The social network-network: size is predicted by brain structure and function in the amygdala and paralimbic regions

The social brain hypothesis proposes that the large size of the primate neocortex evolved to support complex and demanding social interactions. Accordingly, recent studies have reported correlations between the size of an individual’s social network and the density of gray matter (GM) in regions of the brain implicated in social cognition. However, the reported relationships between GM density and social group size are somewhat inconsistent with studies reporting correlations in different brain regions. One factor that might account for these discrepancies is the use of different measures of social network size (SNS). This study used several measures of SNS to assess the relationships SNS and GM density. The second goal of this study was to test the relationship between social network measures and functional brain activity. Participants performed a social closeness task using photos of their friends and unknown people. Across the VBM and functional magnetic resonance imaging analyses, individual differences in SNS were consistently related to structural and functional differences in three regions: the left amygdala, right amygdala and the right entorhinal/ventral anterior temporal cortex.     

Social skills training to teach prosocial behaviors in an organically impaired and retarded patient

A social skills training program consisting of behavior rehearsal, modeling, instruction, feedback, and reinforcement was used to teach prosocial behaviors (e.g. number of words spoken, eye contact, smiles) in an organically impaired and intellectually deficient young adult. Six months following initial treatment, booster sessions were used to bolster the effects of initial training. All behaviors improved initially; decrements in skill performance seen over the six months of no treatment were reinstituted in booster sessions. The effects of treatment were evaluated in a multiple baseline design across behaviors.     

Socioeconomic status and depressive symptoms in older people with the mediation role of social support: A population‐based longitudinal study

BackgroundDepressive symptoms has become an increasingly important public health issue, contributing to disability and disease burden around the world. Higher socioeconomic status (SES) has been found to be associated with lower prevalence of depression, but there are few studies about the older Chinese adults with long‐term follow up and rigorous prospective design. Meanwhile, there is little conclusive evidence about the mechanisms through which SES influences the onset of depressive symptoms.ObjectiveTo prospectively examine the association of baseline socioeconomic factors with the risks of developing depressive symptoms during 7‐year follow up in older Chinese population, and to study the mechanism by which SES impacts the prevalence of depressive symptoms.MethodsA total of 5677 individuals over 45 years who participated in an ongoing nationally representative prospective cohort study, China Health and Retirement Longitudinal Study, were free from depressive symptoms at baseline, and completed 7‐year follow‐up were included. Depressive symptoms were assessed using the 10‐item Center for Epidemiological Studies Depression Scale score. Cox proportional hazards regression models were used to examine the association of SES and the incidence of depressive symptoms in 2011 to 2018. Generalized structural equation model was used to analyze the mediation effects of social support on the relation between SES and depressive symptoms.ResultsDuring the 7‐year follow‐up, 2398 (42.2%) cases were identified as depressive symptoms. Compared with the lowest level of household income, participants with the highest level of household income had a 20% reduction in risk (95% CI, 0.70–0.92, P < 0.001). Participants who had junior high school or above education had a 41% lower risk of depressive disorders compared with illiterate participants (95% CI, 0.52–0.69, P < 0.001). The relationship between SES and depressive symptoms was partially mediated by the social support, where higher social support was negatively associated with depressive symptoms. The proportion of mediation effect was even larger for women compared with men.ConclusionSocioeconomic factors were independently associated with the development of depressive symptoms, and the relationship was partially mediated by social support. Social support could be an effective intervention to alleviate the negative effects of lower SES on mental health. Multiple‐level policies should precisely target low‐SES groups, and timely intervention to promote social support for this group should be used to reduce the influence of depression on individuals, family as well as the whole society.     

