It is known that the effectiveness of drug treatment for depression, ammine deficit based, is largely unsatisfactory. In this review, we examine the proposal of a precision therapy has emerged and has received a strong push by the identification of the role of inflammation in depression. However, precision psychiatry risks being caught in the reductionist trap of searching for the molecular switch that resets the whole system and switches off the disease. This is an illusion since the human being is complex and depression is a systemic and variable disorder. In this study, we show the inadequacy of the reductionist paradigm, and, at the same time, illustrate the superiority of the systemic paradigm centered on psychoneuroendocrineimmunology (PNEI). According to the PNEI paradigm, depression is a disease of the whole human being, caused by different sources working together: psychological, biological, and behavioral. This means knowing the biological and psychological history of the subject, identifying relational and biological crisis factors, and building personalized treatments targeting those factors with the tools of medicine and psychology, which are not reducible to the combination of drugs and psychotherapy. Our proposal presents a paradigm shift that is both theoretical and practical, which enables clinicians to assess patients experiencing depression in a unified way and treat them in an integrated manner.

The biology underlying the connection between social relationships and health is largely unknown. Here, leveraging data from 42,062 participants across 2,920 plasma proteins in the UK Biobank, we characterized the proteomic signatures of social isolation and loneliness through proteome-wide association study and protein co-expression network analysis. Proteins linked to these constructs were implicated in inflammation, antiviral responses and complement systems. More than half of these proteins were prospectively linked to cardiovascular disease, type 2 diabetes, stroke and mortality during a 14 year follow-up. Moreover, Mendelian randomization (MR) analysis suggested causal relationships from loneliness to five proteins, with two proteins (ADM and ASGR1) further supported by colocalization. These MR-identified proteins (GFRA1, ADM, FABP4, TNFRSF10A and ASGR1) exhibited broad associations with other blood biomarkers, as well as volumes in brain regions involved in interoception and emotional and social processes. Finally, the MR-identified proteins partly mediated the relationship between loneliness and cardiovascular diseases, stroke and mortality. The exploration of the peripheral physiology through which social relationships influence morbidity and mortality is timely and has potential implications for public health.

Inflammatory stimuli administered to humans and laboratory animals affect mesolimbic and nigrostriatal dopaminergic pathways in association with impaired motivation and motor activity. Alterations in dopaminergic corticostriatal reward and motor circuits have also been observed in depressed patients with increased peripheral inflammatory markers. The effects of peripheral inflammation on dopaminergic pathways and associated neurobiologic mechanisms and consequences have been difficult to measure in patients. Postmortem tissue (n = 11) from an established, translationally-relevant non-human primate model of cytokine-induced depressive behavior involving chronic interferon-alpha (IFN-a) administration was utilized herein to explore the molecular mechanisms of peripheral cytokine effects on striatal dopamine. Dopamine (but not serotonin or norepinephrine) was decreased in the nucleus accumbens (NAcc) and putamen of IFN-a-treated animals (p < 0.05). IFN-a had no effect on number of striatal neurons or dopamine terminal density, suggesting no overt neurodegenerative changes. RNA sequencing examined in the caudate, putamen, substantia nigra, and prefrontal cortical subregions revealed that while IFN-a nominally up-regulated limited numbers of genes enriching inflammatory signaling pathways in all regions, robust, whole genome-significant effects of IFN-a were observed specifically in putamen. Genes upregulated in the putamen primarily enriched synaptic signaling, glutamate receptor signaling, and inflammatory/metabolic pathways downstream of IFN-a, including MAPK and PI3K/AKT cascades. Conversely, gene transcripts reduced by IFN-a enriched oxidative phosphorylation (OXPHOS), protein translation, and pathways regulated by dopamine receptors. Unsupervised clustering identified a gene co-expression module in the putamen that was associated with both IFN-a treatment and low dopamine levels, which enriched similar inflammatory, metabolic, and synaptic signaling pathways. IFN-a-induced reductions in dopamine further correlated with genes related to excitotoxic glutamate, kynurenine, and altered dopamine receptor signaling (r = 0.78-97, p < 0.05). These findings provide insight into the immunologic mechanisms and neurobiological consequences of peripheral inflammation effects on dopamine, which may inform novel treatment strategies targeting inflammatory, metabolic or neurotransmitter systems in depressed patients with high inflammation.

Informal caregivers of older adults usually suffer from loneliness, which makes them vulnerable to reduced health outcomes. This study attempted to explore whether internet usage mitigates the effects of loneliness on subjective health among informal caregivers of older adults. A sample of 1089 informal caregivers (mean age = 58.0 ± 15.7 years, 60.3% females) providing unpaid cares for older adults in the United States were investigated. Their loneliness, subjective health, and utilization of caregiving-related online resources were measured. Descriptive statistics and correlation analyses were conducted to summarize the sample's characteristics and determine the relationships among the study variables, respectively. Finally, a multivariate regression analysis with an interaction term was performed to test the moderating effect of internet usage. Results indicated that loneliness was significantly negatively associated with subjective health. Furthermore, after controlling for demographic and caregiving-related factors, the moderating effect of internet usage on the link between loneliness and subjective health was significant, namely, the negative association between loneliness and subjective health was less pronounced at higher levels of internet usage. Hence, in addition to alleviating loneliness, providing caregiving-related online services and promoting positive utilization of resources on the internet may be potential intervention targets to improve informal caregivers' health.

Social interaction with others is essential to life. Although social isolation and loneliness have been implicated as increased risks of cardiometabolic and cardiovascular diseases and all-cause mortality, the cellular and molecular mechanisms by which social connection maintains cardiometabolic and cardiovascular health remain largely unresolved.

To investigate how social connection protects against cardiometabolic and cardiovascular diseases, atherosclerosis-prone, high-fat diet-fed Apoe-/- mouse siblings were randomly assigned to either individual or grouped housing for 12 weeks. Histological, flow cytometric, biochemical, gene, and protein analyses were performed to assess atherosclerotic lesions, systemic metabolism, inflammation, and stress response. The effects of oxytocin on hepatocytes and subsequent cardiometabolic and cardiovascular function were investigated by in vivo and in vitro approaches.

