The Type I interferon antiviral gene program is impaired by lockdown and preserved by caregiving.

Previous research has linked perceived social isolation (loneliness) to reduced antiviral immunity, but the immunologic effects of the objective social isolation imposed by pandemic "shelter in place" (SIP) policies is unknown. We assessed the immunologic impact of SIP by relocating 21 adult male rhesus macaques from 2,000-m2 field cage communities of 70 to 132 other macaques to 2 wk of individual housing in indoor shelters. SIP was associated with 30% to 50% reductions in all circulating immune cell populations (lymphocytes, monocytes, and granulocytes), down-regulation of Type I interferon (IFN) antiviral gene expression, and a relative up-regulation of CD16- classical monocytes. These effects emerged within the first 48 h of SIP, persisted for at least 2 wk, and abated within 4 wk of return to social housing. A subsequent round of SIP in the presence of a novel juvenile macaque showed comparable reductions in circulating immune cell populations but reversal of Type I IFN reductions and classical monocyte increases observed during individual SIP. Analyses of lymph node tissues showed parallel up-regulation of Type I IFN genes and enhanced control of viral gene expression during juvenile-partnered SIP compared to isolated SIP. These results identify a significant adverse effect of SIP social isolation on antiviral immune regulation in both circulating immune cells and lymphoid tissues, and they suggest a potential behavioral strategy for ameliorating gene regulatory impacts (but not immune cell declines) by promoting prosocial engagement during SIP.

Phenome-wide investigation of health outcomes associated with genetic predisposition to loneliness.

Humans are social animals that experience intense suffering when they perceive a lack of social connection. Modern societies are experiencing an epidemic of loneliness. Although the experience of loneliness is universally human, some people report experiencing greater loneliness than others. Loneliness is more strongly associated with mortality than obesity, emphasizing the need to understand the nature of the relationship between loneliness and health. Although it is intuitive that circumstantial factors such as marital status and age influence loneliness, there is also compelling evidence of a genetic predisposition toward loneliness. To better understand the genetic architecture of loneliness and its relationship with associated outcomes, we extended the genome-wide association study meta-analysis of loneliness to 511 280 subjects, and detect 19 significant genetic variants from 16 loci, including four novel loci, as well as 58 significantly associated genes. We investigated the genetic overlap with a wide range of physical and mental health traits by computing genetic correlations and by building loneliness polygenic scores in an independent sample of 18 498 individuals with EHR data to conduct a PheWAS with. A genetic predisposition toward loneliness was associated with cardiovascular, psychiatric, and metabolic disorders and triglycerides and high-density lipoproteins. Mendelian randomization analyses showed evidence of a causal, increasing, the effect of both BMI and body fat on loneliness. Our results provide a framework for future studies of the genetic basis of loneliness and its relationship to mental and physical health.

Anthropomorphizing without Social Cues Requires the Basolateral Amygdala.

Anthropomorphism, the attribution of distinctively human mental characteristics to nonhuman animals and objects, illustrates the human propensity for extending social cognition beyond typical social targets. Yet, its processing components remain challenging to study because they are typically all engaged simultaneously. Across one pilot study and one focal study, we tested three rare people with basolateral amygdala lesions to dissociate two specific processing components: those triggered by attention to social cues (e.g., seeing a face) and those triggered by endogenous semantic knowledge (e.g., imbuing a machine with animacy). A pilot study demonstrated that, like neurologically intact control group participants, the three amygdala-damaged participants produced anthropomorphic descriptions for highly socially salient stimuli but not for stimuli lacking clear social cues. A focal study found that the three amygdala participants could anthropomorphize animate and living entities normally, but anthropomorphized inanimate stimuli less than control participants. Our findings suggest that the amygdala contributes to how we anthropomorphize stimuli that are not explicitly social.

Associations between loneliness and personality are mostly driven by a genetic association with Neuroticism.