Modeling socially anhedonic syndromes: genetic and pharmacological manipulation of opioid neurotransmission in mice

Social anhedonia, or the diminished capacity to experience pleasure and reward from social affiliation, is a major symptom of different psychiatric disorders, including some forms of infantile autism and schizophrenia spectrum disorders. The brain opioid hypothesis of social attachment is a promising model for achieving insights into how neurobiological and developmental factors contribute to the regulation of social reward. In this study, genetic knocking-out and naltrexone (NTRX) treatment during the first 4 days of life were used to disrupt opioid neurotransmission in mouse pups and their attachment relationships with the mother. Both permanent (genetic) and transient (pharmacological) manipulations of opioid neurotransmission exerted long-term effects on social affiliation. When juveniles, both μ-opioid receptor knockout mice and NTRX-treated pups showed reduced interest in peers and no preference for socially rewarding environment. These results demonstrate that sociability in juvenile mice is highly dependent on the establishment during infancy of a positive affective relationship with their mothers and that opioid neurotransmission has a major role in the regulation of social hedonic capacity. If the validity of this animal model will be confirmed by future research, translational studies focusing on the interaction between early experience and opioid neurotransmission could provide useful insights for identifying endophenotypes of human psychiatric disorders associated with social anhedonia.     

Deficient NRG1-ERBB signaling alters social approach: relevance to genetic mouse models of schizophrenia

Growth factor Neuregulin 1 (NRG1) plays an essential role in development and organization of the cerebral cortex. NRG1 and its receptors, ERBB3 and ERBB4, have been implicated in genetic susceptibility for schizophrenia. Disease symptoms include asociality and altered social interaction. To investigate the role of NRG1-ERBB signaling in social behavior, mice heterozygous for an Nrg1 null allele (Nrg1+/-), and mice with conditional ablation of Erbb3 or Erbb4 in the central nervous system, were evaluated for sociability and social novelty preference in a three-chambered choice task. Results showed that deficiencies in NRG1 or ERBB3 significantly enhanced sociability. All of the mutant groups demonstrated a lack of social novelty preference, in contrast to their respective wild-type controls. Effects of NRG1, ERBB3, or ERBB4 deficiency on social behavior could not be attributed to general changes in anxiety-like behavior, activity, or loss of olfactory ability. Nrg1+/- pups did not exhibit changes in isolation-induced ultrasonic vocalizations, a measure of emotional reactivity. Overall, these findings provide evidence that social behavior is mediated by NRG1-ERBB signaling.     

Vulnerability to chronic subordination stress-induced depression-like disorders in adult 129SvEv male mice

Exposure to stressful life events is intimately linked with vulnerability to neuropsychiatric disorders such as major depression. Pre-clinical animal models offer an effective tool to disentangle the underlying molecular mechanisms. In particular, the 129SvEv strain is often used to develop transgenic mouse models but poorly characterized as far as behavior and neuroendocrine functions are concerned. Here we present a comprehensive characterization of 129SvEv male mice's vulnerability to social stress-induced depression-like disorders and physiological comorbidities. We employed a well characterized mouse model of chronic social stress based on social defeat and subordination. Subordinate 129SvEv mice showed body weight gain, hyperphagia, increased adipose fat pads weight and basal plasma corticosterone. Home cage phenotyping revealed a suppression of spontaneous locomotor activity and transient hyperthermia. Subordinate 129SvEv mice also showed marked fearfulness, anhedonic-like response toward a novel but palatable food, increased anxiety in the elevated plus maze and social avoidance of an unfamiliar male mouse. A direct measured effect of the stressfulness of the living environment, i.e. the amount of daily aggression received, predicted the degree of corticosterone level and locomotor activity but not of the other parameters. This is the first study validating a chronic subordination stress paradigm in 129SvEv male mice. Results demonstrated remarkable stress vulnerability and establish the validity to use this mouse strain as a model for depression-like disorders.     

Altered Peripersonal Space and the Bodily Self in Schizophrenia: A Virtual Reality Study

Self-disturbances such as an anomalous perception of one’s own body boundary are central to the phenomenology of schizophrenia (SZ), but measuring the spatial parameters of the hypothesized self–other boundary has proved to be challenging. Peripersonal space (PPS) refers to the immediate zone surrounding the body where the self interacts physically with the environment; the space that corresponds to hypothesized self–other boundary. PPS is represented by enhanced multisensory integration and faster reaction time (RT) for objects near the body. Thus, multisensory RT tasks can be used to estimate self–other boundary. We aimed to quantify PPS in SZ using an immersive virtual reality visuotactile RT paradigm. Twenty-four participants with SZ and 24 demographically matched controls (CO) were asked to detect tactile vibration while watching a ball approaching them, thrown by either a machine (nonsocial condition) or an avatar (social condition). Parameters of PPS were estimated from the midpoint of the spatial range where the tactile RT decreased most rapidly (size) and the gradient of the RT change at this midpoint (slope). Overall, PPS was smaller in participants with SZ compared with CO. PPS slope for participants with SZ was shallower than CO in the social but not in nonsocial condition, indicating an increased uncertainty of self–other boundary across an extended zone in SZ. Social condition also increased false alarms for tactile detection in SZ. Clinical symptoms were not clearly associated with PPS parameters. These findings suggest the context-dependent nature of weakened body boundary in SZ and underscore the importance of reconciliating objective and subjective aspects of self-disturbances.     

