Outcome In First-episode Psychosis Research Articles

Psychosis Prognosis Predictor: A continuous and uncertainty-aware prediction of treatment outcome in first-episode psychosis.

Machine learning models have shown promising potential in individual-level outcome prediction for patients with psychosis, but also have several limitations. To address some of these limitations, we present a model that predicts multiple outcomes, based on longitudinal patient data, while integrating prediction uncertainty to facilitate more reliable clinical decision-making. We devised a recurrent neural network architecture incorporating long short-term memory (LSTM) units to facilitate outcome prediction by leveraging multimodal baseline variables and clinical data collected at multiple time points. To account for model uncertainty, we employed a novel fuzzy logic approach to integrate the level of uncertainty into individual predictions. We predicted antipsychotic treatment outcomes in 446 first-episode psychosis patients in the OPTiMiSE study, for six different clinical scenarios. The treatment outcome measures assessed at both week 4 and week 10 encompassed symptomatic remission, clinical global remission, and functional remission. Using only baseline predictors to predict different outcomes at week 4, leave-one-site-out validation AUC ranged from 0.62 to 0.66; performance improved when clinical data from week 1 was added (AUC = 0.66-0.71). For outcome at week 10, using only baseline variables, the models achieved AUC = 0.56-0.64; using data from more time points (weeks 1, 4, and 6) improved the performance to AUC = 0.72-0.74. After incorporating prediction uncertainties and stratifying the model decisions based on model confidence, we could achieve accuracies above 0.8 for ~50% of patients in five out of the six clinical scenarios. We constructed prediction models utilizing a recurrent neural network architecture tailored to clinical scenarios derived from a time series dataset. One crucial aspect we incorporated was the consideration of uncertainty in individual predictions, which enhances the reliability of decision-making based on the model's output. We provided evidence showcasing the significance of leveraging time series data for achieving more accurate treatment outcome prediction in the field of psychiatry.

Amphetamine-Induced Dopamine Release Predicts 1-Year Outcome in First-Episode Psychosis: A Naturalistic Observation

Abstract Background and Hypothesis The dopamine theory of schizophrenia suggests that antipsychotics alleviate symptoms by blocking dopamine D2/3 receptors, yet a significant subset of patients does not respond adequately to treatment. To investigate potential predictors, we evaluated d-amphetamine-induced dopamine release and 1-year clinical outcomes in 21 antipsychotic-naive patients with first-episode schizophrenia. Study Design Twenty-one antipsychotic-naive patients (6 female) underwent dopamine D2/3 receptor radioligand [11C]-(+)-PHNO positron emission tomography. For estimating dopamine release, scans were performed with and without d-amphetamine pretreatment. The Positive and Negative Syndrome Scale was performed at regular intervals over 1 year while receiving treatment in a naturalistic setting (Clinical Trial Registry: EUDRACT 2010-019586-29). Study Results A group analysis revealed no significant differences in d-amphetamine-induced dopamine release between patients with or without clinically significant improvement. However, d-amphetamine-induced dopamine release in ventral striatum was significantly associated with reductions in positive symptoms (r = 0.54, P = .04; uncorrected P-values); release in globus pallidus correlated with a decrease in PANSS negative (r = 0.58, P = .02), general (r = 0.53, P = .04), and total symptom scores (r = 0.063, P = .01). Higher dopamine release in substantia nigra/ventral tegmental area predicted larger reductions in general symptoms (r = 0.51, P = .05). Post-amphetamine binding in putamen correlated positively with negative symptom scores at baseline (r = 0.66, P = .005) and throughout all follow-up visits. Conclusions These exploratory results support a relationship between d-amphetamine-induced dopamine release and the severity and persistence of symptoms during the first year of psychosis.

Clinical and cognitive outcomes in first-episode psychosis: focus on the interplay between cannabis use and genetic variability in endocannabinoid receptors.