Apoe-/- mice housed individually developed larger vulnerable atherosclerotic lesions by disrupted lipid metabolism compared with those of mice in regular group housing, irrespective of body weight, eating behavior, feeding conditions, sympathetic nervous activity, glucocorticoid response, or systemic inflammation. Mechanistically, the chronic isolation reduced the hypothalamic production of oxytocin, which controls bile acid production and LPL (lipoprotein lipase) activity through the peripheral OXTR (oxytocin receptor) in hepatocytes, whose downstream targets include Cyp7a1, Angptl4, and Angptl8. While hepatocyte-specific OXTR-null mice and mice receiving adeno-associated virus targeting OXTR on hepatocytes led to severe dyslipidemia and aggravated atherosclerosis, oral oxytocin supplementation to socially isolated mice, but not to hepatocyte-specific OXTR conditional knockout mice, improved lipid profiles and retarded atherosclerosis development.

These results identify a novel brain-liver axis that links sociality to hepatic lipid metabolism, thus proposing a potential therapeutic strategy for loneliness-associated atherosclerosis progression.

Loneliness is a complex human trait that is highly polygenic and found to affect gene expression related to inflammatory and immunological functioning. To date, no epigenome-wide association studies of loneliness have tested whether differentially methylated sites are annotated to genes associated with inflammatory and immunological processes. Using 281 individual adult twins' DNA methylation data from the Louisville Twin Study, we performed an epigenome-wide analysis of loneliness to address this gap in the literature. In the discovery analysis, 169 twins were used to prioritize probes and test associations with DNA methylation age acceleration, and 56 independent monozygotic (MZ) twin pairs (112 individuals) were used in a within-family replication analysis. Among the 837,274 sites analyzed, no probe sites were statistically significant at the genome-wide level (p < 5.97 × 10-8), but 25 suggestive sites (p < 5 × 10-5) were annotated to genes related to various biological processes, including inflammatory response and protein-binding functions that extend prior findings. The nominal associations at these suggestive probe sites were highly correlated (r = .72) between the discovery sample and the MZ pair replication sample. Finally, loneliness significantly correlated with the DunedinPACE DNA methylation measure, suggesting that higher levels of loneliness were associated with accelerated epigenetic age as quantified by a measure that indexes longitudinal changes across multiple organ systems.

Gold-standard psychotherapies like cognitive-behavioral therapy (CBT) show beneficial effects, but patient responses vary, indicating a need to predict and optimize treatment efficacy. Gene expression analysis may offer insights into the interplay between psychosocial processes and biological factors that impact psychopathology and therapeutic response. This integrative review examines 17 studies that assess gene expression in the context of psychotherapy, highlighting innovative frameworks for incorporating gene expression analysis in diagnosis, predicting treatment response, and monitoring treatment progress. Current evidence points to transcriptional control pathways downstream of the hypothalamic-pituitary-adrenal (HPA)-axis and sympathetic nervous system (SNS) signaling pathways, particularly their effects on immune cells (e.g., pro-inflammatory processes and wound healing), as key areas for future research. Higher-level pathway analyses, whether theory-based or empirically driven, appear to offer the most robust framework for future studies. This review also discusses significant limitations of current literature and proposes directions for future research.

Social isolation (SI) and loneliness (L) are the long-standing critical concerns impacting the mental well-being of older adults. The COVID-19 pandemic has exacerbated existing vulnerabilities, leading to a notable rise in perceived social isolation (PSI) and its associated risks among an aging population. Reportedly, nearly 35% of older Americans felt lonely before the pandemic, with the pandemic further intensifying these feelings. This commentary examines the multifaceted factors contributing to PSI, including demographic and socio-economic characteristics.

We outline the health risks associated with PSI, including cardiovascular diseases and mental health conditions.

This commentary addresses the potential of information and communication technology (ICT) to alleviate loneliness, despite significant barriers such as the digital divide and technological anxiety among older adults.

This commentary advocates targeted digital literacy interventions and theoretical frameworks to enhance technology adoption and mitigate PSI, ultimately aiming to improve health outcomes and quality of life for the aging population.

Neighborhoods represent complex environments with unique social, cultural, physical, and economic attributes that have major impacts on disparities in health, disease, and survival. Neighborhood disadvantage is associated with shorter breast cancer recurrence-free survival (RFS) independent of individual-level (race, ethnicity, socioeconomic status, insurance, tumor characteristics) and health system-level determinants of health (receipt of guideline-concordant treatment). This persistent disparity in RFS suggests unaccounted mechanisms such as more aggressive tumor biology among women living in disadvantaged neighborhoods compared with advantaged neighborhoods. The objective of this article was to provide a clear framework and biological mechanistic explanation for how neighborhood disadvantage affects cancer survival.

Development of a translational epidemiological framework that takes a translational disparities approach to study cancer outcome disparities through the lens of social genomics and social epigenomics.

The social genomic determinants of health, defined as the physiological gene regulatory pathways (ie, neural/endocrine control of gene expression and epigenetic processes) through which contextual factors, particularly one's neighborhood, can affect activity of the cancer genome and the surrounding tumor microenvironment to alter disease progression and treatment outcomes.

We propose a novel, multilevel determinants of health model that takes a translational epidemiological approach to evaluate the interplay between political, health system, social, psychosocial, individual, and social genomic determinants of health to understand social disparities in oncologic outcomes. In doing so, we provide a concrete biological pathway through which the effects of social processes and social epidemiology come to affect the basic biology of cancer and ultimately clinical outcomes and survival.

The association between poor social relationships and post-stroke mortality remains uncertain, and the evidence regarding the relationship between poor social relationships and the risk of stroke is inconsistent. In this meta-analysis, we aim to elucidate the evidence concerning the risk of stroke and post-stroke mortality among individuals experiencing a poor social relationships, including social isolation, limited social networks, lack of social support, and loneliness.

A thorough search of PubMed, Embase, and the Cochrane Library databases to systematically identify pertinent studies. Data extraction was independently performed by two researchers. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using either a random-effects or fixed-effects model. Sensitivity analyses were conducted to evaluate the reliability of the results. Random-effects meta-regression was performed to explore the sources of heterogeneity in stroke risk estimates between studies. Assessment for potential publication bias was carried out using Egger's and Begg's tests.

Nineteen studies were included, originating from 4 continents and 12 countries worldwide. A total of 1,675,707 participants contributed to this meta-analysis. Pooled analyses under the random effect model revealed a significant association between poor social relationships and the risk of stroke (OR = 1.30; 95%CI: 1.17-1.44), as well as increased risks for post-stroke mortality (OR = 1.36; 95%CI: 1.07-1.73). Subgroup analyses demonstrated associations between limited social network (OR = 1.52; 95%CI = 1.04-2.21), loneliness (OR = 1.31; 95%CI = 1.13-1.51), and lack of social support (OR = 1.66; 95%CI = 1.04-2.63) with stroke risk. The meta-regression explained 75.21% of the differences in reported stroke risk between studies. Random-effect meta-regression results indicate that the heterogeneity in the estimated risk of stroke may originate from the continent and publication year of the included studies.

