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.

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 ±â€¯0.047) was statistical significantly increased than that in CHR group (0.873 ±â€¯0.036) (p = 0.005)；at 30-Hz, ERSP in HC group (0.536 ±â€¯0.024) was increased than that in CHR group (0.483 ±â€¯0.019), but the difference was trend statistical significance (p = 0.083)；at 20-Hz, ERSP in HC group (0.452 ±â€¯0.017) was not different significantly from CHR group (0.418 ±â€¯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.

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.

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.

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.

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.

Visual contrast sensitivity in clinical high risk and first episode psychosis.

BACKGROUND: Individuals at Clinical High Risk (CHR) for psychosis or in their First Episode (FE) of psychosis are in a pivotal time in adolescence or young adulthood when illness can greatly impact their functioning. Finding relevant biomarkers for psychosis in the early stages of illness can contribute to early diagnosis, therapeutic management and prediction of outcome. One such biomarker that has been studied in schizophrenia (SZ) is visual contrast sensitivity (VCS). VCS can be used to differentiate visual information processing function in the magnocellular versus parvocellular visual pathways. Few studies have assessed VCS in early psychosis. METHODS: Participants included CHR (n = 68), FE psychosis (n = 34) and Healthy Comparison (HC) (n = 63). All were clinically assessed and completed a VCS paradigm that involved near threshold luminance and chromatic stimuli. RESULTS: CHR and FE participants had lower VCS in the luminance condition (F[2166] = 3.42, p < 0.05) compared to HC. There was also a significant sex X group interaction (F[5163] = 4.3, p < 0.001) in the luminance condition (F[5163] = 4.3, p < 0.001) as FE males (p < 0.01) and CHR females (p < 0.01) had the greatest deficits compared to male and female HC participants respectively. VCS deficits in the luminance condition were associated with more thought disorder, slower processing speed, worse executive functioning and poor global functioning (r's 0.25-0.50, p < 0.05). CONCLUSION: This study supports the hypothesis that there are deficits in visual information processing, particularly in tasks that emphasize the magnocellular pathway, in patients experiencing early psychosis. VCS therefore has the potential to be used as a biomarker in this population.

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 fMRI. We hypothesized 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 Human Connectome Project for Early Psychosis (n=183) to identify links between connectivity and ACPT performance. We then analyzed the North American Prodrome Longitudinal Study 2 (n=345), a multi-site 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 controls. 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 controls (n=132). CONCLUSIONS: This connectome-wide association study identified reproducible links between connectivity and cognition in separate samples of 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.

Clinical high risk for psychosis and service disengagement: Incidence and predictors across 2 years of follow-up.

BACK: Service disengagement is common in subjects at CHR-P (clinical high risk for psychosis), potentially worsening daily functioning and increasing the duration of untreated psychosis. That is why to identify baseline predictors of service disengagement could help better tailoring follow-up on every CHR-P individual. AIMS: Since there are few studies on this topic, the goals of this examination were: (1) to calculate service disengagement rates in a CHR-P sample along 2-years of follow-up; and (2) to examine the most relevant predictive factors of disengagement at baseline. METHODS: All young CHR-P participants were enrolled within the 'Parma At-Risk Mental States' (PARMS) protocol. At entry, the Global Assessment of Functioning (GAF) scale and the positive and negative syndrome scale (PANSS) were completed. Cox regression analyses were used. RESULTS: Hundred and eighty CHR-P subjects were recruited in this examination. During the follow-up, a 2-year service disengagement prevalence rate of 15% was observed. A statistically robust predictive factor of service disengagement was a lower prescription of antidepressant drug at entry. Other relevant baseline predictive factors were migrant status, higher GAF score, lower levels of anxious-depressive symptoms and a lower acceptance of psychosocial interventions. DISCUSSION: Baseline presence of anxious-depressive features in CHR-P individuals could favour engagement to specialized EIP services. However, implementing strategies to improve patients' motivation and involvement in care are needed.

Sex differences in clinical presentation in youth at high risk for psychosis who transition to psychosis.