Supramodal neural networks support top‐down processing of social signals

The perception of facial and vocal stimuli is driven by sensory input and cognitive top‐down influences. Important top‐down influences are attentional focus and supramodal social memory representations. The present study investigated the neural networks underlying these top‐down processes and their role in social stimulus classification. In a neuroimaging study with 45 healthy participants, we employed a social adaptation of the Implicit Association Test. Attentional focus was modified via the classification task, which compared two domains of social perception (emotion and gender), using the exactly same stimulus set. Supramodal memory representations were addressed via congruency of the target categories for the classification of auditory and visual social stimuli (voices and faces). Functional magnetic resonance imaging identified attention‐specific and supramodal networks. Emotion classification networks included bilateral anterior insula, pre‐supplementary motor area, and right inferior frontal gyrus. They were pure attention‐driven and independent from stimulus modality or congruency of the target concepts. No neural contribution of supramodal memory representations could be revealed for emotion classification. In contrast, gender classification relied on supramodal memory representations in rostral anterior cingulate and ventromedial prefrontal cortices. In summary, different domains of social perception involve different top‐down processes which take place in clearly distinguishable neural networks.     

Eyes on me: an fMRI study of the effects of social gaze on action control

Previous evidence suggests that ‘social gaze’ can not only cause shifts in attention, but also can change the perception of objects located in the direction of gaze and how these objects will be manipulated by an observer. These findings implicate differences in the neural networks sub-serving action control driven by social cues as compared with nonsocial cues. Here, we sought to explore this hypothesis by using functional magnetic resonance imaging and a stimulus–response compatibility paradigm in which participants were asked to generate spatially congruent or incongruent motor responses to both social and nonsocial stimuli. Data analysis revealed recruitment of a dorsal frontoparietal network and the locus coeruleus for the generation of incongruent motor responses, areas previously implicated in controlling attention. As a correlate for the effect of ‘social gaze’ on action control, an interaction effect was observed for incongruent responses to social stimuli in sub-cortical structures, anterior cingulate and inferior frontal cortex. Our results, therefore, suggest that performing actions in a—albeit minimal—social context significantly changes the neural underpinnings of action control and recruits brain regions previously implicated in action monitoring, the reorienting of attention and social cognition.     

The effect of oxytocin on cooperation in a prisoner’s dilemma depends on the social context and a person’s social value orientation

The interactionist approach to the study of exogenous oxytocin (OT) effects on prosocial behavior has emphasized the need to consider both contextual cues and individual differences. Therefore, an experiment was set up to examine the joint effect of intranasal OT, a salient social cue and the personality trait social value orientation on cooperative behavior in one-shot prisoner’s dilemma games. The outcome of these mixed-motive games is known to be highly dependent on values and on social information that might reveal the partner’s intent. Consistent with an a priori hypothesis, OT and social information interact significantly to affect the behavior of individuals with a proself value orientation: after prior contact with the game partner, OT enhances cooperative behavior, whereas in anonymous conditions, it exacerbates their intrinsic self-interested behavior. These effects of OT do not hold for individuals with a prosocial value orientation, whose cooperation levels appear to be more influenced by prior contact with the game partner. Follow-up hypotheses for why prosocial and proself individuals respond differently to exogenous OT were developed.     

