Social isolation (SI) has detrimental effects on human and animal cognitive functions. In particular, acute isolation in adult mice impairs social recognition memory (SRM). Previous accounts of this impairment have focused primarily on memory consolidation. However, the current study suggests that impaired SRM results from enhanced forgetting. SI accelerates SRM decay without affecting memory formation. The impairment is caused by elevated Rac1 activity in the hippocampus. Using adeno-associated-virus-based genetic manipulation, we found that inhibition of Rac1 activity blocked forgetting of SRM in isolated adult mice, whereas activation of Rac1 accelerated forgetting in group-housed mice. Moreover, resocialization reversed the accelerated forgetting following isolation in correlation with suppression of Rac1 activity. In addition, accelerated long-term potentiation (LTP) decay in isolated mice brain slices was rescued by inhibition of Rac1 activity. Taken together, the findings lead us to conclude that social memory deficits in isolated mice are mediated by enhanced Rac1-dependent forgetting.

Social isolation in adolescence leads to lasting deficits, including emotional and cognitive dysregulation. It remains unclear, however, how social isolation affects certain processes of memory and what molecular mechanisms are involved. In this study, we found that social isolation during the post-weaning period resulted in forgetting of the long-term fear memory, which was attributable to the downregulation of synaptic function in the hippocampal CA1 region mediated by EphB2, a receptor tyrosine kinase which involves in the glutamate receptor multiprotein complex. Viral-mediated EphB2 knockdown in CA1 mimicked the memory defects in group-housed mice, whereas restoration of EphB2 by either viral overexpression or resocialization reversed the memory decline in isolated mice. Taken together, our finding indicates that social isolation gives rise to memory forgetting by disrupting EphB2-mediated synaptic plasticity, which may provide a potential target for preventing memory loss caused by social isolation or loneliness.

Many species use social networks to buffer the effects of stress. The mere absence of a social network, however, may also be stressful. We examined neuroendocrine, PVN CRH neurons and report that social isolation alters the intrinsic properties of these cells in sexually dimorphic fashion. Specifically, isolating preadolescent female mice from littermates for <24 hr increased first spike latency (FSL) and decreased excitability of CRH neurons. These changes were not evident in age-matched males. By contrast, subjecting either males (isolated or grouped) or group housed females to acute physical stress (swim), increased FSL. The increase in FSL following either social isolation or acute physical stress was blocked by the glucocorticoid synthesis inhibitor, metyrapone and mimicked by exogenous corticosterone. The increase in FSL results in a decrease in the excitability of CRH neurons. Our observations demonstrate that social isolation, but not acute physical stress has sex-specific effects on PVN CRH neurons.

Loneliness is a painful condition associated with increased risk for premature mortality. The formation of new, positive social relationships can alleviate feelings of loneliness, but requires rapid trustworthiness decisions during initial encounters and it is still unclear how loneliness hinders interpersonal trust. Here, a multimodal approach including behavioral, psychophysiological, hormonal, and neuroimaging measurements is used to probe a trust-based mechanism underlying impaired social interactions in loneliness. Pre-stratified healthy individuals with high loneliness scores (n = 42 out of a screened sample of 3678 adults) show reduced oxytocinergic and affective responsiveness to a positive conversation, report less interpersonal trust, and prefer larger social distances compared to controls (n = 40). Moreover, lonely individuals are rated as less trustworthy compared to controls and identified by the blinded confederate better than chance. During initial trust decisions, lonely individuals exhibit attenuated limbic and striatal activation and blunted functional connectivity between the anterior insula and occipitoparietal regions, which correlates with the diminished affective responsiveness to the positive social interaction. This neural response pattern is not mediated by loneliness-associated psychological symptoms. Thus, the results indicate compromised integration of trust-related information as a shared neurobiological component in loneliness, yielding a reciprocally reinforced trust bias in social dyads.

Subjective feeling of social isolation, as can be measured by perceived burdensomeness (PB), is a major risk factor for alcohol misuse. Heightened PB is associated with elevated stress response and diminished cognitive control, both of which contribute to problem drinking. Here, we sought to identify the neural substrates underlying the relationship between PB and alcohol misuse.