Sex differences have been observed in individuals with schizophrenia and for those at clinical high risk (CHR) for psychosis. However, specific differences in CHR individuals who transition to psychosis remain inconsistent and understudied. This study aimed to investigate sex differences in 156 CHR individuals who made the transition to psychosis. A wide range of demographics, positive and negative symptoms, depression, anxiety, social and role functioning, trauma, and substance use were assessed at baseline and symptoms and diagnoses at the time of transition. Fluctuations in positive and negative symptoms and different medications were also assessed. No sex differences were observed at baseline for those who later transitioned to psychosis. At transition, males were significantly more likely to be diagnosed as having schizophrenia or schizophreniform disorder and through the course of the study, males were more likely to be taking stimulants. Limitations in this study was the lack of longitudinal follow-up post transition. The study highlights the need for further research on sex differences in individuals who transition to psychosis. Understanding these differences can have implications for treatment and monitoring of CHR individuals.

Overlap of obsessive compulsive and psychosis risk symptoms in a specialized clinic.

AIM: Psychotic disorders and obsessive-compulsive disorder (OCD) commonly co-occur. Likewise, subthreshold psychosis symptoms (clinical high risk for psychosis; CHR) and obsessive compulsive symptoms (OCS) often overlap and may be difficult to differentiate. This study aimed to replicate research investigating the prevalence of OCD in a CHR clinic sample, validate and investigate factor structure of a self-report OCS measure in a CHR sample, explore how OCS may relate to CHR and co-occurring symptoms, and investigate whether real-world CHR treatment improves OCS and CHR symptoms. METHOD: This study analysed archival clinical data from baseline and 6-month follow-up assessments collected by a specialist outpatient CHR clinic. Data included assessments of CHR symptoms, OCS, and clinician-rated diagnosis. Exploratory factor analysis examined the OCS measure. RESULTS: Within this CHR clinic sample, 13.5% experienced co-morbid OCD. The self-report OCS measure had two factors: (1) checking and counting behaviours and (2) intrusive thoughts and images of harm/guilt. The checking and counting factor correlated with depression and social anxiety. The intrusive thoughts and images of harm/guilt factor significantly correlated with unusual thought content and social anxiety. Between baseline to 6-month follow-up, clients exhibited CHR symptom improvement regardless of OCD diagnosis. However, OCS did not change. CONCLUSIONS: These findings support validity of a self-report OCS measure in a CHR clinic sample and that types of OCS experiences may exhibit different clinical patterns. Additionally, it appears that individuals with comorbid OCD responded similarly to CHR treatment compared to those without OCD.

A pilot study investigating the effect of the BEGIN psychoeducation intervention for people at clinical high risk for psychosis on emotional and stigma-related experiences.

AIM: There is concern that the provision of the clinical high risk for psychosis (CHR) label is stigmatizing. Prior research suggests people have nuanced reactions to feedback involving the CHR label, including a positive experience receiving feedback and improvement in negative emotions (e.g., shame), while also exhibiting concerns about self-perception and perceptions from others related to the label. The current pilot study aimed to evaluate whether individuals at CHR showed changes in emotional and stigma-related experiences following a CHR psychoeducation intervention, BEGIN: Brief Educational Guide for Individuals in Need. METHOD: Participants at CHR (N = 26) identified via the Structured Interview for Psychosis-Risk Syndromes completed the Mental Health Attitudes Interview measuring symptom-related and CHR label-related stigma at pre- and post-intervention. RESULTS: Stigma did not increase and participants had greater positive emotions (e.g., feeling hopeful and relieved), post-BEGIN. CONCLUSION: This study suggests that standardized CHR psychoeducation does not increase stigma in individuals at CHR.

Clinical High-Risk for Psychosis (CHR-P) circa 2024: Synoptic analysis and synthesis of contemporary treatment guidelines.