Research data show the impact of the endocannabinoid system on psychosis through its neurotransmission homeostatic functions. However, the effect of the endocannabinoid system genetic variability on the relationship between cannabis use and psychosis has been unexplored, even less in first-episode patients. Here, through a case-only design, we investigated the effect of cannabis use and the genetic variability of endocannabinoid receptors on clinical and cognitive outcomes in first-episode psychosis (FEP) patients. The sample comprised 50 FEP patients of European ancestry (mean age (sd) = 26.14 (6.55) years, 76% males), classified as cannabis users (58%) or cannabis non-users. Two Single Nucleotide Polymorphisms (SNP) were genotyped at the cannabinoid receptor type 1 gene (CNR1 rs1049353) and cannabinoid receptor type 2 gene (CNR2 rs2501431). Clinical (PANSS, GAF) and neuropsychological (WAIS, WMS, BADS) assessments were conducted. By means of linear regression models, we tested the main effect of cannabis use and its interaction with the polymorphic variants on the clinical and cognitive outcomes. First, as regards cannabis effects, our data showed a trend towards more severe positive symptoms (PANSS, p = 0.05) and better performance in manipulative abilities (matrix test-WAIS, p = 0.041) among cannabis users compared to non-users. Second, concerning the genotypic effects, the T allele carriers of the CNR1 rs1049353 presented higher PANSS disorganization scores than CC homozygotes (p = 0.014). Third, we detected that the observed association between cannabis and manipulative abilities is modified by the CNR2 polymorphism (p = 0.022): cannabis users carrying the G allele displayed better manipulative abilities than AA genotype carriers, while the cannabis non-users presented the opposite genotype-performance pattern. Such gene-environment interaction significantly improved the overall fit of the cannabis-only model (Δ-R2 = 8.4%, p = 0.019). Despite the preliminary nature of the sample, our findings point towards the role of genetic variants at CNR1 and CNR2 genes in the severity of the disorganized symptoms of first-episode psychosis and modulating cognitive performance conditional to cannabis use. This highlights the need for further characterization of the combined role of endocannabinoid system genetic variability and cannabis use in the understanding of the pathophysiology of psychosis.

Childhood trauma and treatment resistance in first-episode psychosis: Investigating the role of premorbid adjustment and duration of untreated psychosis

BackgroundEarly identification of treatment non-response in first-episode psychosis (FEP) is essential to outcome. Despite indications that exposure to childhood trauma (CT) can have adverse effects on illness severity, its impact on treatment non-response and the interplay with other pre-treatment characteristics is sparsely investigated. We use a lack of clinical recovery as an early indicator of treatment resistance to investigate the relationship between CT and treatment resistance status at one-year follow-up and the potential mediation of this effect by other pre-treatment characteristics. MethodsThis prospective one-year follow-up study involved 141 participants recruited in their first year of treatment for a schizophrenia-spectrum disorder. We investigated clinical status, childhood trauma (CT), premorbid adjustment (PA), and duration of untreated psychosis (DUP) at baseline and clinical status at one-year follow-up. Ordinal regression analyses were conducted to investigate how PA and DUP affected the relationship between CT and one-year outcome in FEP. Results45 % of the FEP sample reported moderate to severe CT, with significantly higher levels of CT in the early treatment resistant group compared to participants with full or partial early recovery. Ordinal regression analysis showed that CT was a significant predictor of being in a more severe outcome group (OR = 4.59). There was a partial mediation effect of PA and a full mediation effect of DUP on the effect of CT on outcome group membership. DiscussionOur findings indicate that reducing treatment delays may mitigate the adverse effects of CT on clinical outcomes and support the inclusion of broad trauma assessment in FEP services.