Early-life social isolation has profound effects on adult social competence. This is often expressed as increased aggression or inappropriate displays of courtship-related behaviors. The social incompetence exhibited by isolated animals could be in part due to an altered ability to participate in communicatory exchanges. House mice (Mus musculus) present an excellent model for exploring this idea, because social isolation has a well-established influence on their social behavior, and mice engage in communication via multiple sensory modalities. Here, we tested the prediction that social isolation during early life would influence ultrasonic vocalizations (USVs) emitted by adult male mice during same-sex social encounters. Starting at three weeks of age, male mice were housed individually or in social groups of four males for five weeks, after which they were placed in one of three types of paired social encounters. Pair types consisted of: two individually housed males, two socially housed males, or an individually housed and a socially housed male ("mixed" pairs). Vocal behavior (USVs) and non-vocal behaviors were recorded from these 15-minute social interactions. Pairs of mice consisting of at least one individually housed male emitted more and longer USVs, with a greater proportional use of USVs containing frequency jumps and 50-kHz components. Individually housed males in the mixed social pairs exhibited increased levels of mounting behavior towards the socially housed males. Mounting in these pairs was positively correlated with increased number and duration of USVs as well as increased proportional use of spectrally more complex USVs. These findings demonstrate that USVs are part of the suite of social behaviors influenced by early-life social isolation, and suggest that altered vocal communication following isolation reflects reduced social competence.

No systematic review has appeared so far synthesizing the evidence regarding multimorbidity and loneliness, social isolation, or social frailty. Consequently, our aim was to fill this gap. Three electronic databases (PubMed, PsycINFO, and CINAHL) were searched in our study. Observational studies examining the link between multimorbidity and loneliness, social isolation, and social frailty were included, whereas disease-specific samples were excluded. Data extraction included methods, characteristics of the sample, and the main results. A quality assessment was conducted. Two reviewers performed the study selection, data extraction, and quality assessment. In sum, eight studies were included in the final synthesis. Some cross-sectional and longitudinal studies point to an association between multimorbidity and increased levels of loneliness. However, the associations between multimorbidity and social isolation as well as social frailty remain largely underexplored. The quality of the studies included was rather high. In conclusion, most of the included studies showed a link between multimorbidity and increased loneliness. However, there is a lack of studies examining the association between multimorbidity and social isolation as well as social frailty. Future studies are required to shed light on these important associations. This is particularly important in times of the COVID-19 pandemic.

Social isolation has affected a large number of people and may lead to impairment of physical and mental health. Although stress resulting from social isolation may increase cancer progression, its interference on tumorigenesis is poorly known. In this study, we used a preclinical model to evaluate the effects of social isolation stress on chemically induced oral carcinogenesis. Sixty-two 21-day-old male Wistar rats were divided into isolated and grouped groups. After 90 days of age, the rats from both groups underwent oral carcinogenesis with 4-nitroquinoline 1-oxide (4NQO) for 20 weeks. All rats were assessed for depressive-like behavior and euthanized for oral squamous cell carcinoma (OSCC) diagnosis and measurement of inflammatory mediators in the tumor microenvironment. Social isolation stress increased the OSCC occurrence by 20.4% when compared to control. Isolated rats also showed higher tumor volume and cachexia than the grouped rats. Social isolation did not induce changes in the depressive-like behavior after carcinogenic induction. Tumors from stressed rats had increased levels of the inflammatory mediators, TNF-alpha, IL1-beta and MCP-1. The concentrations of TNF-alpha and MCP-1 were significantly increased in the large tumors from isolated animals. Higher tumor levels of TNF-alpha, IL-6, IL1-beta and MCP-1 were positively correlated with OSCC growth. This study provides the first evidence that social isolation stress may facilitate OSCC occurrence and tumor progression, an event accompanied by increased local levels of inflammatory mediators.

Although medial prefrontal cortex (mPFC) is known to play important roles in social behaviors, how early social experiences affect the mPFC and its subcortical circuit remains unclear. We report that mice singly housed (SH) for 8 weeks after weaning show a social recognition deficit, even after 4 weeks of resocialization. In SH mice, prefrontal infralimbic (IL) neurons projecting to the shell region of nucleus accumbens (NAcSh) show decreased excitability compared with group-housed (GH) mice. NAcSh-projecting IL neurons are activated when GH mice encounter a familiar conspecific, which is not observed in SH mice. Chemogenetic inhibition of NAcSh-projecting IL neurons in normal mice impairs social recognition without affecting social preference, whereas activation of these neurons reverses social recognition deficit in SH mice. Our findings demonstrate that early social experience critically affects mPFC IL-NAcSh projection, the activation of which is required for social recognition by encoding information for social familiarity.

To investigate associations between level and changes in social isolation and in memory in older men and women.