The construct of Clinical-High Risk for Psychosis (CHR-P) identifies young help-seeking subjects in putative prodromal stages of psychosis and is a central component of the Early Intervention (EI) paradigm in Mental Health, aimed at facilitating rapid entry into appropriate care pathways to prevent the onset of psychosis or mitigate is biopsychosocial consequences. This approach, which promotes an innovative culture of care for early, at risk situations, is inspired by a clinical staging concept as a guide to optimal treatment. The objective of this article is to map the existing guidelines in the field of CHR-P treatment recommendations, examine overlaps and differences, and critically evaluate blind spots to be addressed in future guideline updated. The search identified 9 guidelines focused on CHR-P or schizophrenia and other psychotic conditions but containing a specific section on CHR-P or prodromal psychosis. All guidelines acknowledge that psychosis is preceded by more or less pronounced prodromal stages, and most detail CHR-P criteria. Among guidelines, 8 out of 9 indicate cognitive-behavioural therapy as the best psychotherapeutic option and 7 out of 9 suggest that antipsychotics can be prescribed as second option in case psychosocial and/or other pharmacological interventions prove insufficient or inadequate in reducing clinical severity and subjective suffering. Antidepressants, mood stabilizers, and benzodiazepines were considered for the treatment of comorbid disorders. Only the European Psychiatric Association Guidance paper distinguished treatment recommendations for adults and minors. Agreements in treatment guidelines were discussed in light of recent meta-analytical evidences on pharmacological and non-pharmacological treatments for CHR-P, suggesting the need to provide an updated, age-sensitive consensus on how to manage CHR-P individuals.

Occasional cannabis use is associated with higher premorbid functioning and IQ in youth at clinical high-risk (CHR) for psychosis: Parallel findings to psychosis cohorts.

BACKGROUND: Neurocognitive deficits have been widely reported in clinical high-risk for psychosis (CHR) populations. Additionally, rates of cannabis use are high among CHR youth and are associated with greater symptom severity. Cannabis use has been sometimes shown to be associated with better neurocognition in more progressed psychosis cohorts, therefore in this study we aimed to determine whether a similar pattern was present in CHR. METHODS: CHR participants ages 12-30 from the North American Prodromal Longitudinal Study (NAPLS-3) (N = 698) were grouped according to: "minimal to no cannabis use" (n = 406), "occasional use" (n = 127), or "frequent use" (n = 165). At baseline, cannabis use groups were compared on neurocognitive tests, clinical, and functional measures. Follow-up analyses were used to model relationships between cannabis use frequency, neurocognition, premorbid, and social functioning. RESULTS: Occasional cannabis users performed significantly better than other use-groups on measures of IQ, with similar trend-level patterns observed across neurocognitive domains. Occasional cannabis users demonstrated better social, global, and premorbid functioning compared to the other use-groups and less severe symptoms compared to the frequent use group. Follow-up structural equation modeling/path analyses found significant positive associations between premorbid functioning, social functioning, and IQ, which in turn was associated with occasional cannabis use frequency. DISCUSSION: Better premorbid functioning positively predicts both better social functioning and higher IQ which in turn is associated with a moderate cannabis use pattern in CHR, similar to reports in first-episode and chronic psychosis samples. Better premorbid functioning likely represents a protective factor in the CHR population and predicts a better functional outcome.

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.

Harmonizing early intervention strategies: scoping review of clinical high risk for psychosis and borderline personality disorder.