Social isolation, limited social networks, lack of social support, and feelings of loneliness have emerged as distinct risk factors contributing to both the onset and subsequent mortality following a stroke. It is imperative for public health policies to prioritize the multifaceted influence of social relationships and loneliness in stroke prevention and post-stroke care.

The protocol was registered on May 1, 2024, on the Prospero International Prospective System with registration number CRD42024531036.

Advancing sexual and reproductive health is essential for promoting human rights and women's empowerment, and combating the HIV/AIDS epidemic. A large body of literature across the social sciences emphasizes the importance of social capital, generated through the strength of social networks, for shaping health behaviours. However, large-scale measurement of social capital and social networks remains elusive, especially in the context of low-income countries. Here we delve into the role of social capital dynamics, and in particular social connectedness across communities as measured through Facebook friendship links, in shaping knowledge diffusion and behaviour related to sexual and reproductive health in 495 regions across 33 countries in Africa. Our findings demonstrate that regions with higher levels of social connectedness are more similar in their knowledge about contraception and HIV testing, as well as their adoption of these behaviours. We further observe that the influence of social connectedness becomes stronger when the knowledge gaps between regions are larger. In other words, regions are more similar in behaviours, despite knowledge gaps, when they are socially connected. These insights carry significant policy implications, especially for the design and targeting of public health campaigns. We highlight that social connectedness can serve both as a driver and an obstacle in behaviour formation, underscoring the importance of understanding its influence on health-related outcomes.

Loneliness has been linked to a host of harmful physical and mental health outcomes, detrimental effects that may stem from increases in threat-responding caused by altered fear learning in lonely individuals. In particular, the heightened threat-vigilance that is a hallmark of loneliness may augment the processes by which fear learning occurs, ultimately resulting in a greater number of perceived threatening cues in the environment. However, almost no research has examined how loneliness alters fear learning processes in humans. Here, we investigated the effect of loneliness on fear learning during an evaluative learning procedure in which participants (n = 782) were taught to associate fearful, positive, or neutral control stimuli with neutral images. Results showed that reduced extinction of evaluative fear associations occurred in high (vs. low) lonely individuals, but there was no difference in extinction of evaluative appetitive (also known as positive or reward) associations, suggesting this effect is specific to fear learning. In addition to shedding light on the link between loneliness and poor health, these results represent an important step forward in the growing understanding of the powerful impact of social bonds on fear learning processes.

The present study aimed to investigate the association between COVID-19 and the cumulative incidence of depression and the potential role of sick leave in a large representative sample of German adults.

This retrospective cohort study was based on the Disease Analyzer database (IQVIA) data. This study included individuals aged ≥16 years with a COVID-19 diagnosis in 1284 general practices in Germany between March 2020 and December 2021, and the propensity score matched cohort without COVID-19. Univariable Cox regression analysis assessed the association between COVID-19 and depression.

The present study included 61,736 individuals with and 61,736 without COVID-19 (mean age 46.1 years; 49 % women). Patients visited their physicians about 4.3 times per year during the follow-up period. About 25.5 % of patients were diagnosed with COVID-19 in 2020 and 74.5 % in 2021. In this representative sample of German adults, COVID-19 infection was associated with a higher cumulative incidence of depression, and this cumulative incidence was greater in women than men. As compared with non-COVID-19, COVID-19 with ≤2 weeks sick leave duration was associated with 17 % higher depression risk (HR: 1.17; 95 % CI: 1.09-2.16), COVID-19 with >2-4 weeks sick leave duration with 37 % higher depression risk (HR: 1.37; 95 % CI: 1.11-1.69), and COVID-19 with >4 weeks sick leave duration with 2 times higher depression risk (HR: 2.00; 95 % CI: 1.45-2.76).

COVID-19 sick leave was positively associated with a risk for depression, and the longer the duration of sick leave, the higher the cumulative incidence of depression.

Psychological stress is a major contributing factor to several health problems (e.g., depression, cardiovascular disease). Around 35 % of the world's population suffers from it, including younger generations. Physiologically, stress manifests through neuroendocrine pathways (Hypothalamic-Pituitary-Adrenal (HPA) axis and Sympathetic-Adrenal-Medullary (SAM) system) which culminate in the production of stress mediators like cortisol, epinephrine and norepinephrine. Stress and its mediators have been associated to body aging, through molecular mechanisms such as telomere attrition, mitochondrial dysfunction, cellular senescence, chronic inflammation, and dysbiosis, among others. Regarding its impact in the skin, stress impacts its structural integrity and physiological function. Despite this review focusing on several hallmarks of aging, emphasis was placed on skin microbiota dysbiosis. In this line, several studies, comprising different age groups, demographic contexts and body sites, have reported skin microbiota alterations associated with aging, and some effects of stress mediators on skin microbiota have also been reviewed in this paper. From a different perspective, since it is not a "traditional" stress mediator, oxytocin, a cortisol antagonist, has been related to glucorticoids inhibition and to display positive effects on cellular aging. This hormone dysregulation has been associated to psychological issues such as depression, whereas its upregulation has been linked to positive social interaction.

The COVID-19 pandemic posed unique challenges to cancer-related care as health systems balanced competing risks of timely delivery of care and minimizing exposure to infection in a high-risk, immunocompromised patient population. This study aimed to better understand how pandemic-related factors affected the patient experience of cancer care during this time.

We conducted fifteen semi-structured interviews with adults from rural counties in Maryland who were diagnosed with and/or actively treated for cancer at the TidalHealth healthcare network between January 2020 and October 2022.

Interviews from fifteen participants were analyzed. Two major themes emerged including COVID Impact on Care, and COVID Impact on Mental Health. Subthemes under COVID Impact on Care include Staffing Shortages, Hospital Regulations, Visitation, Importance of Advocacy, and Telehealth Utilization, and subthemes under COVID Impact on Mental Health include Loneliness, Support Networks, and Perceptions of COVID and Personal Protection. Overall, participants described positive care experiences despite notable delays, disruptions to continuity of care, difficult transitions to telemedicine, visitation policies that limited patient support, increased mental health struggles related to social distancing measures, and greater desire for patient advocacy.