Disruption to social dyadic interactions but not emotional/anxiety-related behaviour in mice with heterozygous 'knockout' of the schizophrenia risk gene neuregulin-1

Clinical genetic studies have implicated neuregulin-1 [NRG1] as a leading susceptibility gene for schizophrenia. NRG1 is known to play a significant role in the developing brain, which is consistent with the prevailing neurodevelopmental model of schizophrenia. Thus, the emotional and social phenotype of adult mice with heterozygous 'knockout' of transmembrane [TM]-domain NRG1 was examined further in both sexes. Emotional/anxiety-related behaviour was assessed using the elevated plus-maze and the light-dark test. Social behaviour was examined in terms of dyadic interactions between NRG1 mutants and an unfamiliar C57BL6 conspecific in a novel environment. There was no effect of NRG1 genotype on performance in either test of emotionality/anxiety. However, previous reports of hyperactivity in NRG1 mutants were confirmed in both paradigms. In the test of social interaction, aggressive following was increased in NRG1 mutants of both sexes, together with an increase in walkovers in female mutants. These findings elaborate the specificity of the NRG1 phenotype for the social rather than the emotional/anxiety-related domain. They indicate that NRG1 is involved in the regulation of reciprocal social interaction behaviour and thus suggest a putative role for NRG1 in a schizophrenia-related endophenotype.     

Central odor processing in subjects experiencing helplessness

The aim of the present study was to investigate whether central nervous odor processing is affected by the temporary experience of helplessness. To induce helplessness, an unsolvable social discrimination test in combination with false feedback was used. The EEG was recorded from 60 scalp locations, while two standard odors were presented via a constant-flow olfactometer. Helplessness attenuated olfactory stimulus processing at an early perceptual stage: the P2 and P3-1 amplitudes were reduced in response to both odors. Furthermore, the early potentials (N1, P2 and P3-1) of the chemosensory event-related potential (CSERP) appeared with longer latencies when subjects received negative feedback. The state effects of helplessness resemble the deviations in the CSERP found in depressed patients, suggesting a general mood effect.     

Combined effect of maternal serotonin transporter genotype and prenatal stress in modulating offspring social interaction in mice

Several studies suggest that prenatal stress is a possible risk factor in the development of autism spectrum disorders. However, many children exposed to stress prenatally are born healthy and develop typically, suggesting that other factors must contribute to autism. Genes that contribute to stress reactivity may, therefore, exacerbate prenatal stress-mediated behavioral changes in the adult offspring. One candidate gene linked to increased stress reactivity encodes the serotonin transporter. Specifically, an insertion/deletion (long/short allele) polymorphism upstream of the serotonin transporter gene correlates with differential expression and function of the serotonin transporter and a heightened response to stressors. Heterozygous serotonin transporter knockout mice show reductions in serotonin transporter expression similar to the human short polymorphism. In this study, the role of prenatal stress and maternal serotonin transporter genotype were assessed in mice to determine whether their combined effect produces reductions in social behavior in the adult offspring. Pregnant serotonin transporter heterozygous knockout and wild-type dams were placed in either a control condition or subjected to chronic variable stress. The adult offspring were subsequently assessed for social interaction and anxiety using a three-chamber social approach task, ultrasonic vocalization detection, elevated-plus maze and an open field task. Results indicated that prenatal stress and reduced serotonin transporter expression of the dam may have the combined effect of producing changes in social interaction and social interest in the offspring consistent with those observed in autism spectrum disorder. This data indicates a possible combined effect of maternal serotonin transporter genotype and prenatal stress contributing to the production of autistic-like behaviors in offspring.     

Socially isolated rats exhibit changes in dopamine homeostasis pertinent to schizophrenia

Post-weaning social isolation of rats produces an array of behavioral and neurochemical changes indicative of altered dopamine function. It has therefore been suggested that post-weaning social isolation mimics some aspects of schizophrenia. Here we replicate and extent these findings to include an investigation of prefrontal cortical dopamine dynamics using in vivo microdialysis.Social isolation for 12 weeks after weaning caused increased locomotor activity in response to novelty and amphetamine challenge. In vivo microdialysis experiments revealed that while social isolation did not change basal dopamine levels in the nucleus accumbens, it did cause a significant reduction of basal dopamine release in the prefrontal cortex. In addition, social isolation lead to a significantly larger dopamine response to an amphetamine challenge, in both the nucleus accumbens and the prefrontal cortex compared to group housed controls. Taken together, these results indicate that post-weaning social isolation alters dopaminergic function with changes resembling subcortical hyperdopaminergia and prefrontal hypodopaminergia similar to what has been observed in schizophrenic patients.     

