Psychosis Spectrum Symptoms Research Articles

Psychosis Spectrum Symptoms Before and After Adolescent Cannabis Use Initiation.

Adolescent cannabis use has been consistently posited to contribute to the onset and progression of psychosis. However, alternative causal models may account for observed associations between cannabis use and psychosis risk, including shared vulnerability for both cannabis use and psychosis or efforts to self-medicate distress from psychosis spectrum symptomology. To test 3 hypotheses that may explain cannabis-psychosis risk associations by modeling psychosis spectrum symptom trajectories prior to and after cannabis initiation across adolescent development (approximately 10-15 years of age). This cohort study used data from 5 waves across 4 years of follow-up from the Adolescent Brain Cognitive Development (ABCD) Study. The ABCD study is an ongoing large-scale, longitudinal study of brain development and mental and physical health of children in the US launched in June 2016. Data are collected from 21 research sites. The study included data from 11 868 adolescents aged 9 to 10 years at baseline. Three participants were excluded from the present analysis owing to missing data. Data analysis was performed from September 2023 to July 2024. Discontinuous growth curve modeling was used to assess trajectories of psychosis spectrum symptoms before and after cannabis initiation. Control variables considered for this investigation were age, sex, internalizing and externalizing symptoms, socioeconomic status, parental mental health, and other substance use. Among the 11 858 participants at wave 1, the mean (SD) age was 9.5 (0.5) years; 6182 (52%) participants were male. Consistent with a shared vulnerability hypothesis, adolescents who used cannabis at any point during the study period reported a greater number of psychosis spectrum symptoms (B, 0.86; 95% CI, 0.68-1.04) and more distress (B, 1.17; 95% CI, 0.96-1.39) from psychosis spectrum symptoms relative to those who never used cannabis. Additionally, consistent with a self-medication hypothesis, the number of psychosis spectrum symptoms (B, 0.16; 95% CI, 0.12-0.20) and distress (B, 0.23; 95% CI, 0.21-0.26) from psychosis spectrum symptoms increased in the time leading up to cannabis initiation. We observed mixed evidence for an increase in psychosis symptoms after cannabis initiation (ie, contributing risk hypothesis). The findings underscore the importance of accounting for shared vulnerability and self-medication effects when modeling cannabis-psychosis risk associations.

408. Deviations From Normative Brain Models Mental Health Treatment Seeking Youth With Psychosis Spectrum Symptoms: Data From the Toronto Adolescent and Youth (TAY) CAMH Cohort Study

408. Deviations From Normative Brain Models Mental Health Treatment Seeking Youth With Psychosis Spectrum Symptoms: Data From the Toronto Adolescent and Youth (TAY) CAMH Cohort Study

Associations Between Cortical Thickness and Adverse Life Events in Children and Adolescents With Psychosis-Spectrum Symptoms

Associations Between Cortical Thickness and Adverse Life Events in Children and Adolescents With Psychosis-Spectrum Symptoms

Psychosis spectrum symptoms among individuals with schizophrenia-associated copy number variants and evidence of cerebellar correlates of symptom severity

The 3q29 deletion (3q29Del) is a copy number variant (CNV) with one of the highest effect sizes for psychosis-risk (>40-fold). Systematic research offers avenues for elucidating mechanism; however, compared to CNVs like 22q11.2Del, 3q29Del remains understudied. Emerging findings indicate that posterior fossa abnormalities are common among carriers, but their clinical relevance is unclear. We report the first in-depth evaluation of psychotic symptoms in participants with 3q29Del (N=23), using the Structured Interview for Psychosis-Risk Syndromes, and compare this profile to 22q11.2Del (N=31) and healthy controls (N=279). We also explore correlations between psychotic symptoms and posterior fossa abnormalities. Cumulatively, 48% of the 3q29Del sample exhibited a psychotic disorder or attenuated positive symptoms, with a subset meeting criteria for clinical high-risk. 3q29Del had more severe ratings than controls on all domains and only exhibited less severe ratings than 22q11.2Del in negative symptoms; ratings demonstrated select sex differences but no domain-wise correlations with IQ. An inverse relationship was identified between positive symptoms and cerebellar cortex volume in 3q29Del, documenting the first clinically-relevant neuroanatomical connection in this syndrome. Our findings characterize the profile of psychotic symptoms in the largest 3q29Del sample reported to date, contrast with another high-impact CNV, and highlight cerebellar involvement in psychosis-risk.

