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Social isolation and 59 common health conditions: insights from observational and genetics analyses.

BACKGROUND: The impacts of social isolation on diverse health conditions and how it contributes to health risks remain unclear. We aimed to investigate the associations of social isolation with 59 health conditions among older adults. METHODS: Participants from the UK Biobank without baseline diagnosis of the included diseases were selected. Social isolation was assessed with three questions. The 59 health conditions included all-cause mortality, 5 cause-specific mortalities, and 53 diseases. We used an instrumental variable from multivariable common factor GWAS in Mendelian randomization (MR) to explore causal links of social isolation with diseases. Omics analyses were conducted to assess the roles of Olink plasma proteins and metabolomics, and PERM was calculated to evaluate the influence of other factors. RESULTS: A total of 489,741 individuals [266,706 (54.5%) women; mean age 56.5 years (SD 8.1)] were included. During a median follow-up of 12.5 years, social isolation was uncorrelated with the majority of 59 health conditions. Significantly, it was associated with increased risks of all-cause [adjusted HR (aHR) 1.28, 95% CI 1.25-1.32], 5 cause-specific mortalities (aHR range, 1.18-1.38), and 11 specific diseases (aHR range, 1.08-1.17). Living alone was the strongest item of isolation in predicting mortality (aHR range, 1.18-1.45) and selected diseases. MR analyses offered little evidence to support a causal link between social isolation and these diseases. The proteins involved in these associations are predominantly related to "response to stimulus". Proteomic signatures (PERM, 36%-49%), health behaviours (32%-59%), and socioeconomic factors (22%-42%) were the main explanatory factors linking social isolation to 8 health outcomes. CONCLUSIONS: Social isolation is associated with elevated risks of 17 out of the 59 examined adverse health outcomes, predominantly mortality-related conditions; however, MR analyses indicate an absence of evidence supporting causality for these associations.

Humans

Post-weaning social isolation increases reward-seeking behavior in mice.

Social isolation is a growing public health concern. Although isolation at any age is harmful, previous studies have shown that isolation during adolescence, correlating with critical periods of brain development, can impair cognitive function and increase the risk for psychiatric illness later in life. In this study, we utilized a mouse model of social isolation (SI) during adolescence (postnatal day 21-35) and compared performance of isolated and group-housed mice on a touchscreen-based continuous performance test (rCPT) and fixed ratio/progressive ratio (FR/PR) tasks in adulthood. SI improved performance in the rCPT and the improvement in performance was consistent across time bins within the 45-minute testing session. There were no effects of SI on reaction times or reward retrieval latencies. A possible confound for performance in the rCPT would be SI-induced changes in reward-seeking or motivation for the strawberry milk reward. We next compared the SI mice to their group-housed littermate controls on both PR and FR schedules of reinforcement and found that SI mice had higher breakpoints on a PR4 schedule and earned significantly more reinforcers on an FR1 schedule of reinforcement compared to their group-housed littermates, suggesting that high performance in the CPT may be due to increased motivation for food rewards. These data indicate that SI during adolescence has significant effects on reward-seeking behavior in adult mice and may provide a useful behavioral model for studying the link between SI and risk for neuropsychiatric disorders.

Animals

Social Isolation and Loneliness Among Older Asian Immigrants Through the Lens of Sense of Coherence: Systematic Review of Qualitative Studies.

AIM: To explore the meaning older Asian immigrants attribute to social isolation and loneliness, their management strategies, utilisation of resources and impact on health. DESIGN: Systematic review of qualitative studies. DATA SOURCES: AgeLine, CINAHL, MEDLINE, ProQuest, PsycINFO, Scopus, and Web of Science databases were searched in September 2024. METHODS: Inclusion criteria: participants were Asian immigrants to Western countries aged 65 and over, community-living and experiencing social isolation and loneliness. Antonovsky's Sense of Coherence was used to frame the thematic analysis. RESULTS: Ten papers were included and analysed deductively using elements of the sense of coherence framework: • Comprehensibility: Social isolation and loneliness are viewed as multifaceted, influenced by cultural and environmental dislocation, language barriers, intergenerational conflicts, deteriorating health and mobility, and socioeconomic challenges. • Manageability: included engaging in culture-specific community programs, family and ethnic community support and living within ethnic enclaves mitigated isolation and loneliness. • Meaningfulness: Strong family ties, active community involvement, spirituality, volunteerism, and cultural practices fostered resilience. However, accepting the changing values of their new world, living independently, and carving their own niche provided meaning to their transformed reality. CONCLUSION: Older Asian immigrants experience social isolation and loneliness through a cultural lens, shaped by migration experiences, language barriers, and shifting family dynamics. Cultural roots, family ties, spirituality, community, acceptance, and independence enhance sense of coherence. Recognising the dynamic interplay between cultural identity, resilience, and adaptation is key to understanding their lived experience. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: This review informs culturally sensitive interventions, guiding healthcare, community services, and policy to support social participation, mitigate loneliness through ethno-specific activities, and improve the quality of life for aging immigrant populations in Western countries. REPORTING METHOD: The review was undertaken and reported using the PRISMA guidelines. PATIENT OR PUBLIC INVOLVEMENT: None. PROTOCOL REGISTRATION: PROSPERO (CRD42023425752).