Our findings reveal significant impacts of the COVID-19 pandemic on experiences of cancer treatment and survivorship in a more vulnerable, rural patient population with lower healthcare access and income level. Our findings suggest areas for targeted interventions to limit disruptions to quality care in future public health emergencies.

Stress resilience is the phenomenon that some people maintain their mental health despite exposure to adversity or show only temporary impairments followed by quick recovery. Resilience research attempts to unravel the factors and mechanisms that make resilience possible and to harness its insights for the development of preventative interventions in individuals at risk for acquiring stress-related dysfunctions. Biological resilience research has been lagging behind the psychological and social sciences but has seen a massive surge in recent years. At the same time, progress in this field has been hampered by methodological challenges related to finding suitable operationalizations and study designs, replicating findings, and modeling resilience in animals. We embed a review of behavioral, neuroimaging, neurobiological, and systems biological findings in adults in a critical methods discussion. We find preliminary evidence that hippocampus-based pattern separation and prefrontal-based cognitive control functions protect against the development of pathological fears in the aftermath of singular, event-type stressors [as found in fear-related disorders, including simpler forms of posttraumatic stress disorder (PTSD)] by facilitating the perception of safety. Reward system-based pursuit and savoring of positive reinforcers appear to protect against the development of more generalized dysfunctions of the anxious-depressive spectrum resulting from more severe or longer-lasting stressors (as in depression, generalized or comorbid anxiety, or severe PTSD). Links between preserved functioning of these neural systems under stress and neuroplasticity, immunoregulation, gut microbiome composition, and integrity of the gut barrier and the blood-brain barrier are beginning to emerge. On this basis, avenues for biological interventions are pointed out.

To determine the association between objective (geospatial) and subjective (perceived) measures of neighborhood disadvantage (ND) and aggressive breast cancer tumor biology, defined using validated social adversity-associated transcription factor (TF) activity and clinical outcomes.

ND is associated with shorter breast cancer recurrence-free survival (RFS), independent of individual, tumor, and treatment characteristics, suggesting potential unaccounted biological mechanisms by which ND influences RFS.

We quantified TF-binding motif prevalence within promoters of differentially expressed genes for 147 tissue samples prospectively collected on the protocol. Covariate-adjusted multivariable regression analyzed objective and subjective ND scores with 5 validated TFs of social adversity and aggressive biology-pro-inflammatory activity [nuclear factor-κB ( NF-kB ), activator protein 1 ( AP-1 )], sympathetic nervous system (SNS) activity [cyclic 3'-5' adenosine monophosphate response element-binding protein ( CREB )], and protective cellular responses [interferon-regulatory factor ( IRF ) and signal transducer and activator of transcription ( STAT )]. To clinically validate these TFs as prognostic biomarkers of aggressive biology, logistic regression and multivariable Cox proportional-hazards models analyzed their association with Oncotype DX scores and RFS, respectively.

Increasing objective ND was associated with aggressive tumor biology (up-regulated NF-kB , activator protein 1, down-regulated IRF , and signal transducer and activator of transcription) and SNS activation (up-regulated CREB ). Increasing subjective ND (eg, threat to safety) was associated with up-regulated NF-kB and CREB and down-regulated IRF . These TF patterns were associated with high-risk Oncotype DX scores and shorter RFS.

In the largest human social genomics study, objective and subjective ND were significantly associated with TFs of aggressive biology and SNS activation. These TFs also correlated with worse clinical outcomes, implicating SNS activation as one potential mechanism behind ND survival disparities. These findings remain to be validated in a national cohort.

Having associations with a range of adverse physical health outcomes including mortality, loneliness is increasingly recognized as a pressing public health concern, but the mechanisms studied to date do not yet explain all loneliness-related health risk. We sought to evaluate whether epigenetic influences on DNA methylation could help explain the relationship between loneliness and health. To do so, we first estimated associations between loneliness and epigenetic age acceleration (EAA) in a subsample of participants in the study of midlife in the United States (n = 1,310), before testing whether EAA mediated and/or moderated the association between loneliness and the onset of chronic health conditions in older adulthood (n = 445 completing longitudinal follow-ups). Greater loneliness was weakly associated with greater EAA in the Horvath, DunedinPACE, and GrimAge measures after accounting for demographic (0.08 ≤ β ≤ 0.11) and behavioral (0.06 ≤ β ≤ 0.08) covariates. Loneliness also predicted increases in chronic condition counts and these effects were more pronounced for individuals with higher DunedinPACE EAA values (interaction term β = 0.09, p = .009), suggesting possible synergistic impacts. EAA measures appear to be promising in helping to understand individual variations in the health impacts of loneliness, but the specific mechanisms involved require further research. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Loneliness is a growing public health concern associated with substantial negative mental and physical health outcomes. Loneliness is especially relevant for individuals with a chronic illness, perhaps more so if their illness is rare. Little is known about the psychosocial experience of individuals with a rare chronic illness, and whether and how it may differ from the experience of individuals with common chronic illnesses. We compared the magnitude of loneliness in persons with a rare or common chronic illness and examined theoretically guided predictors of loneliness as follows: stigma, illness intrusiveness, social comparison, social support, support from healthcare providers, and self-efficacy.

Individuals with a chronic illness (common or rare) completed an anonymous online survey (N = 952).

Individuals with common chronic illnesses were as lonely as those with a rare chronic illness. Loneliness in both groups was higher than that in population norms. Regression analyses reveal that independent of other predictors, loneliness was especially high among people who feel stigmatized by others, those who have less social support available, and people whose functioning is more disrupted by their illness (all p values < 0.01).

The similarity of loneliness in these groups reinforces the value of further systematic research to identify the needs of individuals with any type of chronic illness. Study findings highlight the importance of examining internalized stigma and social support as possible targets of intervention to reduce loneliness among individuals with a chronic illness, recognizing some of the unique features and challenges of their disorders, whether common or rare.

The COVID-19 pandemic has intensified feelings of loneliness, especially among postpartum women. This nationwide Japanese longitudinal study assessed the impact of such feelings on depressive symptoms and mother-to-infant bonding difficulties (MIBD), two pivotal determinants of maternal and infant well-being.

Starting with a baseline survey conducted between July and August 2021, we tracked 1254 postpartum Japanese women who initially reported minimal depressive symptoms (i.e., Edinburgh Postnatal Depression Scale < 9) and MIBD (i.e., Mother-to-Infant Bonding Scale < 5), over a follow-up period of approximately 6 months. Baseline loneliness was evaluated with the UCLA Loneliness Scale Short-Form (UCLA-LS3-SF3).

