Changes in well-being among socially isolated older people during the COVID-19 pandemic: An outcome-wide analysis.

Older adults experienced major changes during the COVID-19 pandemic and ensuing restrictions, and it might be expected that those who were already socially isolated before the pandemic were particularly vulnerable. We apply an outcome-wide longitudinal design on 4,636 participants (mean age 66.8 y) from the English Longitudinal Study of Ageing, observed in 2018/19 and early (June/July 2020) and later (November/December 2020) in the pandemic. Social isolation is defined using an index including marital status, social contact, and social participation in 2018/19. Using mixed models, we compare changes in well-being, health, health behaviors, financial well-being, and Internet use, between isolated and nonisolated participants. From before to during the pandemic, isolated participants (29%) experienced smaller declines in life satisfaction and quality of life and a smaller increase in loneliness. They showed greater declines in smoking and physical activity and were more likely to remain worried about their future financial situation. They also did not change in their likelihood of regular Internet use, contrasting with nonisolated participants who increased in this regard. The groups followed a similar trend for general health and sleep quality (no change), depression and anxiety (increase), and expectations of future financial difficulties (decrease). Although isolated older adults generally show poorer outcomes than their socially connected counterparts, they were somewhat protected during the pandemic on some fronts. Our findings highlight the need to continually care for isolated older adults but also to be attentive in times of unexpected crises to those experiencing extreme changes related to necessary policy responses.

Social experience in adolescence shapes prefrontal cortex structure and function in adulthood.

During adolescence, the prefrontal cortex (PFC) undergoes dramatic reorganization. PFC development is profoundly influenced by the social environment, disruptions to which may prime the emergence of psychopathology across the lifespan. We investigated the neurobehavioral consequences of isolation experienced in adolescence in mice, and in particular, the long-term consequences that were detectable even despite normalization of the social milieu. Isolation produced biases toward habit-like behavior at the expense of flexible goal seeking, plus anhedonic-like reward deficits. Behavioral phenomena were accompanied by neuronal dendritic spine over-abundance and hyper-excitability in the ventromedial PFC (vmPFC), which was necessary for the expression of isolation-induced habits and sufficient to trigger behavioral inflexibility in socially reared controls. Isolation activated cytoskeletal regulatory pathways otherwise suppressed during adolescence, such that repression of constituent elements prevented long-term isolation-induced neurosequelae. Altogether, our findings unveil an adolescent critical period and multi-model mechanism by which social experiences facilitate prefrontal cortical maturation.

The impact of psychosocial adversity on brain and behaviour: an overview of existing knowledge and directions for future research.

Environmental experiences play a critical role in shaping the structure and function of the brain. Its plasticity in response to different external stimuli has been the focus of research efforts for decades. In this review, we explore the effects of adversity on brain's structure and function and its implications for brain development, adaptation, and the emergence of mental health disorders. We are focusing on adverse events that emerge from the immediate surroundings of an individual, i.e., microenvironment. They include childhood maltreatment, peer victimisation, social isolation, affective loss, domestic conflict, and poverty. We also take into consideration exposure to environmental toxins. Converging evidence suggests that different types of adversity may share common underlying mechanisms while also exhibiting unique pathways. However, they are often studied in isolation, limiting our understanding of their combined effects and the interconnected nature of their impact. The integration of large, deep-phenotyping datasets and collaborative efforts can provide sufficient power to analyse high dimensional environmental profiles and advance the systematic mapping of neuronal mechanisms. This review provides a background for future research, highlighting the importance of understanding the cumulative impact of various adversities, through data-driven approaches and integrative multimodal analysis techniques.

Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior.