Cognitive functioning related to quality of life in schizophrenia

The present study compared the cognitive function of patients with schizophrenia to that of healthy subjects, and investigated the relationships between cognitive function and quality of life (QOL). Participants consisted of 53 patients meeting DSM-IV criteria for schizophrenia and 31 normal controls. All participants completed a neuropsychological test battery assessing executive function, verbal memory, and social knowledge. QOL was rated using the Schizophrenia Quality of Life Scale. Patients with schizophrenia showed lower performance across various cognitive measures of memory, including the Sentence Memory Test, the Verbal Learning Test, and the Script Test, as well as the Rule Shift Cards Test of executive function. Multiple regression analyses were used to evaluate the neuropsychological measures and clinical symptoms to predict QOL. The QOL total score, the social initiative score or the empathy score were significantly predicted by the Script or/and the Sentence Memory. Neuropsychological functioning was unrelated to most QOL scores in the presence of clinical symptoms, while ability of empathy in the QOL was predicted by performance of the Sentence Memory Test. These results demonstrated patients with schizophrenia have deficits in executive function, memory and learning, and social knowledge, and that social knowledge and memory are related to QOL. Thus, in patients with schizophrenia, deficits in social knowledge appear to be associated with current QOL in general, and specifically with the capacity for empathy and social initiative.     

Interaction between polygenic risk for cigarette use and environmental exposures in the Detroit neighborhood health study

Cigarette smoking is influenced both by genetic and environmental factors. Until this year, all large-scale gene identification studies on smoking were conducted in populations of European ancestry. Consequently, the genetic architecture of smoking is not well described in other populations. Further, despite a rich epidemiologic literature focused on the social determinants of smoking, few studies have examined the moderation of genetic influences (for example, gene–environment interactions) on smoking in African Americans. In the Detroit Neighborhood Health Study (DNHS), a sample of randomly selected majority African American residents of Detroit, we constructed a genetic risk score (GRS), in which we combined top (P-value <5 × 10⁻⁷) genetic variants from a recent meta-analysis conducted in a large sample of African Americans. Using regression (effective n=399), we first tested for association between the GRS and cigarettes per day, attempting to replicate the findings from the meta-analysis. Second, we examined interactions with three social contexts that may moderate the genetic association with smoking: traumatic events, neighborhood social cohesion and neighborhood physical disorder. Among individuals who had ever smoked cigarettes, the GRS significantly predicted the number of cigarettes smoked per day and accounted for ∼3% of the overall variance in the trait. Significant interactions were observed between the GRS and number of traumatic events experienced, as well as between the GRS and average neighborhood social cohesion; the association between genetic risk and smoking was greater among individuals who had experienced an increased number of traumatic events in their lifetimes, and diminished among individuals who lived in a neighborhood characterized by greater social cohesion. This study provides support for the utility of the GRS as an alternative approach to replication of common polygenic variation, and in gene–environment interaction, for smoking behaviors. In addition, this study indicates that environmental determinants have the potential to both exacerbate (traumatic events) and diminish (neighborhood social cohesion) genetic influences on smoking behaviors.     

Alcohol-induced neuronal death in central extended amygdala and pyriform cortex during the postnatal period of the rat

Mothers who consume alcohol during pregnancy may cause a neurotoxic syndrome defined as fetal alcohol spectrum disorder (FASD) in their offspring. This disorder is characterized by reduction in brain size, cognitive deficits and emotional/social disturbances. These alterations are thought to be caused by an alcohol-induced increase in apoptosis during neurodevelopment. Little is known about neuroapoptosis in the central extended amygdala and the pyriform cortex, which are key structures in emotional/social behaviors. The goal of this study was to determine the vulnerability of neuroapoptotic alcohol effects in those areas. Rats were administered alcohol (2.5 g/kg s.c. at 0 and 2 h) or saline on postnatal day (PND) 7, 15 and 20. The Amino-cupric-silver technique was used to evaluate neurodegeneration and immunohistochemistry to detect activated caspases 3–8 and 9 at 2 h, 4, 6, 8, 12 and 24 h after drug administration. We measured blood alcohol levels each hour, from 2 to 8 h post second administration of alcohol in each of the ages studied. Results showed alcohol induced apoptotic neurodegeneration in the central extended amygdala on PND 7 and 15, and pyriform cortex on PND 7, 15 and 20. These structures showed activation of caspase 3 and 9 but not of caspase 8 suggesting that alcohol-induced apoptosis could occur by the intrinsic pathway. The pharmacokinetic differences between ages did not associate with the neurodegeneration age dependence. In conclusion, these limbic areas are damaged by alcohol, and each one has their own window of vulnerability during the postnatal period. The possible implications in emotional/social features in FASD are discussed.     