OBJECTIVE: Loneliness is an aversive response to a discrepancy between desired and actual social relationships and correlates with personality. We investigate the relationship of loneliness and personality in twin family and molecular genetic data. METHOD: Phenotypic correlations between loneliness and the Big Five personality traits were estimated in 29,625 adults, and in a group with genome-wide genotype data (N = 4,222), genetic correlations were obtained. We explored whether genetic correlations may reflect causal relationships by investigating within monozygotic twin pair differences (Npairs = 2,662), by longitudinal within-subject changes in personality and loneliness (N = 4,260-9,238 longitudinal comparisons), and by longitudinal cross-lagged panel analyses (N = 15,628). Finally, we tested whether genetic correlations were due to cross-trait assortative mating (Nspouse pairs = 4,436). RESULTS: The strongest correlations with loneliness were observed for Neuroticism (r = .55) and Extraversion (r = -.33). Only Neuroticism showed a high correlation with loneliness independent of other personality traits (r = .50), so follow-up analyses focused on Neuroticism. The genetic correlation between loneliness and Neuroticism from genotyped variants was .71; a significant reciprocal causal relationship and nonsignificant cross-trait assortative mating imply that this is at least partly due to mediated pleiotropy. CONCLUSIONS: We show that the relationship between loneliness and personality is largely explained by its relationship with Neuroticism, which is substantially genetic in nature.

Trait and State Levels of Loneliness in Early and Late Adolescents: Examining the Differential Reactivity Hypothesis.

According to the differential reactivity hypothesis, lonely individuals respond differently to their environment compared to nonlonely individuals, which may sustain their loneliness levels. However, this interesting hypothesis has not yet been explored in daily life: Do lonely individuals feel lonely all the time, or do they feel more or less lonely in specific social contexts? The main aim of the present study was to test the differential reactivity hypothesis in daily life by examining in three samples whether trait levels of loneliness affected the levels of state loneliness in different social contexts. We used baseline questionnaires to measure trait loneliness and the Experience Sampling Method to collect data on state loneliness, in early adolescents (N = 269, Mage = 14.49, 59% female) and late adolescents (N = 223, Mage = 19.60, 91% female) from the Netherlands and late adolescents from the United States (N = 126, Mage = 19.20, 51% female). Results provided evidence for the differential reactivity hypothesis in the total sample, as high lonely adolescents experienced higher levels of state loneliness in situations in which they were alone than low lonely adolescents, but also benefited more from being with intimate company than low lonely adolescents. In sum, the present study provided evidence for the differential reactivity hypothesis and showed that the experience of loneliness in daily life was remarkably similar across age and culture. Our findings provide important insights into the daily experiences of trait lonely people, which may provide starting points for interventions.

Myeloid differentiation architecture of leukocyte transcriptome dynamics in perceived social isolation.

To define the cellular mechanisms of up-regulated inflammatory gene expression and down-regulated antiviral response in people experiencing perceived social isolation (loneliness), we conducted integrative analyses of leukocyte gene regulation in humans and rhesus macaques. Five longitudinal leukocyte transcriptome surveys in 141 older adults showed up-regulation of the sympathetic nervous system (SNS), monocyte population expansion, and up-regulation of the leukocyte conserved transcriptional response to adversity (CTRA). Mechanistic analyses in a macaque model of perceived social isolation confirmed CTRA activation and identified selective up-regulation of the CD14(++)/CD16(-) classical monocyte transcriptome, functional glucocorticoid desensitization, down-regulation of Type I and II interferons, and impaired response to infection by simian immunodeficiency virus (SIV). These analyses identify neuroendocrine-related alterations in myeloid cell population dynamics as a key mediator of CTRA transcriptome skewing, which may both propagate perceived social isolation and contribute to its associated health risks.

Perceived social isolation is associated with altered functional connectivity in neural networks associated with tonic alertness and executive control.