Forty-nine percent of the sample reported the presence of baseline feelings of loneliness. After propensity score matching on sociodemographics and various pregnancy, childbirth, and COVID-19-related aspects, baseline loneliness was associated with increased risks of later depressive symptoms but not MIBD. Using restricted cubic spline logistic regression and considering loneliness as a continuous variable, we found a positive increasing quadratic relationship with depressive symptoms. As loneliness increased, so did the risk of later depressive symptoms. However, there was no significant association between loneliness and MIBD. These results were confirmed through a sensitivity analysis using inverse probability weighting to address attrition bias.

Feelings of postpartum loneliness are associated with future risks of depressive symptoms. The data suggests that addressing loneliness in postpartum women early is crucial to safeguarding their well-being and that of their infants.

The COVID-19 pandemic emphasized the pivotal role of the social environment, prompting a surge in research on its impact on well-being and health. This article aims to examine the link between the social environment, the immune system, and health outcomes, with a particular focus on positive aspects like social support and prosocial behaviors that are under-explored. Different aspects of the social environment are examined: the negative effects of loneliness and adverse social conditions, contrasted with the benefits of social support and prosocial behaviors. While the mechanisms behind negative effects are partially studied, those driving the positive effects remain elusive. Understanding the mechanisms of lack of social connection and their effects will allow us to explore the benefits of social connections and whether they can reverse the adverse outcomes. Potential psychoneuroimmunology mechanisms are proposed, highlighting the promotion of a 'safe' state by the vagus nerve, oxytocin circuits, and the additional contribution of the reward pathways. This article reviews the need to bridge knowledge gaps, urging further research to study the causal effects of positive social interactions on immune response and health outcomes to raise clinical awareness and interventions. Such interventions may include integrating lonely individuals with prosocial activities, thereby improving their physical and mental health. There is growing potential to harness the power of social connections for the betterment of individual health and society as a whole.

Takotsubo syndrome (TTS) is a cardiomyopathy that clinically presents as a transient and reversible left ventricular wall motion abnormality (LVWMA). Recovery can occur spontaneously within hours or weeks. Studies have shown that it mainly affects older people. In particular, there is a higher prevalence in postmenopausal women. Physical and emotional stress factors are widely discussed and generally recognized triggers. In addition, the hypothalamic-pituitary-adrenal (HPA) axis and the associated glucocorticoid-dependent negative feedback play an important role in the resulting immune response. This review aims to highlight the unstudied aspects of the trigger factors of TTS. The focus is on emotional stress/chronic unpredictable mild stress (CUMS), which is influenced by estrogen concentration and noradrenaline, for example, and can lead to changes in the behavioral, hormonal, and autonomic systems. Age- and gender-specific aspects, as well as psychological effects, must also be considered. We hypothesize that this leads to a stronger corticosteroid response and altered feedback of the HPA axis. This may trigger proinflammatory markers and thus immunosuppression, inflammaging, and sympathetic overactivation, which contributes significantly to the development of TTS. The aim is to highlight the importance of CUMS and psychological triggers as risk factors and to make an exploratory proposal based on the new knowledge. Based on the imbalance between the sympathetic and parasympathetic nervous systems, transcutaneous vagus nerve stimulation (tVNS) is presented as a possible new therapeutic approach.

The COVID-19 pandemic has brought significant changes in daily life for humanity and has had a profound impact on mental health. As widely acknowledged, the pandemic has led to notable increases in rates of anxiety, depression, distress, and other mental health-related issues, affecting both infected patients and non-infected individuals. COVID-19 patients and survivors face heightened risks for various neurological and psychiatric disorders and complications. Vulnerable populations, including those with pre-existing mental health conditions and individuals living in poverty or frailty, may encounter additional challenges. Tragically, suicide rates have also risen, particularly among young people, due to factors such as unemployment, financial crises, domestic violence, substance abuse, and social isolation. Efforts are underway to address these mental health issues, with healthcare professionals urged to regularly screen both COVID-19 and post-COVID-19 patients and survivors for psychological distress, ensuring rapid and appropriate interventions. Ongoing periodic follow-up and multidimensional, interdisciplinary approaches are essential for individuals experiencing long-term psychiatric sequelae. Preventive strategies must be developed to mitigate mental health problems during both the acute and recovery phases of COVID-19 infection. Vaccination efforts continue to prioritize vulnerable populations, including those with mental health conditions, to prevent future complications. Given the profound implications of mental health problems, including shorter life expectancy, diminished quality of life, heightened distress among caregivers, and substantial economic burden, it is imperative that political and health authorities prioritize the mental well-being of all individuals affected by COVID-19, including infected individuals, non-infected individuals, survivors, and caregivers.

Animals respond to changes in the environment which affect their internal state by adapting their behaviors. Social isolation is a form of passive environmental stressor that alters behaviors across animal kingdom, including humans, rodents, and fruit flies. Social isolation is known to increase violence, disrupt sleep and increase depression leading to poor mental and physical health. Recent evidences from several model organisms suggest that social isolation leads to remodeling of the transcriptional and epigenetic landscape which alters behavioral outcomes. In this review, we explore how manipulating social experience of fruit fly Drosophila melanogaster can shed light on molecular and neuronal mechanisms underlying isolation driven behaviors. We discuss the recent advances made using the powerful genetic toolkit and behavioral assays in Drosophila to uncover role of neuromodulators, sensory modalities, pheromones, neuronal circuits and molecular mechanisms in mediating social isolation. The insights gained from these studies could be crucial for developing effective therapeutic interventions in future.

This review describes associations between dementia and loneliness on the neurobiological and epidemiological levels according to the recent body of literature. The aim of this study was to highlight major lines of research in this field. Sociocognitive skills and social interactions present complex interdependencies with dementia which may be explained by two theories. According to the first one, not sufficiently engaging in social or cognitive activities results in brain atrophy. The second one claims that brain neurogenesis and synaptic density are being increased by social connections. The relationship between loneliness and dementia could be mediated by sensory loss, including hearing and visual impairment, as well as depression and psychotic symptoms. Loneliness itself might cause a depletion in sensory and cognitive stimulation which results in a decrease in neural reserve. Certain changes in the structures of the brain caused by loneliness were found in imaging examination. Loneliness appears to be a crucial risk factor for dementia in recent times due to the modern lifestyle and consequences of the outbreak of COVID-19. Additional studies are required to understand more completely the key tenets of this topic and therefore to improve the prevention and treatment of dementia.

