The separate and joint effects of recent interpersonal abuse and cannabis use on psychotic experiences: findings from students in higher education in the United States.

BACKGROUND: Various forms of interpersonal abuse (e.g., physical, emotional, sexual) and cannabis use across the lifespan have both been known to increase odds of psychotic experiences; however, there have been few studies examining their separate and joint effects in the United States. METHODS: We analyzed data from the Healthy Minds Study (2020-2021) and used multivariable logistic regression and interaction contrast ratios to assess separate and joint effects of interpersonal abuse (past 12 months) and cannabis use (past 30 days) on psychotic experiences (past 12 months). RESULTS: Students who only used cannabis had significantly greater odds of psychotic experiences (aOR: 1.70; 95% CI 1.58-1.82), as well as those who only experienced interpersonal abuse (aOR: 2.40; 95% CI 2.25-2.56). However, those who reported both cannabis use and interpersonal abuse had the greatest odds, exceeding the sum of these individual effects (the combined effect aOR: 3.46; 95% CI 3.19-3.76). CONCLUSIONS: Recent interpersonal abuse and recent cannabis use both separately and jointly increase odds of having recent psychotic experiences. Future research should continue to examine the potential interactive and additive impact of multiple known exposures to better inform primary and secondary prevention efforts.

Regional Vulnerability Indices in Youth With Persistent and Distressing Psychoticlike Experiences.

Importance: Distressing and persistent psychoticlike experiences (PLEs) in youth are associated with greater odds of developing psychiatric conditions in adulthood. Despite this risk, it is unclear whether early PLEs show similar brain patterns compared with adults with psychiatric and neurologic conditions. Objective: To examine the degree to which persistent and distressing PLEs exhibit neural metrics that show similarity to adults with chronic psychiatric and neurologic conditions. Design, Setting, and Participants: This cohort study used Adolescent Brain Cognitive Development (ABCD) Study examining the persistence and distress associated with PLEs across the first 3 waves of data with baseline structural magnetic resonance imaging data. Analyzed data were collected between September 1, 2016, and September 27, 2021. Children were recruited from 21 research sites across the US. Exposures: Psychoticlike experiences were assessed using the Prodromal Questionnaire-Brief Child Version, and participants were categorized into groups based on the persistence and distress associated with PLEs. Main Outcomes and Measures: Cortical and subcortical regional vulnerability indices (RVIs) were created by quantifying the similarity of participants' baseline neuroimaging measures to the expected patterns found in adult neuropsychiatric samples. The PLE groups were compared on the following RVI cortical and subcortical metrics: schizophrenia spectrum disorders, bipolar disorder, major depressive disorder, Parkinson disease, Alzheimer disease, and metabolic diseases. Results: Analyses examined PLE groups created from 8242 children in the ABCD sample (52.5% male; mean [SD] age, 9.93 [0.63] years; and 56.3% White), including persistent distressing PLEs (n = 329), transient distressing PLEs (n = 396), persistent nondistressing PLEs (n = 234), transient nondistressing PLEs (n = 390), and low distressing PLEs (n = 6893) groups. Participants with persistent or transient distressing PLEs broadly showed increased subcortical RVI scores across most RVI metrics, with persistent distressing PLEs additionally showing increased scores for cortical RVI metrics. The greatest effect sizes were found for persistent distressing PLEs with cortical RVI-schizophrenia spectrum disorders (ß estimate, 1.055; 95% CI, 0.326-1.786) and RVI-Alzheimer disease (ß estimate, 2.473; 95% CI, 0.930-4.018). Conclusions and Relevance: In this cohort study of ABCD participants, the findings suggest that especially the persistent distressing PLEs in children were associated with neural metrics resembling those observed in adults with severe psychiatric and neurologic conditions. These findings support the potential use of brain-based risk scores for early identification and precision medicine approaches in the assessment of PLEs.

Associations Between Polygenic Scores for Cognitive and Non-cognitive Factors of Educational Attainment and Measures of Behavior, Psychopathology, and Neuroimaging in the Adolescent Brain Cognitive Development Study.