Microglia and brain-derived neurotrophic factor (BDNF) are essential for the neuroplasticity that characterizes critical developmental periods. The experience-dependent development of social behaviors-associated with the medial prefrontal cortex (mPFC)-has a critical period during the juvenile period in mice. However, whether microglia and BDNF affect social development remains unclear. Herein, we aimed to elucidate the effects of microglia-derived BDNF on social behaviors and mPFC development. Mice that underwent social isolation during p21-p35 had increased Bdnf in the microglia accompanied by reduced adulthood sociability. Additionally, transgenic mice overexpressing microglial Bdnf-regulated using doxycycline at different time points-underwent behavioral, electrophysiological, and gene expression analyses. In these mice, long-term overexpression of microglial BDNF impaired sociability and excessive mPFC inhibitory neuronal circuit activity. However, administering doxycycline to normalize BDNF from p21 normalized sociability and electrophysiological function in the mPFC, whereas normalizing BDNF from later ages (p45-p50) did not normalize electrophysiological abnormalities in the mPFC, despite the improved sociability. To evaluate the possible role of BDNF in human sociability, we analyzed the relationship between adverse childhood experiences and BDNF expression in human macrophages, a possible proxy for microglia. Results show that adverse childhood experiences positively correlated with BDNF expression in M2 but not M1 macrophages. In summary, our study demonstrated the influence of microglial BDNF on the development of experience-dependent social behaviors in mice, emphasizing its specific impact on the maturation of mPFC function, particularly during the juvenile period. Furthermore, our results propose a translational implication by suggesting a potential link between BDNF secretion from macrophages and childhood experiences in humans.

Distinct neural dynamics of the observed ostracism effect in decision-making under risk and ambiguity.

Observational ostracism, as a form of social exclusion, can significantly affect human behavior. However, the effects of observed ostracism on risky and ambiguous decision-making and the underlying neural mechanisms remain unclear. This event-related potential study investigated these issues by involving participants in a wheel-of- fortune task, considering observed ostracism and inclusion contexts. The results showed that the cue-P3 component was more enhanced during the choice phase for risky decisions than for ambiguous decisions in the observed inclusion contexts but not in the observed ostracism contexts. During the outcome evaluation phase, feedback-related negativity amplitudes following both risky and ambiguous decisions were higher in the no-gain condition than in the gain condition in the observed inclusion context. In contrast, this effect was only observed following risky decisions in the observed ostracism context. The feedback-P3 component did not exhibit an observed ostracism effect in risky and ambiguous decision-making tasks. Risk levels further modulated the cue-P3 and feedback-related negativity components, while ambiguity levels further modulated the feedback-P3 components. These findings demonstrate a neural dissociation between risk and ambiguity decision-making during observed ostracism that unfolds from the choice phase to the outcome evaluation phase.

Systemic histone deacetylase inhibition ameliorates the aberrant responses to acute stress in socially isolated male mice.

Adverse experiences in early life can induce maladaptive responses to acute stress in later life. Chronic social isolation during adolescence is an early life adversity that can precipitate stress-related psychiatric disorders. We found that male mice after 8 weeks of adolescent social isolation (SI) have markedly increased aggression after being exposed to 2 h of restraint stress (RS), which was accompanied by a significant increase of AMPA receptor- and NMDA receptor-mediated synaptic transmission in prefrontal cortex (PFC) pyramidal neurons of SIRS males. Compared to group-housed counterparts, SIRS males exhibited a significantly decreased level of histone H3 acetylation in PFC. Systemic administration of class I histone deacetylase inhibitors, romidepsin or MS-275, ameliorated the aggressive behaviour, as well as general social interaction deficits, of SIRS males. Electrophysiological recordings also found normalization of PFC glutamatergic currents by romidepsin treatment of SIRS male mice. These results revealed an epigenetic mechanism and intervention avenue for aggression induced by chronic social isolation. KEY POINTS: Adolescent chronic social isolation can precipitate stress-related psychiatric disorders. A significant increase of glutamatergic transmission is found in the prefrontal cortex (PFC) of socially isolated male mice exposed to an acute stress (SIRS). Treatment with class I histone deacetylase (HDAC) inhibitors ameliorates the aggressive behaviour and social interaction deficits of SIRS males, and normalizes glutamatergic currents in PFC neurons. It provides an epigenetic mechanism and intervention avenue for aberrant stress responses induced by chronic social isolation.

Psychosocial Health and the Association Between Cerebral Small Vessel Disease Markers With Dementia: The ARIC Study.