Institutional pathways to psychosis for Indigenous Māori: A qualitative exploration of experiences

BackgroundInequities in the incidence and outcomes of first episode psychosis (FEP) for Indigenous peoples are impacted by multiple institutional systems. This study examines Indigenous experiences of these systems to gain an understanding of how to improve institutional responses to FEP inequity. MethodsCritical race theory informed the methods used. Twenty-three participants participated in four focus group interviews, and thirteen individual interviews, including nine Māori youth and young adults with FEP, ten family members, and four Māori health professionals. Participants were asked about lifetime experiences of institutions (health, social, and criminal-justice). An adapted WHO framework for addressing mental health inequities was used to organize and analyse the first round of structural coding, followed by descriptive and pattern coding. ResultsTwo themes were identified. The first theme signposted opportunities for institutional intervention. Participants critique being processed quickly through institutions that are driven by socio-political agendas, namely perceived risk, threat or crisis. Subsequently, opportunities for meaningful intervention were missed. The second theme identified scope for family orientated responses across sectors. Participants described short-term social interventions and institutional structures that focused on individuals rather than families, emphasizing the need to broaden cross-sector scope to structural interventions for families. DiscussionThe findings highlight institutional responses are focused on organisational drivers and downstream issues, that fail to address the fabric of the family social-environmental conditions that maintain Indigenous exposure to psychosis risk and poor outcomes. A pathway to equity would require a shared framework of social responsibility across sectors, that targets structural factors responsive to Indigenous family needs.

Predicting the Outcome of First Episode Psychosis Subjects by Assessing Dorsolateral Prefrontal Cortex Volume

Aim: Dorsolateral prefrontal cortex (DLPFC), Neurological Soft Signs (NSS) and Cognitive impairment have been described as predictors of outcome of First Episode Psychosis (FEP), therefore we aimed to find the predictors of clinical, social and functional outcome variables in a cohort of first episode non affective psychotic subjects. Subjects and Methods: A prospective follow up study was conducted from August 2018 to August 2020 in a tertiary care hospital of South India. A semi-structured questionnaire was given to all subjects for socio-demographic details. All subjects were assessed with Heidelberg scale, Bender Gestalt Test (BGT) and underwent MRI Brain 3D volumetric scan to examine NSS, cognitive impairment, and DLPFC volume at baseline respectively. Brief Psychiatric Rating Scale (BPRS) and Social and Occupational Functioning Assessment Scale scales (SOFAS) were administered at baseline, 1 month and at three month follow up. At 3 months, clinical and socio-functional outcome was defined by BPRS scores and SOFAS scores. Pearson’s correlation was found between DLPFC volume of all subjects, BPRS, BGT scores at baseline with BPRS and SOFAS at 3 months. To test the statistical significance of the comparison of mean values of all continuous clinical and demographic parameters between two groups of BPRS and SOFAS, Mann Whitney U test was used. Results: Smaller DLPFC volume predicted clinical, socio-functional outcome significantly. A significant moderate correlation was found between NSS and BPRS scores at baseline. Conclusion: Baseline right DLPFC volume can be an important predictor of clinical and socio-functional outcome in FEP.

Duration of Untreated Psychosis and Outcomes in First-Episode Psychosis: Systematic Review and Meta-analysis of Early Detection and Intervention Strategies.

