Psychosis Risk: Time to Look Empirically at a First-step Economical-pragmatic Way to Examine Anomalous Self-experience. Exploring the SQuEASE-11.

BACKGROUND: Since the late 1990s, there has been a worldwide surge of scientific interest in the pre-psychotic phase, resulting in the introduction of several clinical tools for early detection. The predictive accuracy of these tools has been limited, motivating the need for methodological and perspectival improvements. The EASE manual supports systematic assessment of anomalous self-experience, and proposes an overall model of understanding how most psychotic experiences may be initially generated on the basis of a unifying, fundamental, pre-reflective distortion of subjectivity. STUDY DESIGN: The EASE is time-consuming, so in order to spread the use of this essential perspective of psychosis risk we selected prototypical and frequent phenomena from the EASE, combining them into SQuEASE-11. To investigate this instrument for clinical relevance, basic psychometric properties, factor structure, and relationships with gold standard instruments and the full EASE, it was administered as an interview in the STEP intervention trial (Melbourne, Australia), with 328 clinical high-risk for psychosis (CHR-P) patients. STUDY RESULTS: The SQuEASE-11 had moderate internal consistency and revealed two correlated factors. Significant relationships were observed between the SQuEASE-11 and the widely used and validated instruments CAARMS, BPRS, SANS, MADRS, DACOBS, and SOFAS. The correlation with the full EASE was very strong. CONCLUSIONS: These 11 items do not necessarily relate specifically to ipseity disturbance, but the SQuEASE-11 seems to be a clinically relevant and brief supplementary first-line interview in CHR-P subjects. It may give a qualified indication of the need for a complete EASE interview, and it may also, importantly, inform treatment planning.

Are factors that predict conversion to psychosis associated with initial transition to a high risk state? An adolescent brain cognitive development study analysis.

OBJECTIVE: Previous work suggests that cognitive and environmental risk factors may predict conversion to psychosis in individuals at clinical high risk (CHRs) for the disorder. Less clear, however, is whether these same factors are also associated with the initial emergence of the high risk state in individuals who do not meet current threshold criteria for being considered high risk. METHOD: Here, using data from the Adolescent Brain Cognitive Development (ABCD) study, we examined associations between factors previously demonstrated to predict conversion to psychosis in CHRs with transition to a "high risk" state, here defined as having a distress score between 2 and 5 on any unusual thought content question in the Prodromal Questionnaire-Brief Child version. Of a sample of 5237 children (ages 11-12) studied at baseline, 470 transitioned to the high-risk state the following year. A logistic regression model was evaluated using age, cognition, negative and traumatic experiences, decline in school performance, and family history of psychosis as predictors. RESULTS: The overall model was significant (χ2 = 100.89, R2 = 0.042, p < .001). Significant predictors included number of negative life events, decline in school performance, number of trauma types, and verbal learning task performance. CONCLUSIONS: These results suggest that factors that predict conversion in CHR teenagers are also associated with initial emergence of a "high-risk" state in preadolescents. Limitations regarding the degree to which model factors and outcome in this study parallel those used in previous work involving psychosis risk in older teenagers are discussed.

Resting-state electroencephalogram in drug-free subjects with at-risk mental states who later developed psychosis: a low-resolution electromagnetic tomography analysis.

Background and objectives: Several studies have reported on the resting-state electroencephalogram (EEG) power in patients with schizophrenia, with a decrease in α (especially α2) and an increase in δ and ß1 power compared with healthy control; however, reports on at-risk mental states (ARMS) are few. In this study, we measured the resting-state EEG power in ARMS, and investigated its features and the relationship between the power of the frequency bands and their diagnostic outcomes. Methods: Patients with ARMS who were not on any psychotropic medication and met the Comprehensive Assessment of At-Risk Mental State criteria were included. Patients who developed psychotic disorders were labeled as the ARMS-P group, while patients with ARMS who were followed up prospectively for more than 2 years and did not develop psychotic disorders were classified as the ARMS-NP group. EEGs were measured in the resting state, and frequencies were analyzed using standardized low-resolution brain electromagnetic tomography (sLORETA). Seven bands (δ, θ, α1, α2, ß1-3) underwent analysis. The sLORETA values (current source density [CSD]) were compared between the ARMS-P and ARMS-NP groups. Clinical symptoms were assessed at the time of EEG measurements using the Positive and Negative Syndrome Scale (PANSS). Results: Of the 39 patients included (25 males, 14 females, 18.8 ± 4.5 years old), eight developed psychotic disorders (ARMS-P). The ARMS-P group exhibited significantly higher CSD in the ß1 power within areas of the left middle frontal gyrus (MFG) compared with the ARMS-NP group (best match: X = -35, Y = 25, Z = 50 [MNI coordinates], Area 8, CSD = 2.33, p < 0.05). There was a significant positive correlation between the ß1/α ratio of the CSD at left MFG and the Somatic concern score measured by the PANSS. Discussion: Increased ß1 power was observed in the resting EEG before the onset of psychosis and correlated with a symptom. This suggests that resting EEG power may be a useful marker for predicting future conversion to psychosis and clinical symptoms in patients with ARMS.

