Genetic Contributions to Loneliness and Their Relevance to the Evolutionary Theory of Loneliness.

Loneliness is a negative and distressing emotional state that arises from a discrepancy between one's desired and achieved levels of social connectedness. The evolutionary theory of loneliness (ETL) posits that experiencing loneliness is an inherited adaptation that signals that salutary social relations are endangered or damaged and prompts people to reconnect to significant others. The basic tenets of the ETL has led researchers to examine the genetic underpinnings of loneliness. The current review provides an updated overview of genetic studies on loneliness and discusses the importance of genetic research for the ETL. The most recent studies suggest that the many genes that contribute to a small degree to differences in loneliness partially overlap with genes that contribute to neuroticism, but not with depression. In addition, the genetic studies discussed in this review show that genes are unlikely to have a direct effect on loneliness. Instead, environmental factors determine in a dynamic fashion how genes that contribute to loneliness are expressed. Future research on epigenetic processes, such as DNA methylation, can further elucidate the dynamic interplay between genes and the environment and how this interplay contributes to loneliness.

Predicting loneliness with polygenic scores of social, psychological and psychiatric traits.

Loneliness is a heritable trait that accompanies multiple disorders. The association between loneliness and mental health indices may partly be due to inherited biological factors. We constructed polygenic scores for 27 traits related to behavior, cognition and mental health and tested their prediction for self-reported loneliness in a population-based sample of 8798 Dutch individuals. Polygenic scores for major depressive disorder (MDD), schizophrenia and bipolar disorder were significantly associated with loneliness. Of the Big Five personality dimensions, polygenic scores for neuroticism and conscientiousness also significantly predicted loneliness, as did the polygenic scores for subjective well-being, tiredness and self-rated health. When including all polygenic scores simultaneously into one model, only 2 major depression polygenic scores remained as significant predictors of loneliness. When controlling only for these 2 MDD polygenic scores, only neuroticism and schizophrenia remain significant. The total variation explained by all polygenic scores collectively was 1.7%. The association between the propensity to feel lonely and the susceptibility to psychiatric disorders thus pointed to a shared genetic etiology. The predictive power of polygenic scores will increase as the power of the genome-wide association studies on which they are based increases and may lead to clinically useful polygenic scores that can inform on the genetic predisposition to loneliness and mental health.

Why may allopregnanolone help alleviate loneliness?

Impaired biosynthesis of Allopregnanolone (ALLO), a brain endogenous neurosteroid, has been associated with numerous behavioral dysfunctions, which range from anxiety- and depressive-like behaviors to aggressive behavior and changes in responses to contextual fear conditioning in rodent models of emotional dysfunction. Recent animal research also demonstrates a critical role of ALLO in social isolation. Although there are likely aspects of perceived social isolation that are uniquely human, there is also continuity across species. Both human and animal research show that perceived social isolation (which can be defined behaviorally in animals and humans) has detrimental effects on physical health, such as increased hypothalamic pituitary adrenal (HPA) activity, decreased brain-derived neurotrophic factor (BDNF) expression, and increased depressive behavior. The similarities between animal and human research suggest that perceived social isolation (loneliness) may also be associated with a reduction in the synthesis of ALLO, potentially by reducing BDNF regulation and increasing HPA activity through the hippocampus, amygdala, and bed nucleus of the stria terminalis (BNST), especially during social threat processing. Accordingly, exogenous administration of ALLO (or ALLO precursor, such as pregnenolone), in humans may help alleviate loneliness. Congruent with our hypothesis, exogenous administration of ALLO (or ALLO precursors) in humans has been shown to improve various stress-related disorders that show similarities between animals and humans i.e., post-traumatic stress disorders, traumatic brain injuries. Because a growing body of evidence demonstrates the benefits of ALLO in socially isolated animals, we believe our ALLO hypothesis can be applied to loneliness in humans, as well.

