Proximity to high streets, social isolation and social support in British adolescents: A longitudinal analysis of sociospatial influences on social connectedness using geospatial data.

High streets have been shown to be central to socio-economic activity, given their diverse residential, leisure, and commercial activities. This study explores the link between adolescent social isolation and proximity to, and land use mix in, high streets. Hypothesising that greater distance from high streets might increase social isolation, measured via social activities, friend contact frequency, and social support, we used multilevel modelling with data from the Millennium Cohort Study. We did not observe a relationship between proximity to high streets and these social isolation indicators, suggesting that high streets may either not significantly influence adolescent social engagement or that young people are willing to travel greater distances.

Mapping gray and white matter volume abnormalities in early-onset psychosis: an ENIGMA multicenter voxel-based morphometry study.

INTRODUCTION: Regional gray matter (GM) alterations have been reported in early-onset psychosis (EOP, onset before age 18), but previous studies have yielded conflicting results, likely due to small sample sizes and the different brain regions examined. In this study, we conducted a whole brain voxel-based morphometry (VBM) analysis in a large sample of individuals with EOP, using the newly developed ENIGMA-VBM tool. METHODS: 15 independent cohorts from the ENIGMA-EOP working group participated in the study. The overall sample comprised T1-weighted MRI data from 482 individuals with EOP and 469 healthy controls. Each site performed the VBM analysis locally using the standardized ENIGMA-VBM tool. Statistical parametric T-maps were generated from each cohort and meta-analyzed to reveal voxel-wise differences between EOP and healthy controls as well as the individual-based association between GM volume and age of onset, chlorpromazine (CPZ) equivalent dose, and other clinical variables. RESULTS: Compared with healthy controls, individuals with EOP showed widespread lower GM volume encompassing most of the cortex, with the most marked effect in the left median cingulate (Hedges' g = 0.55, p = 0.001 corrected), as well as small clusters of lower white matter (WM), whereas no regional GM or WM volumes were higher in EOP. Lower GM volume in the cerebellum, thalamus and left inferior parietal gyrus was associated with older age of onset. Deficits in GM in the left inferior frontal gyrus, right insula, right precentral gyrus and right superior frontal gyrus were also associated with higher CPZ equivalent doses. CONCLUSION: EOP is associated with widespread reductions in cortical GM volume, while WM is affected to a smaller extent. GM volume alterations are associated with age of onset and CPZ equivalent dose but these effects are small compared to case-control differences. Mapping anatomical abnormalities in EOP may lead to a better understanding of the role of psychosis in brain development during childhood and adolescence.

The social cognitive and neural mechanisms that underlie social functioning in individuals with schizophrenia - a review.

In many individuals with a diagnosis of schizophrenia social functioning is impaired across the lifespan. Social cognition has emerged as one of the possible factors that may contribute to these challenges. Neuroimaging research can give further insights into the underlying mechanisms of social (cognitive) difficulties. This review summarises the evidence on the associations between social cognition in the domains of theory of mind and emotion perception and processing, and individuals' social functioning and social skills, as well as associated neural mechanisms. Eighteen behavioural studies were conducted since the last major review and meta-analysis in the field (inclusion between 7/2017 and 1/2022). No major review has investigated the link between the neural mechanisms of social cognition and their association with social functioning in schizophrenia. Fourteen relevant studies were included (from 1/2000 to 1/2022). The findings of the behavioural studies showed that associations with social outcomes were slightly stronger for theory of mind than for emotion perception and processing. Moreover, performance in both social cognitive domains was more strongly associated with performance on social skill measures than questionnaire-based assessment of social functioning in the community. Studies on the underlying neural substrate of these associations presented mixed findings. In general, higher activation in various regions of the social brain was associated with better social functioning. The available evidence suggests some shared regions that might underlie the social cognition-social outcome link between different domains. However, due to the heterogeneity in approaches and findings, the current knowledge base will need to be expanded before firm conclusions can be drawn.

Ecological momentary assessment (EMA) combined with unsupervised machine learning shows sensitivity to identify individuals in potential need for psychiatric assessment.

Ecological momentary assessment (EMA), a structured diary assessment technique, has shown feasibility to capture psychotic(-like) symptoms across different study groups. We investigated whether EMA combined with unsupervised machine learning can distinguish groups on the continuum of genetic risk toward psychotic illness and identify individuals with need for extended healthcare. Individuals with psychotic disorder (PD, N = 55), healthy individuals (HC, N = 25) and HC with first-degree relatives with psychosis (RE, N = 20) were assessed at two sites over 7 days using EMA. Cluster analysis determined subgroups based on similarities in longitudinal trajectories of psychotic symptom ratings in EMA, agnostic of study group assignment. Psychotic symptom ratings were calculated as average of items related to hallucinations and paranoid ideas. Prior to EMA we assessed symptoms using the Positive and Negative Syndrome Scale (PANSS) and the Community Assessment of Psychic Experience (CAPE) to characterize the EMA subgroups. We identified two clusters with distinct longitudinal EMA characteristics. Cluster 1 (NPD = 12, NRE = 1, NHC = 2) showed higher mean EMA symptom ratings as compared to cluster 2 (NPD = 43, NRE = 19, NHC = 23) (p < 0.001). Cluster 1 showed a higher burden on negative (p < 0.05) and positive (p < 0.05) psychotic symptoms in cross-sectional PANSS and CAPE ratings than cluster 2. Findings indicate a separation of PD with high symptom burden (cluster 1) from PD with healthy-like rating patterns grouping together with HC and RE (cluster 2). Individuals in cluster 1 might particularly profit from exchange with a clinician underlining the idea of EMA as clinical monitoring tool.

Reading the mind in the eyes and cognitive ability in schizophrenia- and autism spectrum disorders.

BACKGROUND: Schizophrenia (SZ) and autism spectrum disorders (ASD) are characterized by difficulties in theory of mind (ToM). We examined group differences in performance on a ToM-related test and associations with an estimated IQ. METHODS: Participants [N = 1227, SZ (n = 563), ASD (n = 159), and controls (n = 505), 32.2% female] completed the Reading the Mind in the Eyes Test (RMET) and assessments of cognitive ability. Associations between IQ and group on RMET were investigated with regression analyses. RESULTS: SZ (d = 0.73, p < 0.001) and ASD (d = 0.37, p < 0.001) performed significantly worse on the RMET than controls. SZ performed significantly worse than ASD (d = 0.32, p = 0.002). Adding IQ to the model, SZ (d = 0.60, p < 0.001) and ASD (d = 0.44, p < 0.001) continued to perform significantly worse than controls, but no longer differed from each other (d = 0.13, p = 0.30). Small significant negative correlations between symptom severity and RMET performance were found in SZ (PANSS positive: r = -0.10, negative: r = -0.11, both p < 0.05). A small non-significant negative correlation was found for Autism Diagnostic Observation Schedule scores and RMET in ASD (r = -0.08, p = 0.34). CONCLUSIONS: SZ and ASD are characterized by impairments in RMET. IQ contributed significantly to RMET performance and accounted for group differences in RMET between SZ and ASD. This suggests that non-social cognitive ability needs to be included in comparative studies of the two disorders.

Neuroimaging glutamatergic mechanisms differentiating antipsychotic treatment-response.

Glutamatergic dysfunction is associated with failure to respond to antipsychotic medication in individuals with schizophrenia. Our objective was to combine neurochemical and functional brain imaging methods to investigate glutamatergic dysfunction and reward processing in such individuals compared with those with treatment responsive schizophrenia, and healthy controls. 60 participants played a trust task, while undergoing functional magnetic resonance imaging: 21 classified as having treatment-resistant schizophrenia, 21 patients with treatment-responsive schizophrenia, and 18 healthy controls. Proton magnetic resonance spectroscopy was also acquired to measure glutamate in the anterior cingulate cortex. Compared to controls, treatment responsive and treatment-resistant participants showed reduced investments during the trust task. For treatment-resistant individuals, glutamate levels in the anterior cingulate cortex were associated with signal decreases in the right dorsolateral prefrontal cortex when compared to those treatment-responsive, and with bilateral dorsolateral prefrontal cortex and left parietal association cortex when compared to controls. Treatment-responsive participants showed significant signal decreases in the anterior caudate compared to the other two groups. Our results provide evidence that glutamatergic differences differentiate treatment resistant and responsive schizophrenia. The differentiation of cortical and sub-cortical reward learning substrates has potential diagnostic value. Future novel interventions might therapeutically target neurotransmitters affecting the cortical substrates of the reward network.

Age-Related Social Cognitive Performance in Individuals With Psychotic Disorders and Their First-Degree Relatives.

BACKGROUND: Social cognitive impairment is a recognized feature of psychotic disorders. However, potential age-related differences in social cognitive impairment have rarely been studied. STUDY DESIGN: Data came from 905 individuals with a psychotic disorder, 966 unaffected siblings, and 544 never-psychotic controls aged 18-55 who participated in the Genetic Risk and Outcome of Psychosis (GROUP) study. Multilevel linear models were fitted to study group main effects and the interaction between group and age on emotion perception and processing (EPP; degraded facial affect recognition) and theory of mind (ToM; hinting task) performance. Age-related differences in the association between socio-demographic and clinical factors, and EPP and ToM were also explored. STUDY RESULTS: Across groups, EPP performance was associated with age (ß = -0.02, z = -7.60, 95% CI: -0.02, -0.01, P < .001), with older participants performing worse than younger ones. A significant group-by-age interaction on ToM (X2(2) = 13.15, P = .001) indicated that older patients performed better than younger ones, while no age-related difference in performance was apparent among siblings and controls. In patients, the association between negative symptoms and ToM was stronger for younger than older patients (z = 2.16, P = .03). CONCLUSIONS: The findings point to different age-related performance patterns on tests of 2 key social cognitive domains. ToM performance was better in older individuals, although this effect was only observed for patients. EPP was less accurate in older compared with younger individuals. These findings have implications with respect to when social cognitive training should be offered to patients.

Do loneliness and social exclusion breed paranoia? An experience sampling investigation across the psychosis continuum.

Background: The role of loneliness and social exclusion in the development of paranoia is largely unexplored. Negative affect may mediate potential associations between these factors. We investigated the temporal relationships of daily-life loneliness, felt social exclusion, negative affect, and paranoia across the psychosis continuum. Method: Seventy-five participants, including 29 individuals with a diagnosis of non-affective psychosis, 20 first-degree relatives, and 26 controls used an Experience Sampling Method (ESM) app to capture the fluctuations in loneliness, feelings of social exclusion, paranoia, and negative affect across a 1-week period. Data were analysed with multilevel regression analyses. Results: In all groups, loneliness and feelings of social exclusion were independent predictors of paranoia over time (b = 0.05, p < .001 and b = 0.04, p < .05, respectively). Negative affect predicted paranoia (b = 0.17, p < .001) and partially mediated the associations between loneliness, social exclusion, and paranoia. It also predicted loneliness (b = 0.15, p < .0001), but not social exclusion (b = 0.04, p = .21) over time. Paranoia predicted social exclusion over time, with more pronounced effects in controls (b = 0.43) than patients (b = 0.19; relatives: b = 0.17); but not loneliness (b = 0.08, p = .16). Conclusion: Paranoia and negative affect worsen in all groups following feelings of loneliness and social exclusion. This highlights the importance of a sense of belonging and being included for mental well-being. Loneliness, feeling socially excluded, and negative affect were independent predictors of paranoid thinking, suggesting they represent useful targets in its treatment.

Comparing two measures of schizotypy and their relationship with psychological distress in British university students.

AIMS: Schizotypy reflects the vulnerability to schizophrenia in the general population. Different questionnaires have been developed to measure aspects of schizotypy. Higher schizotypy scores have also been linked with depression, anxiety, and stress sensitivity. Here we examine the associations of schizotypy with symptoms of depression and anxiety in a sample of university students, using two different measures (N = 271). METHODS: A series of confirmatory factor analyses was used to examine two distinct and frequently employed measures of schizotypy: the Community Assessment of Psychic Experiences (CAPE), and the Schizotypy Personality Questionnaire (SPQ). We assessed their relationship with each other and their predictive validity for anxiety, depression, and stress sensitivity. RESULTS: Our results indicated the brief 7-factor SPQ (SPQ-BR) factor solution for the SPQ and the 15-item and 3 factor solution for the CAPE (i.e., CAPE-P15) as best fitting models. Particularly the CAPE dimension of persecutory ideation was a strong predictor of anxiety, depression, and stress sensitivity, whereas the SPQ dimensions of no close friends and social anxiety predicted psychological distress and stress in our student sample. CONCLUSIONS: Our findings extend earlier work in general and patient samples and point to the importance of understanding the contribution of particularly positive schizotypy symptoms and different interpersonal aspects to psychological distress.

Neuroimaging oxytocin modulation of social reward learning in schizophrenia.

BACKGROUND: Conventional pharmacological approaches have limited effectiveness for schizophrenia. There is interest in the application of oxytocin, which is involved in social cognition. Clinical trials have yielded mixed results, with a gap in understanding neural mechanisms. AIMS: To evaluate the behavioural impact of oxytocin administration on a social learning task in individuals with schizophrenia, and elucidate any differential neural activity produced. METHOD: We recruited 20 clinically stable right-handed men diagnosed with schizophrenia or schizoaffective disorder. In a double-blind cross-over randomised controlled study, 40 IU of oxytocin or placebo were administered before functional magnetic resonance imaging of participants playing a multi-round economic exchange game of trust. Participants had the role of investors (investment trials) receiving repayment on their investments (repayment trials), playing one session against a computer and a second against a player believed to be human. RESULTS: During investment trials, oxytocin increased neural signalling in the right lateral parietal cortex for both human and computer player trials, and attenuated signalling in the right insula for human player trials. For repayment trials, oxytocin elicited signal increases in left insula and left ventral caudate, and a signal decrease in right amygdala during the human player trials; conversely it resulted in right dorsal caudate activation during the computer player trials. We did not find a significant change in behavioural performance associated with oxytocin administration, or any associations with symptoms. CONCLUSIONS: During a social learning task oxytocin modulates cortical and limbic substrates of the reward-processing network. These perturbations can be putatively linked to the pathoaetiology of schizophrenia.

Functional neurodevelopment of working memory in early-onset schizophrenia: A longitudinal FMRI study.

Schizophrenia, a debilitating disorder with typical manifestation of clinical symptoms in early adulthood, is characterized by cognitive impairments in executive processes such as in working memory (WM). However, there is a rare case of individuals with early-onset schizophrenia (EOS) starting before their 18th birthday, while WM and its neural substrates are still undergoing maturation. Using the WM n-back task with functional magnetic resonance imaging, we assessed the functional neurodevelopment of WM in adolescents with EOS and age- and gender-matched typically developing controls. Participants underwent neuroimaging in the same scanner twice, once at age 17 and at 21 (mean interscan interval = 4.3 years). General linear model analysis was performed to explore WM neurodevelopmental changes within and between groups. Psychopathological scores were entered in multiple regressions to detect brain regions whose longitudinal functional change was predicted by baseline symptoms in EOS. WM neurodevelopment was characterized by widespread functional reductions in frontotemporal and cingulate brain areas in patients and controls. No between-group differences were found in the trajectory of WM change. Baseline symptom scores predicted functional neurodevelopmental changes in frontal, cingulate, parietal, occipital, and cerebellar areas. The adolescent brain undergoes developmental processes such as synaptic pruning, which may underlie the refinement WM of network. Prefrontal and parietooccipital activity reduction is affected by clinical presentation of symptoms. Using longitudinal neuroimaging methods in a rare diagnostic sample of patients with EOS may help the advancement of neurodevelopmental biomarkers intended as pharmacological targets to tackle WM impairment.

A Systematic Review of Studies Describing the Effectiveness, Acceptability, and Potential Harms of Place-Based Interventions to Address Loneliness and Mental Health Problems.

Given the links between the built environment and loneliness, there is interest in using place-based approaches (addressing built environment characteristics and related socio-spatial factors) in local communities to tackle loneliness and mental health problems. However, few studies have described the effectiveness, acceptability, or potential harms of such interventions. This review aimed to synthesize the literature describing local community-based interventions that target place-based factors to address loneliness and mental health problems, informing the development of future public health approaches. We searched PsycINFO, Medline, and Embase using a structured search strategy to identify English-language studies evaluating the effectiveness, acceptability, and potential harms of place-based community interventions in addressing loneliness and mental health problems, both in general and clinical populations. Seven studies met the inclusion criteria, classified as evaluating provision of community facilities (such as clubhouses), active engagement in local green spaces, and housing regeneration. None were randomised trials. Quantitative and qualitative findings suggested promising effects and/or acceptability of six interventions, with minimal potential harms. There is a clear need for randomised trials or quasi-experimental studies of place-based interventions to describe their effectiveness in addressing loneliness and mental health problems, as well as complementary qualitative work investigating acceptability. This will inform future policy development.

Lifespan evolution of neurocognitive impairment in schizophrenia - A narrative review.

Cognitive impairment is a well-recognized key feature of schizophrenia. Here we review the evidence on (1) the onset and sensitive periods of change in cognitive impairment before and after the first psychotic episode, and (2) heterogeneity in neurocognitive presentations across cognitive domains between and within individuals. Overall, studies suggest that mild cognitive impairment in individuals who develop schizophrenia or related disorders is already present during early childhood. Cross-sectional studies further suggest increasing cognitive impairments from pre- to post-psychosis onset, with the greatest declines between adolescence, the prodrome, and the first psychotic episode and with some variability between domains. Longitudinal studies with more than 10 years of observation time are scarce but support mild cognitive declines after psychosis onset until late adulthood. Whether and how much this cognitive decline exceeds normal aging, proceeds further in older patients, and is specific to certain cognitive domains and subpopulations of patients remains to be investigated. Finally, studies show substantial heterogeneity in cognitive performance in schizophrenia and suggest a variety of impairment profiles. This review highlights a clear need for long-term studies that include a control group and individuals from adolescence to old age to better understand critical windows of cognitive change and their predictors. The available evidence stresses the importance of interventions that aim to counter cognitive decline during the prodromal years, as well as careful assessment of cognition in order to determine who will profit most from which cognitive training.

Loneliness, positive, negative and disorganised Schizotypy before and during the COVID-19 pandemic.

Loneliness is common in psychosis and occurs along a continuum. Here we investigate inter-relationships between loneliness, three-dimensional schizotypy, and depressive symptoms before and during the COVID-19 pandemic. The sample included 507 university students (48.3% participated before and 51.7% during the COVID-19 pandemic) who completed the Multidimensional Schizotypy Scale-Brief, the Counseling Center Assessment of Psychological Symptoms depression scale and the University of California, Los Angeles Loneliness Scale. Schizotypy and depression scores were regressed onto loneliness individually and in multiple regressions. The cohorts did not differ in any of the schizotypy domains (all p > .29). Depressive symptoms (p = .05) and loneliness (p = .006) were higher during the pandemic than before. Across cohorts, loneliness was significantly associated with positive (ß = 0.23, p < .001), negative (ß = 0.44, p < .001), and disorganised schizotypy (ß = 0.44, p < .001), and with depression (ß = 0.72, p < .001). Schizotypy together explained a significant amount of variance in loneliness (R2 = 0.26), with significant associations with positive (ß = -0.09, p = .047), negative (ß = 0.31, p < .001) and disorganised schizotypy (ß = 0.34, p < .001). When depression was included (ß = 0.69, p < .001), only positive (ß = -0.09, p = .008) and negative schizotypy (ß = 0.22, p < .001) significantly predicted loneliness. When all schizotypy dimensions and depression were considered together, only negative schizotypy and depression significantly predicted loneliness. Loneliness and depressive symptoms were higher during the pandemic, but this did not relate to cohort differences in schizotypy.

Intracranial and subcortical volumes in adolescents with early-onset psychosis: A multisite mega-analysis from the ENIGMA consortium.

Early-onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early-onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early-onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early-onset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixed-effects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = -0.39) and hippocampal (d = -0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early-onset schizophrenia (d = -0.34) and affective psychosis (d = -0.42), and early-onset schizophrenia showed lower hippocampal (d = -0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = -0.42). The findings demonstrate a similar pattern of brain alterations in early-onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early-onset psychosis.

Social isolation and psychosis: an investigation of social interactions and paranoia in daily life.

Social isolation has been suggested to foster paranoia. Here we investigate whether social company (i.e., being alone vs. not) and its nature (i.e., stranger/distant vs. familiar other) affects paranoia differently depending on psychosis risk. Social interactions and paranoid thinking in daily life were investigated in 29 patients with clinically stable non-affective psychotic disorders, 20 first-degree relatives, and 26 controls (n = 75), using the experience sampling method (ESM). ESM was completed up to ten times daily for 1 week. Patients experienced marginally greater paranoia than relatives [b = 0.47, p = 0.08, 95% CI (- 0.06, 1.0)] and significantly greater paranoia than controls [b = 0.55, p = 0.03, 95% CI (0.5, 1.0)], but controls and relatives did not differ [b = 0.07, p = 0.78, 95% CI (- 0.47, 0.61)]. Patients were more often alone [68.5% vs. 44.8% and 56.2%, respectively, p = 0.057] and experienced greater paranoia when alone than when in company [b = 0.11, p = 0.016, 95% CI (0.02, 0.19)]. In relatives this was reversed [b = - 0.17, p < 0.001, 95% CI (- 0.28, - 0.07)] and in controls non-significant [b = - 0.02, p = 0.67, 95% CI (- 0.09, 0.06)]. The time-lagged association between being in social company and subsequent paranoia was non-significant and paranoia did not predict the likelihood of being in social company over time (both p's = 0.68). All groups experienced greater paranoia in company of strangers/distant others than familiar others [X2(2) = 4.56, p = 0.03] and being with familiar others was associated with lower paranoia over time [X2(2) = 4.9, p = 0.03]. Patients are frequently alone. Importantly, social company appears to limit their paranoia, particularly when being with familiar people. The findings stress the importance of interventions that foster social engagement and ties with family and friends.

Neural, behavioural and real-life correlates of social context sensitivity and social reward learning during interpersonal interactions in the schizophrenia spectrum.

OBJECTIVE: Recent findings suggest that diminished processing of positive contextual information about others during interactions may contribute to social impairment in the schizophrenia spectrum. This could be due to general social context processing deficits or specific biases against positive information. We studied the impact of positive and negative social contextual information during social interactions using functional neuroimaging and probed whether these neural mechanisms were associated with real-life social functioning in schizophrenia spectrum disorders. METHODS: Patients with a schizophrenia spectrum disorder (N = 23) and controls disorder (N = 25) played three multi-round trust games during functional magnetic resonance imaging scanning, with no, positive and negative information about the counterpart's trustworthiness, while all counterparts were programmed to behave trustworthy. The main outcome variable was the height of the shared amount in the trust game, i.e. investment, representing an indication of trust. The first investment in the game was considered to be basic trust, since no behavioural feedback was given yet. We performed region-of-interest analyses and examined the association with real-life social functioning using the experience sampling method. RESULTS: Social contextual information had no effect on patients' first investments, whereas controls made the lowest investment after negative and the highest investments after positive contextual information was provided. Over trials, patients decreased investments, suggesting reduced social reward learning, whereas controls increased investments in response to behavioural feedback in the negative context. Patients engaged the dorsolateral prefrontal cortex less than controls during context presentation and showed reduced activity within the caudate during repayments. In patients, lower investments were associated with more time spent alone and social exclusion and lower caudate activation was marginally significantly associated with higher perceived social exclusion. CONCLUSION: The failure to adapt trust to positive and negative social contexts suggests that patients have a general insensitivity to prior social information, indicating top-down processing impairments. In addition, patients show reduced sensitivity to social reward, i.e. bottom-up processing deficits. Moreover, lower trust and lower neural activation were related to lower real-life social functioning. Together, these findings indicate that improving trust and social interactions in schizophrenia spectrum needs a multi-faceted approach that targets both mechanisms.