Understanding the Developmental Lines of Psychosis Spectrum Symptoms: Efforts and Early Insights From the Toronto Adolescent and Youth Cohort Study

Understanding the Developmental Lines of Psychosis Spectrum Symptoms: Efforts and Early Insights From the Toronto Adolescent and Youth Cohort Study

A mixed-methods study to evaluate the feasibility and preliminary efficacy of delivering the optimal health program (OHP) for youth at clinical high risk (CHR) for psychosis: A study protocol.

Individuals with clinical high risk (CHR) for psychosis experience significant distress, impaired general functioning and a high lifetime risk of self-harm and attempted suicide. The CHR period is an important phase in an individual's mental health where appropriate interventions may reduce the risk of progression to several negative outcomes, including the development of schizophrenia. Given that up to 80% of individuals with CHR have another diagnosable mental illness and almost half experience poor psychosocial functioning, developing interventions that address psychosocial functioning in young people with CHR is of great importance. This mixed-methods study aims to employ qualitative and quantitative methods to adapt an evidence-based comprehensive psychosocial and mental health self-efficacy program, the Optimal Health Program (OHP), and evaluate the feasibility, acceptability and preliminary clinical efficacy in young people with CHR. We aim to recruit 30 CHR participants (age 16-29 years) in a single-arm 12-week exploratory clinical trial. Feasibility metrics will include recruitment, retention, and data completion rates. Acceptability will be informed by the Client Satisfaction Questionnaire. Clinical assessments (psychosis spectrum symptoms, depression, and anxiety), functional measures, and cognitive outcomes will be completed at study entry and repeated post-intervention at 12-weeks. We will run pre-post test data analysis to examine changes following engagement in the OHP intervention. Qualitative interviews will be conducted post-intervention to further evaluate the acceptability of the intervention and the trial design, and will be analyzed using thematic analysis. OHP may enhance the long-term mental health, well-being and functioning of CHR youth. However, the intervention must first be adapted to a CHR population; then, the feasibility and preliminary efficacy of delivering an intervention tailored around the varied needs of the CHR group must be established before a larger-scale appropriately powered study is pursued. Trial registration: The trial is registered with ClinicalTrials.gov NCT05757128.

Cognition and Educational Achievement in the Toronto Adolescent and Youth Cohort Study: Rationale, Methods, and Early Data

BackgroundBoth cognition and educational achievement in youths are linked to psychosis risk. One major aim of the Toronto Adolescent and Youth (TAY) Cohort Study is to characterize how cognitive and educational achievement trajectories inform the course of psychosis spectrum symptoms (PSSs), functioning, and suicidality. Here, we describe the protocol for the cognitive and educational data and early baseline data. MethodsThe cognitive assessment design is consistent with youth population cohort studies, including the NIH Toolbox, Rey Auditory Verbal Learning Test, Wechsler Matrix Reasoning Task, and Little Man Task. Participants complete an educational achievement questionnaire, and report cards are requested. Completion rates, descriptive data, and differences across PSS status are reported for the first participants (N = 417) ages 11 to 24 years, who were recruited between May 4, 2021, and February 2, 2023. ResultsNearly 84% of the sample completed cognitive testing, and 88.2% completed the educational questionnaire, whereas report cards were collected for only 40.3%. Modifications to workflows were implemented to improve data collection. Participants who met criteria for PSSs demonstrated lower performance than those who did not on numerous key cognitive indices (p < .05) and also had more academic/educational problems. ConclusionsFollowing youths longitudinally enabled trajectory mapping and prediction based on cognitive and educational performance in relation to PSSs in treatment-seeking youths. Youths with PSSs had lower cognitive performance and worse educational outcomes than youths without PSSs. Results show the feasibility of collecting data on cognitive and educational outcomes in a cohort of youths seeking treatment related to mental illness and substance use.