Obsessive-compulsive symptoms in individuals at clinical high risk for psychosis: A 2-year longitudinal study.

Aim - Recent findings suggest that OCS are prevalent in individuals with early psychosis. However, their clinical relevance still needs to be clarified. This research specifically explored OCS in subjects at Clinical High Risk for Psychosis (CHRP), with the aims of determining their baseline prevalence, examining their 2-year stability, and analyzing their association with sociodemographic data, clinical characteristics and outcomes. Methods - Clinical assessments at baseline and during the 2-year follow-up period included: the Comprehensive Assessment of At-Risk Mental states (CAARMS), the Positive And Negative Syndrome Scale (PANSS), and the Global Assessment of Functioning (GAF). OCS were identified using the CAARMS item 7.6 subscore. Results - Among 180 CHR-P participants, 66 (36.7 %) had OCS at baseline. CHR-P with OCS had higher PANSS scores and greater antidepressant prescription rates. OCS severity levels improved in the first year, but plateaued over two years, correlating with longitudinal changes in GAF and PANSS total scores. OCS improvement was specifically associated with antidepressant use and intensity of individual psychotherapy sessions. CHR-P subjects with OCS had higher service engagement rates. Conclusions - The presence of OCS could characterize a distinct CHR-P subtype with specific clinical and prognostic characteristics, requiring tailored diagnostic and therapeutic approaches. Recognizing the heterogeneity in CHR-P population is crucial for optimizing care.

Effort-based decision-making in ultra-high-risk for psychosis and bipolar disorder.

BACKGROUND: Effort-based decision-making has been proposed as a potential mechanism contributing to transdiagnostic motivational deficits in psychotic disorder and bipolar disorder. However, very limited information is available about deficits in effort-cost-decision-making in the early stages of psychotic disorder and no study has investigated effort allocation deficits before the onset of bipolar disorder. Our aim was to investigate effort-based-decision-making in ultra-high-risk for psychosis (UHR-P) and bipolar disorder (UHR-BD). METHODS: Effort-cost decision-making performance was evaluated in UHR-P (n = 72) and UHR-BD (n = 68) and healthy controls (n = 38). Effort-Expenditure for Reward Task (EEfRT) was used. RESULTS: Compared to controls, both UHR-P and UHR-BD groups were associated with a reduced possibility to choose the harder task when the reward magnitudes and/or the likelihood of receiving the reward were high. In both groups, effort allocation abnormalities were associated with poor social functioning. CONCLUSIONS: The current findings suggest that difficulties in effort-cost computation are transdiagnostic markers of illness liability in psychotic and bipolar disorders. In early intervention services, effort-based decision-making abnormalities should be considered as a target for interventions to manage motivational deficits in individuals at high risk for psychosis and BD.

Impaired 40-Hz and intact hierarchical organization mode of auditory steady-state responses among individuals with clinical high-risk for psychosis.