Social isolation and loneliness are two common but undervalued conditions associated with a poor quality of life, decreased overall health and mortality. In this review, we aim to discuss the health consequences of social isolation and loneliness. We first provide the potential causes of these two conditions. Then, we explain the pathophysiological processes underlying the effects of social isolation and loneliness in disease states. Afterwards, we explain the important associations between these conditions and different non-communicable diseases, as well as the impact of social isolation and loneliness on health-related behaviours. Finally, we discuss the current and novel potential management strategies for these conditions. Healthcare professionals who attend to socially isolated and/or lonely patients should be fully competent in these conditions and assess their patients thoroughly to detect and properly understand the effects of isolation and loneliness. Patients should be offered education and treatment alternatives through shared decision-making. Future studies are needed to understand the underlying mechanisms better and to improve the treatment strategies for both social isolation and loneliness.

Loneliness is linked to declining physical health across cardiovascular, inflammatory, metabolic, and cognitive domains. As a result, loneliness is increasingly being recognized as a public health threat, though the mechanisms that have been studied do not yet explain all loneliness-related health risk. Potential mechanisms include loneliness having 1.) direct, causal impacts on health, possibly maintained by epigenetic modification, 2.) indirect effects mediated through health-limiting behaviors, and 3.) artifactual associations perhaps related to genetic overlap and reverse causation. In this scoping review, we examine the evidence surrounding each of these pathways, with a particular emphasis on emerging research on epigenetic effects, in order to evaluate how loneliness becomes biologically embedded. We conclude that there are significant gaps in our knowledge of how psychosocial stress may lead to physiological changes, so more work is needed to understand if, how, and when loneliness has a direct influence on health. Hypothalamic-pituitary adrenocortical axis disruptions that lead to changes in gene expression through methylation and the activity of transcription factor proteins are one promising area of research but are confounded by a number of unmeasured factors. Therefore, wok is needed using causally informative designs, such as twin and family studies and intensively longitudinal diary studies.

Although the role of life stressors in breast cancer remains unclear, social isolation is consistently associated with increased breast cancer risk and mortality. Social isolation can be defined as loneliness or an absence of perceived social connections. In female mice and rats, social isolation is mimicked by housing animals 1 per cage. Social isolation causes many biological changes, of which an increase in inflammatory markers and disruptions in mitochondrial and cellular metabolism are commonly reported. It is not clear how the 2 traditional stress-induced pathways, namely, the hypothalamic-pituitary-adrenocortical axis (HPA), resulting in a release of glucocorticoids from the adrenal cortex, and autonomic nervous system (ANS), resulting in a release of catecholamines from the adrenal medulla and postganglionic neurons, could explain the increased breast cancer risk in socially isolated individuals. For instance, glucocorticoid receptor activation in estrogen receptor positive breast cancer cells inhibits their proliferation, and activation of β-adrenergic receptor in immature immune cells promotes their differentiation toward antitumorigenic T cells. However, activation of HPA and ANS pathways may cause a disruption in the brain-gut-microbiome axis, resulting in gut dysbiosis. Gut dysbiosis, in turn, leads to an alteration in the production of bacterial metabolites, such as short chain fatty acids, causing a systemic low-grade inflammation and inducing dysfunction in mitochondrial and cellular metabolism. A possible causal link between social isolation-induced increased breast cancer risk and mortality and gut dysbiosis should be investigated, as it offers new tools to prevent breast cancer.

Epidemiological studies have reported associations between subjective well-being (SWB), depression, and suicide with COVID-19 illness, but the causality has not been established. We performed a two-sample Mendelian randomization (MR) analysis to investigate the causal link between SWB, depression, suicide and COVID-19 susceptibility and severity.

Summary statistics for SWB (298,420 cases), depression (113,769 cases) and suicide (52,208 cases) were obtained from three large-scale GWAS. Data on the associations between the Single Nucleotide Polymorphisms (SNPs) and COVID-19 (159,840 cases), hospitalized COVID-19 (44,986 cases), and severe COVID-19 (18,152 cases) were collected from the COVID-19 host genetics initiative. The causal estimate was calculated by the Inverse Variance Weighted, MR Egger and Weighted Median methods. Sensitivity tests were used to evaluate the validity of the causal relationship.

Our results showed that genetically predicted SWB (OR = 0.98, 95 % CI: 0.86-1.10, P = 0.69), depression (OR = 0.76, 95 % CI: 0.54-1.06, P = 0.11), and suicide (OR = 0.99, 95 % CI: 0.96-1.02, P = 0.56) were not causally related to COVID-19 susceptibility. Similarly, we did not find a potential causal relationship between SWB, depression, suicide and COVID-19 severity.

This indicated that positive or negative emotions would not make COVID-19 better or worse, and strategies that attempted to use positive emotions to improve COVID-19 symptoms may be useless. Improving knowledge about the SARS-CoV-2 and timely medical intervention to reduce panic during a pandemic is one of the effective measures to deal with the current decrease in well-being and increase in depression and suicide rates.

Social connections are crucial to human health and well-being. Previous research on molecular mechanisms in health has focused primarily on the individual-level perception of social connections (e.g., loneliness). This study adopted socio-centric social network analysis that includes all social ties from the entire population of interest to examine the group-level social connections and their association with a molecular genomic measure of health.

Using socio-centric (global) social network data from an entire village in Korea, we investigated how social network characteristics are related to immune cell gene expression among older adults. Blood samples were collected (N = 53, 65-79 years) and mixed effect linear model analyses were performed to examine the association between social network characteristics and Conserved Transcriptional Response to Adversity (CTRA) RNA expression patterns.

Social network positions measured by k-core score, the degree of cohesive core positions in an entire village, were significantly associated with CTRA downregulation. Such associations emerged above and beyond the effects of perceived social isolation (loneliness) and biobehavioral risk factors (smoking, alcohol, BMI, etc.). Social network size, defined as degree centrality, was also associated with reduced CTRA gene expression, but its association mimicked that of perceived social isolation (loneliness).

The current findings implicate community-level social network characteristics in the regulation of individual human genome function above and beyond individual-level perceptions of connectedness.

Social determinants of health (SDoHs) are nonmedical factors that significantly impact health and longevity. We found no published reviews on the biology of SDoHs in schizophrenia-spectrum psychotic disorders (SSPD).

We present an overview of pathophysiological mechanisms and neurobiological processes plausibly involved in the effects of major SDoHs on clinical outcomes in SSPD.

