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.

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.

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.

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.

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.

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.

The speed of morality: a high-density electrical neuroimaging study.

Neuroscience research indicates that moral reasoning is underpinned by distinct neural networks including the posterior superior temporal sulcus (pSTS), amygdala, and ventromedial prefrontal cortex, which support communication between computational systems underlying affective states, cognitions, and motivational processes. To characterize real-time neural processing underpinning moral computations, high-density event-related potentials were measured in participants while they viewed short, morally laden visual scenarios depicting intentional and accidental harmful actions. Current source density maxima in the right pSTS as fast as 62 ms poststimulus first distinguished intentional vs. accidental actions. Responses in the amygdala/temporal pole (122 ms) and ventromedial prefrontal cortex (182 ms) were then evoked by the perception of harmful actions, indicative of fast information processing associated with early stages of moral cognition. Our data strongly support the notion that intentionality is the first input to moral computations. They also demonstrate that emotion acts as a gain antecedent to moral judgment by alerting the individual to the moral salience of a situation and provide evidence for the pervasive role of affect in moral sensitivity and reasoning.

The common neural bases between sexual desire and love: a multilevel kernel density fMRI analysis.

INTRODUCTION: One of the most difficult dilemmas in relationship science and couple therapy concerns the interaction between sexual desire and love. As two mental states of intense longing for union with others, sexual desire and love are, in fact, often difficult to disentangle from one another. AIM: The present review aims to help understand the differences and similarities between these two mental states using a comprehensive statistical meta-analyses of all functional magnetic resonance imaging (fMRI) studies on sexual desire and love. METHODS: Systematic retrospective review of pertinent neuroimaging literature. MAIN OUTCOME MEASURES: Review of published literature on fMRI studies illustrating brain regions associated with love and sexual desire to date. RESULTS: Sexual desire and love not only show differences but also recruit a striking common set of brain areas that mediate somatosensory integration, reward expectation, and social cognition. More precisely, a significant posterior-to-anterior insular pattern appears to track sexual desire and love progressively. CONCLUSIONS: This specific pattern of activation suggests that love builds upon a neural circuit for emotions and pleasure, adding regions associated with reward expectancy, habit formation, and feature detection. In particular, the shared activation within the insula, with a posterior-to-anterior pattern, from desire to love, suggests that love grows out of and is a more abstract representation of the pleasant sensorimotor experiences that characterize desire. From these results, one may consider desire and love on a spectrum that evolves from integrative representations of affective visceral sensations to an ultimate representation of feelings incorporating mechanisms of reward expectancy and habit learning.

To what extent is psychological resilience protective or ameliorative: Exploring the effects of deployment on the mental health of combat medics.

Exposure to a major traumatic stressor increases the odds of negative mental health and maladaptive behavioral outcomes not only for victims but also for 1st responders and health care professionals who are exposed to the aftermath. This study investigates the extent to which psychological resilience acts as either a Protective (i.e., vaccine-like) or an Ameliorative (i.e., antibiotic-like) factor to reduce the deleterious mental health outcomes associated with exposure to a major stressor. To do so, this pilot study focused on the understudied population of military combat medics, who are exposed to both stressors associated with direct combat and with providing intense battlefield trauma care. Military combat medics who were identified as having deployed to Iraq or Afghanistan shortly after baseline measurements of posttraumatic stress disorder, depression, and aggressive behavioral tendencies and returned from deployment prior to the follow-up assessment (protective model) were compared to those who returned from deployment in Iraq or Afghanistan shortly before the baseline measurements and were not deployed again prior to the follow-up assessments (ameliorative model). Data were collected on combat experiences to equate the stressor for these 2 samples, and a propensity score matching technique was used to ensure that the 2 samples were similar. The findings provide support for both the protective and the ameliorative models of psychological resilience. Results are discussed in terms of the potential benefits of resilience in mental health programs. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Loneliness in monkeys: Neuroimmune mechanisms.

Loneliness, or perceived social isolation, may be evident in any group-living species, although its assessment in nonhumans provides some measurement challenges. It is well-known that loneliness in humans confers significant risk for morbidity and mortality, although mechanisms remain unclear. The authors describe a naturally-occurring model of loneliness in adult male rhesus monkeys that shows many parallels with the phenomenon in humans. Lonely monkeys (those that display high frequencies of social initiations but low frequencies of complex interaction) show elevated sympathetic nervous system activity and down regulated Type I interferon responses. Analysis of data from simian immunodeficiency virus-infected monkeys indicates that these physiological changes have functional consequences. Use of this animal model can help identify mechanisms by which loneliness impacts health.

Behavioral and cardiovascular consequences of disrupted oxytocin communication in cohabitating pairs of male and female prairie voles.