The role of duration of untreated psychosis (DUP) as an early detection and intervention target to improve outcomes for individuals with first-episode psychosis is unknown. PRISMA/MOOSE-compliant systematic review to identify studies until February 1, 2023, with an intervention and a control group, reporting DUP in both groups. Random effects meta-analysis to evaluate (1) differences in DUP in early detection/intervention services vs the control group, (2) the efficacy of early detection strategies regarding eight real-world outcomes at baseline (service entry), and (3) the efficacy of early intervention strategies on ten real-world outcomes at follow-up. We conducted quality assessment, heterogeneity, publication bias, and meta-regression analyses (PROSPERO: CRD42020163640). From 6229 citations, 33 intervention studies were retrieved. The intervention group achieved a small DUP reduction (Hedges' g = 0.168, 95% CI = 0.055-0.283) vs the control group. The early detection group had better functioning levels (g = 0.281, 95% CI = 0.073-0.488) at baseline. Both groups did not differ regarding total psychopathology, admission rates, quality of life, positive/negative/depressive symptoms, and employment rates (P > .05). Early interventions improved quality of life (g = 0.600, 95% CI = 0.408-0.791), employment rates (g = 0.427, 95% CI = 0.135-0.718), negative symptoms (g = 0.417, 95% CI = 0.153-0.682), relapse rates (g = 0.364, 95% CI = 0.117-0.612), admissions rates (g = 0.335, 95% CI = 0.198-0.468), total psychopathology (g = 0.298, 95% CI = 0.014-0.582), depressive symptoms (g = 0.268, 95% CI = 0.008-0.528), and functioning (g = 0.180, 95% CI = 0.065-0.295) at follow-up but not positive symptoms or remission (P > .05). Comparing interventions targeting DUP and control groups, the impact of early detection strategies on DUP and other correlates is limited. However, the impact of early intervention was significant regarding relevant outcomes, underscoring the importance of supporting early intervention services worldwide.

Examining the Effectiveness of a Digital Media Campaign at Reducing the Duration of Untreated Psychosis in New York State: Results From a Stepped-wedge Randomized Controlled Trial.

Longer duration of untreated psychosis (DUP) predicts worse outcomes in First Episode Psychosis (FEP). Searching online represents one of the first proactive step toward treatment initiation for many, yet few studies have informed how best to support FEP youth as they engage in early online help-seeking steps to care. Using a stepped-wedge randomized design, this project evaluated the effectiveness of a digital marketing campaign at reducing DUP and raising rates of referrals to FEP services by proactively targeting and engaging prospective patients and their adult allies online. Throughout the 18-month campaign, 41 372 individuals visited our website, and 371 advanced to remote clinical assessment (median age = 24.4), including 53 allies and 318 youth. Among those assessed (n = 371), 53 individuals (14.3%) reported symptoms consistent with psychotic spectrum disorders (62.2% female, mean age 20.7 years) including 39 (10.5%) reporting symptoms consistent with either Clinical High Risk (ie, attenuated psychotic symptoms; n = 26) or FEP (n = 13). Among those with either suspected CHR or FEP (n = 39), 20 (51.3%) successfully connected with care. The campaign did not result in significant differences in DUP. This study highlights the potential to leverage digital media to help identify and engage youth with early psychosis online. However, despite its potential, online education and professional support alone are not yet sufficient to expedite treatment initiation and reduce DUP.

A good life with psychosis: rate of positive outcomes in first-episode psychosis at 10-year follow-up.

More knowledge about positive outcomes for people with first-episode psychosis (FEP) is needed. An FEP 10-year follow-up study investigated the rate of personal recovery, emotional wellbeing, and clinical recovery in the total sample and between psychotic bipolar spectrum disorders (BD) and schizophrenia spectrum disorders (SZ); and how these positive outcomes overlap. FEP participants (n = 128) were re-assessed with structured clinical interviews at 10-year follow-up. Personal recovery was self-rated with the Questionnaire about the Process of Recovery-15-item scale (total score ⩾45). Emotional wellbeing was self-rated with the Life Satisfaction Scale (score ⩾5) and the Temporal Experience of Pleasure Scale (total score ⩾72). Clinical recovery was clinician-rated symptom-remission and adequate functioning (duration minimum 1 year). In FEP, rates of personal recovery (50.8%), life satisfaction (60.9%), and pleasure (57.5%) were higher than clinical recovery (33.6%). Despite lower rates of clinical recovery in SZ compared to BD, they had equal rates of personal recovery and emotional wellbeing. Personal recovery overlapped more with emotional wellbeing than with clinical recovery (χ2). Each participant was assigned to one of eight possible outcome groups depending on the combination of positive outcomes fulfilled. The eight groups collapsed into three equal-sized main outcome groups: 33.6% clinical recovery with personal recovery and/or emotional wellbeing; 34.4% personal recovery and/or emotional wellbeing only; and 32.0% none. In FEP, 68% had minimum one positive outcome after 10 years, suggesting a good life with psychosis. This knowledge must be shared to instill hope and underlines that subjective and objective positive outcomes must be assessed and targeted in treatment.