Perceived social isolation (PSI), colloquially known as loneliness, is associated with selectively altered attentional, cognitive, and affective processes in humans, but the neural mechanisms underlying these adjustments remain largely unexplored. Behavioral, eye tracking, and neuroimaging research has identified associations between PSI and implicit hypervigilance for social threats. Additionally, selective executive dysfunction has been evidenced by reduced prepotent response inhibition in social Stroop and dichotic listening tasks. Given that PSI is associated with pre-attentional processes, PSI may also be related to altered resting-state functional connectivity (FC) in the brain. Therefore, we conducted the first resting-state fMRI FC study of PSI in healthy young adults. Five-minute resting-state scans were obtained from 55 participants (31 females). Analyses revealed robust associations between PSI and increased brain-wide FC in areas encompassing the right central operculum and right supramarginal gyrus, and these associations were not explained by depressive symptomatology, objective isolation, or demographics. Further analyses revealed that PSI was associated with increased FC between several nodes of the cingulo-opercular network, a network known to underlie the maintenance of tonic alertness. These regions encompassed the bilateral insula/frontoparietal opercula and ACC/pre-SMA. In contrast, FC between the cingulo-opercular network and right middle/superior frontal gyrus was reduced, a finding associated with diminished executive function in prior literature. We suggest that, in PSI, increased within-network cingulo-opercular FC may be associated with hypervigilance to social threat, whereas reduced right middle/superior frontal gyrus FC to the cingulo-opercular network may be associated with diminished impulse control.

The neuroendocrinology of social isolation.

Social isolation has been recognized as a major risk factor for morbidity and mortality in humans for more than a quarter of a century. Although the focus of research has been on objective social roles and health behavior, the brain is the key organ for forming, monitoring, maintaining, repairing, and replacing salutary connections with others. Accordingly, population-based longitudinal research indicates that perceived social isolation (loneliness) is a risk factor for morbidity and mortality independent of objective social isolation and health behavior. Human and animal investigations of neuroendocrine stress mechanisms that may be involved suggest that (a) chronic social isolation increases the activation of the hypothalamic pituitary adrenocortical axis, and (b) these effects are more dependent on the disruption of a social bond between a significant pair than objective isolation per se. The relational factors and neuroendocrine, neurobiological, and genetic mechanisms that may contribute to the association between perceived isolation and mortality are reviewed.

Marital satisfaction and break-ups differ across on-line and off-line meeting venues.

Marital discord is costly to children, families, and communities. The advent of the Internet, social networking, and on-line dating has affected how people meet future spouses, but little is known about the prevalence or outcomes of these marriages or the demographics of those involved. We addressed these questions in a nationally representative sample of 19,131 respondents who married between 2005 and 2012. Results indicate that more than one-third of marriages in America now begin on-line. In addition, marriages that began on-line, when compared with those that began through traditional off-line venues, were slightly less likely to result in a marital break-up (separation or divorce) and were associated with slightly higher marital satisfaction among those respondents who remained married. Demographic differences were identified between respondents who met their spouse through on-line vs. traditional off-line venues, but the findings for marital break-up and marital satisfaction remained significant after statistically controlling for these differences. These data suggest that the Internet may be altering the dynamics and outcomes of marriage itself.

Racial and ethnic differences in diurnal cortisol rhythms: are they consistent over time?

BACKGROUND: Prior research indicates that blacks and Hispanics/Latinos have flatter diurnal cortisol declines across the day, a profile associated with poorer health. The stability of racial and ethnic differences in cortisol levels over time is not well understood, and additional research is needed to establish racial and ethnic differences in psychosocial stress levels as related to changes in cortisol levels. METHODS: With data from a community-based study of 152 adults (mean age = 58 years; 53% women; 34% black, 26% Hispanic/Latino), we examined the magnitude of racial and ethnic differences over a 5-year period. Salivary cortisol samples were obtained 3 times per day for 3 days in Years 1, 3, 4, and 5. Life events and chronic stress were assessed by questionnaires in which participants reported on whether they had experienced specific types of events or stress within the past year. Depressive symptoms scales (Center for Epidemiologic Studies of Depression Scale) were also administered annually. Daily cortisol slopes were calculated by subtracting wakeup cortisol from bedtime levels and dividing by hours awake. RESULTS: Increases in psychosocial stress were associated with flatter cortisol slopes among blacks (ß = 0.010) and Hispanics/Latinos (ß = 0.014), although including cardiovascular disease risk factors attenuates associations in blacks (ß = 0.007; p = .125). Higher income predicts a steepening of cortisol rhythms across the study (ß = -0.003; p = .019). CONCLUSIONS: Racial and ethnic differences in diurnal cortisol rhythms are stable over time. However, the magnitude of changes in cortisol levels associated with chronic stress levels may vary by racial and ethnic subgroups.

