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

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

Corticostriatal Connectivity during Prosocial Decision-making Relates to Giving Behavior during Adolescence.

Prosocial behavior during adolescence becomes more differentiated based on the recipient of the action as well as the perceived value or benefit, relative to the cost to self, for the recipients. The current study investigated how functional connectivity of corticostriatal networks tracked the value of prosocial decisions as a function of target recipient (caregiver, friend, stranger) and age of the giver, and how they related to giving behavior. Two hundred sixty-one adolescents (9-15 and 19-20 years of age) completed a decision-making task in which they could give money to caregivers, friends, and strangers while undergoing fMRI. Results indicated that adolescents were more likely to give to others as the value of the prosocial decision (i.e., the difference between the benefit to other relative to the cost to self) increased; this effect was stronger for known (caregiver and friends) than unknown targets, and increased with age. Functional connectivity between the nucleus accumbens (NAcc) and OFC increased as the value of the prosocial decisions decreased for strangers, but not for known others, irrespective of choice. This differentiated NAcc-OFC functional connectivity during decision-making as a function of value and target also increased with age. Furthermore, regardless of age, individuals who evinced greater value-related NAcc-OFC functional connectivity when considering giving to strangers relative to known others showed smaller differentiated rates of giving between targets. These findings highlight the role of corticostriatal development in supporting the increasing complexity of prosocial development across adolescence.

Null results of oxytocin and vasopressin administration on mentalizing in a large fMRI sample: evidence from a randomized controlled trial.

BACKGROUND: Although potential links between oxytocin (OT), vasopressin (AVP), and social cognition are well-grounded theoretically, most studies have included all male samples, and few have demonstrated consistent effects of either neuropeptide on mentalizing (i.e. understanding the mental states of others). To understand the potential of either neuropeptide as a pharmacological treatment for individuals with impairments in social cognition, it is important to demonstrate the beneficial effects of OT and AVP on mentalizing in healthy individuals. METHODS: In the present randomized, double-blind, placebo-controlled study (n = 186) of healthy individuals, we examined the effects of OT and AVP administration on behavioral responses and neural activity in response to a mentalizing task. RESULTS: Relative to placebo, neither drug showed an effect on task reaction time or accuracy, nor on whole-brain neural activation or functional connectivity observed within brain networks associated with mentalizing. Exploratory analyses included several variables previously shown to moderate OT's effects on social processes (e.g., self-reported empathy, alexithymia) but resulted in no significant interaction effects. CONCLUSIONS: Results add to a growing literature demonstrating that intranasal administration of OT and AVP may have a more limited effect on social cognition, at both the behavioral and neural level, than initially assumed. Randomized controlled trial registrations: ClinicalTrials.gov; NCT02393443; NCT02393456; NCT02394054.

Ventromedial prefrontal cortex activity differentiates sick from healthy faces: Associations with inflammatory responses and disease avoidance motivation.

BACKGROUND: Humans are able to discern the health status of others using olfactory and visual cues, and subsequently shift behavior to make infection less likely. However, little is known about how this process occurs. The present study examined the neural regions involved in differentiating healthy from sick individuals using visual cues. METHODS: While undergoing a functional magnetic resonance imaging scan, participants (N = 42) viewed facial photos of 30 individuals (targets) who had been injected with an inflammatory challenge--low-dose endotoxin (i.e., sick) or placebo (i.e., healthy), and rated how much they liked each face. We examined regions implicated in processing either threat (amygdala, anterior insula) or cues that signal safety (ventromedial prefrontal cortex [VMPFC]), and how this activity related to their liking of targets and cytokine levels (interleukin-6, tumor necrosis factor-α) exhibited by the targets. RESULTS: Photos of sick faces were rated as less likeable compared to healthy faces, and the least liked faces were those individuals with the greatest inflammatory response. While threat-related regions were not significantly active in response to viewing sick faces, the VMPFC was more active in response to viewing healthy (vs. sick) faces. Follow-up analyses revealed that participants tended to have lower VMPFC activity when viewing the least liked faces and the faces of those with the greatest inflammatory response. CONCLUSIONS: This work builds on prior work implicating the VMPFC in signaling the presence of safe, non-threatening visual stimuli, and suggests the VMPFC may be sensitive to cues signaling relative safety in the context of pathogen threats.