Negative social experiences may influence psychological and physiological health via altered central oxytocin communication. The prairie vole is valuable for investigating the potential influence of oxytocin on responses to social experiences. Prairie voles are socially monogamous, live in pairs or family groups, and respond negatively to changes in the social environment. This study investigated the hypothesis that disruptions of oxytocin in one prairie vole of a cohabitating male-female pair would alter social behavior in that specific animal; and these behavioral changes in turn would influence the untreated partner's behavior and physiology. Pharmacological antagonism of oxytocin with the receptor antagonist L-368,899 in the male prairie vole disrupted social behaviors between the male and his untreated female partner. This manipulation also negatively influenced the behavior and cardiovascular function in the untreated female partner, including increased: (a) depression-relevant behaviors in two behavioral stressors, (b) basal mean arterial pressure and heart rate, and (c) cardiovascular reactivity to the behavioral stressors. These results suggest that disruptions of oxytocin and social behavior in one animal may produce indicators of social stress in an untreated social partner. This preliminary research provides a foundation for future studies to investigate mechanisms underlying responses to social experiences in humans.

Spatio-temporal dynamics of the mirror neuron system during social intentions.

Previous research has shown that specific goals and intentions influence a person's allocation of social attention. From a neural viewpoint, a growing body of evidence suggests that the inferior fronto-parietal network, including the mirror neuron system, plays a role in the planning and the understanding of motor intentions. However, it is unclear whether and when the mirror neuron system plays a role in social intentions. Combining a behavioral task with electrical neuroimaging in 22 healthy male participants, the current study investigates whether the temporal brain dynamic of the mirror neuron system differs during two types of social intentions i.e., lust vs. romantic intentions. Our results showed that 62% of the stimuli evoking lustful intentions also evoked romantic intentions, and both intentions were sustained by similar activations of the inferior frontal gyrus and the inferior parietal lobule/angular gyrus for the first 432 ms after stimulus onset. Intentions to not love or not lust, on the other hand, were characterized by earlier differential activations of the inferior fronto-parietal network i.e., as early as 244 ms after stimulus onset. These results suggest that the mirror neuron system may not only code for the motor correlates of intentions, but also for the social meaning of intentions and its valence at both early/automatic and later/more elaborative stages of information processing.

Loneliness predicts a preference for larger interpersonal distance within intimate space.

Loneliness is thought to serve as an adaptive signal indicating the need to repair or replace salutary social connections. Accordingly, loneliness may influence preferences for interpersonal distance. If loneliness simply motivates a desire to socially reconnect, then loneliness may be associated with a preference for smaller interpersonal distances. According to the evolutionary model of loneliness, however, loneliness also signals an inadequacy of mutual aid and protection, augmenting self-preservation motives. If loneliness both increases the motivation to reconnect and increases the motivation for self-protection, then the resulting approach-avoidance conflict should produce a preference for larger interpersonal distance, at least within intimate (i.e., proximal) space. Here, we report two survey-based studies of participants' preferences for interpersonal distance to distinguish between these competing hypotheses. In Study 1 (N = 175), loneliness predicted preferences for larger interpersonal distance within intimate space net gender, objective social isolation, anxiety, depressive symptomatology, and marital status. In Study 2 (N = 405), we replicated these results, and mediation analyses indicated that measures of social closeness could not adequately explain our findings. These studies provide compelling evidence that loneliness predicts preferences for larger interpersonal distance within intimate space, consistent with predictions from the evolutionary model of loneliness.

The neuroscience of persuasion: A review with an emphasis on issues and opportunities.

Persuasion, a prevalent form of social influence in humans, refers to an active attempt to change a person's attitudes, beliefs, or behavior. There is a growing literature on the neural correlates of persuasion. As is often the case in an emerging literature, however, there are a number of questions, concerns, and alternative interpretations that can be raised about the research and interpretations. We provide a critical review of the research, noting potential problems and issues that warrant attention to move the field forward. Among the recommendations are greater integration of neuroimaging approaches with existing behavioral theories and methods on the information processes (cognitive and affective) underlying persuasion, and moving beyond solely correlative approaches for specifying underlying neural mechanisms. Work in this area has the potential to contribute to our understanding of brain-behavior relationships as well as to advance our understanding of persuasion and social influence more generally.

Neuroimaging of Female Sexual Desire and Hypoactive Sexual Desire Disorder.

INTRODUCTION: Recent advances in neuroimaging offer an unprecedented window into the female sexual brain. The small samples and poor statistical power of individual functional magnetic resonance imaging studies have limited what can be gleaned about the systematic brain network that is involved in female sexual desire and female sexual dysfunction (eg, hypoactive sexual desire disorder [HSDD]). AIM: To quantitatively determine the brain network involved in HSDD. METHODS: Systematic retrospective review and statistical meta-analysis of pertinent neuroimaging literature. MAIN OUTCOME MEASURES: Review of published literature on functional magnetic resonance imaging studies illustrating brain regions associated with female sexual desire and female HSDD. RESULTS: HSDD is associated with a specific fronto-limbic-parietal dysfunction characterized by (i) lower blood oxygen level-dependent responses in the sexual desire brain network and (ii) higher blood oxygen level-dependent responses in the self-referential brain network. CONCLUSION: The meta-analytic results are in line with a top-down neurofunctional model of HSDD in which inspecting, monitoring, and evaluating oneself (rather than sensory experience) before or during sexual activities interfere with sexual desire. These results raise new questions regarding the necessity and sufficiency of dysfunctional activation in the sexual desire and self-referential brain networks, whose answers bear on the development and evaluation of personalized treatments for HSDD. Cacioppo S. Neuroimaging of Female Sexual Desire and Hypoactive Sexual Desire Disorder. Sex Med Rev 2017;5:434-444.