Sex, gender, and outcome in first-episode psychosis: The role of premorbid functioning

We examined the associations of sex (biological distinction) and gender (societal distinction) with psychopathology, depressive symptoms and social and occupational functioning over 24 months. We found that lower masculinity scores were associated with worse psychopathology outcomes, independent of sex and other neurodevelopmental factors. These effects were mediated by poor premorbid adjustment, which also mediated the relationship between childhood trauma and masculinity scores as predictors of disorganized symptom outcomes. Our findings highlight the importance of considering gender as a separate construct and the need for further research to understand the clinical implications of sex and gender differences in schizophrenia.

Cognitive subgroups and the relationships with symptoms, psychosocial functioning and quality of life in first-episode non-affective psychosis: a cluster-analysis approach.

Prior research examining cognitive heterogeneity in psychotic disorders primarily focused on chronic schizophrenia, with limited data on first-episode psychosis (FEP). We aimed to identify distinct cognitive subgroups in adult FEP patients using data-driven cluster-analytic approach, and examine relationships between cognitive subgroups and a comprehensive array of illness-related variables. Two-hundred-eighty-nine Chinese patients aged 26-55 years presenting with FEP to an early intervention program in Hong Kong were recruited. Assessments encompassing premorbid adjustment, illness-onset profile, symptom severity, psychosocial functioning, subjective quality-of-life, and a battery of cognitive tests were conducted. Hierarchical cluster-analysis was employed, optimized with k-means clustering and internally-validated by discriminant-functional analysis. Cognitive subgroup comparisons in illness-related variables, followed by multivariable multinominal-regression analyzes were performed to identify factors independently predictive of cluster membership. Three clusters were identified including patients with globally-impaired (n = 101, 34.9%), intermediately-impaired (n = 112, 38.8%) and relatively-intact (n = 76, 26.3%) cognition (GIC, IIC and RIC subgroups) compared to demographically-matched healthy-controls' performance (n = 50). GIC-subgroup was older, had lower educational attainment, greater positive, negative and disorganization symptom severity, poorer insight and quality-of-life than IIC- and RIC-subgroups, and higher antipsychotic-dose than RIC-subgroup. IIC-subgroup had lower education levels and more severe negative symptoms than RIC-subgroup, which had better psychosocial functioning than two cognitively-impaired subgroups. Educational attainment and disorganization symptoms were found to independently predict cluster membership. Our results affirmed cognitive heterogeneity in FEP and identified three subgroups, which were differentially associated with demographic and illness-related variables. Further research should clarify longitudinal relationships of cognitive subgroups with clinical and functional outcomes in FEP.

Prevalence and Outcomes of First-Episode Psychosis With Substance Misuse Within an Outpatient Setting