BACKGROUND: Impaired gamma band oscillation, specifically 40-Hz auditory steady state response (ASSR) has been robustly found in schizophrenia, while there is relatively little evidence characterizing the ASSR before full-blown psychosis. OBJECTIVE: To characterize gamma-band ASSR in populations at clinical high-risk for psychosis (CHR). METHODS: One hundred and seven CHR subjects and sixty-five healthy control (HC) subjects were included and completed clinical assessments, the ASSR paradigm of electroencephalography (EEG) and cognitive assessments. Both indices of event-related spectrum perturbation (ERSP) and intertrial coherence (ITC) in response to 20-Hz, 30-Hz and 40-Hz click sounds were respectively qualified and compared between these two groups, as well as the relationship to clinical psychopathology and cognitive function was assessed. RESULTS: At 40-Hz click sounds, ERSP in HC group (1.042 ± 0.047) was statistical significantly increased than that in CHR group (0.873 ± 0.036) (p = 0.005)；at 30-Hz, ERSP in HC group (0.536 ± 0.024) was increased than that in CHR group (0.483 ± 0.019), but the difference was trend statistical significance (p = 0.083)；at 20-Hz, ERSP in HC group (0.452 ± 0.017) was not different significantly from CHR group (0.418 ± 0.013) (p = 0.104). ERSP of the HC group was the highest at 40-Hz click sounds, followed by 30-Hz, and the lowest at 20-Hz. The difference between any two of the three ERSP showed statistical significance (30-Hz vs. 40-Hz: p < 0.001; 20-Hz vs. 40-Hz: p < 0.001；20-Hz vs. 30-Hz: p = 0.003). Similarly, ERSP of the CHR group was the highest at 40-Hz click sounds, followed by 30-Hz, and the lowest at 20-Hz. The difference between any two of these three ERSP showed statistical significance (30-Hz vs. 40-Hz: p < 0.001; 20-Hz vs. 40-Hz: p < 0.001；20-Hz vs. 30-Hz: p = 0.002). A statistically significant small positive correlation of 40-Hz ERSP with signal processing speed score was observed in the HC group (ρ = 0.27, p = 0.029). A statistically significant small negative correlation of 40-Hz ERSP with visual learning score was observed in the CHR group (ρ = -0.22, p = 0.023). CONCLUSION: Impaired 40-Hz but undamaged hierarchical organization mode of auditory steady state presented in the CHR populations. Abnormal 40 Hz ASSR for CHR might be associated with cognitive functions, such as information processing speed and visual memory.

Exploring the acceptability, barriers, and facilitators to psychosis screening in the integrated behavioral health primary care setting: a qualitative study.

BACKGROUND: A longer duration of untreated psychosis (DUP) is associated with poorer treatment outcomes. Screening for psychosis spectrum disorders in the primary care setting could help support the earlier detection and treatment of individuals in need. However, the acceptability of screening for psychosis in this setting as part of routine care is currently unknown. METHODS: We conducted a qualitative interview study with providers and service users who participated in an early psychosis screening program conducted in an integrated behavioral health primary care (IBH-PC) setting. Interviews were recruited from one of eight WellSpace Federally Qualified Health Center IBH-PC clinics in the Sacramento, CA area. Transcripts of the recorded interviews were analyzed using thematic analysis. RESULTS: In total, 12 providers and eight service users participated in the interviews. Most service user and provider participants were supportive of psychosis screening in an IBH-PC setting, but not as part of the general practitioner consultation due to the brief, non-behavioral health nature of many of the appointments, and the expected low prevalence of psychosis in this population. The support of leadership, adequate training and support, staff turnover, and organizational changes were all seen to impact the successful implementation of the program. Different barriers and facilitators were considered important at each stage of the process from introducing the screening procedures to service users; to determining when, where, and how to screen; and how to effectively manage the referral and post-referral stages. CONCLUSIONS: Despite the additional challenges of screening in an IBH-PC setting relative to secondary mental health services, the process was considered acceptable and feasible to providers and service users. Services that plan to conduct psychosis screening in their clinics need to consider the challenges and their potential solutions to implementation at each stage of the screening process.

Kenya Psychosis-Risk Outcomes Study (KePROS): Development of an Accelerated Medicine Partnership Schizophrenia-Aligned Project in Africa.