You are in sync with me: neural correlates of interpersonal synchrony with a partner.

Interpersonal synchrony is characterized by a temporary alignment of periodic behaviors with another person. This process requires that at least one of the two individuals monitors and adjusts his/her movements to maintain alignment with the other individual (the referent). Interestingly, recent research on interpersonal synchrony has found that people who are motivated to befriend an unfamiliar social referent tend to automatically synchronize with their social referents, raising the possibility that synchrony may be employed as an affiliation tool. It is unknown, however, whether the opposite is true; that is, whether the person serving as the referent of interpersonal synchrony perceives synchrony with his/her partner or experiences affiliative feelings toward the partner. To address this question, we performed a series of studies on interpersonal synchrony with a total of 100 participants. In all studies, participants served as the referent with no requirement to monitor or align their behavior with their partners. Unbeknown to the participants, the timings of their "partner's" movements were actually determined by a computer program based on the participant's (i.e., referent's) behavior. Overall, our behavioral results showed that the referent of a synchrony task expressed greater perceived synchrony and greater social affiliation toward a synchronous partner (i.e., one displaying low mean asynchrony and/or a narrow asynchrony range) than with an asynchronous partner (i.e., one displaying high mean asynchrony and/or high asynchrony range). Our neuroimaging study extended these results by demonstrating involvement of brain areas implicated in social cognition, embodied cognition, self-other expansion, and action observation as correlates of interpersonal synchrony (vs. asynchrony). These findings have practical implications for social interaction and theoretical implications for understanding interpersonal synchrony and social coordination.

Perspective taking is associated with specific facial responses during empathy for pain.

Witnessing the distress of others can result both in empathy and personal distress. Perspective-taking has been assigned a major role in the elicitation and modulation of these vicarious responses. However, little is known about how perspective-taking affects the psychophysiological correlates of empathy vs. personal distress. We recorded facial electromyographic and electrocardiographic activity while participants watched videos of patients undergoing painful sonar treatment. These videos were watched using two distinct perspectives: a) imagining the patient's feelings ('imagine other'), or b) imagining to be in the patient's place ('imagine self'). The results revealed an unspecific frowning response as well as activity over the M. orbicularis oculi region which was specific to the 'imagine self' perspective. This indicates that the pain-related tightening of the patients orbits was matched by participants when adopting this perspective. Our findings provide a physiological explanation for the more direct personal involvement and higher levels of personal distress associated with putting oneself explicitly into someone elses shoes. They provide further evidence that empathy does not only rely on automatic processes, but is also strongly influenced by top-down control and cognitive processes.

Can people feel happy and sad at the same time?

The authors investigated whether people can feel happy and sad at the same time. J. A. Russell and J. M. Carroll's (1999) circumplex model holds that happiness and sadness are polar opposites and, thus, mutually exclusive. In contrast, the evaluative space model (J. T. Cacioppo & G. G. Berntson, 1994) proposes that positive and negative affect are separable and that mixed feelings of happiness and sadness can co-occur. The authors both replicated and extended past research by showing that whereas most participants surveyed in typical situations felt either happy or sad, many participants surveyed immediately after watching the film Life Is Beautiful, moving out of their dormitories, or graduating from college felt both happy and sad. Results suggest that although affective experience may typically be bipolar, the underlying processes, and occasionally the resulting experience of emotion, are better characterized as bivariate.

New ambulatory impedance cardiograph validated against the Minnesota Impedance Cardiograph.

The validity and reliability of a new ambulatory impedance cardiograph (AZCG) was tested against the Minnesota Impedance Cardiograph (ZCG) during rest, orthostasis, and mental stress. Impedance cardiography allows noninvasive assessment of stroke volume, cardiac output, and systolic time intervals. A reliable ambulatory device would allow studies outside the lab. The devices were compared at two sites in healthy subjects. In both studies, the AZCG tracked changes across conditions closely with the ZCG (all Period x Device interactions were nonsignificant). Pearson rs, were .65 to .93, random intraclass correlation coefficients ranged from .80 to .98, indicating high degrees of shared measurement variance, and Cronbach's alpha indicated very good internal reliabilities (.91 to .99). Relative to the ZCG, the new AZCG appears to provide valid and reliable estimates of cardiac function at rest and during behavioral challenges in the lab.