Aims: To map studies assessing both clinical high risk for psychosis (CHR-P) and borderline personality disorder (BPD) in clinical samples, focusing on clinical/research/preventive paradigms and proposing informed research recommendations. Methods: We conducted a PRISMA-ScR/JBI-compliant scoping review (protocol: https://osf.io/8mz7a) of primary research studies (cross-sectional/longitudinal designs) using valid measures/criteria to assess CHR-P and BPD (threshold/subthreshold) in clinical samples, reporting on CHR-P/psychotic symptoms and personality disorder(s) in the title/abstract/keywords, identified in Web of Science/PubMed/(EBSCO)PsycINFO until 23/08/2023. Results: 33 studies were included and categorized into four themes reflecting their respective clinical/research/preventive paradigm: (i) BPD as a comorbidity in CHR-P youth (k = 20), emphasizing early detection and intervention in psychosis; (ii) attenuated psychosis syndrome (APS) as a comorbidity among BPD inpatients (k = 2), with a focus on hospitalized adolescents/young adults admitted for non-psychotic mental disorders; (iii) mixed samples (k = 7), including descriptions of early intervention services and referral pathways; (iv) transdiagnostic approaches (k = 4) highlighting "clinical high at risk mental state" (CHARMS) criteria to identify a pluripotent risk state for severe mental disorders. Conclusion: The scoping review reveals diverse approaches to clinical care for CHR-P and BPD, with no unified treatment strategies. Recommendations for future research should focus on: (i) exploring referral pathways across early intervention clinics to promote timely intervention; (ii) enhancing early detection strategies in innovative settings such as emergency departments; (iii) improving mental health literacy to facilitate help-seeking behaviors; (iv) analysing comorbid disorders as complex systems to better understand and target early psychopathology; (v) investigating prospective risk for BPD; (vi) developing transdiagnostic interventions; (vii) engaging youth with lived experience of comorbidity to gain insight on their subjective experience; (viii) understanding caregiver burden to craft family-focused interventions; (ix) expanding research in underrepresented regions such as Africa and Asia, and; (x) evaluating the cost-effectiveness of early interventions to determine scalability across different countries. Systematic Review Registration: https://osf.io/8mz7a.

The influence of complex psychiatric comorbidities on treatment for clinical high-risk for psychosis: A preliminary study.

AIM: Despite increasingly refined tools for identifying individuals at clinical high-risk for psychosis (CHR-P), less is known about the effectiveness of CHR-P interventions. The significant clinical heterogeneity among CHR-P individuals suggests that interventions may need to be personalized during this emerging illness phase. We examined longitudinal trajectories within-persons during treatment to investigate whether baseline factors predict symptomatic and functional outcomes. METHOD: A total of 36 CHR-P individuals were rated on attenuated positive symptoms and functioning at baseline and each week during CHR-P step-based treatment. RESULTS: Linear mixed-effects models revealed that attenuated positive symptoms decreased during the study period, while functioning did not significantly change. When examining baseline predictors, a significant group-by-time interaction emerged whereby CHR-P individuals with more psychiatric comorbidities at baseline (indicating greater clinical complexity) improved in functioning during the study period relative to CHR-P individuals with fewer comorbidities. CONCLUSION: Individual differences in clinical complexity may predict functional response during the early phases of CHR-P treatment.

Neural dysfunction underlying working memory processing at different stages of the illness course in schizophrenia: a comparative meta-analysis.

Schizophrenia, as a chronic and persistent disorder, exhibits working memory deficits across various stages of the disorder, yet the neural mechanisms underlying these deficits remain elusive with inconsistent neuroimaging findings. We aimed to compare the brain functional changes of working memory in patients at different stages: clinical high risk, first-episode psychosis, and long-term schizophrenia, using meta-analyses of functional magnetic resonance imaging studies. Following a systematic literature search, 56 whole-brain task-based functional magnetic resonance imaging studies (15 for clinical high risk, 16 for first-episode psychosis, and 25 for long-term schizophrenia) were included. The separate and pooled neurofunctional mechanisms among clinical high risk, first-episode psychosis, and long-term schizophrenia were generated by Seed-based d Mapping toolbox. The clinical high risk and first-episode psychosis groups exhibited overlapping hypoactivation in the right inferior parietal lobule, right middle frontal gyrus, and left superior parietal lobule, indicating key lesion sites in the early phase of schizophrenia. Individuals with first-episode psychosis showed lower activation in left inferior parietal lobule than those with long-term schizophrenia, reflecting a possible recovery process or more neural inefficiency. We concluded that SCZ represent as a continuum in the early stage of illness progression, while the neural bases are inversely changed with the development of illness course to long-term course.