Neural Effects of the Social Environment

Epidemiological studies have suggested that the association between city upbringing and minority status with risk for schizophrenia can be explained by social mechanisms. Neuroimaging approaches hold promise for investigating this claim. Recent studies have shown that in healthy individuals, city upbringing and minority status are associated with increased activity in brain circuits involved in emotion regulation during social evaluative processing. These findings support the hypothesis that changes in the ability to regulate social stress contribute to the mechanism of risk. This is in accordance with a body of evidence demonstrating the sensitivity of the human brain to social stress, based on observational studies investigating the neurological sequelae of interpersonal trauma and experimental studies manipulating exposure to interpersonal distress. In this report, we summarize these initial findings, discuss methodological and conceptual challenges of pursuing this line of inquiry in schizophrenia, and suggest an outline for future research

Psychosis and urbanicity – a review of the recent literature from epidemiology to neurourbanism

Purpose of review: Epidemiological studies associate city living with an elevated psychosis risk. Urban (social/economic) stress and exposure to environmental toxins, pollution or disease agents have been proposed to underlie this association. This review provides an update on the recent evidence (May 2017 - November 2018). Recent findings: Of 645-screened studies, 17 on: (1) urbanicity-psychosis associations in worldwide high, middle and low-income countries, (2) explanatory mechanisms, including nature exposure, social and economic stressors and genetic risk; (3) urbanicity effects on the brain and coping; and (4) urbanicity and resources, were included. The reviewed evidence revealed complex patterns of urbanicity-psychosis associations with considerable international variation within Europe and between low, middle and high-income countries worldwide. Social and economic stressors (e.g. migration, ethnic density, economic deprivation), nature exposure and access to resources could only explain part of the urbanicity effects. Risk factors differed between countries and between affective and non-affective psychosis. Summary: Urbanicity-psychosis associations are heterogeneous and driven by multiple risk and protective factors that seem to act differently in different ethnic groups and countries. Interdisciplinary research combining approaches, e.g. from experimental neuroscience and epidemiology, is needed to unravel specific urban mechanisms that in- or decrease psychosis risk

Trust and the city: Linking urban upbringing to neural mechanisms of trust in psychosis

Objective: Elevated prevalence of non-affective psychotic disorders is often found in densely populated areas. This functional magnetic resonance imaging study investigates if reduced trust, a component of impaired social functioning in patients with psychotic disorder, is associated with urban upbringing. Methods: In total, 39 patients (22 first episode and 17 clinical high risk) and 30 healthy controls, aged 16–29, performed two multi-round trust games, with a cooperative and unfair partner during functional magnetic resonance imaging scan-ning. Baseline trust was operationalized as the first investment made, and changes of trust as changes in investments made over the 20 trials during the games. Urban exposure during upbringing (0–15 years) was defined as higher urban (≥2500 inhabitants/km2) or lower urban (<2500 inhabitants/km2). Results: Patients displayed lower baseline trust (first investment) than controls, regardless of urbanicity exposure. During cooperative interactions, lower-urban patients showed increasing investments. In addition, during cooperative interactions, group-by-developmental urbanicity interactions were found in the right and left amygdalae, although for the latter only at trend level. Higher urbanicity was associated with decreased activation of the left amygdala in patients and controls during investments and with increased activation of the right and left amygdalae in patients only, during repayments. During unfair interactions, no associations of urbanicity with behavior or brain activation were found. Conclusion: Urban upbringing was unrelated to baseline trust. Associations with urbanicity were stronger for patients compared to controls, suggesting greater susceptibility to urbanicity effects during the developmental period. Higher-urban patients failed to compensate for the initial distrust specifically during repeated cooperative interactions. This finding highlights potential implications for social functioning. Urban upbringing was linked to dif-ferential amygdala activation, suggesting altered mechanisms of feedback learning, but this was not associated with trust game behavio

Girls-Boys: An Investigation of Gender Differences in the Behavioral and Neural Mechanisms of Trust and Reciprocity in Adolescence