Background and Hypothesis: The Accelerating Medicines Partnership Schizophrenia (AMP SCZ) funds a longitudinal study of 43 research sites across 5 continents to develop tools to stratify developmental trajectories of youth at clinical high risk for psychosis (CHR) and identify homogenous targets for future clinical trials. However, there are no sites in Africa, leaving a critical gap in our knowledge of clinical and biological outcomes among CHR individuals. Study Design: We describe the development of the Kenya Psychosis-Risk Outcomes Study (KePROS), a 5-year NIH-funded project in Kenya designed to harmonize with AMP SCZ. The study will recruit over 100 CHR and 50 healthy participants and conduct multiple clinical and biomarker assessments over 2 years. Capacity building is a key component of the study, including the construction of an electroencephalography (EEG) laboratory and the upgrading of a local 3 T magnetic resonance imaging (MRI) machine. We detail community recruitment, study methodologies and protocols, and unique challenges with this pioneering research in Africa. Study Results: This paper is descriptive only. Planned future analyses will investigate possible predictors of clinical outcomes and will be compared to results from other global populations. Conclusions: KePROS will provide the research community with a rich longitudinal clinical and biomarker dataset from an African country in the developing Global South, which can be used alongside AMP SCZ data to delineate CHR outcome groups for future treatment development. Training in mental health assessment and investment in cutting-edge biomarker assessment and other technologies is needed to facilitate the inclusion of African countries in large-scale research consortia.

N-Acetylcysteine and a Specialized Preventive Intervention for Individuals at High Risk for Psychosis: A Randomized Double-Blind Multicenter Trial.

Background and Hypothesis: Clinical high risk for psychosis (CHR-P) offers a window of opportunity for early intervention and recent trials have shown promising results for the use of N-acetylcysteine (NAC) in schizophrenia. Moreover, integrated preventive psychological intervention (IPPI), applies social-cognitive remediation to aid in preventing the transition to the psychosis of CHR-P patients. Study Design: In this double-blind, randomized, controlled multicenter trial, a 2 × 2 factorial design was applied to investigate the effects of NAC compared to placebo (PLC) and IPPI compared to psychological stress management (PSM). The primary endpoint was the transition to psychosis or deterioration of CHR-P symptoms after 18 months. Study Results: While insufficient recruitment led to early trial termination, a total of 48 participants were included in the study. Patients receiving NAC showed numerically higher estimates of event-free survival probability (IPPI + NAC: 72.7 ±â€…13.4%, PSM + NAC: 72.7 ±â€…13.4%) as compared to patients receiving PLC (IPPI + PLC: 56.1 ±â€…15.3%, PSM + PLC: 39.0 ±â€…17.4%). However, a log-rank chi-square test in Kaplan-Meier analysis revealed no significant difference of survival probability for NAC vs control (point hazard ratio: 0.879, 95% CI 0.281-2.756) or IPPI vs control (point hazard ratio: 0.827, 95% CI 0.295-2.314). The number of adverse events (AE) did not differ significantly between the four groups. Conclusions: The superiority of NAC or IPPI in preventing psychosis in patients with CHR-P compared to controls could not be statistically validated in this trial. However, results indicate a consistent pattern that warrants further testing of NAC as a promising and well-tolerated intervention for CHR patients in future trials with adequate statistical power.

Addressing the elephant in the screening room: an item response theory analysis of the Prodromal Questionnaire (PQ-16) for at-risk symptoms of psychosis.

OBJECTIVE: Within the context of patients at-risk of psychosis, where a variety of symptoms are present, identifying the most discriminative symptoms is essential for efficient detection and management. METHODS: This cross-sectional online study analyzed individuals from the general population in order to better assess their risk of presenting symptoms belonging to the clinical high risk (CHR) for psychosis, called "CHR-related symptoms". The Prodromal Questionnaire-16 (PQ-16) served as a self-report screening tool. Item response theory (IRT) with a graded response model was used to assess the discrimination and difficulty of its criteria. RESULTS: The analysis included 936 participants (mean age: 21.5 years; 28.1% male, 71.9% female). "Déjà vu" stood out for its high discriminative power, while "Voices or whispers" and "Seen things" demonstrated strong precision relatively to the other CHR-related symptoms. Conversely, "Smell or taste" and "Changing face" were associated with the most severe cases relatively to the other CHR-related symptoms. CONCLUSION: This study identified the most indicative CHR-related symptoms to emphasize their significance in accurately assessing severity and guiding targeted preventative interventions.

Unique functional neuroimaging signatures of genetic versus clinical high risk for psychosis.