Resting parasympathetic nervous system activity is associated with greater antiviral gene expression.

Parasympathetic nervous system activity can downregulate inflammation, but it remains unclear how parasympathetic nervous system activity relates to antiviral activity. The present study examined associations between parasympathetic nervous system activity and cellular antiviral gene regulation in 90 adolescents (Mage = 16.28, SD = 0.73; 51.1% female) who provided blood samples and measures of cardiac respiratory sinus arrhythmia (RSA), twice, five weeks apart. Using a multilevel analytic framework, we found that higher RSA (an indicator of higher parasympathetic nervous system activity)-both at rest and during paced breathing-was associated with higher expression of Type I interferon (IFN) response genes in circulating leukocytes, even after adjusting for demographic and biological covariates. RSA was not associated with a parallel measure of inflammatory gene expression. These results identify a previously unrecognized immunoregulatory aspect of autonomic nervous system function and highlight a potential biological pathway by which parasympathetic nervous system activity may relate to health.

Exploring neural mechanisms of the health benefits of gratitude in women: A randomized controlled trial.

BACKGROUND: Gratitude has received growing interest as an emotion that can bring greater happiness and health. However, little is known about the effects of gratitude on objective measures of physical health or the neural mechanisms that underlie these effects. Given strong links between gratitude and giving behavior, and giving and health, it is possible that gratitude may benefit health through the same mechanisms as giving to others. Thus, this study investigated whether gratitude activates a neural 'caregiving system' (e.g., ventral striatum (VS), septal area (SA)), which can downregulate threat responding (e.g., amygdala) and possibly cellular inflammatory responses linked to health. METHODS: A parallel group randomized controlled trial examined the effect of a six-week online gratitude (n = 31) vs. control (n = 30) writing intervention on neural activity and inflammatory outcomes. Pre- and post-intervention, healthy female participants (ages 35-50) reported on support-giving behavior and provided blood samples to assess circulating plasma levels and stimulated monocytic production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)). Post-intervention, participants completed a gratitude task and a threat reactivity task in an fMRI scanner. RESULTS: There were no significant group differences (gratitude vs. control intervention) in neural responses (VS, SA, or amygdala) to the gratitude or threat tasks. However, across the entire sample, those who showed larger pre- to- post-intervention increases in self-reported support-giving showed larger reductions in amygdala reactivity following the gratitude task (vs. control task). Additionally, those who showed larger reductions in amygdala reactivity following the gratitude task showed larger pre-to-post reductions in the stimulated production of TNF-α and IL-6. Importantly, gratitude-related reductions in amygdala reactivity statistically mediated the relationship between increases in support-giving and decreases in stimulated TNF-α production. CONCLUSION: The observed relationships suggest that gratitude may benefit health (reducing inflammatory responses) through the threat-reducing effects of support-giving.

Endotoxin for Alcohol Research: A Call for Experimental Medicine Using Lipopolysaccharide Challenge.

Studies of inflammation in alcohol use disorder (AUD) are overwhelmingly preclinical, and translation to clinical samples is necessary. Endotoxin administration has been used successfully in humans to study mood disorders, offering a translational, reliable and safe model that may be validated in AUD research. We argue for the use of endotoxin challenge to elucidate the interplay between AUD and inflammation.

Evidence from a Randomized Controlled Trial that Altruism Moderates the Effect of Prosocial Acts on Adolescent Well-being.