BACKGROUND: Associations between magnetic resonance imaging markers of cerebral small vessel disease (CSVD) and dementia risk in older adults have been established, but it remains unclear how lifestyle factors, including psychosocial health, may modify this association. METHODS: Social support and social isolation were assessed among participants of the community-based ARIC (Atherosclerosis Risk in Communities) Study, via self-reported questionnaires (1990-1992). Following categorization of both factors, participants were classified as having strong or poor mid-life social relationships. At visit 5 (2011-2013), participants underwent 3T brain magnetic resonance imaging quantifying CSVD measures: white matter hyperintensity volume, microbleeds (subcortical), infarcts (lacunar), and white matter integrity (diffusion tensor imaging). Incident dementia cases were identified from the time of imaging through December 31, 2020 with ongoing surveillance. Associations between CSVD magnetic resonance imaging markers and incident dementia were evaluated using Cox proportional-hazard regressions adjusted for demographic and additional risk factors (from visit 2). Effect modification by mid-life social relationships was evaluated. RESULTS: Of the 1977 participants with magnetic resonance imaging, 1617 participants (60.7% women; 26.5% Black participants; mean age at visit 2, 55.4 years) were examined. In this sample, mid-life social relationships significantly modified the association between white matter hyperintensity volume and dementia risk (P interaction=0.001). Greater white matter hyperintensity volume was significantly associated with risk of dementia in all participants, yet, more substantially in those with poor (hazard ratio, 1.84 [95% CI, 1.49-2.27]) versus strong (hazard ratio, 1.26 [95% CI, 1.08-1.47]) mid-life social relationships. Although not statistically significant, subcortical microbleeds in participants with poor mid-life social relationships were associated with a greater risk of dementia, relative to those with strong social relationships, in whom subcortical microbleeds were no longer associated with elevated dementia risk. CONCLUSIONS: The elevated risk of dementia associated with CSVD may be reduced in participants with strong mid-life social relationships. Future studies evaluating psychosocial health through the life course and the mechanisms by which they modify the relationship between CSVD and dementia are needed.

The effect of acute social isolation on neural molecular responses in components of the social decision-making network.

Prolonged or chronic social isolation has pronounced effects on animals, ranging from altered stress responses, increased anxiety and aggressive behaviour, and even increased mortality. The effects of shorter periods of isolation are much less well researched; however, short periods of isolation are used routinely for testing animal behaviour and physiology. Here, we studied how a 3 h period of isolation from a cagemate affected neural gene expression in three brain regions that contain important components of the social decision-making network, the hypothalamus, the nucleus taeniae of the amygdala, and the bed nucleus of the stria terminalis, using a gregarious bird as a model (zebra finches). We found evidence suggestive of altered neural activity, synaptic transmission, metabolism, and even potentially pain perception, all of which could create cofounding effects on experimental tests that involve isolating animals. We recommend that the effects of short-term social isolation need to be better understood and propose alternatives to isolating animals for testing.

The impact of loneliness and social isolation on the development of cognitive decline and Alzheimer's Disease.

Alzheimer's Disease (AD) is the leading cause of dementia, observed at a higher incidence in women compared with men. Treatments aimed at improving pathology in AD remain ineffective to stop disease progression. This makes the detection of the early intervention strategies to reduce future disease risk extremely important. Isolation and loneliness have been identified among the major risk factors for AD. The increasing prevalence of both loneliness and AD emphasizes the urgent need to understand this association to inform treatment. Here we present a comprehensive review of both clinical and preclinical studies that investigated loneliness and social isolation as risk factors for AD. We discuss that understanding the mechanisms of how loneliness exacerbates cognitive impairment and AD with a focus on sex differences will shed the light for the underlying mechanisms regarding loneliness as a risk factor for AD and to develop effective prevention or treatment strategies.

Loneliness and Depressive Symptoms Are High Among Older Adults With Digestive Disease and Associated With Lower Perceived Health.