Background: Both cognitive and non-cognitive (e.g., traits like curiosity) factors are critical for social and emotional functioning and independently predict educational attainment. These factors are heritable and genetically correlated with a range of health-relevant traits and behaviors in adulthood (e.g., risk-taking, psychopathology). However, whether these associations are present during adolescence, and to what extent these relationships diverge, could have implications for adolescent health and well-being. Methods: Using data from 5,517 youth of European ancestry from the ongoing Adolescent Brain Cognitive DevelopmentSM Study, we examined associations between polygenic scores (PGS) for cognitive and non-cognitive factors and outcomes related to cognition, socioeconomic status, risk tolerance and decision-making, substance initiation, psychopathology, and brain structure. Results: Cognitive and non-cognitive PGSs were both positively associated with cognitive performance and family income, and negatively associated with ADHD and severity of psychotic-like experiences. The cognitive PGS was also associated with greater risk-taking, delayed discounting, and anorexia, as well as lower likelihood of nicotine initiation. The cognitive PGS was further associated with cognition scores and anorexia in within-sibling analyses, suggesting these results do not solely reflect the effects of assortative mating or passive gene-environment correlations. The cognitive PGS showed significantly stronger associations with cortical volumes than the non-cognitive PGS and was associated with right hemisphere caudal anterior cingulate and pars-orbitalis in within-sibling analyses, while the non-cognitive PGS showed stronger associations with white matter fractional anisotropy and a significant within-sibling association for right superior corticostriate-frontal cortex. Conclusions: Our findings suggest that PGSs for cognitive and non-cognitive factors show similar associations with cognition and socioeconomic status as well as other psychosocial outcomes, but distinct associations with regional neural phenotypes in this adolescent sample.

Ethno-racial variation in psychotic experiences in the United States: Findings from the National Latino and Asian American Survey and the National Survey of American Life.

BACKGROUND: Ethno-racial differences in psychosis risk are documented; however, there is less research on whether these differences extend to sub-threshold psychotic experiences, and whether there is significant variation within ethno-racial categories. METHODS: We analyzed data from the National Latino and Asian American Survey (NLAAS) and the National Survey of American Life (NSAL). Using multivariable logistic regression, we examined the association between race/ethnicity and lifetime psychotic experiences among Latino, Asian, and Black adults in the general population, adjusting for gender, age, nativity, education level, income level, employment status, and everyday discrimination. RESULTS: Puerto Ricans, Cubans, and other Hispanics had greater odds of lifetime psychotic experiences when compared with Mexicans, though differences diminished when adjusting for covariates. Filipino and other Asians had greater odds of lifetime psychotic experiences when compared with Chinese, though again, differences diminished when adjusting for covariates. Among Black Americans, there were no significant ethnic subgroup differences. CONCLUSION: Ethno-racial differences extend across the psychosis continuum. There are nuanced health profiles across and within ethno-racial categories. Differences may be attributable to differences in experiences living in the US, underscoring the need for community-specific interventions.

Distress related to psychotic experiences: Enhancing the world health organization composite international diagnostic interview psychosis screen.

BACKGROUND: The abbreviated version of the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI) psychosis screen tends to yield high prevalence in online samples. Psychotic Experiences (PE) may not necessarily indicate current or imminent psychopathology; however, distressing PE appear to be more clinically informative. METHODS: We analyzed data collected from an online survey administered to a Qualtrics panel (N = 2522 adults). Using multivariable logistic regression, we examined the association between PE (with and without associated distress) and several mental health outcomes, adjusting for age, gender, and race/ethnicity. RESULTS: Individuals with distressing PE had greater odds of most mental health outcomes when compared with individuals with non-distressing PE. This was true for being in mental health treatment, loneliness, probable mental illness, suicidal ideation, and suicide attempt, adjusting for age, gender, race/ethnicity, and education level. The only exception was for hazardous alcohol use, for which there was no significant association with distressing PE. CONCLUSION: As screening for PE gains traction in public health and preventive medicine, using an abbreviated version of the WHO CIDI psychosis screen may be clinically informative, especially when eliciting the distressful nature of PE.

Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders.