Cardiovascular and endocrine reactivity in older females: intertask consistency.

Age-related structural and functional changes in the cardiovascular, sympathoadrenomedullary (SAM), and hypothalamic-pituitary-adrenocortical (HPA) systems may affect the ability to reliably identify individual differences in response to stress. Heart rate, preejection period, respiratory sinus arrhythmia, respiratory rate, norepinephrine, epinephrine, adrenocorticotropic hormone, and cortisol were assessed in 64 healthy older women (mean = 67 years) in response to a mental arithmetic and public-speaking task. All cardiovascular and endocrine measures changed significantly during the tasks. All measures were consistent across the two tasks (r(s)s = .50 to .97). Moreover, a majority of women in this sample exhibited cross-task consistency in the relative activation of the autonomic, SAM, and HPA systems (i.e., response profiles). Further research is recommended to examine the significance of consistent individual differences in response profile.

Mind at ease puts a smile on the face: psychophysiological evidence that processing facilitation elicits positive affect.

The affect system, in its position to monitor organismic-environmental transactions, may be sensitive to the internal dynamics of information processing. Hence, the authors predicted that facilitation of stimulus processing should elicit a brief, mild, positive affective response. In 2 studies, participants watched a series of neutral pictures while the processing ease was unobtrusively manipulated. Affective reactions were assessed with facial electromyography (EMG). In both studies, easy-to-process pictures elicited higher activity over the region of zygomaticus major, indicating positive affect. The EMG data were paralleled by self-reports of positive responses to the facilitated stimuli. The findings suggest a close link between processing dynamics and affect and may help understand several preference phenomena, including the mere-exposure effect. The findings also highlight a potential source of affective biases in social judgments.

Alcohol affects emotion through cognition.

Determining how, cognition and emotion interact is pivotal to an understanding of human behavior and its disorders. Available data suggest that changes in emotional reactivity and behavior associated with drinking are intertwined with alcohol's effects on cognitive processing. In the study reported here, we demonstrated that alcohol dampens anticipatory fear and response inhibition in human participants not by directly suppressing subcortical emotion centers, as posited by traditional tension-reduction theories, but instead by impairing cognitive-processing capacity. During intoxication, reductions in fear response (assessed via startle potentiation) occurred only under dual-stimulus conditions, and coincided with reduced attentional processing of threat cues as evidenced by brain response (assessed via P3 event-related potentials). The results are consistent with higher cortical mediation of alcohol 's effects on fear, and illustrate more broadly how disruption of a cognitive process can lead to alterations in emotional reactivity and adaptive behavior.

Multilevel integrative analyses of human behavior: social neuroscience and the complementing nature of social and biological approaches.

Social and biological explanations traditionally have been cast as incompatible, but advances in recent years have revealed a new view synthesized from these 2 very different levels of analysis. The authors review evidence underscoring the complementing nature of social and biological levels of analysis and how the 2 together can foster understanding of the mechanisms underlying complex behavior and the mind. Specifically, they review the utility of considering social influences on biological processes that are often viewed as outside the social domain including genetic constitution, gene expression, disease, and autonomic, neuroendocrine, and immune activity. This research underscores the unity of psychology and the importance of retaining multilevel integrative research that spans molar and molecular levels of analysis. Especially needed in the coming years is more research on the mechanisms linking social and biological events and processes.

Autonomic and neuroendocrine responses to mild psychological stressors: effects of chronic stress on older women.