BACKGROUND & AIMS: Current approaches to managing digestive disease in older adults fail to consider the psychosocial factors contributing to a person's health. We aimed to compare the frequency of loneliness, depression, and social isolation in older adults with and without a digestive disease and to quantify their association with poor health. METHODS: We conducted an analysis of Health and Retirement Study data from 2008 to 2016, a nationally representative panel study of participants 50 years and older and their spouses. Bivariate analyses examined differences in loneliness, depression, and social isolation among patients with and without a digestive disease. We also examined the relationship between these factors and health. RESULTS: We identified 3979 (56.0%) respondents with and 3131 (44.0%) without a digestive disease. Overall, 60.4% and 55.6% of respondents with and without a digestive disease reported loneliness (P < .001), 12.7% and 7.5% reported severe depression (P < .001), and 8.9% and 8.7% reported social isolation (P = NS), respectively. After adjusting for covariates, those with a digestive disease were more likely to report poor or fair health than those without a digestive disease (odds ratio [OR], 1.25; 95% CI, 1.11-1.41). Among patients with a digestive disease, loneliness (OR, 1.43; 95% CI, 1.22-1.69) and moderate and severe depression (OR, 2.93; 95% CI, 2.48-3.47; and OR, 8.96; 95% CI, 6.91-11.63, respectively) were associated with greater odds of poor or fair health. CONCLUSIONS: Older adults with a digestive disease were more likely than those without a digestive disease to endorse loneliness and moderate to severe depression and these conditions are associated with poor or fair health. Gastroenterologists should feel empowered to screen patients for depression and loneliness symptoms and establish care pathways for mental health treatment.

The effects of acute social ostracism on subsequent snacking behavior and future body mass index in children.

BACKGROUND/OBJECTIVES: Ostracism may lead to increased food intake, yet it is unclear whether greater reactivity to ostracism contributes to higher body mass index (BMI). We investigated whether children who exhibited greater stress to social exclusion subsequently consume more energy and whether this predicts BMI 6- and 18-months later. SUBJECTS/METHODS: Children (8.5 years-old) (N = 262, males = 50.4%; Chinese = 58.4%) completed a laboratory-based manipulation of social exclusion (the Cyberball task) prior to an ad-libitum snack. Heart rate variability (HRV) was measured during the inclusion and exclusion conditions and proportionate changes were calculated as a physiological measure of exclusion-related stress. Social anxiety and social-emotional assets were also measured as moderators. RESULTS: Greater stress (as measured physiologically or by self-report) did not directly, or indirectly via energy intake, predict later BMI (at 9- and 10-years). However, among children reporting higher social anxiety, greater stress as measured by proportionate changes in HRV was associated with increased energy intake (B = 532.88, SE = 226.49, t(255) = 2.35, [CI95 = 86.85,978.92]). A significant moderated mediation was also observed (index: (b = 0.01, bootSE = 0.01, [CI95 = 0.001, 0.036]), such that among children reporting higher social anxiety, greater stress from social exclusion predicted increased energy intake from a subsequent snack, which in turn predicted higher BMI 1.5 years later. CONCLUSION: This prospective study suggests that a pattern of greater snack intake in response to heightened vulnerability to the effects of ostracism may contribute to increases in child BMI scores.

Social Isolation, Loneliness, and Risk of Microvascular Complications Among Individuals With Type 2 Diabetes Mellitus.

RATIONALE & OBJECTIVE: Social disconnection has been associated with poor cardiometabolic health. This study sought to investigate the associations of social isolation and loneliness with diabetic microvascular complications (DMCs) among individuals with type 2 diabetes mellitus (T2DM) and compare these associations versus those related to traditional risk factors. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: A total of 24,297 UK Biobank participants with T2DM and no DMCs at baseline. EXPOSURE: Social isolation and loneliness were measured using self-reported questionnaires. OUTCOME: The incidence of DMCs defined as a composite of diabetic kidney disease, diabetic retinopathy, or diabetic neuropathy. ANALYTICAL APPROACH: Multivariable cause-specific hazards regression. To compare the relative importance of social disconnection with other established factors, the R2 values of the Cox models were calculated. RESULTS: During a median follow-up of 12.6 years, 5,530 patients were documented to experience DMCs (3,458 with diabetic kidney disease, 2,255 with diabetic retinopathy, and 1,146 with diabetic neuropathy). The highest level of social isolation was associated with an increased risk of any DMC component (most vs least: HR, 1.13; 95% CI, 1.05-1.22), especially diabetic kidney disease (HR, 1.14; 95% CI, 1.04-1.25) and neuropathy (HR, 1.31; 95% CI, 1.11-1.53). Any level of loneliness was associated with an increased risk of any DMC component (HR, 1.12; 95% CI, 1.02-1.23) and diabetic kidney disease (HR, 1.16; 95% CI, 1.03-1.30). Social isolation and loneliness exhibited associations with DMCs comparable to those of other conventional risk factors, including smoking, blood pressure, and physical activity. LIMITATIONS: Limited generalizability related to the composition of participants in the UK Biobank Study. CONCLUSIONS: Social isolation and loneliness were independently associated with a higher risk of incident DMCs among individuals with T2DM, with comparable importance to other traditional risk factors. These findings underscore social isolation and loneliness as novel and potentially modifiable risk factors for DMCs. PLAIN-LANGUAGE SUMMARY: Social isolation and loneliness are important social determinants that are associated with adverse cardiometabolic health. Individuals with diabetes are particularly vulnerable to social isolation and loneliness. However, the relationship of social isolation or loneliness with diabetic microvascular complications (DMCs) remains unclear. Our study used the UK Biobank study data to investigate the associations of social isolation and loneliness with the development of DMCs. We found that social isolation and loneliness were independently associated with a higher risk of incident DMCs. Remarkably, their association with DMCs was comparable to those of other lifestyle factors such as smoking, blood pressure, and physical activity. These findings collectively imply that social isolation and loneliness are 2 important potentially modifiable risk factors for DMCs among individuals with type 2 diabetes mellitus.