Genetic liability to substance use disorders can be parsed into loci that confer general or substance-specific addiction risk. We report a multivariate genome-wide association meta-analysis that disaggregates general and substance-specific loci for published summary statistics of problematic alcohol use, problematic tobacco use, cannabis use disorder, and opioid use disorder in a sample of 1,025,550 individuals of European descent and 92,630 individuals of African descent. Nineteen independent SNPs were genome-wide significant (P < 5e-8) for the general addiction risk factor (addiction-rf), which showed high polygenicity. Across ancestries, PDE4B was significant (among other genes), suggesting dopamine regulation as a cross-substance vulnerability. An addiction-rf polygenic risk score was associated with substance use disorders, psychopathologies, somatic conditions, and environments associated with the onset of addictions. Substance-specific loci (9 for alcohol, 32 for tobacco, 5 for cannabis, 1 for opioids) included metabolic and receptor genes. These findings provide insight into genetic risk loci for substance use disorders that could be leveraged as treatment targets.

Associations with youth psychotic-like experiences over time: Evidence for trans-symptom and specific cognitive and neural risk factors.

The current study examined whether impairments in cognitive and neural factors at baseline (ages 9-10) predict initial levels or changes in psychotic-like experiences (PLEs) and whether such impairments generalize to other psychopathology symptoms (i.e., internalizing and externalizing symptoms). Using unique longitudinal Adolescent Brain Cognitive Development Study data, the study examined three time points from ages 9 to 13. Univariate latent growth models examined associations between baseline cognitive and neural metrics with symptom measures using discovery (n = 5,926) and replication (n = 5,952) data sets. For symptom measures (i.e., PLEs, internalizing, externalizing), we examined mean initial levels (i.e., intercepts) and changes over time (i.e., slopes). Predictors included neuropsychological test performance, global structural MRI, and several a priori within-network resting-state functional connectivity metrics. Results showed a pattern whereby baseline cognitive and brain metric impairments showed the strongest associations with PLEs over time. Lower cognitive, volume, surface area, and cingulo-opercular within-network connectivity metrics showed associations with increased PLEs and higher initial levels of externalizing and internalizing symptoms. Several metrics were uniquely associated with PLEs, including lower cortical thickness with higher initial PLEs and lower default mode network connectivity with increased PLEs slopes. Neural and cognitive impairments in middle childhood were broadly associated with increased PLEs over time, and showed stronger associations with PLEs compared with other psychopathology symptoms. The current study also identified markers potentially uniquely associated with PLEs (e.g., cortical thickness). Impairments in broad cognitive metrics, brain volume and surface area, and a network associated with information integration may represent risk factors for general psychopathology. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Review of Major Social Determinants of Health in Schizophrenia-Spectrum Psychotic Disorders: III. Biology.

BACKGROUND: Social determinants of health (SDoHs) are nonmedical factors that significantly impact health and longevity. We found no published reviews on the biology of SDoHs in schizophrenia-spectrum psychotic disorders (SSPD). STUDY DESIGN: We present an overview of pathophysiological mechanisms and neurobiological processes plausibly involved in the effects of major SDoHs on clinical outcomes in SSPD. STUDY RESULTS: This review of the biology of SDoHs focuses on early-life adversities, poverty, social disconnection, discrimination including racism, migration, disadvantaged neighborhoods, and food insecurity. These factors interact with psychological and biological factors to increase the risk and worsen the course and prognosis of schizophrenia. Published studies on the topic are limited by cross-sectional design, variable clinical and biomarker assessments, heterogeneous methods, and a lack of control for confounding variables. Drawing on preclinical and clinical studies, we propose a biological framework to consider the likely pathogenesis. Putative systemic pathophysiological processes include epigenetics, allostatic load, accelerated aging with inflammation (inflammaging), and the microbiome. These processes affect neural structures, brain function, neurochemistry, and neuroplasticity, impacting the development of psychosis, quality of life, cognitive impairment, physical comorbidities, and premature mortality. Our model provides a framework for research that could lead to developing specific strategies for prevention and treatment of the risk factors and biological processes, thereby improving the quality of life and increasing the longevity of people with SSPD. CONCLUSIONS: Biology of SDoHs in SSPD is an exciting area of research that points to innovative multidisciplinary team science for improving the course and prognosis of these serious psychiatric disorders.