Background: Trust and reciprocity toward others have often been found to increase from childhood to adulthood. Gender differences in these social behaviors have been reported in adults. While adolescence is a key-period of change in social behavior, gender differences in trust and reciprocity during this developmental stage have rarely been investigated. Methods: Here we investigate age-related gender differences in trust and reciprocity (n = 100, 51 female) and associated neural mechanisms (n = 44, 20 female) in adolescents between 13 and 19 years of age. Participants played two multi-round trust games with a pre-programmed cooperative and an unfair partner. Forty-four of 100 participants completed the trust game while undergoing functional brain imaging. Results: Participants’ investments were greater toward a cooperative than unfair game partner (p < 0.01), showing sensitivity to the degree of trustworthiness. There were no gender or age or related differences in baseline trust. In repeated cooperative interactions no gender differences were found, but younger adolescents showed slightly steeper increase of investments than older adolescents. In unfair interactions, younger males reacted with stronger decrease of investments than older males. Region of interest analysis of brain areas associated with in mentalizing, reward learning, conflict processing, and cognitive control revealed gender-by-age interactions on trusting behavior in the temporo-parietal junction (TPJ) and the caudate, showing stronger influence of age in males than in females during cooperation, and the reverse in unfair interactions. Additionally, main effects of gender were found in the TPJ, with higher activation in males, and in the caudate, with females showing greater activation. Conclusion: In first interactions and during repeated cooperative interactions, adolescent males and females showed similar trusting behavior. Younger males showed stronger responses to unfairness by others. Gender-by-age interactions in specific ROIs suggest differential development in mentalizing and reward related cognitive processes. In conjunction with previous research, our findings suggest the presence of subtle gender and age-related changes in trust and cooperation that are only detectable using larger age windows

Endovascular procedures cause transient endothelial injury but do not disrupt mature neointima in Drug Eluting Stents

Extensive application of coronary intravascular procedures has led to the increased need of understanding the injury inflicted to the coronary arterial wall. We aimed to investigate acute and prolonged coronary endothelial injury as a result of guidewire use, repeated intravascular imaging and stenting. These interventions were performed in swine (N = 37) and injury was assessed per coronary segment (n = 81) using an Evans Blue dye-exclusion-test. Scanning electron microscopy and light microscopy were then used to visualize the extent and nature of acute (<4 hours) and prolonged (5 days) endothelial injury. Guidewire and imaging injury was mainly associated with denudation and returned to control levels at 5 days. IVUS and OCT combined (Evans Blue staining 28 ± 16%) did not lead to more acute injury than IVUS alone (33 ± 15%). Stent placement caused most injury (85 ± 4%) and despite early stent re-endothelialization at 5 days, the endothelium proved highly permeable (97 ± 4% at 5 days; p < 0.001 vs acute). Imaging of in-stent neointima at 28 days after stent placement did not lead to neointimal rupture. Guidewire, IVUS and OCT induce acute endothelial cell damage, which does not increase during repeated imaging, and heals within 5 days. Interestingly, endothelial permeability increases 5 days post stenting despite near complete re-endothelialization

Benefits of Social Contact in Individuals With Psychotic Symptoms: Do Closeness of the Contact and Empathic Skills Make the Difference?

Objectives: Social contact is known to be beneficial for humans’ mental health. Individuals with psychotic symptoms (PS) tend to show poorer social and interpersonal functioning. However, in this patient population, social contact may be crucial for their mental wellbeing and treatment success. Additionally, closeness of social contact (familiar versus less familiar others), rather than only the presence or absence of social contacts, may play an important role. Empathy may heighten the beneficial effects of social/close contact on mental health, facilitating interactions. We investigated the association between social contact and closeness of contact on mental health, defined as positive symptoms, positive affect and negative affect in PS and control participants, with empathy as a moderator. Methods: Participants were 16–30 years old. Information regarding social/close contact and mental health was obtained using the experience sampling method in individuals with PS (n = 29) and healthy controls (n = 28). Empathy was measured using a self-report questionnaire. Results: Social contact was associated with higher positive affect in the total sample. Contact with close as opposed to less close others was related to better mental health: It was associated with lower positive symptoms in the PS group, and with more positive affect in the total sample. Empathy moderated the association between closeness of contact and positive affect in the total sample, in which the combination of higher levels of empathy combined with the presence of close contact was associated with higher positive affect in the total sample. However, the direct association between empathy and positive affect was not significant per group of contact. Conclusion: The results suggest that social contact, but especially contact with a close other is important for mental health outcomes: Contact with close others is beneficial for positive affect in the total sample and for positive symptoms in individuals with PS

Vagal nerve stimulation started just prior to reperfusion limits infarct size and no-reflow

Vagal nerve stimulation (VNS) started prior to, or during, ischemia has been shown to reduce infarct size. Here, we investigated the effect of VNS when started just prior to, and continued during early, reperfusion on infarct size and no-reflow and studied the underlying mechanisms. For this purpose, swine (13 VNS, 10 sham) underwent 45 min mid-LAD occlusion followed by 120 min of reperfusion. VNS was started 5 min prior to reperfusion and continued until 15 min of reperfusion. Area at risk, area of no-reflow (% of infarct area) and infarct size (% of area at risk), circulating cytokines, and regional myocardial leukocyte influx were assessed after 120 min of reperfusion. VNS significantly reduced infarct size from 67 ± 2 % in sham to 54 ± 5 % and area of no-reflow from 54 ± 6 % in sham to 32 ± 6 %. These effects were accompanied by reductions in neutrophil (~40 %) and macrophage (~60 %) infiltration in the infarct area (all p < 0.05), whereas systemic circulating plasma levels of TNFα and IL6 were not affected. The degree of cardioprotection could not be explained by the VNS-induced bradycardia or the VNS-induced decrease in the double product of heart rate and left ventricular systolic pressure. In the presence of NO-synthase inhibitor LNNA, VNS no longer attenuated infarct size and area of no-reflow, which was paralleled by similarly unaffected regional leukocyte infiltration. In conclusion, VNS is a promising novel adjunctive therapy that limits reperfusion injury in a large animal model of acute myocardial infarction