This review of the biology of SDoHs focuses on early-life adversities, poverty, social disconnection, discrimination including racism, migration, disadvantaged neighborhoods, and food insecurity. These factors interact with psychological and biological factors to increase the risk and worsen the course and prognosis of schizophrenia. Published studies on the topic are limited by cross-sectional design, variable clinical and biomarker assessments, heterogeneous methods, and a lack of control for confounding variables. Drawing on preclinical and clinical studies, we propose a biological framework to consider the likely pathogenesis. Putative systemic pathophysiological processes include epigenetics, allostatic load, accelerated aging with inflammation (inflammaging), and the microbiome. These processes affect neural structures, brain function, neurochemistry, and neuroplasticity, impacting the development of psychosis, quality of life, cognitive impairment, physical comorbidities, and premature mortality. Our model provides a framework for research that could lead to developing specific strategies for prevention and treatment of the risk factors and biological processes, thereby improving the quality of life and increasing the longevity of people with SSPD.

Biology of SDoHs in SSPD is an exciting area of research that points to innovative multidisciplinary team science for improving the course and prognosis of these serious psychiatric disorders.

Recent theorizing argues that online communication technologies provide powerful, although precarious, means of emotional regulation. We develop this understanding further. Drawing on subjective reports collected during periods of imposed social restrictions under COVID-19, we focus on how this precarity is a source of emotional dysregulation. We make our case by organizing responses into five distinct but intersecting dimensions wherein the precarity of this regulation is most relevant: infrastructure, functional use, mindful design (individual and social), and digital tact. Analyzing these reports, along with examples of mediating technologies (i.e., self-view) and common interactive dynamics (e.g., gaze coordination), we tease out how breakdowns along these dimensions are sources of affective dysregulation. We argue that the adequacy of available technological resources and competencies of various kinds matter greatly to the types of emotional experiences one is likely to have online. Further research into online communication technologies as modulators of both our individual and collective well-being is urgently needed, especially as the echoes of the digital push that COVID-19 initiated are set to continue reverberating into the future.

A systematic scoping review was conducted to explore the current evidence on the experience of loneliness influencing well-being among youths. The electronic databases Scopus, APA PsycINFO, Emerald Insight and One Search were used to identify relevant studies, followed by an analysis of the text words contained in the title and abstract, and of the index terms used to describe the article. Reference lists of all shortlisted articles were searched for additional studies. 20 studies (quantitative, qualitative and mixed) published in the English language were identified for inclusion. Findings illustrate that the experience of loneliness is a complex, evolutionary process influenced by relational and environmental factors. Results from the studies identified factors that promote lower experience of loneliness and better well-being in future life stages. Future research can substantiate the issues related to young individuals being socially isolated from others for a prolonged duration.

Social interaction difficulties are a hallmark of psychotic disorders, which in some cases can be definitely traced back to autoimmunological causes. Interestingly, systemic and intrathecal inflammation have been shown to significantly influence social processing by increasing sensitivity to threatening social stimuli, which bears some resemblance to psychosis. In this article, we review evidence for the involvement of systemic and intrathecal inflammatory processes in psychotic disorders and how this might help to explain some of the social impairments associated with this group of disorders. Vice versa, we also discuss evidence for the immunomodulatory function of social interactions and their potential role for therapeutic interventions in psychotic disorders.

To determine the impact of a solitary lifestyle on health-related quality of life (HRQoL) in adults with obstructive sleep apnea (OSA).

This was a prospective cohort study; patients diagnosed with OSA but not receiving continuous positive airway pressure (CPAP) therapy were enrolled in our study. These participants completed basic information and the Short Form-36 Health Survey (SF-36) at baseline and were divided into the living alone and living with others groups. Telephone follow-up was performed 1 year later to re-evaluate the SF-36. Differences in health status between and within groups were assessed. In addition, variables associated with changes in the health of the whole population were examined.

A total of 402 patients with OSA were enrolled, including 120 in the living alone group and the rest in the living with others group. After a year, mental health scores of the living alone group decreased (55.7 ± 21.5 versus 54.1 ± 22.7, p = 0.001), while physical functioning scores of the living with others group increased significantly (82.1 ± 24.7 versus 82.6 ± 24.2, p = 0.006). In the whole population, the determinants of mental health change after 1 year from baseline were alcohol drinking (beta coefficient - 1.169, 95% CI - 2.03 to - 0.309, p = 0.008) and solitary living (beta coefficient - 1.135, 95% CI - 2.072 to - 0.199, p = 0.018).

Regarding all initial variables, alcohol drinking and solitary living seem to be the predictors of mental health change of patients with OSA in China. We speculate that to improve the quality of life of such people, the medical staff could provide certain social support for them.

The coronavirus disease 2019 (COVID-19) pandemic is an ongoing geriatric health emergency with a substantial increase in the prevalence of medical and mental health issues, particularly among older adults living in residential care homes. The knowledge of the risk and protective factors related to the psychological impact of the COVID-19 pandemic on older adults living in residential care homes is based on limited data. This study aimed to investigate whether loneliness mediates the effects of fear generated by a pandemic on depression. Additionally, we hypothesized that self-compassion moderates the effect of loneliness on depression. A sample comprised 323 older adults (females: n = 141, males: n = 182) with mean age = 74.98 years (standard deviation = 6.59, age 65-90) completed a survey comprising the Fear of COVID-19 Scale, De Jung Gierveld Loneliness Scale, the nine-item Patient Health Questionnaire, and the Self-compassion Scale. The results revealed that the total effect of fear on depression was statistically significant, with a medium effect size (Cohen's f 2 = .14) and this association was partially mediated by loneliness (β = .11, SE = .04, P < .001, t = 2.91, 95% CI 0.04-0.19). The self-compassion also moderated the loneliness effect on depression. The findings of this study support COVID-19 evidence, indicating that a greater level of fear generated by the pandemic is linked to depression and loneliness. The findings support the notion that self-compassion mitigates the adverse effects of stressful events in older adults. Customized self-compassion programs may be effective loneliness-mitigating interventions for older adults living in residential care homes.

The online version contains supplementary material available at 10.1007/s11469-023-01014-0.

The association of cardiovascular (CV) risk with social isolation and loneliness remains poorly studied. The purpose of this cross-sectional study was to investigate the associations between social isolation and loneliness with estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk.

Among 302,553 volunteers of the UK Biobank population, social isolation and loneliness were assessed with a questionnaire. Associations between social isolation and loneliness with ASCVD risk were estimated using multiple gender regressions.