A Phenome-Wide Association Study (PheWAS) of Late Onset Alzheimer Disease Genetic Risk in Children of European Ancestry at Middle Childhood: Results from the ABCD Study.

Genetic risk for Late Onset Alzheimer Disease (AD) has been associated with lower cognition and smaller hippocampal volume in healthy young adults. However, whether these and other associations are present during childhood remains unclear. Using data from 5556 genomically-confirmed European ancestry youth who completed the baseline session of the ongoing the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®), our phenome-wide association study estimating associations between four indices of genetic risk for late-onset AD (i.e., AD polygenic risk scores (PRS), APOE rs429358 genotype, AD PRS with the APOE region removed (ADPRS-APOE), and an interaction between ADPRS-APOE and APOE genotype) and 1687 psychosocial, behavioral, and neural phenotypes revealed no significant associations after correction for multiple testing (all ps > 0.0002; all pfdr > 0.07). These data suggest that AD genetic risk may not phenotypically manifest during middle-childhood or that effects are smaller than this sample is powered to detect.

Review of factors resulting in systemic biases in the screening, assessment, and treatment of individuals at clinical high-risk for psychosis in the United States.

Background: Since its inception, research in the clinical high-risk (CHR) phase of psychosis has included identifying and exploring the impact of relevant socio-demographic factors. Employing a narrative review approach and highlighting work from the United States, sociocultural and contextual factors potentially affecting the screening, assessment, and service utilization of youth at CHR were reviewed from the current literature. Results: Existing literature suggests that contextual factors impact the predictive performance of widely used psychosis-risk screening tools and may introduce systemic bias and challenges to differential diagnosis in clinical assessment. Factors reviewed include racialized identity, discrimination, neighborhood context, trauma, immigration status, gender identity, sexual orientation, and age. Furthermore, racialized identity and traumatic experiences appear related to symptom severity and service utilization among this population. Conclusions: Collectively, a growing body of research from the United States and beyond suggests that considering context in psychosis-risk assessment can provide a more accurate appraisal of the nature of risk for psychosis, render more accurate results improving the field's prediction of conversion to psychosis, and enhance our understanding of psychosis-risk trajectories. More work is needed in the U.S. and across the globe to uncover how structural racism and systemic biases impact screening, assessment, treatment, and clinical and functional outcomes for those at CHR.

Phenome-wide Investigation of Behavioral, Environmental, and Neural Associations with Cross-Disorder Genetic Liability in Youth of European Ancestry.

Etiologic insights into psychopathology may be gained by using hypothesis-free methods to identify associations between genetic risk for broad psychopathology and phenotypes measured during adolescence, including both markers of child psychopathology and intermediate phenotypes such as neural structure that may link genetic risk with outcomes. We conducted a phenome-wide association study (phenotype n=1,269-1,694) of polygenic risk scores (PRS) for broad spectrum psychopathology (i.e., Compulsive, Psychotic, Neurodevelopmental, and Internalizing) in youth of PCA-selected European ancestry (n=5,556; ages 9-13) who completed the baseline and/or two-year follow-up of the ongoing Adolescent Brain Cognitive Development℠ (ABCD) Study. We found that Neurodevelopmental and Internalizing PRS were significantly associated with a host of proximal as well as distal phenotypes (Neurodevelopmental: 187 and 211; Internalizing: 122 and 173 phenotypes at baseline and two-year follow-up, respectively), whereas Compulsive and Psychotic PRS showed zero and one significant associations, respectively, after Bonferroni correction. Neurodevelopmental PRS were further associated with brain structure metrics (e.g., total volume, mean right hemisphere cortical thickness), with only cortical volume indirectly linking Neurodevelopmental PRS to grades in school. Genetic variation influencing risk to psychopathology manifests broadly as behaviors, psychopathology symptoms, and related risk factors in middle childhood and early adolescence.

Characterizing Alcohol Expectancies in the ABCD Study: Associations with Sociodemographic Factors, the Immediate Social Environment, and Genetic Propensities.