We investigated autonomic and endocrine responses to acute stressors in 27 women who were or are presently caring for a spouse with a progressive dementia (high chronic stress) and 37 noncaregivers who were category matched for age and family income (low chronic stress). Measures were taken before (low acute stress) and in response to brief laboratory stressors (high acute stress). We replicated prior research showing that caregivers report greater stress, depression, and loneliness than the comparison groups, and acute stressors elevate autonomic and neuroendocrine activity. We also found that caregivers, relative to noncaregivers, exhibited shorter preejection periods and elevated blood pressure and heart rate, but the magnitude of autonomic and neuroendocrine reactivity to the experimental stressors was comparable across these groups. This pattern of autonomic differentiation replicates prior research showing that caregivers are characterized by higher sympathetic activation than noncaregivers and suggests that the effects of chronic stress on physiological reactivity may be a less robust effect in older adults.

Epstein-Barr virus antibodies in whole blood spots: a minimally invasive method for assessing an aspect of cell-mediated immunity.

OBJECTIVE: Study 1: Introduce and validate a method for measuring EBV p18-VCA antibodies in whole blood spots to provide a minimally invasive marker of cell-mediated immune function. Study 2: Apply this method to a large community-based study of psychopathology in children and adolescents. METHODS: The EBV antibody method was evaluated through analysis of precision, reliability, stability, and comparisons with plasma and indirect immunofluorescence methods. The effects of life events on p18-VCA antibody level were considered in a subsample of 9, 11, and 13 year-old children participating in the Great Smoky Mountains Study in North Carolina. The subsample was stratified by age, sex, and degree of overall life strain. RESULTS: Dried blood spots provided a convenient, sensitive, precise, and reliable method for measuring EBV p18-VCA antibody titer. Life events were positively associated with p18-VCA antibodies in girls but not in boys. CONCLUSIONS: The validity of the blood spot EBV p18-VCA antibody assay, as well as the ease of sample collection, storage, and transportation, may provide an opportunity for psychoneuroimmunology to explore a wider range of stress models in larger, community-based studies.

Lonely traits and concomitant physiological processes: the MacArthur social neuroscience studies.

Loneliness is a complex set of feelings encompassing reactions to unfulfilled intimate and social needs. Although transient for some individuals, loneliness can be a chronic state for others. Prior research has shown that loneliness is a major risk factor for psychological disturbances and for broad-based morbidity and mortality. We examined differences between lonely and socially embedded individuals that might explain differences in health outcomes. Satisfying social relationships were associated with more positive outlooks on life, more secure attachments and interactions with others, more autonomic activation when confronting acute psychological challenges, and more efficient restorative behaviors. Individuals who were chronically lonely were characterized by elevated mean salivary cortisol levels across the course of a day, suggesting more discharges of corticotropin-releasing hormone and elevated activation of the hypothalamic-pituitary-adrenocorticol axis. An experimental manipulation of loneliness further suggested that the way in which people construe their self in relation to others around them has powerful effects on their self concept and, possibly, on their physiology.

Affective picture processing: the late positive potential is modulated by motivational relevance.

Recent studies have shown that the late positive component of the event-related-potential (ERP) is enhanced for emotional pictures, presented in an oddball paradigm, evaluated as distant from an established affective context. In other research, with context-free, random presentation, affectively intense pictures (pleasant and unpleasant) prompted similar enhanced ERP late positivity (compared with the neutral picture response). In an effort to reconcile interpretations of the late positive potential (LPP), ERPs to randomly ordered pictures were assessed, but using the faster presentation rate, brief exposure (1.5 s), and distinct sequences of six pictures, as in studies using an oddball based on evaluative distance. Again, results showed larger LPPs to pleasant and unpleasant pictures, compared with neutral pictures. Furthermore, affective pictures of high arousal elicited larger LPPs than less affectively intense pictures. The data support the view that late positivity to affective pictures is modulated both by their intrinsic motivational significance and the evaluative context of picture presentation.

Psychobiology and social psychology: past, present, and future.