BACKGROUND: 22q11.2 Deletion Syndrome (22qDel) is a copy number variant (CNV) associated with psychosis and other neurodevelopmental disorders. Adolescents at clinical high risk for psychosis (CHR) are identified based on the presence of subthreshold psychosis symptoms. Whether common neural substrates underlie these distinct high-risk populations is unknown. We compared functional brain measures in 22qDel and CHR cohorts and mapped results to biological pathways. METHODS: We analyzed two large multi-site cohorts with resting-state functional MRI (rs-fMRI): 1) 22qDel (n=164, 47% female) and typically developing (TD) controls (n=134, 56% female); 2) CHR individuals (n=244, 41% female) and TD controls (n=151, 46% female) from the North American Prodrome Longitudinal Study-2. We computed global brain connectivity (GBC), local connectivity (LC), and brain signal variability (BSV) across cortical regions, testing case-control differences for 22qDel and CHR separately. Group difference maps were related to published brain maps using autocorrelation-preserving permutation. RESULTS: BSV, LC, and GBC are significantly disrupted in 22qDel compared with TD controls (False Discovery Rate q<0.05). Spatial maps of BSV and LC differences are highly correlated with each other, unlike GBC. In CHR, only LC is significantly altered versus controls, with a different spatial pattern compared to 22qDel. Group differences map onto biological gradients, with 22qDel effects strongest in regions with high predicted blood flow and metabolism. CONCLUSION: 22qDel and CHR exhibit divergent effects on fMRI temporal variability and multi-scale functional connectivity. In 22qDel, strong and convergent disruptions in BSV and LC not seen in CHR individuals suggest distinct functional brain alterations.

A Tale of Three Spectra: Basic Symptoms in Clinical-High-Risk of Psychosis Vary Across Autism Spectrum Disorder, Schizotypal Personality Disorder, and Borderline Personality Disorder.

Background and Hypothesis: The clinical-high-risk (CHR) approach was developed to prevent psychosis through the detection of psychosis risk. CHR services are transdiagnostic in nature, therefore the appropriate management of comorbidity is a central part of care. Differential diagnosis is particularly challenging across 3 common comorbidities, schizotypal personality disorder (SPD), autism spectrum disorder (ASD), and borderline personality disorder (BPD). Phenomenological research indicates a disturbance of "basic self" may differentiate between these commonly comorbid disorders and can be captured by Huber's basic symptoms (BS) concept. We investigated whether BS vary across these disorders and may inform differential diagnosis in young person's meeting CHR criteria. Study Design: A total of 685 participants meeting CHR criteria from the NAPLS-3 cohort completed the COGDIS items of the schizophrenia proneness instrument, a measure of BS, as well as the structured interview for DSM-5 (SCID-5). A logistic regression model was used to investigate the variation of COGDIS across SPD, ASD, and BPD, while controlling for age and SIPs positive severity. Study Results: Meeting COGDIS criteria was positively associated with SPD (OR = 1.72, CI = [1.31-2.28], P = .001) but not ASD nor BPD. Conclusions: Our results indicate that "basic self-disturbance" as indicated by COGDIS differs across SPD, ASD, and BPD. COGDIS may be useful to inform the management of comorbidities in CHR services, by providing insight into subtle subjective experiences that may benefit from disorder-specific interventions.

Facial emotion perception in individuals with clinical high risk for psychosis compared with healthy controls, first-episode psychosis, and in predicting psychosis transition: A systematic review and meta-analysis.

Facial emotion perception deficits, a possible indicator of illness progression and transdiagnostic phenotype, were examined in high-risk psychosis (CHR) patients through a systematic review and meta-analysis of 35 studies (2567 CHR individuals, 1103 non-transitioned [CHR-NT], 212 transitioned [CHR-T], 512 first-episode psychosis [FEP], and 1936 healthy controls [HC]). CHR showed overall (g = -0.369 [95 % CI, -0.485 to -0.253]) and specific impairments in detecting anger, disgust, fear, happiness, neutrality, and sadness compared to HC, except for surprise. FEP revealed a general deficit than CHR (g = -0.378 [95 % CI, -0.509 to -0.247]), and CHR-T displayed more pronounced baseline impairments than CHR-NT (g = -0.217 [95 % CI, -0.365 to -0.068]). FEP only exhibited a poorer ability to perceive fear, but not other individual emotions, compared to CHR. Similar performances in perceiving individual emotions were observed regardless of transition status (CHR-NT and CHR-T). However, literature comparing the perception of individual emotions among FEP, CHR-T, and CHR is limited. This study primarily characterized the general and overall impairments of facial emotion perception in CHR which could predict transition risk, emphasizing the need for future research on multimodal parameters of emotion perception and associations with other psychiatric outcomes.