Alcohol expectancies (AEs) are associated with likelihood of alcohol initiation and subsequent alcohol use disorders. It is unclear whether genetic predisposition to alcohol use and/or related traits contributes to shaping how one expects to feel when drinking alcohol. We used the Adolescent Brain Cognitive Development study to examine associations between genetic propensities (i.e., polygenic risk for problematic alcohol use, depression, risk-taking), sociodemographic factors (i.e., parent income), and the immediate social environment (i.e., peer use and disapproval toward alcohol) and positive and negative AEs in alcohol-naïve children (max analytic N = 5,352). Mixed-effect regression models showed that age, parental education, importance of the child's religious beliefs, adverse childhood experiences, and peer disapproval of alcohol use were associated with positive and/or negative AEs, to varying degrees. Overall, our results suggest several familial and psychosocial predictors of AEs but little evidence of contributions from polygenic liability to problematic alcohol use or related phenotypes.

Youth Mental Health Screening and Linkage to Care.

One Mind, in partnership with Meadows Mental Health Policy Institute, convened several virtual meetings of mental health researchers, clinicians, and other stakeholders in 2020 to identify first steps toward creating an initiative for early screening and linkage to care for youths (individuals in early adolescence through early adulthood, ages 10-24 years) with mental health difficulties, including serious mental illness, in the United States. This article synthesizes and builds on discussions from those meetings by outlining and recommending potential steps and considerations for the development and integration of a novel measurement-based screening process in youth-facing school and medical settings to increase early identification of mental health needs and linkage to evidence-based care. Meeting attendees agreed on an initiative incorporating a staged assessment process that includes a first-stage brief screener for several domains of psychopathology. Individuals who meet threshold criteria on the first-stage screener would then complete an interview, a second-stage in-depth screening, or both. Screening must be followed by recommendations and linkage to an appropriate level of evidence-based care based on acuity of symptoms endorsed during the staged assessment. Meeting attendees proposed steps and discussed additional considerations for creating the first nationwide initiative for screening and linkage to care, an initiative that could transform access of youths to mental health screening and care.

Strengthening associations between psychotic like experiences and suicidal ideation and behavior across middle childhood and early adolescence.

BACKGROUND: Understanding risk factors related to suicidal ideation (SI) and suicidal behaviors (SB) in youth is important for informing prevention and intervention efforts. While it appears that psychotic-like experiences (PLEs) are strongly associated with both SI and SB at different points across the lifespan, the longitudinal nature of this relationship in middle childhood and early adolescence is understudied. METHODS: The study used the unique longitudinal Adolescent Brain Cognitive Development Study data. Mixed effects linear models examined associations between PLEs and SI and SB over time using three time points of data from ages 9-13. RESULTS: First, analyses indicated that endorsement of SI and SB increased as youth grew older for those with increased distressing PLEs. Analyses found evidence of bidirectional relationships between PLEs with SI and SB, with evidence that PLEs at baseline were associated with worsening SI and SB over time, including a transition from SI to SB (ß = 0.032, FDRp = 0.002). Exploratory analyses showed consistent evidence for strengthened associations over time for higher delusional ideation with both SI and SB (ßs > 0.04, FDRps < 0.001), and for perceptual distortions with SB (ßs = 0.046, FDRp < 0.001). When accounting for general psychopathology, for SB, the strengthened associations over time was significantly stronger for PLEs (ß = 0.053, FDRp < 0.001) compared to general psychopathology (ß = 0.022, FDRp = 0.01). CONCLUSIONS: The present study indicates both SI and SB show strengthened associations with PLEs over time, and that baseline PLEs may predict worsening of suicidality over time. The findings are important clarifications about the nature of the associations between youth-reported PLEs and suicidality over time.

Cognitive Dysfunction as a Risk Factor for Psychosis.