The Toronto Adolescent and Youth Cohort Study: Study Design and Early Data Related to Psychosis Spectrum Symptoms, Functioning, and Suicidality

BackgroundPsychosis spectrum symptoms (PSSs) occur in a sizable percentage of youth and are associated with poorer cognitive performance, poorer functioning, and suicidality (i.e., suicidal thoughts and behaviors). PSSs may occur more frequently in youths already experiencing another mental illness, but the antecedents are not well known. The Toronto Adolescent and Youth (TAY) Cohort Study aims to characterize developmental trajectories in youths with mental illness and understand associations with PSSs, functioning, and suicidality. MethodsThe TAY Cohort Study is a longitudinal cohort study that aims to assess 1500 youths (age 11–24 years) presenting to tertiary care. In this article, we describe the extensive diagnostic and clinical characterization of psychopathology, substance use, functioning, suicidality, and health service utilization in these youths, with follow-up every 6 months over 5 years, including early baseline data. ResultsA total of 417 participants were enrolled between May 4, 2021, and February 2, 2023. Participants met diagnostic criteria for an average of 3.5 psychiatric diagnoses, most frequently anxiety and depressive disorders. Forty-nine percent of participants met a pre-established threshold for PSSs and exhibited higher rates of functional impairment, internalizing and externalizing symptoms, and suicidality than participants without PSSs. ConclusionsInitial findings from the TAY Cohort Study demonstrate the feasibility of extensive clinical phenotyping in youths who are seeking help for mental health problems. PSS prevalence is much higher than in community-based studies. Our early data support the critical need to better understand longitudinal trajectories of clinical youth cohorts in relation to psychosis risk, functioning, and suicidality.

Neuroimaging and Biosample Collection in the Toronto Adolescent and Youth Cohort Study: Rationale, Methods, and Early Data

BackgroundThe Toronto Adolescent and Youth (TAY) Cohort Study will characterize the neurobiological trajectories of psychosis spectrum symptoms, functioning, and suicidality (i.e., suicidal thoughts and behaviors) in youth seeking mental health care. Here, we present the neuroimaging and biosample component of the protocol. We also present feasibility and quality control metrics for the baseline sample collected thus far. MethodsThe current study includes youths (ages 11–24 years) who were referred to child and youth mental health services within a large tertiary care center in Toronto, Ontario, Canada, with target recruitment of 1500 participants. Participants were offered the opportunity to provide any or all of the following: 1) 1-hour magnetic resonance imaging (MRI) scan (electroencephalography if ineligible for or declined MRI), 2) blood sample for genomic and proteomic data (or saliva if blood collection was declined or not feasible) and urine sample, and 3) heart rate recording to assess respiratory sinus arrhythmia. ResultsOf the first 417 participants who consented to participate between May 4, 2021, and February 2, 2023, 412 agreed to participate in the imaging and biosample protocol. Of these, 334 completed imaging, 341 provided a biosample, 338 completed respiratory sinus arrhythmia, and 316 completed all 3. Following quality control, data usability was high (MRI: T1-weighted 99%, diffusion-weighted imaging 99%, arterial spin labeling 90%, resting-state functional MRI 95%, task functional MRI 90%; electroencephalography: 83%; respiratory sinus arrhythmia: 99%). ConclusionsThe high consent rates, good completion rates, and high data usability reported here demonstrate the feasibility of collecting and using brain imaging and biosamples in a large clinical cohort of youths seeking mental health care.

Pathways from threat exposure to psychotic symptoms in youth: The role of emotion recognition bias and brain structure.

Research supports an association between threatening experiences in childhood and psychosis. It is possible that early threat exposure disrupts the development of emotion recognition (specifically, producing a bias for facial expressions relating to threat) and the brain structures subserving it, contributing to psychosis development. Using data from the Philadelphia Neurodevelopmental Cohort, we examined associations between threat exposure and both the misattribution of facial expressions to fear/anger in an emotion recognition task, and gray matter volumes in key emotion processing regions. Our sample comprised youth with psychosis spectrum symptoms (N=304), control youth (N=787), and to evaluate specificity, youth with internalizing symptoms (N=92). The moderating effects of group and sex were examined. Both the psychosis spectrum and internalizing groups had higher levels of threat exposure than controls. In the total sample, threat exposure was associated with lower left medial prefrontal cortex (mPFC) volume but not misattributions to fear/anger. The effects of threat exposure did not significantly differ by group or sex. The findings of this study provide evidence for an effect of threat exposure on mPFC morphology, but do not support an association between threat exposure and a recognition bias for threat-related expressions, that is particularly pronounced in psychosis. Future research should investigate factors linking transdiagnostic alterations related to threat exposure with psychotic symptoms, and attempt to clarify the mechanisms underpinning emotion recognition misattributions in threat-exposed youth.