Despite growing public and scientific interest in the positive benefits of prosociality, there has been little research on the causal effects of performing kind acts for others on psychological well-being during adolescence. Developmental changes during adolescence, such as greater perspective taking, can promote prosociality. It was hypothesized that performing kind acts for others would improve adolescent well-being (positive and negative affect, perceived stress) and increase prosocial giving. As part of a randomized controlled trial, 97 adolescents (Mage = 16.224, SD = 0.816, range 14-17; 53.608% female) were assigned to either perform kind acts for others (Kindness to Others, N = 33), perform kind acts for themselves (Kindness to Self, N = 34), or report on daily activities (Daily Report, N = 30) three times per week for four weeks. Well-being factors were measured weekly and giving was tested post-intervention. Overall, changes over time in well-being did not differ across conditions. However, altruism emerged as a significant moderator such that altruistic adolescents in the Kindness to Others condition showed increased positive affect, decreased negative affect, and decreased stress. Increased positive affect was also linked to greater prosocial giving for Kindness to Others adolescents. These findings identify individual differences that may shape the effects of doing kind acts for others on well-being during adolescence.

Effects of stress-induced inflammation on reward processing in healthy young women.

BACKGROUND: Anhedonia, or loss of interest or pleasure, is a feature of depression and transdiagnostic construct in psychopathology. Theory and compelling evidence from preclinical models implicates stress-induced inflammation as a psychobiological pathway to anhedonic behavior; however, this pathway has not been tested in human models. Further, although anhedonia may reflect dysregulation in multiple dimensions of reward, the extent to which stress-induced inflammation alters these dimensions is unclear. Thus, the current experimental study used a standardized laboratory stressor task to elicit an inflammatory response and evaluate effects of stress-induced inflammation on multiple behavioral indices of reward processing. METHODS: Healthy young women (age 18-25) completed behavioral reward tasks assessing reward learning, motivation, and sensitivity and were randomized to undergo an acute psychosocial stressor (n = 37) or a no-stress active control (n = 17). Tasks were re-administered 90-120 min post-stress to coincide with the peak of the stress-induced inflammatory response. Blood samples were collected for assessment of the pro-inflammatory cytokine interleukin-6 (IL-6) at baseline and 90 and 120 min post stressor. RESULTS: Stress-induced IL-6 was associated with increased response bias during reward learning and increased motivation when probability of receiving a reward was low. Sensitivity to reward in the context of a motivation task was not altered in association with stress-induced IL-6. CONCLUSIONS: Contrary to hypotheses, mild increases in IL-6 following acute stress were associated with increased reward responsiveness during reward learning and selective increases in motivation. Results contribute to an emerging and nuanced literature linking inflammation to reward processing, and demonstrate that behavioral effects of stress-induced inflammation may be detected in the laboratory setting. CLINICAL TRIAL REGISTRATION: NCT03828604.

Sleep, inflammation, and perception of sad facial emotion: A laboratory-based study in older adults.

BACKGROUND: Facial emotion perception (FEP) is pivotal for discriminating salient emotional information. Accumulating data indicate that FEP responses, particularly to sad emotional stimuli, are impaired in depression. This study tests whether sleep disturbance and inflammation, two risk factors for depression, contribute to impaired FEP to sad emotional stimuli. METHODS: In older adults (n = 40, 71.7 ± 6.8y, 56.4% female), disturbance of sleep maintenance (i.e., wake time after sleep onset [WASO]) was evaluated by polysomnography. In the morning, plasma concentrations of two markers of systemic inflammation were evaluated (i.e., interleukin [IL]-6, tumor necrosis factor [TNF]-α), followed by two FEP tasks, which assessed delays in emotion recognition (ER) and ratings of perceived emotion intensity (EI) in response to sad facial emotional stimuli, with exploration of FEP responses to happiness and anger. Linear regression models tested whether WASO, IL-6, and TNF-α would be associated with impaired FEP to sad emotional stimuli. In addition, moderation tests examined whether inflammation would moderate the link between sleep disturbance and impaired FEP to sad emotional stimuli. RESULTS: Longer WASO predicted longer ER delays (p < 0.05) and lower EI ratings in response to sad faces (p < 0.01). Further, higher TNF-α (p < 0.05) but not IL-6 predicted longer ER delays for sad faces, whereas higher IL-6 (p < 0.01) but not TNF-α predicted lower EI ratings for sad faces. Finally, TNF-α moderated the relationship between longer WASO and longer ER delays to sad faces (p < 0.001), while IL-6 moderated the relationship between longer WASO and lower EI ratings to sad faces (p < 0.01). Neither sleep nor inflammatory measures were associated with FEP responses to happiness or anger. CONCLUSION: In older adults, disturbance of sleep maintenance is associated with impaired FEP to sad emotion, a relationship that appears to be moderated by inflammation. These data indicate that sleep disturbance and inflammation converge and contribute to impaired FEP with implications for risk for late-life depression.

