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

The Influence of Trial-By-Trial Feedback on Trust in Health, First-Episode and Chronic Psychosis

Trust is crucial to establishing reciprocal, positive social interactions and seems to be compromised in psychosis. The trust game offers methods to assess an individual’s trust responses to trust-reciprocating, positive feedback. Various computational techniques have been implemented to measure trust responsiveness, mostly based on investments. Here, we propose a new method, focusing on feedback response. Psychosis patients show social dysfunction and reduced trust during early and more progressed illness stages. The present study inspects differences in feedback responsiveness of 102 first-episode psychosis patients (FEPs), 43 chronic psychosis patients (CPs), and 39 healthy controls (HCs) by adopting a novel assessment approach. Additionally, baseline trust, the trust exerted without any prior knowledge of the partner’s trustworthiness, and mean trust were examined. Participants performed a multi-round trust game, playing the investor role, and were paired with a computer, programmed to return at least the invested amount, representing a trustworthy partner. The new method detected group differences, more distinguished than the former methods. Contrary to our expectations, baseline trust was intact in patients. Relative to HCs, patients were less responsive to feedback, failing to integrate the positive information into their decision-making process. The magnitude of returns was not associated with increases in trust. This novel method showed promising results and confirmed patients’ deficits within the social interactional domain

Learning to trust: social feedback normalizes trust behavior in first-episode psychosis and clinical high risk

Background Psychosis is characterized by problems in social functioning that exist well before illness onset, and in individuals at clinical high risk (CHR) for psychosis. Trust is an essential element for social interactions that is impaired in psychosis. In the trust game, chronic patients showed reduced baseline trust, impaired response to positive social feedback, and attenuated brain activation in reward and mentalizing areas. We investigated whether first-episode psychosis patients (FEP) and CHR show similar abnormalities in the neural and behavioral mechanisms underlying trust. Methods Twenty-two FEP, 17 CHR, and 43 healthy controls performed two trust games, with a cooperative and an unfair partner in the fMRI scanner. Region of interest analyses were performed on mentalizing and reward processing areas, during the investment and outcome phases of the games. Results Compared with healthy controls, FEP and CHR showed reduced baseline trust, but like controls, learned to trust in response to cooperative and unfair feedback. Symptom severity was not associated with baseline trust, however in FEP associated with reduced response to feedback. The only group differences in brain activation were that CHR recruited the temporo-parietal junction (TPJ) more than FEP and controls during investment in the unfair condition. This hyper-activation in CHR was associated with greater symptom severity. Conclusions Reduced baseline trust may be associated with risk for psychotic illness, or generally with poor mental health. Feedback learning is still intact in CHR and FEP, as opposed to chronic patients. CHR however show distinct neural activation patterns of hyper-activation of the TPJ

Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis

Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface area (SA), cortical thickness (CT), subcortical volume (SV), and intracranial volume (ICV) in CHR-P individuals compared with healthy controls (HC), and in relation to subsequent transition to a first episode of psychosis. The ENIGMA CHR-P consortium applied a harmonised analysis to neuroimaging data across 29 international sites, including 1579 CHR-P individuals and 1243 HC, offering the largest pooled CHR-P neuroimaging dataset to date. Regional heterogeneity was indexed with the Variability Ratio (VR) and Coefficient of Variation (CV) ratio applied at the group level. Personalised estimates of heterogeneity of SA, CT and SV brain profiles were indexed with the novel Person-Based Similarity Index (PBSI), with two complementary applications. First, to assess the extent of within-diagnosis similarity or divergence of neuroanatomical profiles between individuals. Second, using a normative modelling approach, to assess the ‘normativeness’ of neuroanatomical profiles in individuals at CHR-P. CHR-P individuals demonstrated no greater regional heterogeneity after applying FDR corrections. However, PBSI scores indicated significantly greater neuroanatomical divergence in global SA, CT and SV profiles in CHR-P individuals compared with HC. Normative PBSI analysis identified 11 CHR-P individuals (0.70%) with marked deviation (>1.5 SD) in SA, 118 (7.47%) in CT and 161 (10.20%) in SV. Psychosis transition was not significantly associated with any measure of heterogeneity. Overall, our examination of neuroanatomical heterogeneity within the CHR-P state indicated greater divergence in neuroanatomical profiles at an individual level, irrespective of psychosis conversion. Further large-scale investigations are required of those who demonstrate marked deviation.publishedVersio