Men presented a higher estimated 10-year ASCVD risk (8.63% vs. 2.65%, p < 0.001) and higher proportions of social isolation (9.13% vs. 8.45%, p < 0.001) and loneliness (6.16% vs. 5.57%, p < 0.001) than women. In all covariate-adjusted models, social isolation was associated with an increased ASCVD risk in men (B = 0.21 (0.16; 0.26), p < 0.001) and women (B = 0.12 (0.10; 0.14), p < 0.001). Loneliness was associated with an increased ASCVD risk in men (B = 0.08 (0.03; 0.14), p = 0.001) but not in women (p = 0.217). A significant interaction was observed between social isolation and loneliness with ASCVD risk in men (p = 0.009) and women (p = 0.016). After adjustment for all covariates, both social isolation and loneliness were significantly associated with ASCVD risk in men (B = 0.44 (0.28; 0.61), p < 0.001) and women (B = 0.20 (0.12; 0.29), p < 0.001).

Social isolation was associated with a higher estimated 10-year ASCVD risk in both genders but only loneliness among men. Social isolation and loneliness can be considered potential added risk factors for CV risk. Health policies should address these notions in prevention campaigns, in addition to traditional risk factors.

The present study revisits the assumption in American culture, based in "family privilege," that children fare better in two-parent households by longitudinally examining associations between family structure, process, and adolescent behavior.

Societal assumptions and cross-sectional research suggest that there is a difference in child adjustment across varying family structures. Relatedly, the family process literature emphasizes the importance of parent-child relationship quality in addition to family structure on child adjustment.

We utilized a longitudinal, prospective design that assessed family structures on nine occasions covering a 12-year period beginning when the target child was 2 years of age for a large (N = 714), ethnically and racially diverse sample of low-income families. We examined the relation between self-reported, teacher-reported, and primary caregiver-reported adolescent disruptive and internalizing problem behavior across family structures and parent-child relationship quality.

Across seven identified family structures, adolescent behavior did not differ after accounting for middle-childhood adjustment and relevant contextual factors. However, consistent with family process models of child adjustment, positive parent-child relationship quality predicted lower rates of adolescent maladaptive behavior.

These findings serve to combat stigma related to family structures that deviate from married parents raising their children and highlight the need for interventions designed to foster positive parent-child relationships.

Policy makers and practitioners should aim to support efforts to foster positive parent-child relationships across types of family structures and refrain from promoting or discouraging the formations of specific family structure types.

Addressing social disparities in health and well-being requires understanding how the effects of discrimination become biologically embedded, and how embedding processes might vary across different demographic contexts. Emerging research suggests that a threat-related gene expression response may contribute to social disparities in health. We tested a contextual vulnerability model of discrimination embedding using an empirical intersectionality (interaction discovery) analysis of pro-inflammatory gene expression in a national sample of non-institutionalized, English-speaking adults with RNA biomarker data (n = 543). At the time of data collection, the average age of participants was 55 years (SD = 13.26) and approximately half identified as female (50.46%). Most participants identified as White (∼73%) and had some college experience (∼60%). Results showed significant variation in the strength of association between daily discrimination and inflammatory gene expression by race and sex (b = -0.022; 95% CI:-0.038,-0.005, p = .009) with the estimated marginal association larger for racially-minoritized males (b = 0.007; 95% CI:-0.003,0.017, p = .163), compared to White males (b = -0.006; 95% CI:-0.013,0.001, p = .076). This study indicates that the link between daily discrimination and inflammatory gene expression may vary by sociodemographic characteristics. To improve initiatives and policies aimed at ameliorating disparities within populations, greater attention is needed to understand how interlocking systems of inequalities contribute to physiological health.

Since the onset of COVID-19 pandemic, many case reports and case series dealt with new-onset psychotic disorders in patients either infected with SARS-CoV-2 or thematically linked to the pandemic, but without an infection. Our aim was to provide a comprehensive collection of these reports to illustrate the nature of these psychoses.

We conducted a literature search in MEDLINE, Embase, PsycINFO, using search terms regarding first-episode psychotic disorders in the context of corona.

96 case reports or case series covering 146 patients (62 without and 84 with SARS-CoV-2 infection) were found. Compared to patients without infection, patients with infection showed significantly more often visual hallucinations (28.6% vs 8.1%), confusion (36.9% vs 11.3%), an acute onset of illness (88.5% vs 59.6%) and less often depression (13.1% vs 35.5%) and a delusional content related to the pandemic (29.5% vs 78.3%). Both groups had an equally favourable outcome with a duration of psychosis ≤2 weeks in half and full remission in two-thirds of patients. In patients with infection, signs of inflammation were reported in 78.3% and increased CRP in 58.6%. While reports on patients with infection are continuously published, no report about patients without infection was found after July 2020.

Cases without infection were considered reactive and originated all from the first wave of the corona pandemic. In cases with infection, inflammation was considered as the main pathogenetic factor but was not found in all patients. Diagnosis was impeded by the overlap of psychosis with delirium.

Multisystem inflammatory syndrome in children (MIS-C) is a postinfectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related complication that has disproportionately affected racial/ethnic minority children. We conducted a pilot study to investigate risk factors for MIS-C aiming to understand MIS-C disparities.

This case-control study included MIS-C cases and SARS-CoV-2-positive outpatient controls less than 18 years old frequency-matched 4:1 to cases by age group and site. Patients hospitalized with MIS-C were admitted between March 16 and October 2, 2020, across 17 pediatric hospitals. We evaluated race, ethnicity, social vulnerability index (SVI), insurance status, weight-for-age and underlying medical conditions as risk factors using mixed effects multivariable logistic regression.

We compared 241 MIS-C cases with 817 outpatient SARS-CoV-2-positive at-risk controls. Cases and controls had similar sex, age and U.S. census region distribution. MIS-C patients were more frequently previously healthy, non-Hispanic Black, residing in higher SVI areas, and in the 95th percentile or higher for weight-for-age. In the multivariable analysis, the likelihood of MIS-C was higher among non-Hispanic Black children [adjusted odds ratio (aOR): 2.07; 95% CI: 1.23-3.48]. Additionally, SVI in the 2nd and 3rd tertiles (aOR: 1.88; 95% CI: 1.18-2.97 and aOR: 2.03; 95% CI: 1.19-3.47, respectively) were independent factors along with being previously healthy (aOR: 1.64; 95% CI: 1.18-2.28).

In this study, non-Hispanic Black children were more likely to develop MIS-C after adjustment for sociodemographic factors, underlying medical conditions, and weight-for-age. Investigation of the potential contribution of immunologic, environmental, and other factors is warranted.