Humans

Changes in cortical dendritic branching subsequent to partial social isolation in stumptailed monkeys.

Stumptailed monkeys were reared from 1 week after birth to 6 months of age in either a colony condition with the mother or in partial social isolation that allowed visual contact with the colony animals, but not physical contact. At 6 months of age the animals were killed and selected areas of the neocortex stained by the Golgi-Cox method. Relatively nonspiney cells of Layer IV were drawn and analyzed for complexity of dendritic branching. Isolation-reared animals had significantly decreased branching complexity in Motor I cortex when compared to the control animals. A transform of the data that related the number of branches to the number of previous branches showed a slight rearing effect in Somatosensory I cortex with the deprived animals having a lower rate of branching than the controls. We conclude that social isolation also includes a motoric deprivation that could account for these data.

Animals

Social isolation and other behavioral changes in groups of adult vervet monkeys (Cercopithecus aethiops) produced by low, nonchronic doses of d-amphetamine.

Doses (0.1--0.7 mg/kg body weight) d-amphetamine were administered to three independent groups of green vervet monkeys (Cerecopithecus aethiops). Each group formed a triad with one male and two females. Amphetamine changed both the individual and the social behavior patterns significantly. Stereotypy and social isolation (withdrawal) were characteristic features of the amphetaminized animals. Also stereotyped social grooming was observed. The results are discussed in relation to behavior changes seen in amphetamine psychoses and in naturally occurring endogenous psychoses. It is emphasized that the study of patterns of behavior is an important object of research and relevant line in future investigations on psychopathology.

Animals

Influence of sociality following isolation on feeding rhythms of monkeys entrained to artificial light schedules.

Socialization following a period of isolation disrupted the feeding rhythms of monkeys entrained to artificial light schedules. When isolation was reinstituted, the performances of the subjects, which had shifted during socialization, reverted to profiles similar to but not the same as they were in the initial isolation period. The strength of the social factor may have derived, in part, from the effects of the isolation which preceded the socialization phase.

Animals

A Systematic Review of Quantitative Studies of Depression and Loneliness in Black Women with Hypertension in the United States.

INTRODUCTION: Hypertension disproportionately affects Black women with subsequent complications that can extend beyond physical health. Notably, there is a significant relationship between hypertension, depression, and loneliness, with hypertensive Black women more likely to exhibit symptoms of depression. Since loneliness and social isolation are predictors of depression, recognizing and addressing these interconnected health concerns could improve patient outcomes and quality of life. This systematic review presents a synthesis of findings on depression screening practices, depression symptoms, and loneliness in quantitative studies of Black women with hypertension in the United States. METHODS: Using the EbscoHost platform, a comprehensive literature search for studies measuring depression and loneliness in Black women with hypertension was conducted. The following databases were selected: Medline Complete, CINAHL Complete, APA PsychArticles, and PsychINFO. RESULTS: Twenty-three articles were included; 16 focused on depression, and these studies highlighted a significant burden of depression in this demographic compared to their counterparts. Five studies reported loneliness and its relation to depression and hypertension. Loneliness and social isolation, as independent risk factors, exacerbated symptoms of depression and contributed to the onset and progression of hypertension. Two prior reviews corroborated these findings. Studies have emphasized the role of trust in clinical interactions and the importance of appropriate therapeutic interventions. DISCUSSION: Black women with hypertension are at a heightened risk for symptoms of depression, compounded by feelings of loneliness. Loneliness and depression are linked to physiological stress, contributing to hypertension. These problems are underrecognized and undertreated across populations, and this lack of recognition and treatment contributes to health inequity.

Humans

Environmentally induced differences in susceptibility of rats to CNS stimulants and CNS depressants: evidence against a unitary explanation.

It has been suggested that socially isolated rats are more aroused then rats raised in social groups. This hypothesis was tested by examining amphetamine-induced activity and stereotypy in social and isolated rats of both sexes in both the active and inactive phases of their diurnal activity cycle. In socially raised rats it was possible to produce behavioural profiles similar to those of isolated rats by increasing the arousal level of the social rat. However, the complex interaction of housing conditions, diurnal variation and gender with drug dose suggests that one intervening variable such as arousal is too simplistic an explanation. In subsequent experiments, stereotypy was enhanced by a familiar environment, and there was a clear dissociation between the effects of CNS stimulants and CNS depressants. The increased susceptibility of isolates to CNS stimulants depends on social isolation for a short period before 45 days of age; the decreased susceptibility of isolates to CNS depressants may be produced by isolation at any age. We conclude that there is no evidence that isolated rats are hyperaroused.