Feeling needed: Effects of a randomized generativity intervention on well-being and inflammation in older women.

Generativity, or concern for and contribution to the well-being of younger generations, plays an important role in successful aging. The purpose of this study was to develop a novel, writing-based intervention to increase feelings of generativity and test the effect of this intervention on well-being and inflammation in a sample of older women. Participants in this study (n = 73; mean age = 70.9 years, range 60-86 years) were randomly assigned to a 6-week generativity writing condition (writing about life experiences and sharing advice with others) or a control writing condition (neutral, descriptive writing). Self-reported measures of social well-being, mental health, and physical health, as well as objective measures of systemic and cellular levels of inflammation (plasma pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-α; genome-wide RNA transcriptional profiling), were assessed pre- and post-intervention. The generativity intervention led to significant improvements across multiple domains, including increases in participation in social activities, decreases in psychological distress, more positive expectations regarding aging in the physical health domain, and decreases in pro-inflammatory gene expression. Thus, this study provides preliminary evidence for the ability of a novel, low-cost, low-effort intervention to favorably impact inflammation and well-being in older women.

Emotions in Social Relationships and Their Implications for Health and Disease: Introduction to the Special Issue of Psychosomatic Medicine.

Social relationships and emotions are important to health and disease, but research in this area has largely progressed along parallel and distinct historical paths. These areas are critically linked because relationships are among the most powerful elicitors of health-relevant emotions and emotions can in turn influence relationships for better or worse. Conceptually, relationships and emotions can have mediational, reciprocal, and interactive influences on health outcomes, associations that seem dependent on the broader sociocultural context. The articles in this issue of Psychosomatic Medicine are based on a joint meeting of the American Psychosomatic Society and the Society for Affective Science titled "Emotions in social relationships: implications for health and disease." Recent research and conceptual models that fall at the interface of relationships, emotions, and health are highlighted in this special issue. Future work that capitalizes on these links will be critical if this area is to fulfill its potential in terms of new scientific insights and intervention opportunities.

Two Distinct Immune Pathways Linking Social Relationships With Health: Inflammatory and Antiviral Processes.

OBJECTIVE: Social relationships can both influence and be influenced by immune processes. Past work implicates two distinct pathways along which this interaction may occur: inflammatory processes and antiviral processes. This article reviews how social behavior is modulated by these two immune processes and how such processes may in turn regulate social behavior. METHODS: This narrative review outlines existing work on social behavior and both inflammatory and antiviral processes. We propose an evolutionary framework that aims to integrate these findings. Specifically, social isolation has evolutionarily increased the likelihood of wounding and therefore increased the need for inflammation, which works to promote healing. Conversely, broader social networks provide protection from physical threats but also lead to increased pathogen exposure, necessitating a more robust antiviral response. RESULTS: This review highlights that social adversity, such as social exclusion or loneliness, is associated with increased inflammation, whereas social contact is associated with increased antiviral immunity. Furthermore, increased inflammation leads to sensitivity to social stimuli, presumably to avoid hostile conspecifics and approach allies who may provide care while vulnerable. Individuals with inadequate antiviral immunity engage in behaviors that minimize pathogen exposure, such as reduced affiliative behavior. CONCLUSIONS: This review suggests that adverse social experiences (social isolation, perceived social threat) may induce inflammatory responses while suppressing antiviral immunity, whereas positive experiences of social connection may reduce inflammation and bolster antiviral responses. Although acutely elevated inflammation would be adaptive under conditions where wounding is likely, chronic inflammation related to continued social adversity may have detrimental health consequences.