The reported effects of neuroscience literacy and belief in neuromyths among parents of adolescents

Neuroscience research has increased our understanding of brain development, but little is known about how parents of adolescents engage with this neuroscientific information. Dutch parents completed a digital survey on neuromyths, neuroscience literacy and views of the adolescent brain and behaviour. These parents believed 44.7% of neuromyths and showed reasonable neuroscience literacy (79.8%). Stronger neuromyth belief predicted a more negative view on adolescent brain development. About 68% of the parents reported that they had changed their parenting behaviour based on their understanding of neuroscientific findings. These self-reported changes most often reflected changes to parents’ own behaviour. The results of this study underline the importance for scientists and parents to engage in scientific activities to promote respectful and trusting relationships between them. These relationships have the potential to make communication about adolescent brain development between scientists and parents more effective and will empower parents to use correct information as a basis for their decisions around raising their adolescents

Depressive symptoms are associated with (sub)clinical psychotic symptoms in patients with non-affective psychotic disorder, siblings and healthy controls

Background. Depression is a clinically relevant dimension, associated with both positive and negative symptoms, in patients with schizophrenia. However, in siblings it is unknown whether depression is associated with subclinical positive and negative symptoms. Method. Depressive symptoms and their association with positive and negative symptoms were examined in 813 healthy siblings of patients with a non-affective psychotic disorder, 822 patients and 527 healthy controls. Depressive episodes meeting DSM-IV-TR criteria (lifetime) and depressed mood (lifetime) were assessed with the Comprehensive Assessment of Symptoms and History (CASH) in all three groups. In the patient group, the severity of positive and negative psychosis symptoms was assessed with the CASH. In the siblings and healthy controls, the severity of subclinical psychosis symptoms was assessed with the Community Assessment of Psychic Experiences (CAPE). Results. Patients reported more lifetime depressed mood and more depressive episodes than both siblings and controls. Siblings had a higher chance of meeting lifetime depressive episodes than the controls; no significant differences in depressed mood were found between siblings and controls. In all three groups the number and duration of depressive symptoms were associated with (sub) clinical negative symptoms. In the patients and siblings the number of depressive symptoms was furthermore associated with (sub) clinical positive symptoms. Finally, lifetime depressed mood showed familial clustering but this clustering was absent for lifetime depressive episodes. Conclusions. These findings suggest that a co-occurring genetic vulnerability for both depressive and psychotic symptomatology exists on a clinical and a subclinical level

The effect of bioresorbable vascular scaffold implantation on distal coronary endothelial function in dyslipidemic swine with and without diabetes

Background: We studied the effect of bioresorbable vascular scaffold (BVS) implantation on distal coronary endothelial function, in swine on a high fat diet without (HFD) or with diabetes (DM + HFD). Methods: Five DM + HFD and five HFD swine underwent BVS implantation on top of coronary plaques, and were studied six months later. Conduit artery segments >. 5. mm proximal and distal to the scaffold and corresponding control segments of non-scaffolded coronary arteries, as well as segments of small arteries within the flow-territories of scaffolded and non-scaffolded arteries were harvested for in vitro vasoreactivity studies. Results: Conduit segments proximal and distal to the BVS edges showed reduced endothelium-dependent vasodilation as compared to control vessels (p <. 0.01), with distal segments being most prominently affected (p <. 0.01). Endothelial dysfunction was only observed in DM + HFD swine and was principally due to a loss of NO. Endothelium-independent vasodilation and vasoconstriction were unaffected. Surprisingly, segments from the microcirculation distal to the BVS showed enhanced endothelium-dependent vasodilation (p <. 0.01), whereas endothelium-independent vasodilation and vasoconstriction were unaltered. This enhanced vasorelaxation was only observed in DM + HFD swine, and did not appear to be either NO- or EDHF-mediated. Conclusions: Six months of BVS implantation in DM + HFD swine causes NO-mediated endothelial dysfunction in nearby coronary segments, which is accompanied by a, possibly compensatory, increase in endothelial function of the distal microcirculation. Endothelial dysfunction extending into coronary conduit segments beyond the implantation-site, is in agreement with recent reports expressing concern for late scaffold thrombosis and of early BVS failure in diabetic patients