Animals

The biology of social attachments: opiates alleviate separation distress.

The possibility that brain opiate systems participate in the control of social affect was assessed by determining capacity of low doses of exogenous opiates (0.125-0.50 mg/kg oxymorphone, and 0.10-0.50 mg/kg morphine sulfate) to reduce distress vocalizations of socially isolated puppies. Low doses of opiates were capable of profoundly reducing crying as well as the motor agitation they exhibit during brief periods of social isolation. Since reductions in crying could be obtained with morphine in the absence of any gross behavioral disturbances, the possibility is entertained that brain opiates may function to control the intensity of emotions arising from social separation. Possible parallels between the biological nature of narcotic addiction and the formation of social bonds are discussed.

Animals

Large-Scale Neuroimaging and Genetic Analyses of the Human Thalamus in Loneliness.

BACKGROUND: Although loneliness is prevalent and significantly impacts society globally, its neural and genetic bases remain poorly understood. The thalamus, which receives sensory information from the environment, may have a more significant role in social interactions than previously recognized. Here, we integrate neuroimaging and genetic approaches to characterize structural differences within the thalamus associated with loneliness. METHODS: We obtained thalamic nuclei volumes on brain scans from 45,834 individuals (age range: 45-82 years) in the UK Biobank and grouped them into 6 anatomical groups. We investigated effects of loneliness and social isolation using self-reported data. Then, we performed a genome-wide association study (GWAS) analysis on the genetic overlap between thalamic volumes and loneliness. RESULTS: The volumes of the whole thalamus and its medial, lateral, and posterior nuclei are significantly reduced in individuals with loneliness compared with those who do not feel lonely. Loneliness with frequent social contact is associated with smaller volumes, whereas social isolation without loneliness shows no such reduction in thalamus volumes. Leveraging data from GWASs on thalamic volumes (n = 30,114) and loneliness (n = 370,342) in the UK Biobank, we identified shared loci between thalamus structure and loneliness. CONCLUSIONS: Our findings support the emerging view that the thalamus plays important roles in social interactions and in the experience of loneliness.

Genetic architecture

The role of serotonergic pathways in isolation-induced aggression in mice.

Male mice that became aggressive following four weeks of social isolation were treated with seven known serotonin receptor antagonists. All of the antiserotonergic drugs selectively antagonized the fighting behavior of the isolated mice; the antiaggressive activity was selective since, at antifighting doses, none of the drugs either significantly altered spontaneous motor activity or impaired inclined-screen performance. Antagonism of 5-HTP-induced head-twitch was used as an in vivo measure of antiserotonergic activity and a statistically significant correlation existed between potency as an antiserotonergic and potency as an antiaggressive. PCPA, a serotonin depletor, also significantly antagonized isolation-induced aggression for at least 24 hr postdrug administration. The interrelationship between cholinergic and serotonergic mechanisms in the mediation of isolation aggression was investigated. The involvement of serotonergic systems in isolation-induced aggression is discussed.

5-Hydroxytryptophan

[Isolation, loneliness and suicidal ideas in the aged (author's transl)].

The relationship between various dimensions of social isolation, loneliness and suicidal ideas among a group of 406 respondents over 65 years of age were analyzed. The survey findings show that suicidal ideas emerge as a result of both, a loss of or a social denial to intimate and highly valued personal relationships. Generally, these suicidal ideas are connected to feelings of loneliness which are unrelated to the quantity of other social contacts. It seems to be of particular relevance whether the disengagement occurred voluntarily and whether the personal life style showed consistency of persistency resp. Based on these findings the fundamental problems of a social psychological approach to gerontology are discussed. These problems arise out of the more or less perfect correspondence between objective indicators of a social situation and its subjective correlates.

Aged

A 21-year psycho-social follow-up of 524 unselected cases of down's syndrome and their families.

The death rate was followed, and a life table has been constructed. Three crucial events were examined: 1. the period of diagnosis, 2. the problem of institutionalization versus homecare, 3. the ageing and death of the parents and its consequences for the person with D.S. Several other medical problems, psychological implications and social consequences for the person with D.S., for his parents and siblings are highlighted. The worst problem for parents with the child at home was social isolation; for the parents with the child at an institution it was the very existence of the child. To both groups the most encouraging fact was that their child was happy, friendly and in good spirits. Finally, emphasis is laid upon the medical and paramedical problems which must be discussed and solved to make a harmonious and social life for the person with D.S., for his normal siblings, and for the parents.

Adolescent