Long-term effects of juvenile nicotine exposure on abstinence-related social anxiety-like behavior and amygdalar cannabinoid receptor 1 (CB1R) mRNA expression in the novelty-seeking phenotype

A rat model of novelty-seeking phenotype predicts vulnerability to nicotine relapse where locomotor reactivity to novelty is used to rank high (HR) versus low (LR) responders. Present study investigates implication of cannabinoid receptor 1 (CB1R) in the basolateral (BLA) and the central (CeA) nuclei of amygdala in behaviorally sensitizing effects of nicotine and accompanying social anxiety following juvenile nicotine training and a 1- or 3-wk injection-free period in the novelty-seeking phenotype. Sprague-Dawley rats were phenotype screened, and received four, saline (1 ml/kg; s.c) or nicotine (0.35 mg/kg; s.c) injections, followed by a 1- or 3-wk injection-free period. Subsequently, animals were challenged with a low dose of nicotine (0.1 mg/kg; s.c.), subjected to the social interaction test and sacrificed. In situ hybridization histochemistry was used to assess CB1R messenger RNA (mRNA) levels in the amygdala. Nicotine pre-trained HRs displayed expression of locomotor sensitization to nicotine challenge along with enhanced social anxiety compared to saline pre-trained controls following a 1- or 3-wk injection-free period. HR-specific behavioral effects were accompanied by decreased CB1R mRNA levels in the CeA and the BLA following a 1-wk injection-free period. Decreased CB1R mRNA levels in both compartments of the amygdala were also observed following nicotine challenge in saline pre-trained HRs after a 3-wk injection-free period compared to HRs after a 1-wk injection-free period. These findings show robust, long-lasting expression of behavioral sensitization to nicotine in HRs associated with changes in amygdalar CB1R mRNA as a potential substrate for abstinence-related anxiety.     

Social support predicts hemodynamic recovery from mental stress in patients with implanted defibrillators

OBJECTIVE: Emotionally stressful events appear to trigger malignant ventricular arrhythmias and myocardial infarction in cardiac patients. However, the physiological pathways linking psychological stress to arrhythmias and adverse disease outcomes remain incompletely understood. In patients with implanted cardioverter-defibrillators (ICD) we investigated the impact of emotions and social support on cardiovascular recovery from mental stress. The hypothesis tested was that psychosocial resources help to maintain adaptive hemodynamic responses to mental stress. METHODS: In 55 ICD patients we noninvasively measured hemodynamic and autonomic parameters during two sequentially performed mental stress tests (arithmetic and anger recall tests). The cardiovascular data obtained were associated with results from well-validated psychometric self-rating tests for anxiety and depression (HADS), anger (STAXI), and perceived social support (FSozU). RESULTS: In the rest period after mental stress application the majority of the study participants (82%) showed a rapid fall in cardiac index, arterial blood pressure, and heart rate, as well as an increase in high-frequency heart rate variability, while the remainder had no or unexpected changes in the hemodynamic parameters examined. Patients missing hemodynamic recovery in the post-stress phase reported significantly less social support than normally reacting patients (P<.05). Multivariate logistic regression models confirm that social support is an independent and significant predictor of preserved hemodynamic recovery from mental stress, even after controlling for somatic confounders (multivariate odds ratio 4.1; 95% confidence interval 1.3-12.7; P=.015). CONCLUSIONS: Our data indicate that in ICD patients better perceived social support is associated with a more pronounced hemodynamic recovery after mental stress.