Lessons Learnt From Running a Transition-Age Youth Mental Health Outpatient Clinic in Italy: The PRecocity of Intervention in Adolescent Medicine (PRIMA) Experience.

AIM: This study assessed whether transition age between adolescence and young adulthood poses a challenge for both patients and mental health services. METHODS: We retrospectively examined the baseline characteristics, diagnoses and treatments of 99 individuals aged 16-35 presenting to the PRecocity of Intervention in Adolescent Medicine (PRIMA) transition-age mental health outpatient clinic, Italy, over a 24-month period. RESULTS AND DISCUSSION: Most patients were female, aged 20 or younger, employed and did not experience impairment in daily autonomies. About half patients were referred by general practitioners or self-referred, often as initial contact with any adult mental health services, complaining with multiple symptoms (88%), mainly including anxiety, affective disturbances and insomnia. Most of them received a single diagnosis (68%), one out of three being diagnosed with a neurodevelopmental disorder. Patients presenting with anxiety (63% vs. 32%; OR = 3.55, p = 0.01) and affective symptoms (56% vs .23%; OR = 4.26, p = 0.01) and receiving multiple diagnoses (30% vs. 9%; χ2(2) = 19.7, p < 0.01) were more likely to be prescribed with psychopharmacological medication at the first visit. At a 6-month follow-up, one in two patients remained in PRIMA, while the others required different services tailored to their specific conditions, especially neurodevelopmental disorders. CONCLUSION: Findings from this study warrant the need for specialised mental healthcare facilities ensuring timely and high-quality interventions for adolescents transitioning into young adulthood.

The Relationship between Clinical and Psychophysical Assessments of Visual Perceptual Disturbances in Individuals at Clinical High Risk for Psychosis: A Preliminary Study.

This study investigated relations between a measure of early-stage visual function and self-reported visual anomalies in individuals at clinical high risk for psychosis (CHR-P). Eleven individuals at CHR identified via the Structured Interview for Psychosis-Risk Syndromes (SIPS) were recruited from a CHR-P research program in NYC. The sample was ~36% female, ranging from 16 to 33 years old (M = 23.90, SD = 6.14). Participants completed a contrast sensitivity task on an iPad with five spatial frequencies (0.41-13 cycles/degree) and completed the self-report Audio-Visual Abnormalities Questionnaire. Higher contrast sensitivity (better performance) to low spatial frequencies was associated with higher perceptual (r = 0.616, p = 0.044) and visual disturbances (r = 0.667, p = 0.025); lower contrast sensitivity to a middle spatial frequency was also associated with higher perceptual (r = -0.604, p = 0.049) and visual disturbances (r = -0.606, p = 0.048). This relation between the questionnaire and contrast sensitivity to low spatial frequency may be indicative of a reduction in lateral inhibition and "flooding" of environmental stimuli. The association with middle spatial frequencies, which play a critical role in face processing, may result in a range of perceptual abnormalities. These findings demonstrate that self-reported perceptual anomalies occur in these individuals and are linked to performance on a measure of early visual processing.

Robust Brain Correlates of Cognitive Performance in Psychosis and Its Prodrome.