The sensitivity of somatic pain could be affected by social isolation; however, few studies have examined the impact of social isolation on visceral pain. In the present study, the effect of acute brief social isolation on visceral pain response was investigated.

Suicide is a major public health problem and a cause of premature mortality. With a view to prevention, a great deal of research has been devoted to the determinants of suicide, focusing mostly on individual risk factors, particularly depression. In addition to causes intrinsic to the individual, the social environment has also been widely studied, particularly social isolation. This paper examines the social dimension of suicide etiology through a review of the literature on the relationship between suicide and social isolation.

Studies examining the effect of social isolation on cognitive function typically involve older adults and/or specialist groups (e.g., expeditions). We considered the effects of COVID-19-induced social isolation on cognitive function within a representative sample of the general population. We additionally considered how participants 'shielding' due to underlying health complications, or living alone, performed. We predicted that performance would be poorest under strictest, most-isolating conditions. At five timepoints over 13 weeks, participants (N = 342; aged 18-72 years) completed online tasks measuring attention, memory, decision-making, time-estimation, and learning. Participants indicated their mood as 'lockdown' was eased. Performance typically improved as opportunities for social contact increased. Interactions between participant sub-groups and timepoint demonstrated that performance was shaped by individuals' social isolation levels. Social isolation is linked to cognitive decline in the absence of ageing covariates. The impact of social isolation on cognitive function should be considered when implementing prolonged pandemic-related restrictive conditions.

Chronic stressors, such as chronic isolation in social mammals, can elevate glucocorticoids, which can affect cellular mechanisms of aging, including increased levels of oxidative stress and shortened telomere lengths. Recent work in the selectively social prairie vole (Microtus ochrogaster) suggests that oxytocin and social support may mitigate some of the negative consequences of social isolation, possibly by reducing glucocorticoid levels. We investigated the influences of isolation, social support, and daily oxytocin injections in female prairie voles. Glucocorticoid levels, oxidative damage, telomere length, and anhedonia, a behavioral index of depression, were measured throughout the study. We found that six weeks of chronic isolation led to increased glucocorticoid levels, oxidative damage, telomere degradation and anhedonia. However, daily oxytocin injections in isolated voles prevented these negative consequences. These findings demonstrate that chronic social isolation in female prairie voles is a potent stressor that results in depression-like behavior and accelerated cellular aging. Importantly, oxytocin can completely prevent the negative consequences of social isolation.

Long-term social isolation can alter the sensitivity to somatic pain, however, its impact on visceral pain sensitivity remains unknown. The purpose of this study is to investigate the effect of long-term social isolation on visceral pain sensitivity in rats. 4-week social isolation rearing significantly increased CRD-induced AWR score and decreased pain threshold as compared to group rearing. There was no significant difference in the number of spontaneous visceral pain behaviors between group and isolation rearing rats. The number of fecal bolus produced by isolation rearing rats was comparable to that produced by group rearing rats. Consistent with 4-week isolation, CRD-induced AWR score in 8-week isolation rearing rats was higher than that in group rearing rats. While, pain threshold was lower in 8-week isolation rearing rats than in group rearing rats. There was no significant difference in the number of spontaneous visceral pain behaviors and fecal bolus between 8-week isolation and group rearing rats. There results indicated that long-term social isolation induces visceral hypersensitivity in rats, but this effect is unrelated to an increase in stress levels.

The objective of the study was to identify latent variables that can be used to inform theoretical models of perinatal influences on postnatal depressed mood and maternal-infant attachment. A routine survey of mothers with newborn infants was commenced in South Western Sydney in 2000. The survey included the Edinburgh Postnatal Depression Scale (EPDS) and 46 psychosocial and health-related variables. Mothers (n = 15,389) delivering in 2002 and 2003 were surveyed at 2-3 weeks for depressive symptoms. Nonlinear principal components analysis was undertaken to identify dimensions that might represent latent variables. Correlations between latent variables and EPDS >12 were assessed by logistic regression. A five-dimension solution was identified, which accounted for 51% of the variance among the items studied. The five dimensions identified were maternal responsiveness, social exclusion, infant behavior, migrant social isolation, and family size. In addition, the variable maternal expectation contributed significantly to total variance and was included in the regression analysis. Regression on EPDS >12 was predictive for all variables except for maternal responsiveness, which was considered an outcome variable. The findings are consistent with the proposition that social exclusion, infant behavior, social isolation among migrant mothers, and maternal expectations are determinants of maternal mood.