International Efforts to Study Trajectories of Psychosis Spectrum Symptoms and Their Impact on Child and Youth Mental Health

International Efforts to Study Trajectories of Psychosis Spectrum Symptoms and Their Impact on Child and Youth Mental Health

Evaluation of a new intrinsic and extrinsic motivation scale in youth with psychosis spectrum symptoms

BackgroundImpairment in intrinsic motivation (IM), the drive to satisfy internal desires like mastery, may play a key role in disability in psychosis. However, we have limited knowledge regarding relative impairments in IM compared to extrinsic motivation (EM) or general motivation (GM), in part due to limitations in existing measures. MethodsHere we address this gap using a novel Trait Intrinsic and Extrinsic Motivation self-report scale in a sample of n = 243 participants including those with schizophrenia, psychosis-risk, and healthy controls. Each of the 7 IM and 6 EM items used a 7-point Likert scale assessing endorsement of dispositional statements. Bifactor analyses of these items yielded distinct IM, EM, and GM factor scores. Convergent and discriminant validity were examined in relation to General Causality Orientation Scale (GCOS-CP) and Quality of Life 3-item IM measure (QLS-IM). Utility was assessed in relation to psychosis-spectrum (PS) status and CAINS clinical amotivation. ResultsIM and EM showed acceptable inter-item consistency (IM: α = 0.88; EM: α = 0.66); the bifactor model exhibited fit that varied from good to borderline to inadequate depending on the specific fit metric (SRMR = 0.038, CFI = 0.94, RMSEA = 0.106 ± 0.014). IM scores correlated with established IM measures: GCOS-CP Autonomy (rho = 0.38, p < 0.01) and QLS-IM (rho = 0.29, p < 0.01). Supporting discriminant validity, IM did not correlate with GCOS-CP Control (rho = −0.14, p > 0.05). Two-year stability in an available longitudinal subset (n = 35) was strong (IM: rho = 0.64, p < 0.01; EM: rho = 0.55, p < 0.01). Trait IM was lower in PS youth (t = 4.24, p < 0.01), and correlated with clinical amotivation (rho = −0.36, p < 0.01); EM did not show significant clinical associations. ConclusionsThese results demonstrate the clinical relevance of IM in psychosis risk. They also provide preliminary support for the reliability, validity and utility of this new Trait IM-EM scale, which addresses a measurement gap and can facilitate identification of neurobehavioral and clinical correlates of IM deficits.

Working memory performance is related to childhood trauma but not psychotic-like experiences in a nonpsychiatric sample.

This project seeks to clarify the impact of childhood trauma and psychotic-like experiences (PLEs) on working memory (WM) and explore gender differences in these relationships. The effect of childhood trauma on WM performance has yet to be explored in individuals with PLEs, despite consistent associations between trauma, psychosis spectrum symptoms, and WM performance. In 466 undergraduates, positive PLEs (Prodromal Questionnaire) and trauma (Childhood Trauma Questionnaire) were examined to determine contributions to WM performance on a spatial n-back task. We conducted hierarchical linear regressions on the total sample and stratified by gender to examine the effects of childhood trauma, positive PLEs, and their interaction on WM performance. Supplemental analyses explored attenuated negative and disorganized symptoms. Controlling for age, there were no significant main effects of positive PLEs, childhood trauma, their interaction, or three-way interaction including gender in predicting WM. After stratifying by gender, childhood trauma was significantly associated with poorer WM in females only. Post hoc analyses revealed that in the full sample, physical neglect predicted WM performance and was a trend for females, while sexual abuse trended toward predicting WM in males. Supplemental analyses of attenuated negative and disorganized symptoms revealed childhood trauma significantly predicted WM in the full sample and females only for negative symptoms. Females who have experienced childhood trauma may be at greater risk for WM problems, irrespective of co-occurring PLEs, suggesting that cognitive difficulties may be partially attributable to history of trauma. These findings have potential implications for intervention strategies in trauma-exposed individuals. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

N400 event-related brain potential index of semantic processing and two-year clinical outcomes in persons at high risk for psychosis: A longitudinal study.