Social psychology and psychobiology have a rich historical connection, although over the last half century these two disciplines have seemingly become estranged. To a significant extent, that alienation arose from an archaic and nonviable model of behavioral biology that retarded the development of both disciplines. With the emergence of modern biological perspectives, this impediment no longer limits fruitful collaborations among social psychologists and psychobiologists. Indeed, some of the most exciting contemporary developments are emerging from the areas of social neuroscience, cognitive neuroscience, and behavioral neuroscience. We review the history of links between social psychology and psychobiology, the factors that led to the segregation of these subdisciplines, and the modern biological perspectives that provide the basis for reintegration of these disciplines.

Impedance pneumography: noise as signal in impedance cardiography.

Thoracic impedance is modulated by events within the respiratory cycle, which represents a source of "noise" in impedance cardiography. Respiration itself, however, is a physiological rhythm of interest to psychophysiologists. We report here methods and validation for deriving impedance pneumographic measures of respiration from impedance cardiography signals, based on standard tetrapolar band electrodes. We recorded the change in impedance (delta Z), the first derivative of the change in impedance (dZ/dt), output from a strain-gauge respirometer, and criterion spirometry from eight healthy adults during rest, paced breathing, abdominal breathing, thoracic breathing, and a mental arithmetic task. Transfer function analyses revealed that a delta Zd signal (derived by integration of the dZ/dt signal) provided the best estimate of the criterion spirometric measure for all parameters (coherence, phase, and gain), accounting for almost 90% of the variance in respiratory waveform morphology. The results document the potential utility of impedance pneumography, as derived from standard impedance cardiography signals.

Chronic stress associated with spousal caregiving of patients with Alzheimer's dementia is associated with downregulation of B-lymphocyte GH mRNA.

BACKGROUND: It has been demonstrated that growth hormone (GH) is synthesized and secreted by human peripheral mononuclear cells (PBMC), and the expression of GH mRNA can be found throughout the human immune system. METHODS: We studied a population of female caregivers of patients with Alzheimer's dementia (AD) who suffered from the stress of caring for these patients. We utilized quantitative RT-PCR to determine GH mRNA levels in T- and B-cell populations from PBMC. Subjects were nine caregivers of AD patients and nine age- and sex-matched controls. RESULTS: In the control group we found a threefold greater GH mRNA expression in B cells than in T cells. This finding was consistent with our previous in situ hybridization observation, suggesting GH mRNA in predominately B-cell areas of immune organs in humans. We also found that the expression of GH mRNA from total peripheral blood mononuclear cells and B cells in caregivers was 50% and 60% respectively less than that in the control group. CONCLUSIONS: Because the B-cell population is the source of antibody production, our findings suggest that the decrease in B-cell GH mRNA may contribute to the poor immune response to influenza virus vaccination that has been reported previously in chronically stressed caregivers.

Emotion.

We review recent trends and methodological issues in assessing and testing theories of emotion, and we review evidence that form follows function in the affect system. Physical limitations constrain behavioral expressions and incline behavioral predispositions toward a bipolar organization, but these limiting conditions appear to lose their power at the level of underlying mechanisms, where a bivalent approach may provide a more comprehensive account of the affect system.

Negative information weighs more heavily on the brain: the negativity bias in evaluative categorizations.

Negative information tends to influence evaluations more strongly than comparably extreme positive information. To test whether this negativity bias operates at the evaluative categorization stage, the authors recorded event-related brain potentials (ERPs), which are more sensitive to the evaluative categorization than the response output stage, as participants viewed positive, negative, and neutral pictures. Results revealed larger amplitude late positive brain potentials during the evaluative categorization of (a) positive and negative stimuli as compared with neutral stimuli and (b) negative as compared with positive stimuli, even though both were equally probable, evaluatively extreme, and arousing. These results provide support for the hypothesis that the negativity bias in affective processing occurs as early as the initial categorization into valence classes.