Social Isolation, Physical Activity, and Subsequent Changes in Cognition Among Middle- and Older-Aged Adults: Results From the Canadian Longitudinal Study on Aging.

OBJECTIVE: The objectives of this study were to a) evaluate associations between social isolation and change in cognition over a 3-year period, and b) evaluate whether physical activity mediates the association between social isolation and cognition change. METHODS: Using baseline and follow-up 1 data from the Canadian Longitudinal Study on Aging, latent change score models, incorporating direct and indirect pathways, were constructed to estimate the indirect effect of social isolation on cognitive change through physical activity. Multigroup models were constructed based on age group (45-65 versus 65+ years) and sex to allow for varying estimates across age and sex. The final analytic sample included 51,338 participants. RESULTS: Indirect effects of social isolation on cognition through physical activity were evident in men and women 65+ years old for memory change ( = -0.005 [99.9% confidence interval = -0.007 to -0.002], p < .001 in both groups) and in male adults 65+ years old for executive function change ( = -0.01 [99.9% confidence interval = -0.02 to -0.006], p < .001). Statistically significant indirect effects were not observed for adults between 45 and 65 years old. CONCLUSIONS: Social isolation is associated with diminished physical activity, and in turn, diminished physical activity is associated with decline in memory in older women and men, with larger declines in executive function in older men. Public health initiatives to promote physical activity-perhaps incorporating social interaction-among older adults experiencing social isolation could be one way to mitigate the negative impact of social isolation on cognitive health.

Interventions to Reduce Loneliness in Community-Living Older Adults: a Systematic Review and Meta-analysis.

BACKGROUND: The problem of loneliness has garnered increased attention from policymakers, payors, and providers due to higher rates during the pandemic, particularly among seniors. Prior systematic reviews have in general not been able to reach conclusions about effectiveness of interventions. METHODS: Computerized databases were searched using broad terms such as "loneliness" or "lonely" or "social isolation" or "social support" from Jan 1, 2011 to June 23, 2021. We reference mined existing systematic reviews for additional and older studies. The Social Interventions Research & Evaluation Network database and Google were searched for gray literature on Feb 4, 2022. Eligible studies were RCTs and observational studies of interventions to reduce loneliness in community-living adults that used a validated loneliness scale; studies from low- or middle-income countries were excluded, and studies were excluded if restricted to populations where all persons had the same disease (such as loneliness in persons with dementia). RESULTS: A total of 5971 titles were reviewed and 60 studies were included in the analysis, 36 RCTs and 24 observational studies. Eleven RCTs and 5 observational studies provided moderate certainty evidence that group-based treatment was associated with reduced loneliness (standardized mean difference for RCTs = - 0.27, 95% CI - 0.48, - 0.08). Five RCTs and 5 observational studies provided moderate certainty evidence that internet training was associated with reduced loneliness (standardized mean difference for RCTs = - 0.22, 95% CI - 0.30, - 0.14). Low certainty evidence suggested that group exercises may be associated with very small reductions in loneliness. Evidence was insufficient to reach conclusions about group-based activities, individual in-person interactions, internet-delivered interventions, and telephone-delivered interventions. DISCUSSION: Low-to-moderate certainty evidence exists that group-based treatments, internet training, and possibly group exercises are associated with modest reductions in loneliness in community-living older adults. These findings can inform the design of supplemental benefits and the implementation of evidence-based interventions to address loneliness. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO ( CRD42021272305 ).