The N400 event-related brain potential (ERP) semantic priming effect reflects greater activation of contextually related versus unrelated concepts in long-term semantic memory. Deficits in this measure have been found in persons with schizophrenia and those at clinical high risk (CHR) for this disorder. In CHR patients, we previously found that these deficits predict poorer social functional outcomes after 1 year. In the present study, we tested whether these deficits predicted greater psychosis-spectrum symptom severity and functional impairment over 2 years. We measured N400 semantic priming effects at baseline in CHR patients (n = 47) who viewed prime words each followed by a related/unrelated target word at stimulus-onset asynchronies (SOAs) of 300 or 750 ms. We measured psychosis-spectrum symptoms using the Structured Interview for Prodromal Symptoms and role and social functioning with the Global Functioning: Role and Social scales, at baseline, 1 (n = 29) and 2 years (n = 25). There was a significant interaction between the N400 semantic priming effect at the 300-ms SOA and time on GF:Role scores, indicating that, contrary to expectations, smaller baseline N400 semantic priming effects were associated with more improvement in role functioning from baseline to Year 1, but baseline N400 priming effects did not predict role functioning at Year 2. N400 priming effects were not significantly associated with different trajectories in psychosis-spectrum symptoms or social functioning. Thus, CHR patients' N400 semantic priming effects did not predict clinical outcomes over 2 years, suggesting that this ERP measure may have greater value as a state or short-term prognostic neurophysiological biomarker.

Empirically-derived dimensions of childhood adversity and cumulative risk: associations with measures of depression, anxiety, and psychosis-spectrum psychopathology

ABSTRACT Background: Investigating different approaches to operationalizing childhood adversity and how they relate to transdiagnostic psychopathology is relevant to advance research on mechanistic processes and to inform intervention efforts. To our knowledge, previous studies have not used questionnaire and interview measures of childhood adversity to examine factor-analytic and cumulative-risk approaches in a complementary manner. Objective: The first aim of this study was to identify the dimensions underlying multiple subscales from three well-established childhood adversity measures (the Childhood Trauma Questionnaire, the Childhood Experience of Care and Abuse Interview, and the Interview for Traumatic Events in Childhood) and to create a cumulative risk index based on the resulting dimensions. The second aim of the study was to examine the childhood adversity dimensions and the cumulative risk index as predictors of measures of depression, anxiety, and psychosis-spectrum psychopathology. Method: Participants were 214 nonclinically ascertained young adults who were administered questionnaire and interview measures of depression, anxiety, psychosis-spectrum phenomena, and childhood adversity. Results: Four childhood adversity dimensions were identified that captured experiences in the domains of Intrafamilial Adversity, Deprivation, Threat, and Sexual Abuse. As hypothesized, the adversity dimensions demonstrated some specificity in their associations with psychopathology symptoms. Deprivation was uniquely associated with the negative symptom dimension of psychosis (negative schizotypy and schizoid symptoms), Intrafamilial Adversity with schizotypal symptoms, and Threat with depression, anxiety, and psychosis-spectrum symptoms. No associations were found with the Sexual Abuse dimension. Finally, the cumulative risk index was associated with all the outcome measures. Conclusions: The findings support the use of both the empirically-derived adversity dimensions and the cumulative risk index and suggest that these approaches may facilitate different research objectives. This study contributes to our understanding of the complexity of childhood adversity and its links to different expressions of psychopathology.

Family members' experiences of seeking help for a young person with symptoms associated with the psychosis spectrum: A narrative review and synthesis.

Young people often rely on family carers to access support for their mental health. However, stigma can be a barrier to help seeking for young people and families. Little research has been undertaken with young people who experience highly stigmatised symptoms, such as psychosis spectrum symptoms, and even less research has been conducted with parents and carers, meaning barriers to help go unchallenged. Therefore, this narrative review aimed to explore stories of family experiences of seeking help for young people with symptoms associated with the psychosis spectrum. Sources searched were PsycINFO and PubMed. Reference lists of the selected papers were also cross-checked to ensure the search had not missed potential papers for inclusion. Searches returned 139 results, of which 12 were identified for inclusion. A narrative analytic approach was adopted to synthesise qualitative findings to provide a nuanced interpretation of help-seeking experiences. The narrative synthesis provided an opportunity to identify differences, similarities, and patterns across the studies to tell a cumulative emancipatory narrative of family experiences of seeking help for psychosis spectrum symptoms. Help-seeking experiences had a relational impact on families, with stress adding to conflict and anxieties inhibiting hopefulness, although families could emerge stronger and assertively with compassionate support.

Psychosis spectrum features, neurocognition and functioning in a longitudinal study of youth with 22q11.2 deletion syndrome.