Effects of Social Exclusion on Cardiovascular and Affective Reactivity to a Socially Evaluative Stressor.

PURPOSE: Socially disconnected individuals have worse health than those who feel socially connected. The mechanisms through which social disconnection influences physiological and psychological outcomes warrant study. The current study tested whether experimental manipulations of social exclusion, relative to inclusion, influenced subsequent cardiovascular (CV) and affective reactivity to socially evaluative stress. METHODS: Young adults (N = 81) were assigned through block randomization to experience either social exclusion or inclusion, using a standardized computer-based task (Cyberball). Immediately after exposure to Cyberball, participants either underwent a socially evaluative stressor or an active control task, based on block randomization. Physiological activity (systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR)) and state anxiety were assessed throughout the experiment. RESULTS: Excluded participants evidenced a significant increase in cardiovascular and affective responses to a socially evaluative stressor. Included participants who underwent the stressor evidenced similar increases in anxiety, but systolic blood pressure, diastolic blood pressure, and heart rate did not change significantly in response to the stressor. CONCLUSIONS: Results contribute to the understanding of physiological consequences of social exclusion. Further investigation is needed to test whether social inclusion can buffer CV stress reactivity, which would carry implications for how positive social factors may protect against the harmful effects of stress.

The dorsal anterior cingulate cortex is selective for pain: Results from large-scale reverse inference.

Dorsal anterior cingulate cortex (dACC) activation is commonly observed in studies of pain, executive control, conflict monitoring, and salience processing, making it difficult to interpret the dACC's specific psychological function. Using Neurosynth, an automated brainmapping database [of over 10,000 functional MRI (fMRI) studies], we performed quantitative reverse inference analyses to explore the best general psychological account of the dACC function P(Ψ process|dACC activity). Results clearly indicated that the best psychological description of dACC function was related to pain processing--not executive, conflict, or salience processing. We conclude by considering that physical pain may be an instance of a broader class of survival-relevant goals monitored by the dACC, in contrast to more arbitrary temporary goals, which may be monitored by the supplementary motor area.

The pain of social disconnection: examining the shared neural underpinnings of physical and social pain.

Experiences of social rejection, exclusion or loss are generally considered to be some of the most 'painful' experiences that we endure. Indeed, many of us go to great lengths to avoid situations that may engender these experiences (such as public speaking). Why is it that these negative social experiences have such a profound effect on our emotional well-being? Emerging evidence suggests that experiences of social pain--the painful feelings associated with social disconnection--rely on some of the same neurobiological substrates that underlie experiences of physical pain. Understanding the ways in which physical and social pain overlap may provide new insights into the surprising relationship between these two types of experiences.

The Neurobiology of Giving Versus Receiving Support: The Role of Stress-Related and Social Reward-Related Neural Activity.