Loneliness and social behaviours in a virtual social environment.

Feeling lonely motivates people to reconnect with others, but it can also trigger a vicious cycle of cognitions and behaviours that reinforces their loneliness. In this study, we examined the behavioural consequences of loneliness in a virtual social environment. A total of 176 participants navigated a character (protagonist) through a two-dimensional browser game and rated the character's loneliness multiple times during the game. In the first part of the game, another character is introduced as the protagonist's spouse. At one point, the spouse leaves for an undetermined period of time but later returns. Immediately before this separation, higher ascribed loneliness of the protagonist was associated with more frequent interactions with the spouse. After the reunion, however, higher ascribed loneliness was associated with less frequent interactions with the spouse. Ascribed loneliness was not significantly related to the frequency of interactions with others nor to the frequency of solitary activities. These patterns held after controlling for ascribed positive affect. Participants' levels of loneliness were related to the level of ascribed loneliness only when the spouse was present but not when the spouse was absent. In sum, these findings suggest that the conditions that trigger the vicious cycle of loneliness are person- and situation-specific.

Love is in the gaze: an eye-tracking study of love and sexual desire.

Reading other people's eyes is a valuable skill during interpersonal interaction. Although a number of studies have investigated visual patterns in relation to the perceiver's interest, intentions, and goals, little is known about eye gaze when it comes to differentiating intentions to love from intentions to lust (sexual desire). To address this question, we conducted two experiments: one testing whether the visual pattern related to the perception of love differs from that related to lust and one testing whether the visual pattern related to the expression of love differs from that related to lust. Our results show that a person's eye gaze shifts as a function of his or her goal (love vs. lust) when looking at a visual stimulus. Such identification of distinct visual patterns for love and lust could have theoretical and clinical importance in couples therapy when these two phenomena are difficult to disentangle from one another on the basis of patients' self-reports.

Influence of social environment on loneliness in older adults: Moderation by polymorphism in the CRHR1.

OBJECTIVE: Both adverse social environments and genetic factors contribute to loneliness in old age. Mixed findings between older adults' social relations with their children and their levels of loneliness suggested that a gene × social environment interaction may be operating. We examine whether the effects of infrequent contact with children and low levels of perceived social support from children on loneliness in older adults are moderated by two candidate single nucleotide polymorphisms (i.e., rs1876831 and rs242938) in the corticotrophin releasing hormone receptor 1 (CRHR1) gene. DESIGN: This was a longitudinal observational study. SETTING: and PARTICIPANTS: A population-based sub-sample of 1,374 community-dwelling older adults aged 65 years and older was examined from both the 2003-2004 and 2006-2007 English Longitudinal Study of Aging assessments. MEASUREMENTS: Our main outcome measure is loneliness, which was assessed by four items extracted from the ULCA loneliness scale. RESULTS: Compared with older adults carrying the CT/TT genotypes, individuals homozygous for the C allele of rs1876831 reported higher levels of loneliness in the context of infrequent social contact with children and lower levels of perceived social support from children. No gene × social environment interactions were found for loneliness between rs242938 and an adverse social environment related to children. CONCLUSIONS: This study provides the first evidence in humans that the CRHR1 gene interacts with exposure to a negative social environment to predict loneliness in older adults.

Transcript origin analysis identifies antigen-presenting cells as primary targets of socially regulated gene expression in leukocytes.

To clarify the biological rationale for social regulation of gene expression, this study sought to identify the specific immune cell types that are transcriptionally sensitive to subjective social isolation (loneliness). Using reference distributions for the expression of each human gene in each major leukocyte subtype, we mapped the cellular origin of transcripts found to be differentially expressed in the circulating immune cells from chronically lonely individuals. Loneliness-associated genes derived primarily from plasmacytoid dendritic cells, monocytes, and, to a lesser extent, B lymphocytes. Those dynamics reflected per-cell changes in the expression of inducible genes and related more strongly to the subjective experience of loneliness than to objective social network size. Evolutionarily ancient myeloid antigen-presenting cells appear to have evolved a transcriptional sensitivity to socioenvironmental conditions that may allow them to shift basal gene expression profiles to counter the changing microbial threats associated with hostile vs. affine social conditions.