BACKGROUND: Neurocognitive impairment is a well-known phenomenon in schizophrenia that begins prior to psychosis onset. Connectome-wide association studies have inconsistently linked cognitive performance to resting-state functional magnetic resonance imaging. We hypothesized that a carefully selected cognitive instrument and refined population would allow identification of reliable brain-behavior associations with connectome-wide association studies. To test this hypothesis, we first identified brain-cognition correlations via a connectome-wide association study in early psychosis. We then asked, in an independent dataset, if these brain-cognition relationships would generalize to individuals who develop psychosis in the future. METHODS: The Seidman Auditory Continuous Performance Task (ACPT) effectively differentiates healthy participants from those with psychosis. Our connectome-wide association study used the HCP-EP (Human Connectome Project for Early Psychosis) (n = 183) to identify links between connectivity and ACPT performance. We then analyzed data from the NAPLS2 (North American Prodrome Longitudinal Study 2) (n = 345), a multisite prospective study of individuals at risk for psychosis. We tested the connectome-wide association study-identified cognition-connectivity relationship in both individuals at risk for psychosis and control participants. RESULTS: Our connectome-wide association study in early-course psychosis identified robust associations between better ACPT performance and higher prefrontal-somatomotor connectivity (p < .005). Prefrontal-somatomotor connectivity was also related to ACPT performance in at-risk individuals who would develop psychosis (n = 17). This finding was not observed in nonconverters (n = 196) or control participants (n = 132). CONCLUSIONS: This connectome-wide association study identified reproducible links between connectivity and cognition in separate samples of individuals with psychosis and at-risk individuals who would later develop psychosis. A carefully selected task and population improves the ability of connectome-wide association studies to identify reliable brain-phenotype relationships.

Novel N100 area reliably captures aberrant sensory processing and is associated with neurocognition in early psychosis.

BACKGROUND: Despite findings from translational and genetic studies in the event-related potential (ERP) literature, the validity and reliability of P50 suppression as a schizophrenia spectrum endophenotype has been questioned. Here, we aimed to examine sensory registration and gating measures derived from P50 and N100 amplitude, as well as N100 area-a novel approach proposed herein-in early psychosis versus health. METHODS: Individuals at clinical high risk for psychosis (CHR; n = 77), first-episode psychosis (FE; n = 52), and healthy controls (HC; n = 65) were assessed in a paired-click auditory ERP paradigm. Eight CHR converted to psychosis (CHRC) and 39 did not (CHR-NC) by 24 months, while 30 CHR were lost to follow-. Group differences, test-retest reliability, and associations with neurocognitive function were assessed in nine ERP measures. RESULTS: Significant differences were observed in N100 S1 amplitude, S1 area, and area difference between HC and FE, as well as in N100 S1 area between HC and CHR, among the total population. Furthermore, significant differences were found in N100 S1 area between HC and CHR-NC (Cliff's delta, Δ = 0.32), as well as in N100 area difference between HC and CHR-C (Δ = 0.55). Both N100 S1 area and area difference demonstrated moderate to acceptable reliability (intraclass correlation coefficients: 0.61-0.78). Processing speed negatively correlated with both N100 S1 area and area difference, while executive function negatively correlated with N100 S1 area alone in CHR and FE. CONCLUSION: Among the ERP measures studied, N100 area measures may serve as a reliable biomarker of aberrant sensory processing and neurocognition in early psychosis.

Neurocognition in adolescents and young adults at clinical high risk for psychosis: Predictive stability for social and role functioning.

The prodromal phase of schizophrenia provides an optimal opportunity to mitigate the profound functional disability that is often associated with fully expressed psychosis. Considerable evidence supports the importance of neurocognition in the development of interpersonal (social) and academic (role) skills. Further findings from adolescents and young adults at clinical high risk for developing psychosis (CHRP) suggest that treatment for functioning might be most effective when targeting early and specific neurocognitive deficits. The current study addresses this critical intervention issue by examining the potential of neurocognitive deficits at intake for predicting social and role functioning over time in CHR-P youth. The study included 345 CHR-P participants from the second phase of the North American Prodrome Longitudinal Study (NAPLS2) with baseline neurocognition and 2-year follow-up data on social and role functioning. Slower baseline processing speed consistently predicted poor social functioning over time, while attention deficits predicted poor role functioning at baseline and follow-up. In addition, the impact of processing speed and attention impairments on social and role functioning, respectively, persisted even when adjusting the regression models for attenuated positive, negative, and disorganized symptoms, and transition status. The current study demonstrates for, arguably the first time, that processing speed and attention are strongly predictive of social and role functioning over time, respectively, above and beyond the impact of symptoms and those CHR-P individuals that develop psychosis over the course of the study. These findings imply that early neurocognition is a critical treatment target linked to the developmental trajectory of social and role functioning.