AimsMisuse of certain drugs is a common precipitant of first-episode psychosis (FEP). Substance misuse is known to exacerbate psychotic symptoms, and it is unclear if substance misuse at the time of initial presentation impacts outcomes of care in FEP. Here, in this quality improvement project (QIP), we aimed to quantify the prevalence of drug misuse within an outpatient early intervention service (EIS) and determine the outcomes (in terms of time-to-discharge and discharge destination) of service users based on their substance misuse history.MethodsIn this QIP, we randomly sampled 100 patients referred to and discharged from an outpatient service for psychosis (Barnet EIS). We excluded patients who were referred to the service but were discharged due to referral rejection, non-attendance at psychiatry review and/or other reasons. Data regarding demographic and clinical information, the nature of substance misuse, and discharge destinations were obtained through a review of electronic health records, including GP letters and hospital notes. The time-to-discharge was defined as the time between referral acceptance and discharge from EIS. As this work is part of a QIP, written consent was not obtained to conduct this project.ResultsOf 100 patients obtained from the discharged caseload, 38 patients were accepted and reviewed in Barnet EIS. 24 patients (63.2%) had no substance misuse history at the time of initial FEP, while 14 patients (36.8%) had some substance misuse history. Of the 14 patients with substance misuse, cannabis was most frequently used. The average age of patients was 27.2 ± 1.4 years old. The age of onset of psychosis was similar between patients with and without substance misuse (two-sample t-test, p = 0.74).In terms of discharge destination, patients with and without substance misuse were discharged back to their GPs at similar proportions (chi-square test, p = 0.81). Finally, the number of days patients spent under the care of Barnet EIS was similar between patients with and without substance misuse (two-sample t-test, p = 0.54).ConclusionIn this QIP, over 30% of patients presenting with FEP reported substance misuse. The most common recreational drug used was cannabis. Discharge destinations and the time spent in EIS were broadly similar between patients with and without substance misuse. The relatively high rates of substance misuse in FEP found in this study have important implications for commissioning additional services – such as urine drug testing or drug liaison services – within EIS teams.

Context and Expectations Matter: Social, Recreational, and Independent Functioning among Youth with Psychosis in Chennai, India and Montreal, Canada.

Most cross-cultural psychosis research has focused on a limited number of outcomes (generally symptom-related) and perspectives (often clinician-/observer-rated). It is unknown if the purported superior outcomes for psychosis in some low- and middle-income countries extend to patient-reported measures of social, recreational, and independent functioning. Addressing this gap, this study aimed to compare these outcomes in first-episode psychosis at a high-income site and a lower middle-income site. Patients receiving similarly designed early intervention for psychosis in Chennai, India (N = 164) and Montreal, Canada (N = 140) completed the self-reported Social Functioning Scale-Early Intervention, which measures prosocial, recreation, and independence-performance functioning. Their case managers rated expected independence-performance functioning. Both sets of assessments were done at entry and Months 6, 18, and 24. Linear mixed model analyses of differences between sites and over time were conducted, accounting for other pertinent variables, especially negative symptoms. Linear mixed models showed that prosocial, recreation, and independence-performance functioning scores were significantly higher in Montreal than Chennai and did not change over time. Expected independence-performance was also higher in Montreal and increased over time. Negative symptoms and education independently predicted prosocial, recreation, and expected independence-performance functioning. When added to the model, expected independence-performance predicted actual independence-performance and site was no longer significant. At both sites, prosocial and recreation scores were consistently lower (<40%) than independence-performance (40-65%). This is the first cross-cultural investigation of prosocial, recreation, and independent functioning in early psychosis. It demonstrates that these outcomes differ by socio-cultural context. Differing levels of expectations about patients, themselves shaped by cultural, illness, and social determinants, may contribute to cross-cultural variations in functional outcomes. At both sites, social, recreational, and independent functioning were in the low-to-moderate range and there was no improvement over time, underscoring the need for effective interventions specifically designed to impact these outcomes.

Outcome of First Episode Psychosis in Bangladesh-Report from A Pioneer Tertiary Referral Service

Limited research exists looking at outcome data in First Episode Psychosis in low income countries. This prospective analytical study looks at remission rates in psychotic symptoms on Positive and Negative Symptom Score (PANSS) following first contact with a pioneer Early Intervention Service based at a tertiary referral center in Dhaka, Bangladesh (DEIS). The study found that the remission rate at 6 months was 62% on PANSS. The study also found that a shorter Duration of Untreated Psychosis (DUP) was positively correlated with improved remission rates at 3- and 6-months follow-up. As a secondary finding, the study established that 62% of individuals attending the service had attempted to access spiritual or traditional healers prior to entering into mental health services

Vitamin D and cardiometabolic outcomes in first episode psychosis (FEP): A prospective cohort study