Evolutionary mechanisms for loneliness.

Robert Weiss (1973) conceptualised loneliness as perceived social isolation, which he described as a gnawing, chronic disease without redeeming features. On the scale of everyday life, it is understandable how something as personally aversive as loneliness could be regarded as a blight on human existence. However, evolutionary time and evolutionary forces operate at such a different scale of organisation than we experience in everyday life that personal experience is not sufficient to understand the role of loneliness in human existence. Research over the past decade suggests a very different view of loneliness than suggested by personal experience, one in which loneliness serves a variety of adaptive functions in specific habitats. We review evidence on the heritability of loneliness and outline an evolutionary theory of loneliness, with an emphasis on its potential adaptive value in an evolutionary timescale.

Spatial affect learning restricted in major depression relative to anxiety disorders and healthy controls.

Detecting and learning the location of unpleasant or pleasant scenarios, or spatial affect learning, is an essential skill that safeguards well-being (Crawford & Cacioppo, 2002). Potentially altered by psychiatric illness, this skill has yet to be measured in adults with and without major depressive disorder (MDD) and anxiety disorders (AD). This study enrolled 199 adults diagnosed with MDD and AD (n=53), MDD (n=47), AD (n=54), and no disorders (n=45). Measures included clinical interviews, self-reports, and a validated spatial affect task using affective pictures (IAPS; Lang, Bradley, & Cuthbert, 2005). Participants with MDD showed impaired spatial affect learning of negative stimuli and irrelevant learning of pleasant pictures compared with non-depressed adults. Adults with MDD may use a "GOOD is UP" heuristic reflected by their impaired learning of the opposite correlation (i.e., "BAD is UP") and performance in the pleasant version of the task.

The negativity bias: conceptualization, quantification, and individual differences.

There is an extensive literature on the negativity bias, including its conceptualization, measurement, temporal stability (individual differences), and neural and genetic associations. Hibbing et al. posit that the difference across individuals in the negativity bias is a key factor in determining political predisposition. The measures and paradigms developed in this literature provide a means of testing this hypothesis.

Thinking About One's Subjective Well-Being: Average Trends and Individual Differences.

In two studies, participants reported what they had been thinking about while completing measures of subjective well-being (SWB). These thought reports were analyzed with respect to life domain, valence, and how strongly they were related to actual levels of SWB. Most people focused on their life circumstances (e.g., career) rather than on dispositional predictors (e.g., personality) of SWB. The domains mentioned most frequently (career, family, romantic life) were also the ones that were most strongly related to actual SWB, indicating that most of people think about things that actually contribute to their SWB. Some domains are predominantly mentioned in positive contexts (e.g., family) whereas others are predominantly mentioned in negative contexts (e.g., money). On average, people thought more about positive than about negative things, a result that is magnified for respondents high in extraversion or emotional stability. In sum, these findings provide insight into what people think contributes to their SWB; beliefs that may guide them as they make important decisions.

Exploring the association between well-being and psychopathology in adolescents.

Promotion of mental well-being and prevention of emotional and behavioral problems are suggested to go hand in hand. The present study examined the association between subjective well-being (SWB) and psychopathology and investigated the etiology of this association in a large population-based cohort study of adolescent twins (n = 9,136) and their non-twin siblings (n = 1,474) aged 12-20 years. Phenotypic, genetic, and environmental correlations between SWB and psychopathology were obtained from multivariate genetic modeling conditional on sex. An SWB factor score was used based on measures of subjective happiness, satisfaction with life, and quality of life. Psychopathology was obtained from all syndrome and broad-band scales of the Dutch version of the ASEBA Youth Self Report. Males reported significantly higher levels of SWB than females. Females reported significantly more internalizing problems while males report significantly higher levels of externalizing behavior. In both sexes, significant negative associations were found between SWB and psychopathology, with the strongest associations seen for SWB and the YSR syndrome scale anxious/depression behavior. The observed associations were primarily explained by genetic correlations while non-shared environmental influences were mainly domain specific. The genetic liability to lower levels of SWB are indicative of a genetic liability to higher levels of psychopathology, suggesting that it might be feasible to screen for emotional and behavioral problems before clear signs are present by screening on indices of subjective well-being.