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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.

When faced with a morally charged situation, individuals engage in an ethical decision-making process to resolve the ethical dilemma. This paper outlines a model that describes the steps in the ethical decision-making process and identifies situational factors, collectively termed moral intensity, which may influence this process. The use of a case study, presenting an ethical dilemma relevant for professionals, offers an opportunity to apply the ethical decision-making model. This model can be used as a teaching and training tool to enhance research administrators' professional development in research ethics. (Contains 1 figure.)

This systematic review and meta-analysis investigates if ethnoracial groups in the US differ in risk of schizophrenia and other psychotic disorders, clinical high risk for psychosis, and psychotic symptoms and experiences. Key Points: Question: Do ethnoracial groups in the US differ in risk of schizophrenia and other psychotic disorders, clinical high risk for psychosis (CHR-P), and psychotic symptoms (PSs) and experiences (PEs)? Findings: In this systematic review and meta-analysis including 64 studies of which 47 studies were included in the meta-analysis, risk of schizophrenia diagnosis was significantly increased among Black individuals and those categorized as other ethnoracial group compared with White individuals, and risk of PSs/PEs was significantly increased among both Black and Latinx groups. Findings regarding CHR-P were equivocal. Meaning: Ethnoracial risk variation in the US is present across multiple psychosis-related outcomes, suggesting that factors other than diagnostic bias alone underlie these disparities. 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. [ABSTRACT FROM AUTHOR]

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.

This article addresses the issue of properly assenting children with psychotic disorders to participate in clinical research. Due to the protective concerns with such a vulnerable population, additional precautions are necessary to ensure that youth with psychotic disorders assent to research with an appropriate level of understanding regarding study procedures. Current literature suggests that positive/negative symptoms and minor cognitive deficits do not interfere with the ability to comprehend study-related information for adults with psychosis if the study information is presented through an educative process. Similarly, youth benefit from repeated presentation of procedures and periodic assessment of their comprehension. An integrated educative process is proposed that emphasizes the importance of an interactive consent through repetition and participant/investigator feedback. [ABSTRACT FROM AUTHOR]

Social anhedonia (SA) is a debilitating characteristic of schizophrenia, a common feature in individuals at psychosis-risk, and a vulnerability for developing schizophreniaspectrum 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. [ABSTRACT FROM AUTHOR]

Theory of mind (ToM), the ability to attribute and reason about the mental states of others, is a strong determinant of social functioning among individuals with schizophrenia. Identifying the neural bases of ToM and their relationship to social functioning may elucidate functionally relevant neurobiological targets for intervention. ToM ability may additionally account for other social phenomena that affect social functioning, such as social anhedonia (SocAnh). Given recent research in schizophrenia demonstrating improved neural functioning in response to increased use of cognitive skills, it is possible that SocAnh, which decreases one's opportunity to engage in ToM, could compromise social functioning through its deleterious effect on ToM-related neural circuitry. Here, twenty individuals with schizophrenia and 18 healthy controls underwent fMRI while performing the False-Belief Task. Aspects of social functioning were assessed using multiple methods including self-report (Interpersonal Reactivity Index, Social Adjustment Scale), clinician-ratings (Global Functioning Social Scale), and performance-based tasks (MSCEIT—Managing Emotions). SocAnh was measured with the Revised Social Anhedonia Scale. Region-of-interest and whole-brain analyses revealed reduced recruitment of medial prefrontal cortex (MPFC) for ToM in individuals with schizophrenia. Across all participants, activity in this region correlated with most social variables. Mediation analysis revealed that neural activity for ToM in MPFC accounted for the relationship between SocAnh and social functioning. These findings demonstrate that reduced recruitment of MPFC for ToM is an important neurobiological determinant of social functioning. Furthermore, SocAhn may affect social functioning through its impact on ToM-related neural circuitry. Together, these findings suggest ToM ability as an important locus for intervention.

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. [ABSTRACT FROM AUTHOR]

LPFC dysfunction is a well-established neural impairment in schizophrenia and is associated with worse symptoms. However, how LPFC activation influences symptoms is unclear. Previous findings in healthy individuals demonstrate that lateral prefrontal cortex (LPFC) activation during cognitive control of emotional information predicts mood and behavior in response to interpersonal conflict, thus impairments in these processes may contribute to symptom exacerbation in schizophrenia. We investigated whether schizophrenia participants show LPFC deficits during cognitive control of emotional information, and whether these LPFC deficits prospectively predict changes in mood and symptoms following real-world interpersonal conflict. During fMRI, 23 individuals with schizophrenia or schizoaffective disorder and 24 healthy controls completed the Multi-Source Interference Task superimposed on neutral and negative pictures. Afterwards, schizophrenia participants completed a 21-day online daily-diary in which they rated the extent to which they experienced mood and schizophrenia-spectrum symptoms, as well as the occurrence and response to interpersonal conflict. Schizophrenia participants had lower dorsal LPFC activity (BA9) during cognitive control of task-irrelevant negative emotional information. Within schizophrenia participants, DLPFC activity during cognitive control of emotional information predicted changes in positive and negative mood on days following highly distressing interpersonal conflicts. Results have implications for understanding the specific role of LPFC in response to social stress in schizophrenia, and suggest that treatments targeting LPFC-mediated cognitive control of emotion could promote adaptive response to social stress in schizophrenia.