In schizophrenia and schizoaffective disorder cognitive deficits are a reliable characteristic predicting a poor functional outcome. It has been theorized that both the default mode network (DMN) and the salience network (SN) play a crucial role in cognitive processes and aberrant functional connectivity within these networks in psychotic patients has been reported. The goal of this study was to reveal potential links between aberrant functional connectivity within these networks and impaired cognitive performance in psychosis.We chose two approaches for cognitive assessment, first the MATRICS Consensus Cognitive Battery (MCCB) combined into a global score and second the disorganization factor derived from a five-factor model of the Positive and Negative Syndrome Scale (PANSS) known to be relevant for cognitive performance. DMN and SN were identified using independent component analysis on resting-state functional magnetic resonance imaging data.We found significantly decreased connectivity within the right supplementary motor area (SMA) and bilateral putamen in patients with psychosis (n = 70; 27F/43M) compared to healthy controls (n = 72; 28F/44M). Within patients, linear regression analysis revealed that aberrant SMA connectivity was associated with impaired global cognition, while dysfunctional bilateral putamen connectivity predicted disorganization. There were no significant changes in connectivity within the DMN.Results support the hypothesis that SN dysfunctional connectivity is important in the pathobiology of cognitive deficits in psychosis. For the first time we were able to show the involvement of dysfunctional SMA connectivity in this context. We interpret the decreased SN connectivity as evidence of reduced functionality in recruiting brain areas necessary for cognitive processing.

Impact of early use of long-acting injectable antipsychotics on functional outcome in first episode psychosis: a 3-year longitudinal study

Objectives To describe, in a naturalistic setting, the impact of the early use of LAI-AP on functional outcomes of early psychosis patients as compared to oral antipsychotics (OAP). Methods Longitudinal prospective 3-year naturalistic study of all consecutive admissions (n = 416) to two Early intervention services (EIS) for psychosis comparing baseline characteristics and the evolution of global functioning, occupation (work and studies), and living arrangements autonomy according to the route of administration of the antipsychotic medication. The cohort was divided into four groups: LAI-AP first (started on LAI-AP and later received OAP), OAP first, LAI-AP only, and OAP only. Results Global assessment of functioning (GAF) improved in all groups, but our mixed-effect model did not show any significant association between the route of administration and the GAF outcome. The LAI-AP only group was significantly less likely to have extreme residential instability at 3 years than the other groups despite its highest proportion of homeless youth and their poor prognostic factors at baseline. Conclusions Our naturalistic study suggests a significant protective effect of LAI-AP on extreme residential instability for the most vulnerable patients, but no impact of the first AP administration route on other functional outcomes was observed at 3 years of follow-up. Key points Long-acting injectable antipsychotics seem promising to avoid extreme residential instability in early psychosis. Global assessment of functioning (GAF) improved in all groups. There was no significant association between the first route of administration and global functionning.

Characterizing Use of a Multicomponent Digital Intervention to Predict Treatment Outcomes in First-Episode Psychosis: Cluster Analysis.