There are growing calls from researchers and policy makers to redefine loneliness and social isolation (SI) as public health issues, and to move towards a transdisciplinary, systems-based approach, due to their association with significant health risks, particularly in older people. Research about loneliness and SI in older people has typically adopted a narrow focus, evaluating effects of individual and inter-personal factors on these experiences. Less is known about the community and societal influences that may be used to inform public health interventions. We conducted a scoping review applying Joanna Briggs Institute methodology and the social-ecological model framework in order to: i) identify the available evidence for the influence of the community and societal factors on loneliness and SI as experienced by older people; ii) examine how quantitative research about community- and societal-level factors of loneliness and SI in the older population is conducted; and iii) identify current knowledge gaps in relation to the use of the social-ecological model in this area. A total of 52 articles from 30 countries met the inclusion criteria, including 33 observational studies, primarily cross-sectional (88%), and 19 interventions, mostly (89%) pre-post evaluations. The majority of included articles measured loneliness only (n = 34, 65%), while 11 measured both loneliness and SI (21%). To measure these outcomes validated scales were frequently used. Eighteen community/societal factors were investigated in relation to loneliness and/or SI, most commonly neighbourhood safety, access to public third-places and cultural practices. Three societal-level interventions were found: two campaigns to reduce ageism and one which explored the impact of free public transport. Community-based interventions were either educational or enlisted volunteers to foster connections. There is a need for longitudinal studies to better understand the mechanisms through which community- and societal- level factors affect loneliness and SI, which in turn will guide interventions that utilise the social-ecological framework for these issues.

Adolescence is a critical period for neurodevelopment. Evidence from animal studies suggests that isolated rearing can exert negative effects on behavioral and brain development. The present study aimed to investigate the effects of adolescent social isolation on latent inhibition and brain-derived neurotrophic factor levels in the forebrain of adult rats. Male Wistar rats were randomly divided into adolescent isolation (isolated housing, 38-51 days of age) and social groups. Latent inhibition was tested at adulthood. Brain-derived neurotrophic factor levels were measured in the medial prefrontal cortex and nucleus accumbens by an enzyme-linked immunosorbent assay. Adolescent social isolation impaired latent inhibition and increased brain-derived neurotrophic factor levels in the medial prefrontal cortex of young adult rats. These data suggest that adolescent social isolation has a profound effect on cognitive function and neurotrophin levels in adult rats and may be used as an animal model of neurodevelopmental disorders.

Social isolation negatively affects health, induces detrimental behaviors, and shortens lifespan in social species. Little is known about the mechanisms underpinning these effects because model species are typically short-lived and non-social. Using colonies of the carpenter ant Camponotus fellah, we show that social isolation induces hyperactivity, alters space-use, and reduces lifespan via changes in the expression of genes with key roles in oxidation-reduction and an associated accumulation of reactive oxygen species. These physiological effects are localized to the fat body and oenocytes, which perform liver-like functions in insects. We use pharmacological manipulations to demonstrate that the oxidation-reduction pathway causally underpins the detrimental effects of social isolation on behavior and lifespan. These findings have important implications for our understanding of how social isolation affects behavior and lifespan in general.

Background: Several empirical studies have shown an association between informal caregiving for adults and loneliness or social isolation. Nevertheless, a systematic review is lacking synthesizing studies which have investigated these aforementioned associations. Therefore, our purpose was to give an overview of the existing evidence from observational studies. Materials and Methods: Three electronic databases (Medline, PsycINFO, CINAHL) were searched in June 2021. Observational studies investigating the association between informal caregiving for adults and loneliness or social isolation were included. In contrast, studies examining grandchild care or private care for chronically ill children were excluded. Data extractions covered study design, assessment of informal caregiving, loneliness and social isolation, the characteristics of the sample, the analytical approach and key findings. Study quality was assessed based on the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Each step (study selection, data extraction and evaluation of study quality) was conducted by two reviewers. Results: In sum, twelve studies were included in our review (seven cross-sectional studies and five longitudinal studies)-all included studies were either from North America or Europe. The studies mainly showed an association between providing informal care and higher loneliness levels. The overall study quality was fair to good. Conclusion: Our systematic review mainly identified associations between providing informal care and higher loneliness levels. This is of great importance in assisting informal caregivers in avoiding loneliness, since it is associated with subsequent morbidity and mortality. Moreover, high loneliness levels of informal caregivers may have adverse consequences for informal care recipients.