Normative modeling of brain morphometry in clinical high risk for psychosis

Importance The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in individuals at psychosis risk may be nested within the range observed in healthy individuals. Objective To quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder. Design, Setting, and Participants This case-control study used clinical-, IQ-, and neuroimaging software (FreeSurfer)–derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1340 individuals with CHR-P and 1237 healthy individuals pooled from 29 international sites participating in the Enhancing Neuroimaging Genetics Through Meta-analysis (ENIGMA) Clinical High Risk for Psychosis Working Group. Healthy individuals and individuals with CHR-P were matched on age and sex within each recruitment site. Data were analyzed between September 1, 2021, and November 30, 2022. Main Outcomes and Measures For each regional morphometric measure, deviation scores were computed as z scores indexing the degree of deviation from their normative means from a healthy reference population. Average deviation scores (ADS) were also calculated for regional CT, SA, and SV measures and globally across all measures. Regression analyses quantified the association of deviation scores with clinical severity and cognition, and 2-proportion z tests identified case-control differences in the proportion of individuals with infranormal (z &lt; −1.96) or supranormal (z &gt; 1.96) scores. Results Among 1340 individuals with CHR-P, 709 (52.91%) were male, and the mean (SD) age was 20.75 (4.74) years. Among 1237 healthy individuals, 684 (55.30%) were male, and the mean (SD) age was 22.32 (4.95) years. Individuals with CHR-P and healthy individuals overlapped in the distributions of the observed values, regional z scores, and all ADS values. For any given region, the proportion of individuals with CHR-P who had infranormal or supranormal values was low (up to 153 individuals [&lt;11.42%]) and similar to that of healthy individuals (&lt;115 individuals [&lt;9.30%]). Individuals with CHR-P who converted to a psychotic disorder had a higher percentage of infranormal values in temporal regions compared with those who did not convert (7.01% vs 1.38%) and healthy individuals (5.10% vs 0.89%). In the CHR-P group, only the ADS SA was associated with positive symptoms (β = −0.08; 95% CI, −0.13 to −0.02; P = .02 for false discovery rate) and IQ (β = 0.09; 95% CI, 0.02-0.15; P = .02 for false discovery rate). Conclusions and Relevance In this case-control study, findings suggest that macroscale neuromorphometric measures may not provide an adequate explanation of psychosis risk

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

Exploring the association between social behaviour, trust, and its neural correlates in first episode psychosis patients and in individuals at clinical high risk for psychosis

OBJECTIVES: Psychosis is characterized by paranoid delusions, social withdrawal, and distrust towards others. Trust is essential for successful social interactions. It remains unknown which aspects of social functioning are associated with reduced trust in psychosis. Therefore, we investigated the association between social behaviour, trust, and its neural correlates in a group of individuals with psychotic symptoms (PS-group), consisting of first episode psychosis patients combined with individuals at clinical high risk. METHODS: We compared 24 PS individuals and 25 healthy controls. Affect and social withdrawal were assessed using the Experience Sampling Method. Trust was measured during functional magnetic resonance imaging (fMRI) scanning, using a trust game with a cooperative and unfair counterpart. RESULTS: The PS-group showed lower baseline trust compared to controls and reported less positive and more negative general affect. Social withdrawal did not differ between the groups. Social withdrawal and social reactivity in affect (i.e., changes in affect when with others compared to when alone) were not associated with trust. On the neural level, in controls but not in the PS-group, social withdrawal was associated with caudate activation during interactions with an unfair partner. An increase in positive social reactivity, was associated with reduced insula activation in the whole sample. CONCLUSIONS: Social withdrawal and social reactivity were not associated with reduced initial trust in the PS-group. Like controls, the PS-group showed a positive response in affect when with others, suggesting a decrease in emotional distress. Supporting patients to keep engaging in social interactions, may alleviate their emotional distress. PRACTITIONER POINTS: Individuals with psychotic symptoms show reduced initial trust towards unknown others. Trust in others is not associated with social withdrawal and reported affect when with others, nor when alone. Like controls, individuals with psychotic symptoms showed reduced negative affect and increased positive affect when with others compared to when alone. We emphasize to support individuals with psychotic symptoms to keep engaging in social interactions, given it may reduce social withdrawal and alleviate their emotional distress

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

Association of Structural Magnetic Resonance Imaging Measures With Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis: An ENIGMA Working Group Mega-analysis

Importance: The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk. Objective: To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-). Design, setting, and participants: In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020. Main outcomes and measures: Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group). Results: Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (ρ = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (ρ = 0.43; 95% CI, 0.20 to 0.61; P = .001). Conclusions and relevance: This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes