Ethnoracial Risk Variation Across the Psychosis Continuum in the US: A Systematic Review and Meta-Analysis.

Importance: Studies suggest a higher risk of schizophrenia diagnoses in Black vs White Americans, yet a systematic investigation of disparities that include other ethnoracial groups and multiple outcomes on the psychosis continuum is lacking. Objective: To identify ethnoracial risk variation in the US across 3 psychosis continuum outcomes (ie, schizophrenia and other psychotic disorders, clinical high risk for psychosis [CHR-P], and psychotic symptoms [PSs] and psychotic experiences [PEs]). Data Sources: PubMed, PsycINFO and Embase were searched up to December 2022. Study Selection: Observational studies on ethnoracial differences in risk of 3 psychosis outcomes. Data Extraction and Synthesis: Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Using a random-effects model, estimates for ethnoracial differences in schizophrenia and PSs/PEs were pooled and moderation by sampling and setting was determined, along with the assessment of heterogeneity and risk of bias. Main Outcomes and Measures: Risk of schizophrenia and other psychotic disorder, CHR-P, and conversion to psychosis among CHR-P and PSs/PEs. Results: Of 64 studies in the systematic review, 47 were included in the meta-analysis comprising 54 929 people with schizophrenia and 223 097 with data on PSs/PEs. Compared with White individuals, Black individuals had increased risk of schizophrenia (pooled odds ratio [OR], 2.07; 95% CI, 1.64-2.61) and PSs/PEs (pooled standardized mean difference [SMD], 0.10; 95% CI, 0.03-0.16), Latinx individuals had higher risk of PSs/PEs (pooled SMD, 0.15; 95% CI, 0.08-0.22), and individuals classified as other ethnoracial group were at significantly higher risk of schizophrenia than White individuals (pooled OR, 1.81; 95% CI, 1.31-2.50). The results regarding CHR-P studies were mixed and inconsistent. Sensitivity analyses showed elevated odds of schizophrenia in Asian individuals in inpatient settings (pooled OR, 1.84; 95% CI, 1.19-2.84) and increased risk of PEs among Asian compared with White individuals, specifically in college samples (pooled SMD, 0.16; 95% CI, 0.02-0.29). Heterogeneity across studies was high, and there was substantial risk of bias in most studies. Conclusions and Relevance: Findings of this systematic review and meta-analysis revealed widespread ethnoracial risk variation across multiple psychosis outcomes. In addition to diagnostic, measurement, and hospital bias, systemic influences such as structural racism should be considered as drivers of ethnoracial disparities in outcomes across the psychosis continuum in the US.

The Neural Basis of Social Cognition in Typically Developing Children and Its Relationship to Social Functioning.

Theory of mind (ToM), the ability to think about the perspectives, beliefs, and feelings of another, develops throughout childhood and adolescence and is an important skill for social interactions. This study examines neural activity in typically developing children during a novel ToM task - the Movie Mentalizing Task- and tests its relations to ToM behavioral performance and social functioning. In this fMRI task, children ages 8-13years (N=25) watched a brief movie clip and were asked to predict a character's mental state after a social interaction. Engaging in the Movie Mentalizing Task activated the ToM neural network. Moreover, greater neural activity in the ToM network, including the superior temporal gyrus and inferior frontal gyrus, was associated with better behavioral performance on independent ToM tasks and was related to better social functioning, though these results do not survive correction for multiple comparisons. Results offer a new affective theory of mind task for children in the scanner that robustly recruits activity in theory of mind regions.

Psychosis proneness, loneliness, and hallucinations in nonclinical individuals.

Hallucinations occur along a continuum of normal functioning. Investigating the factors related to this experience in nonclinical individuals may offer important information for understanding the etiology of hallucinations in psychiatric populations. In this study we test the relationship between psychosis proneness, loneliness, and auditory hallucinations in a nonclinical sample using the White Christmas paradigm. Seventy-six undergraduate students participated in this study. We found that slightly more than half of our participants endorsed a hallucinatory experience during the White Christmas paradigm. However, we did not observe a relationship between the number of hallucinatory experiences and schizotypy, propensity to hallucinate, or loneliness. Moreover, there were no differences on these measures between individuals who reported hearing a hallucination during the White Christmas paradigm relative to those who did not. Thus, there may be other contextual factors not investigated in this study that might clarify the mechanism by which auditory hallucinations are experienced in a nonclinical population.

From Womb to Neighborhood: A Racial Analysis of Social Determinants of Psychosis in the United States.

The authors examine U.S.-based evidence that connects characteristics of the social environment with outcomes across the psychosis continuum, from psychotic experiences to schizophrenia. The notion that inequitable social and economic systems of society significantly influence psychosis risk through proxies, such as racial minority and immigrant statuses, has been studied more extensively in European countries. While there are existing international reviews of social determinants of psychosis, none to the authors' knowledge focus on factors in the U.S. context specifically-an omission that leaves domestic treatment development and prevention efforts incomplete and underinformed. In this review, the authors first describe how a legacy of structural racism in the United States has shaped the social gradient, highlighting consequential racial inequities in environmental conditions. The authors offer a hypothesized model linking structural racism with psychosis risk through interwoven intermediary factors based on existing theoretical models and a review of the literature. Neighborhood factors, cumulative trauma and stress, and prenatal and perinatal complications were three key areas selected for review because they reflect social and environmental conditions that may affect psychosis risk through a common pathway shaped by structural racism. The authors describe evidence showing that Black and Latino people in the United States suffer disproportionately from risk factors within these three key areas, in large part as a result of racial discrimination and social disadvantage. This broad focus on individual and community factors is intended to provide a consolidated space to review this growing body of research and to guide continued inquiries into social determinants of psychosis in U.S. contexts.

Social exclusion and rejection across the psychosis spectrum: A systematic review of empirical research.

Social exclusion and rejection have deleterious effects on psychological well-being. Research documents the negative effects of social exclusion and rejection on psychiatric problems like depression, social anxiety disorder, and non-suicidal self-injury. Additionally, prior research suggests that individuals with and at-risk for psychosis spectrum disorders may also be negatively affected by exclusion and rejection. Moreover, those on the psychosis spectrum may be at an even greater risk to experience social exclusion due to poor social functioning and the stigma surrounding the disorder. This systematic review aimed to investigate how individuals across the psychosis spectrum respond to social exclusion and rejection. We systematically searched PubMed and PsycINFO databases to identify studies that met the following eligibility criteria: 1) investigated social exclusion or rejection, 2) targeted a psychosis-related sample or symptoms, and 3) was an empirical study. 13 studies satisfied our eligibility criteria and were subsequently reviewed. Despite methodological variation and samples spanning the psychosis spectrum, the majority of the literature supports the conclusion that those with psychosis spectrum disorders report similar levels of exclusion-induced distress compared to healthy controls, but process and cope with exclusion differently, both behaviorally and neurobiologically.

Simulation and social behavior: an fMRI study of neural processing during simulation in individuals with and without risk for psychosis.

Social dysfunction is a risk indicator for schizophrenia spectrum disorders, with at-risk individuals demonstrating a range of social behavior impairments. Variability in social ability may be explained by individual differences in the psychological processes of social behavior. In particular, mental simulation, the process by which an individual generates an internal representation of the thoughts or feelings of another, may explain variation in social behavior. This study investigates the neural process of simulation in healthy individuals and individuals at risk for psychosis. Using a novel fMRI pain paradigm, individuals watch videos of another person's hand or foot experiencing pain. After each video, individuals are asked to simulate the observed painful situation on their own hand or foot. Neural activity during simulation in the somatosensory cortex was associated with real-world self-reported social behavior, such that a stronger neural response in the somatosensory cortex was associated with greater rates of positive social experiences and affective empathy across all participants. These findings suggest that the neural mechanisms that underlie simulation are important for social behavior, and may explain individual variability in social functioning in healthy and at-risk populations.

Neural correlates of theory-of-mind are associated with variation in children's everyday social cognition.

Theory of mind (ToM), the capacity to reason about others' mental states, is central to healthy social development. Neural mechanisms supporting ToM may contribute to individual differences in children's social cognitive behavior. Employing a false belief functional magnetic resonance imaging paradigm, we identified patterns of neural activity and connectivity elicited by ToM reasoning in school-age children (N = 32, ages 9-13). Next, we tested relations between these neural ToM correlates and children's everyday social cognition. Several key nodes of the neural ToM network showed greater activity when reasoning about false beliefs (ToM condition) vs non-mentalistic false content (control condition), including the bilateral temporoparietal junction (RTPJ and LTPJ), precuneus (PC) and right superior temporal sulcus. In addition, children demonstrated task-modulated changes in connectivity among these regions to support ToM relative to the control condition. ToM-related activity in the PC was negatively associated with variation in multiple aspects of children's social cognitive behavior. Together, these findings elucidate how nodes of the ToM network act and interact to support false belief reasoning in school-age children and suggest that neural ToM mechanisms are linked to variation in everyday social cognition.

Altered reward processing following an acute social stressor in adolescents.

Altered reward processing is a transdiagnostic factor implicated in a wide range of psychiatric disorders. While prior animal and adult research has shown that stress contributes to reward dysfunction, less is known about how stress impacts reward processing in youth. Towards addressing this gap, the present study probed neural activation associated with reward processing following an acute stressor. Healthy adolescents (n = 40) completed a clinical assessment, and fMRI data were acquired while participants completed a monetary guessing task under a no-stress condition and then under a stress condition. Based on prior literature, analyses focused on a priori defined regions-of-interest, specifically the striatum (win trials) and dorsal anterior cingulate cortex [dACC] and insula (loss trials). Two main findings emerged. First, reward-related neural activation (i.e., striatum) was blunted in the stress relative to the no-stress condition. Second, the stress condition also contributed to blunted neural response following reward in loss-related regions (i.e., dACC, anterior insula); however, there were no changes in loss sensitivity. These results highlight the importance of conceptualizing neural vulnerability within the presence of stress, as this may clarify risk for mental disorders during a critical period of development.

Social impairment and social language deficits in children and adolescents with and at risk for psychosis.

INTRO: One of the more debilitating functional outcomes of schizophrenia-spectrum disorders is social impairment. Previous studies have identified impaired social functioning both in the prodromal phase of psychosis and after acute symptoms abate, suggesting that social impairment represents a core deficit in psychosis not directly linked to psychotic episodes or symptom severity. To date, research in this area has focused primarily on adult populations rather than children, and has not directly assessed social language in individuals across the psychosis continuum. METHODS: 81 youth ages 7-18 (N = 24 Typically Developing [TD], N = 36 Clinical High Risk [CHR], N = 21 Psychotic Disorder [PD]) were recruited. Youth participants were administered the Social Language Development Test (SLDT), and parent(s)/guardian(s) completed the Social Responsiveness Scale-II (SRS-II). RESULTS: Social language ability was not associated with social impairment. PD participants performed significantly worse on the SLDT than TD participants. CHR and PD participants were both rated as having experienced significantly greater social impairment than TD participants on every subscale of the SRS-II. DISCUSSION: Deficits in social language ability and social functioning are strong candidates for phenotypic markers of psychosis, and may be evident earlier in development than previous work has demonstrated. Additionally, the severity of social impairment did not differ between CHR and PD participants, further supporting that social cognitive deficits and social impairment, while related to symptom severity, are discrete deficits in individuals with and at risk for psychosis. These results highlight the importance of addressing social skills for individuals presenting in clinical settings with psychotic symptoms, including children.

Non-Suicidal self-injury and suicide in depressed Adolescents: Impact of peer victimization and bullying.

BACKGROUND: While prior research has demonstrated that peer victimization and bully perpetration contribute to non-suicidal self-injury (NSSI) and suicidal thoughts and behaviors (STBs), it remains unclear whether these interpersonal processes differentiate self-injuring adolescent suicide ideators and attempters. METHODS: The study included adolescents aged 13-18 years (n = 223; M = 15.31, SD = 1.34) recruited from an acute inpatient program. Participants were divided into two groups: (1) NSSISI (n = 106): endorsed past year NSSI, current suicide ideation, and no lifetime suicide attempts and (2) NSSISI+SA (n = 117): endorsed past year NSSI, current suicide ideation, and lifetime suicide attempts. Adolescents completed clinical interviews (i.e., mental disorders, NSSI, and STBs) and self-report measures assessing peer victimization, bully perpetration, and depression severity. RESULTS: NSSISI+SA youth reported higher levels of peer victimization and bully perpetration than NSSISI youth (ps < 0.01, ds = 0.36-0.37). Among the NSSISI+SA youth, bully perpetration was associated with a greater number of past month suicide attempts (p = 0.02, RR = 1.07). Only peer victimization was associated with greater NSSI behaviors in the past month (p = 0.04, RR = 1.01). LIMITATIONS: The study is cross-sectional, and reports of peer victimization and bully perpetration rely on self-report assessment. CONCLUSIONS: Peer victimization and bully perpetration differentiated adolescent suicide ideators and attempters, highlighting the need to address bully perpetration in addition to peer victimization in suicide interventions and research.

De novo ATP1A3 and compound heterozygous NLRP3 mutations in a child with autism spectrum disorder, episodic fatigue and somnolence, and muckle-wells syndrome.

Complex phenotypes may represent novel syndromes that are the composite interaction of several genetic and environmental factors. We describe an 9-year old male with high functioning autism spectrum disorder and Muckle-Wells syndrome who at age 5  years of age manifested perseverations that interfered with his functioning at home and at school. After age 6, he developed intermittent episodes of fatigue and somnolence lasting from hours to weeks that evolved over the course of months to more chronic hypersomnia. Whole exome sequencing showed three mutations in genes potentially involved in his clinical phenotype. The patient has a predicted pathogenic de novo heterozygous p.Ala681Thr mutation in the ATP1A3 gene (chr19:42480621C>T, GRCh37/hg19). Mutations in this gene are known to cause Alternating Hemiplegia of Childhood, Rapid Onset Dystonia Parkinsonism, and CAPOS syndrome, sometimes accompanied by autistic features. The patient also has compound heterozygosity for p.Arg490Lys/p.Val200Met mutations in the NLRP3 gene (chr1:247588214G>A and chr1:247587343G>A, respectively). NLRP3 mutations are associated in an autosomal dominant manner with clinically overlapping auto-inflammatory conditions including Muckle-Wells syndrome. The p.Arg490Lys is a known pathogenic mutation inherited from the patient's father. The p.Val200Met mutation, inherited from his mother, is a variant of unknown significance (VUS). Whether the de novoATP1A3mutation is responsible for or plays a role in the patient's episodes of fatigue and somnolence remains to be determined. The unprecedented combination of two NLRP3 mutations may be responsible for other aspects of his complex phenotype.

Neural simulation mechanisms and social-emotional function in schizophrenia.

Impairment in simulation, i.e., the generation of internal representations of experiences, may contribute to social dysfunction in schizophrenia spectrum disorders (SZ). Using a novel fMRI task, we identified neural representations generated during simulation of sensorimotor experiences and evaluated their associations with socioemotional function in 19 individuals with SZ and 24 psychiatrically-healthy controls (HC). Participants watched videos depicting a painful sensorimotor experience in the hand or foot of another person and were then asked to imagine how unpleasant it would be to undergo that experience themselves, eliciting simulation. A localizer task identified regions-of-interest (ROIs) within each participant's sensorimotor cortices (SC) recruited by firsthand sensory experiences in hands and feet. Simulation engaged these ROIs in HC and SZ. Simulation-related activation in ROIs did not differ between groups but was associated with participants' social function. Findings indicate that simulation elicits specific neural representations within the SC and the strength of these representations might be linked to social function.

Suicidal behaviors and their relationship with psychotic-like symptoms in children and adolescents at clinical high risk for psychosis.

BACKGROUND: Previous research has demonstrated elevated rates of suicide attempts and ideation in individuals with psychosis. This study investigated rates and severity of suicidal behavior in youth with and at clinical high risk for psychosis, and examined the positive, negative, and disorganized symptoms associated with suicidal behaviors among the clinical high risk group. METHODS: Eighty-six youth ages 7-18 (n=21 non-clinical controls [NCC], n=40 clinical high risk [CHR], n=25 diagnosed psychotic disorder [PD]) were recruited. CHR and PD participants were identified using the Structured Interview for Prodromal Symptoms (SIPS) and Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (KSADS-PL). All participants completed the Suicide Behaviors Questionnaire-Revised (SBQ-R). RESULTS: Findings indicated significantly higher levels of suicidal behavior among CHR and PD relative to NCC participants (F=7.64, p=0.001). 17.5% of CHR participants had previously attempted suicide. Dysphoric Mood and Odd Behavior or Appearance were significantly correlated with suicidal behavior severity among CHR youth. CONCLUSION: Suicidal behavior was observed with greater frequency and severity in the CHR and PD groups than in the NCC group. CHR suicidal behavior severity was correlated most strongly with Dysphoric Mood and Odd Behavior or Appearance, a relationship which warrants further investigation.

Social cognitive impairment in 22q11 deletion syndrome: A review.

Individuals with 22q11.2 deletion syndrome (22q11DS) exhibit a broad array of physical and psychiatric features, of which impaired social cognition and poor social functioning are common. This review seeks to (1) characterize the current understanding of impairment across social cognitive domains in the context of 22q11DS, and (2) synthesize the relevant literature on social cognition and psychosis, given that the prevalence of psychosis in 22q11DS is especially high compared to the general population. A total of 16 papers examining social cognition in 22q11DS were identified through a comprehensive literature search conducted using electronic databases such as PubMed and PSYCInfo. Results suggest that individuals with 22q11DS exhibit impaired emotion processing and complex theory of mind relative to their typically developing peers, though some findings were accounted for by neurocognitive and intellectual abilities. Further, no studies have examined the domains of attribution bias or social perception in 22q11DS, highlighting a critical gap in the extant literature. More research is needed to better elucidate the trajectory of how and why social cognitive impairment develops in 22q11DS, and to explore possible relationships to psychiatric comorbidities like psychosis. Treatment implications and future steps are considered.

A Developmental Perspective on Social-Cognition Difficulties in Youth at Clinical High Risk for Psychosis.

LEARNING OBJECTIVES: After participating in this activity, learners should be better able to:• Evaluate the evolution of social cognitive abilities as a developmental process• Assess the evidence regarding social cognition difficulties in youth at clinical high risk for psychosisIndividuals at clinical high risk (CHR) for psychosis exhibit a broad range of difficulties, including impaired social cognition, which may represent a target for early identification and intervention. Several studies have examined various domains of social cognition in CHR individuals. Most focus on adolescent and young adult populations, but given the accumulating evidence that impairment exists before the onset of psychotic disorders, it is critically important to begin to look for these risk markers in younger children. The present article reviews 25 studies on CHR that examine any of the following four domains of social cognition: emotion processing, theory of mind, social perception, or attribution bias. Eligible studies were identified through a comprehensive literature search, conducted using electronic databases, including PubMed/MEDLINE and PsycINFO, and combinations of key social-cognition and CHR search terms. Despite some mixed results, the existing literature establishes that CHR individuals display social-cognitive impairment, though it remains unclear as to how and when that impairment develops. Thus, by using the literature on social cognition in typically developing children as a model and reference, and by looking at the evolution of social-cognitive abilities as a developmental process, our review presents a valuable new perspective that indicates the necessity of further investigation in younger, at-risk populations. Implications for treatment and future research are discussed.

Suicidal behaviors in children and adolescents with psychotic disorders.

Suicide is the leading cause of premature death in individuals with psychotic disorders. Risk for onset of suicidal behaviors tends to begin in adolescence, remaining high into young adulthood. The present study aims to evaluate the interplay of early onset psychosis and suicide risk by examining suicidal behaviors (ideation, planning, and attempts) in children and adolescents with psychotic disorders (PD) compared to typically developing peers (TD). Twenty five youths were recruited and were diagnostically evaluated for psychosis. We found that the PD children exhibited significantly higher levels of suicidal behaviors than TD children, even when parsed into individual at-risk behaviors.

Adults with high social anhedonia have altered neural connectivity with ventral lateral prefrontal cortex when processing positive social signals.

Social anhedonia (SA) is a debilitating characteristic of schizophrenia, a common feature in individuals at psychosis-risk, and a vulnerability for developing schizophrenia-spectrum disorders. Prior work (Hooker et al., 2014) revealed neural deficits in the ventral lateral prefrontal cortex (VLPFC) when processing positive social cues in a community sample of people with high SA. Lower VLPFC neural activity was related to more severe self-reported schizophrenia-spectrum symptoms as well as the exacerbation of symptoms after social stress. In the current study, psycho-physiological interaction (PPI) analysis was applied to further investigate the neural mechanisms mediated by the VLPFC during emotion processing. PPI analysis revealed that, compared to low SA controls, participants with high SA exhibited reduced connectivity between the VLPFC and the motor cortex, the inferior parietal and the posterior temporal regions when viewing socially positive (relative to neutral) emotions. Across all participants, VLPFC connectivity correlated with behavioral and self-reported measures of attentional control, emotion management, and reward processing. Our results suggest that impairments to the VLPFC mediated neural circuitry underlie the cognitive and emotional deficits associated with social anhedonia, and may serve as neural targets for prevention and treatment of schizophrenia-spectrum disorders.

Neural structure and social dysfunction in individuals at clinical high risk for psychosis.

Individuals at a clinical high risk (CHR) for psychosis have gray matter volume (GMV) abnormalities that are similar to, though less severe than, those in individuals with schizophrenia. Less GMV in schizophrenia is related to worse social cognition and social functioning, but the relationship between GMV and social functioning in CHR individuals has yet to be investigated. The aim of this study was to (1) investigate differences in GMV between healthy controls (HC) and CHR individuals, and (2) evaluate the relationship between GMV and social functioning in these two groups. Participants comprised 22 CHR and 21 HC individuals who completed a structural magnetic resonance imaging (MRI) scan as well as self-reported and interviewer-rated measures of social functioning. Processing and analysis of structural images were completed using voxel based morphometry (VBM). Results showed that the CHR group had less GMV in the left postcentral gyrus, bilateral parahippocampual gyri, and left anterior cingulate cortex. Reduced GMV in the postcentral gyrus and the anterior cingulate was related to self-reported social impairment across the whole group. This study has implications for the neurobiological basis of social dysfunction present before the onset of psychosis.

Attentional control mediates the relationship between social anhedonia and social impairment.

Social anhedonia (SA), a trait-like disinterest in social contact and diminished capacity to experience pleasure from social interactions, is consistently associated with social impairments in both healthy and clinical populations. However, the mechanisms underlying the relationship between SA and social impairment are poorly understood. Attentional control, selecting and focusing on relevant information and inhibiting irrelevant, may be one such mechanism. We examined individual differences in SA, attentional control, and social impairment in 108 healthy adults. High SA related to low attentional control and high social impairment. Moreover, attentional control mediated the relationship between SA and social impairment, establishing attentional control as one mechanism underlying aberrations in the fundamental human need for social contact. Although both attentional deficits and social impairment have been separately noted in SA, the relationship between SA, attentional control and social impairment in this non-clinical sample reflects a novel contribution.