Interaction between mental disorders and social disconnectedness on mortality: a population-based cohort study.

BACKGROUND: Despite the recognised importance of mental disorders and social disconnectedness for mortality, few studies have examined their co-occurrence. AIMS: To examine the interaction between mental disorders and three distinct aspects of social disconnectedness on mortality, while taking into account sex, age and characteristics of the mental disorder. METHOD: This cohort study included participants from the Danish National Health Survey in 2013 and 2017 who were followed until 2021. Survey data on social disconnectedness (loneliness, social isolation and low social support) were linked with register data on hospital-diagnosed mental disorders and mortality. Poisson regression was applied to estimate independent and joint associations with mortality, interaction contrasts and attributable proportions. RESULTS: A total of 162 497 individuals were followed for 886 614 person-years, and 9047 individuals (5.6%) died during follow-up. Among men, interaction between mental disorders and loneliness, social isolation and low social support, respectively, accounted for 47% (95% CI: 21-74%), 24% (95% CI: -15 to 63%) and 61% (95% CI: 35-86%) of the excess mortality after adjustment for demographics, country of birth, somatic morbidity, educational level, income and wealth. In contrast, among women, no excess mortality could be attributed to interaction. No clear trends were identified according to age or characteristics of the mental disorder. CONCLUSIONS: Mortality among men, but not women, with a co-occurring mental disorder and social disconnectedness was substantially elevated compared with what was expected. Awareness of elevated mortality rates among socially disconnected men with mental disorders could be of importance to qualify and guide prevention efforts in psychiatric services.

Social cognition and social motivation in schizophrenia and bipolar disorder: are impairments linked to the disorder or to being socially isolated?

BACKGROUND: People with schizophrenia on average are more socially isolated, lonelier, have more social cognitive impairment, and are less socially motivated than healthy individuals. People with bipolar disorder also have social isolation, though typically less than that seen in schizophrenia. We aimed to disentangle whether the social cognitive and social motivation impairments observed in schizophrenia are a specific feature of the clinical condition v. social isolation generally. METHODS: We compared four groups (clinically stable patients with schizophrenia or bipolar disorder, individuals drawn from the community with self-described social isolation, and a socially connected community control group) on loneliness, social cognition, and approach and avoidance social motivation. RESULTS: Individuals with schizophrenia (n = 72) showed intermediate levels of social isolation, loneliness, and social approach motivation between the isolated (n = 96) and connected control (n = 55) groups. However, they showed significant deficits in social cognition compared to both community groups. Individuals with bipolar disorder (n = 48) were intermediate between isolated and control groups for loneliness and social approach. They did not show deficits on social cognition tasks. Both clinical groups had higher social avoidance than both community groups. CONCLUSIONS: The results suggest that social cognitive deficits in schizophrenia, and high social avoidance motivation in both schizophrenia and bipolar disorder, are distinct features of the clinical conditions and not byproducts of social isolation. In contrast, differences between clinical and control groups on levels of loneliness and social approach motivation were congruent with the groups' degree of social isolation.

The association between neighborhood-level social fragmentation and distressing psychotic-like experiences in early adolescence: the moderating role of close friends.