Neuropsychiatric disorders are common in 22q11.2 Deletion Syndrome (22q11DS) with about 25% of affected individuals developing schizophrenia spectrum disorders by young adulthood. Longitudinal evaluation of psychosis spectrum features and neurocognition can establish developmental trajectories and impact on functional outcome. 157 youth with 22q11DS were assessed longitudinally for psychopathology focusing on psychosis spectrum symptoms, neurocognitive performance and global functioning. We contrasted the pattern of positive and negative psychosis spectrum symptoms and neurocognitive performance differentiating those with more prominent Psychosis Spectrum symptoms (PS+) to those without prominent psychosis symptoms (PS-). We identified differences in the trajectories of psychosis symptoms and neurocognitive performance between the groups. The PS+ group showed age associated increase in symptom severity, especially negative symptoms and general nonspecific symptoms. Correspondingly, their level of functioning was worse and deteriorated more steeply than the PS- group. Neurocognitive performance was generally comparable in PS+ and PS- groups and demonstrated a similar age-related trajectory. However, worsening executive functioning distinguished the PS+ group from PS- counterparts. Notably, of the three executive function measures examined, only working memory showed a significant difference between the groups in rate of change. Finally, structural equation modeling showed that neurocognitive decline drove the clinical change. Youth with 22q11DS and more prominent psychosis features show worsening of symptoms and functional decline driven by neurocognitive decline, most related to executive functions and specifically working memory. The results underscore the importance of working memory in the developmental progression of psychosis.

Differential diagnosis of psychosis and dissociative disorder: a case report

IntroductionPsychosis and dissociative disorders are both described in the DSM-5 as different diagnostic categories. However, a high comorbidity of these diagnoses has been observed in different studies, perhaps due to the overlapping of symptoms between them.ObjectivesA systematic review about overlapping symptoms in psychotic spectrum and dissociative disordersMethodsPresentation of the case of a patient and review of the existing literature on the differential diagnosis between dissociative disorder and other psychotic spectrum disorders.ResultsBoth similarities and differences have been found between both diagnoses. Patients with dissociative disorder experienced more dissociative and positive symptoms while those on the psychotic spectrum experienced more negative symptoms. The literature reflects that the two entities overlap on many of their diagnostic symptoms. On some occasions, more dissociation has been detected in patients diagnosed with the psychotic spectrum than those with a diagnosis of dissociative disorder.ConclusionsDespite the fact of being different diagnostic entities, the literature does not reflect clear boundaries between psychosis spectrum symptoms and dissociative disorder.Disclosure of InterestNone Declared

Activation of Internal Correctness Monitoring Circuitry in Youths With Psychosis Spectrum Symptoms

BackgroundSelf-directed performance monitoring is a critical contributor to cognitive performance and general functioning and is impacted by psychiatric symptoms and personality traits, but has been understudied in psychosis-risk states. We have shown that ventral striatum (VS) responds to correctness during cognitive tasks where no explicit feedback is required, and this intrinsic reinforcement response is reduced in schizophrenia. MethodsHere, we examined this phenomenon in youths (n = 796, age range 11–22 years) from the Philadelphia Neurodevelopmental Cohort (PNC) performing a working memory functional magnetic resonance imaging task. We hypothesized that VS would respond to internal correctness monitoring, while classic salience network regions, such as dorsal anterior cingulate cortex and anterior insular cortex, would reflect internal error monitoring and that these responses would increase with age. We expected that neurobehavioral measures of performance monitoring would be reduced in youths with subclinical psychosis spectrum features and would correlate with amotivation severity. ResultsSupporting these hypotheses, we found correct>incorrect activation in VS and incorrect>correct activation in anterior cingulate cortex and anterior insular cortex. Furthermore, VS activation was positively correlated with age, reduced in youths with psychosis spectrum features, and inversely correlated with amotivation. However, these patterns were not significant in anterior cingulate cortex and anterior insular cortex. ConclusionsThese findings advance our understanding of the neural underpinnings of performance monitoring and its impairment in adolescents with psychosis spectrum features. Such understanding can facilitate investigation of the developmental trajectory of normative and aberrant performance monitoring; contribute to early identification of youths at elevated risk for poor academic, occupational, or psychiatric outcomes; and provide potential targets for therapeutic development.

Which Came First: The Hallucination or the Neural Alteration?

Efforts to understand the etiology of psychosis spectrum symptoms, including hallucinations, indicate that these experiences likely arise from a confluence of pathophysiological, genetic, and environmental risk factors (Figure 1). To better understand the pathogenesis of these symptoms, research has increasingly examined early pathophysiological markers of subthreshold psychosis spectrum symptoms or psychotic-like experiences. Large population-based samples such as the Generation R Study are needed to understand small effect-sized associations, such as those between neural metrics and psychopathology symptoms.