OBJECTIVES: There is a strong association between supportive ties and health. However, most research has focused on the health benefits that come from the support one receives while largely ignoring the support giver and how giving may contribute to good health. Moreover, few studies have examined the neural mechanisms associated with support giving or how giving support compares to receiving support. METHOD: The current study assessed the relationships: a) between self-reported receiving and giving social support and vulnerability for negative psychological outcomes and b) between receiving and giving social support and neural activity to socially rewarding and stressful tasks. Thirty-six participants (mean [standard deviation] age = 22.36 [3.78] years, 44% female) completed three tasks in the functional magnetic resonance imaging scanner: 1) a stress task (mental arithmetic under evaluative threat), b) an affiliative task (viewing images of close others), and c) a prosocial task. RESULTS: Both self-reported receiving and giving social support were associated with reduced vulnerability for negative psychological outcomes. However, across the three neuroimaging tasks, giving but not receiving support was related to reduced stress-related activity (dorsal anterior cingulate cortex [r = -0.27], left [r = -0.28] and right anterior insula [r = -0.33], and left [r = -0.32] and right amygdala [r = -0.32]) to a stress task, greater reward-related activity (left [r = 0.42] and right ventral striatum [VS; r = 0.41]) to an affiliative task, and greater caregiving-related activity (left VS [r = 0.31], right VS [r = 0.31], and septal area [r = 0.39]) to a prosocial task. CONCLUSIONS: These results contribute to an emerging literature suggesting that support giving is an overlooked contributor to how social support can benefit health.

A Safe Haven: Investigating Social-Support Figures as Prepared Safety Stimuli.

Although fear-conditioning research has demonstrated that certain survival-threatening stimuli, namely prepared fear stimuli, are readily associated with fearful events, little research has explored whether a parallel category exists for safety stimuli. We examined whether social-support figures, who have typically benefited survival, can serve as prepared safety stimuli, a category that has not been explored previously. Across three experiments, we uncovered three key findings. First, social-support figures were less readily associated with fear than were strangers or neutral stimuli (in a retardation-of-acquisition test). Second, social-support stimuli inhibited conditional fear responses to other cues (in a summation test), and this inhibition continued even after the support stimulus was removed. Finally, these effects were not simply due to familiarity or reward because both familiar and rewarding stimuli were readily associated with fear, whereas social-support stimuli were not. These findings suggest that social-support figures are one category of prepared safety stimuli that may have long-lasting effects on fear-learning processes.

Self-Affirmation Activates the Ventral Striatum: A Possible Reward-Related Mechanism for Self-Affirmation.

Self-affirmation (reflecting on important personal values) has been shown to have a range of positive effects; however, the neural basis of self-affirmation is not known. Building on studies showing that thinking about self-preferences activates neural reward pathways, we hypothesized that self-affirmation would activate brain reward circuitry during functional MRI (fMRI) studies. In Study 1, with college students, making judgments about important personal values during self-affirmation activated neural reward regions (i.e., ventral striatum), whereas making preference judgments that were not self-relevant did not. Study 2 replicated these results in a community sample, again showing that self-affirmation activated the ventral striatum. These are among the first fMRI studies to identify neural processes during self-affirmation. The findings extend theory by showing that self-affirmation may be rewarding and may provide a first step toward identifying a neural mechanism by which self-affirmation may produce a wide range of beneficial effects.

Links between inflammation, amygdala reactivity, and social support in breast cancer survivors.

Psychosocial stress can affect inflammatory processes that have important consequences for cancer outcomes and the behavioral side effects of cancer treatment. To date, however, little is known about the upstream neural processes that may link psychosocial stressors and inflammation in cancer patients and survivors. To address this issue, 15 women who had been diagnosed with early-stage breast cancer and completed cancer treatment and 15 age- and ethnicity-matched women with no cancer history were recruited for a neuroimaging study. Participants provided a blood sample for levels of circulating inflammatory markers (CRP and IL-6), underwent an fMRI scan in which they completed a threat reactivity task designed to elicit activity in the amygdala, and reported their levels of perceived social attachment/support. There were no significant differences between cancer survivors and controls in levels of CRP or IL-6, in amygdala reactivity to the socially threatening images, or in levels of perceived social support. However, results showed a strong, positive correlation between CRP concentration and left amygdala reactivity in the survivor group that was not apparent in controls. Higher levels of social support in the survivor group were also associated with reduced amygdala reactivity and CRP. These data suggest the possibility of a stronger "neural-immune pipeline" among breast cancer survivors, such that peripheral inflammation is more strongly associated with neural activity in threat-related brain regions.