The current chapter summarizes recent evidence for cognition as a risk factor for the development of psychosis, including the range of cognitive impairments that exist across the spectrum of psychosis risk symptoms. The chapter examines several possible theories linking cognitive deficits with the development of psychotic symptoms, including evidence that cognitive deficits may be an intermediate risk factor linking genetic and/or neural metrics to psychosis spectrum symptoms. Although there is not strong evidence for unique cognitive markers associated specifically with psychosis compared to other forms of psychopathology, psychotic disorders are generally associated with the greatest severity of cognitive deficits. Cognitive deficits precede the development of psychotic symptoms and may be detectable as early as childhood. Across the psychosis spectrum, both the presence and severity of psychotic symptoms are associated with mild to moderate impairments across cognitive domains, perhaps most consistently for language, cognitive control, and working memory domains. Research generally indicates the size of these cognitive impairments worsens as psychosis symptom severity increases. The chapter points out areas of unclarity and unanswered questions in each of these areas, including regarding the mechanisms contributing to the association between cognition and psychosis, the timing of deficits, and whether any cognitive systems can be identified that function as specific predictors of psychosis risk symptoms.

Associations Between Cannabis Use, Polygenic Liability for Schizophrenia, and Cannabis-related Experiences in a Sample of Cannabis Users.

BACKGROUND AND HYPOTHESIS: Risk for cannabis use and schizophrenia is influenced in part by genetic factors, and there is evidence that genetic risk for schizophrenia is associated with subclinical psychotic-like experiences (PLEs). Few studies to date have examined whether genetic risk for schizophrenia is associated with cannabis-related PLEs. STUDY DESIGN: We tested whether measures of cannabis involvement and polygenic risk scores (PRS) for schizophrenia were associated with self-reported cannabis-related experiences in a sample ascertained for alcohol use disorders (AUDs), the Collaborative Study on the Genetics of Alcoholism (COGA). We analyzed 4832 subjects (3128 of European ancestry and 1704 of African ancestry; 42% female; 74% meeting lifetime criteria for an AUD). STUDY RESULTS: Cannabis use disorder (CUD) was prevalent in this analytic sample (70%), with 40% classified as mild, 25% as moderate, and 35% as severe. Polygenic risk for schizophrenia was positively associated with cannabis-related paranoia, feeling depressed or anhedonia, social withdrawal, and cognitive difficulties, even when controlling for duration of daily cannabis use, CUD, and age at first cannabis use. The schizophrenia PRS was most robustly associated with cannabis-related cognitive difficulties (ß = 0.22, SE = 0.04, P = 5.2e-7). In an independent replication sample (N = 1446), associations between the schizophrenia PRS and cannabis-related experiences were in the expected direction and not statistically different in magnitude from those in the COGA sample. CONCLUSIONS: Among individuals who regularly use cannabis, genetic liability for schizophrenia-even in those without clinical features-may increase the likelihood of reporting unusual experiences related to cannabis use.

Religiousness and psychotic experiences among young adult college students in the United States.

BACKGROUND: Religiousness and psychotic experiences have been related, though findings have been mixed, with little attention paid to specific religious affiliations and religious importance. METHODS: We analyzed data from the Healthy Minds Study (2020-2021), which was an online survey administered at 140 college campuses across the United States. We used multivariable logistic regression to examine the associations between religiousness (affiliation and importance) and 12-month psychotic experiences, adjusting for age, gender, and race/ethnicity. RESULTS: Only Christian religious affiliation was associated with lower odds of psychotic experiences (aOR: 0.79; 95% CI: 0.75, 0.84), while Non-Christian religious affiliation (aOR: 1.34; 95% CI: 1.19, 1.50) and Multiple religious affiliation s were associated with greater odds (aOR: 1.28; 95% CI: 1.15, 1.42). Overall, increased religious importance was associated with lower odds of psychotic experiences (aOR: 0.96; 95% CI: 0.94-0.99). After stratifying by affiliation, religious importance was only associated with lower odds of psychotic experiences among people who identified as Other Christian, Mormon, and Other World Religion. Religious importance was associated with greater odds of psychotic experiences among Atheists, Agnostics, Buddhists, Nothing in Particular, and Multiple Religions. CONCLUSION: Religious affiliation and importance had varying associations with psychotic experiences, depending on type of religious affiliation. More research is needed to explore the modifying effects of religiousness. Responsiveness to religious beliefs and practices may be critical when assessing risk for psychosis.

Association of Mental Health Burden With Prenatal Cannabis Exposure From Childhood to Early Adolescence: Longitudinal Findings From the Adolescent Brain Cognitive Development (ABCD) Study.

This study assesses whether associations of prenatal cannabis exposure and psychopathology persist into early adolescence.