10 heterosexual pairs of Saimiri, seven Callicebus (5 males and 2 females), and 17 Saimiri (9 males and 8 females) Mate for at least 39.3 months for Callicebus (range: 2 to 113) and 41.6 months for Saimiri (range: 3 to 110) Relative to basal levels Plasma cortisol levels Cortisol levels

  • The two species respond differently to separation: Squirrel monkeys do not show any differences, whereas titi monkeys show higher cortisol levels during separation, compared to their basal levels
Sapolsky et al. (1997) Yellow baboons (Papio cynocephalus) Adult 2 months of observation 12 males Relative to median values of the group Socially connected animals Cortisol concentrations from blood samples Cortisol levels

  • Socially isolated animals have significantly higher basal concentrations than males that are well-connected socially
Smith et al. (2011) Geoffroy’s tufted-ear marmosets (Callithrix geoffroyi) 3.1 years on average (SE = 0.3) 6 to 20 weeks 4 male and 4 female marmosets that were removed from their natal group and paired with a novel, opposite-sex conspecific after a period of social isolation (ISO-P) Natal group (4 males and 4 females) Natal group (4 males and 4 females) + marmosets that were removed from their natal group and immediately paired with a novel, opposite-sex conspecific (Natal-P: 2 males, 3 females) Urinary cortisol levels Cortisol levels

  • ISO-P marmosets have significantly higher cortisol levels after pairing than do Natal-P, especially during the first 10 days of pairing
Smith & French (1997) Wied’s black- tufted-ear marmosets (Callithrix kuhlii) 1.2–10.2 years 11 hours 9 females and 7 males Marmosets housed in family groups, or breeding pairs, or trios that had been established for at least 6 months A group of animals (4 males and 4 females) housed in their home cage with their normal social or family group (control group) + a group of animals that were held in gloved hands for 5 minutes (handling stressor) and then socially isolated for 11 hours (H + SI group) Urinary cortisol levels Cortisol levels

  • Exposing marmosets to the stressors of social isolation or H + SI produces significant elevations in levels of cortisol

  • Diurnal modulations: Social isolation increases cortisol levels, especially in the afternoons; H + SI stressor increases cortisol levels in both the mornings and afternoons
Dogs
Tuber et al. (1996) Mongrel dogs (Canis familiaris) 7–9 years 4 hours of walk alone in a familiar environment (alone home condition) or in a novel environment (alone novel condition) 3 males and 5 females From a familiar dog they’ve known for 7–9 years (either with a same-sex peer or an opposite-sex peer) Control condition (kennel mates were walked together in a familiar environment) + in-person novel condition (dog alone placed in a novel environment with a familiar human caretaker) Plasma glucocorticoid levels Glucocorticoid levels

  • Placement of dogs into a novel environment while either alone or with the familiar kennel mate elevates glucocorticoid levels over those in the control condition

  • The presence of a human caretaker in a novel environment reduces glucocorticoid levels (compared to the alone novel condition)

  • No other comparisons were significant
Cows
Higashiyama et al. (2009) Shorthorn cows 2–12 years 3 days 6 cows 13 other cows Compared to their basal-level preisolation Urinary cortisol and catecholamine levels Cortisol levels

  • Social isolation increases cortisol levels on the first day but not during the next two days

Catecholamine levels

  • Social isolation increases epinephrine levels on the first day but not during the next two days

  • No significant effect of social isolation on norepinephrine
Munksgaard & Simonsen (1996) Friesian cows Adult 4 and 8 weeks 6 cows 29 other cows A control group kept in stalls; a group deprived of lying down from 900 to 1600 and 2200 to 0500 Plasma cortisol and ACTH levels Cortisol levels

  • No difference in baseline cortisol concentrations at any sampling time among treatments

ACTH levels

  • No difference in baseline ACTH concentrations among treatments
Rushen et al. (1999) Holstein cows Adult 15 minutes of social isolation; injection with saline 12 cows 11 other cows Each cow was subjected to different treatments (with a 2-day to 4-day interval) in a balanced order following a Latin square design.
Control treatment condition: cow was injected with saline, then walked to the door of the room containing the isolation chamber at t = 0 minutes, but then returned to its stall for 15 minutes, after which it was again walked to the door of the room containing the isolation chamber and then returned		 Plasma cortisol levels Cortisol levels

  • Cortisol levels increase after social isolation, reaching maximum values at t = 20 minutes and then decreasing until baseline levels were reached at t = 60 minutes
Sheep
Parrot et al. (1988) Wethers of the Clun Forest breed Adult 105 minutes. Each sheep was tested with or without mirror panel 6 males Group of sheep Relative to baseline levels Plasma cortisol levels Cortisol levels

  • Cortisol levels increase within the 15 minutes of social isolation under both experimental conditions (with or without mirror), then decrease to baseline levels after about 30 minutes, and then rise again at 90 minutes
Goats
Carbonaro et al. (1992) Nubian and Alpine dairy goats Adult 30 minutes 4 Nubian and 4 Alpine female goats 3 other same-sex peers and then a peer with which the experimental animal was paired for 8 days prior to isolation 4 Nubian and 4 Alpine female goats that were paired with an experimental animal Plasma concentrations of cortisol, thyroxine (T4), triiodothyronine (T3), norepinephrine (NOR), and epinephrine (EPI) at 0 minutes (prior to isolation); 10, 20, and 30 minutes (during isolation); and 40, 50, and 60 minutes (after return to their group) Cortisol levels

  • No effect of social isolation on cortisol levels

Catecholamine levels

  • Response to isolation was characterized physiologically by increased plasma concentrations of NOR (especially during the 30 minutes of social isolation) but not EPI

  • The Nubian reacts more strongly (elevated NOR) to isolation than the Alpine does

Thyroid hormone levels

  • No effect of social isolation on T3 or T4 levels
*

Unless specified, the authors did not report the number of animals tested in their methods sections.