BACKGROUND: Early exposure to neighborhood social fragmentation has been shown to be associated with schizophrenia. The impact of social fragmentation and friendships on distressing psychotic-like experiences (PLE) remains unknown. We investigate the relationships between neighborhood social fragmentation, number of friends, and distressing PLE among early adolescents. METHODS: Data were collected from the Adolescent Brain Cognitive Development Study. Generalized linear mixed models tested associations between social fragmentation and distressing PLE, as well as the moderating role of the number of total and close friends. RESULTS: Participants included 11 133 adolescents aged 9 to 10, with 52.3% being males. Greater neighborhood social fragmentation was associated with higher levels of distressing PLE (adjusted ß = 0.05; 95% CI: 0.01-0.09). The number of close but not total friends significantly interacted with social fragmentation to predict distressing PLE (adjusted ß = -0.02; 95% CI: -0.04 to <-0.01). Among those with fewer close friends, the association between neighborhood social fragmentation and distressing PLE was significant (adjusted ß = 0.07; 95% CI: 0.03-0.11). However, among those with more close friends, the association was non-significant (adjusted ß = 0.03; 95% CI: -0.01 to 0.07). CONCLUSIONS: Greater neighborhood social fragmentation is associated with higher levels of distressing PLE, particularly among those with fewer close friends. Further research is needed to disentangle aspects of the interaction between neighborhood characteristics and the quality of social interactions that may contribute to psychosis, which would have implications for developing effective interventions at the individual and community levels.

The temporal association between social isolation, distress, and psychotic experiences in individuals at clinical high-risk for psychosis.

BACKGROUND: Psychotic experiences (PEs) and social isolation (SI) seem related during early stages of psychosis, but the temporal dynamics between the two are not clear. Literature so far suggests a self-perpetuating cycle wherein momentary increases in PEs lead to social withdrawal, which, subsequently, triggers PEs at a next point in time, especially when SI is associated with increased distress. The current study investigated the daily-life temporal associations between SI and PEs, as well as the role of SI-related and general affective distress in individuals at clinical high risk (CHR) for psychosis. METHODS: We used experience sampling methodology in a sample of 137 CHR participants. We analyzed the association between SI, PEs, and distress using time-lagged linear mixed-effects models. RESULTS: SI did not predict next-moment fluctuations in PEs, or vice versa. Furthermore, although SI-related distress was not predictive of subsequent PEs, general affective distress during SI was a robust predictor of next-moment PEs. CONCLUSIONS: Our results suggest that SI and PEs are not directly related on a moment-to-moment level, but a negative emotional state when alone does contribute to the risk of PEs. These findings highlight the role of affective wellbeing during early-stage psychosis development.

The reciprocal associations between social deficits, social engagement, and inflammation: Longitudinal evidence comparing venous blood samples and dried blood spots and mapping the modifying role of phenotypic and genotypic depression.

BACKGROUND: Social psychoneuroimmunology suggests an interplay between social deficits (loneliness and isolation) and chronic inflammation, but the direction of these relationships remains unclear. We estimated the reciprocal associations of social deficits and social engagement with levels of C-reactive protein (CRP), compared the consistency of the findings depending on the biological sampling method used, and examined the modifying role of phenotypic and genotypic depression. METHODS: We used longitudinal nationally representative data from the US (Health and Retirement Study, 3 waves, 2006-16) and England (English Longitudinal Study of Ageing, 4 waves, 2004-18). Loneliness, social isolation, and social engagement were self-reported. CRP was measured using dried blood spots (US) and venous blood samples (England). Cross-lagged panel models were fitted and tested interactions with phenotypic depression (above-threshold depressive symptom scores) and genotypic depression (polygenic score for major depressive disorder). RESULTS: We included 15,066 participants (mean age = 66.1 years, SD = 9.8) in the US and 10,290 (66.9 years, SD = 10.5) in England. We found reciprocal associations between loneliness and CRP using dried blood spots and venous blood samples. Higher CRP predicted higher subsequent loneliness and higher loneliness predicted elevated CRP. Both phenotypic and genotypic depression modified this reciprocal association. There were also reciprocal associations for social engagement in venous blood samples: higher CRP predicted lower social engagement and greater social engagement predicted lower subsequent CRP. Associations between social isolation and CRP were inconsistent and unidirectional. CONCLUSIONS: Loneliness may increase chronic inflammation, whereas social engagement may reduce inflammation. As these relationships were reciprocal, there may be a loop between inflammation, loneliness, and social engagement. This loop was stronger in those with depression or at high genetic risk for major depressive disorder. This relationship for loneliness was present in both blood sampling methods despite contrasting methods of CRP measurement, indicating that the finding is not attributable to measurement bias in biomarkers.