BackgroundMulticomponent digital interventions offer the potential for tailored and flexible interventions that aim to address high attrition rates and increase engagement, an area of concern in digital mental health. However, increased flexibility in use makes it difficult to determine which components lead to improved treatment outcomes.ObjectiveThis study aims to identify user profiles on Horyzons, an 18-month digital relapse prevention intervention for first-episode psychosis that incorporates therapeutic content and social networking, along with clinical, vocational, and peer support, and to examine the predictive value of these user profiles for treatment outcomes. A secondary objective is to compare each user profile with young people receiving treatment as usual (TAU).MethodsParticipants comprised 82 young people (aged 16-27 years) with access to Horyzons and 84 receiving TAU, recovering from first-episode psychosis. In addition, 6-month use data from the therapy and social networking components of Horyzons were used as features for K-means clustering for joint trajectories to identify user profiles. Social functioning, psychotic symptoms, depression, and anxiety were assessed at baseline and 6-month follow-up. General linear mixed models were used to examine the predictive value of user profiles for treatment outcomes and between each user profile with TAU.ResultsA total of 3 user profiles were identified based on the following system use metrics: low use, maintained use of social components, and maintained use of both therapy and social components. The maintained therapy and social group showed improvements in social functioning (F2,51=3.58; P=.04), negative symptoms (F2,51=4.45; P=.02), and overall psychiatric symptom severity (F2,50=3.23; P=.048) compared with the other user profiles. This group also showed improvements in social functioning (F1,62=4.68; P=.03), negative symptoms (F1,62=14.61; P<.001), and overall psychiatric symptom severity (F1,63=5.66; P=.02) compared with the TAU group. Conversely, the maintained social group showed increases in anxiety compared with the TAU group (F1,57=7.65; P=.008). No differences were found between the low use group and the TAU group on treatment outcomes.ConclusionsContinued engagement with both therapy and social components might be key in achieving long-term recovery. Maintained social use and low use outcomes were broadly comparable with TAU, emphasizing the importance of maintaining engagement for improved treatment outcomes. Although the social network may be a key ingredient to increase sustained engagement, as users engaged with this more consistently, it should be leveraged as a tool to engage young people with therapeutic content to bring about social and clinical benefits.

Central Oxidative Stress and Early Vocational Outcomes in First Episode Psychosis: A 7-Tesla Magnetic Resonance Spectroscopy Study of Glutathione.

Following the first episode of psychosis, some patients develop poor social and occupational outcomes, while others display a pattern of preserved functioning. Evidence from preclinical, genetic, and biochemical studies suggest a role for high oxidative stress in poor functional outcomes among patients. The measurement of intracortical glutathione (GSH) using magnetic resonance spectroscopy (MRS) enables investigating the relationship between central antioxidant tone and functional outcomes at the time of first-episode psychosis (FEP). We hypothesized that patients with higher central antioxidant tone at first presentation will have better functional outcomes in early stages of illness. We scanned 57 patients with FEP and 30 matched healthy controls and estimated GSH resonance using 7-Tesla MRS. We minimized the confounding effects of illness chronicity, long-term treatment exposure, and metabolic complications by recruiting patients with <2 weeks of lifetime antipsychotic exposure on average and followed up this cohort for the next 1 year to determine functional outcomes. Patients who achieved employment/education or training status (EET) in the first year, had higher GSH at the baseline than healthy controls. Social and occupational functioning assessment scale (SOFAS) scores were also significantly higher in patients with higher GSH levels at the outset, after adjusting for various confounds including baseline SOFAS. Patients who were not in EET did not differ from healthy subjects in their GSH levels. Our observations support a key role for the central antioxidant tone in the functional outcomes of early psychosis.

Letter to the editor about ‘Context and outcome of first-episode psychosis in India and Canada’

Letter to the editor about ‘Context and outcome of first-episode psychosis in India and Canada’

Prediction models in first-episode psychosis: systematic review and critical appraisal.

People presenting with first-episode psychosis (FEP) have heterogenous outcomes. More than 40% fail to achieve symptomatic remission. Accurate prediction of individual outcome in FEP could facilitate early intervention to change the clinical trajectory and improve prognosis. We aim to systematically review evidence for prediction models developed for predicting poor outcome in FEP. A protocol for this study was published on the International Prospective Register of Systematic Reviews, registration number CRD42019156897. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance, we systematically searched six databases from inception to 28 January 2021. We used the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies and the Prediction Model Risk of Bias Assessment Tool to extract and appraise the outcome prediction models. We considered study characteristics, methodology and model performance. Thirteen studies reporting 31 prediction models across a range of clinical outcomes met criteria for inclusion. Eleven studies used logistic regression with clinical and sociodemographic predictor variables. Just two studies were found to be at low risk of bias. Methodological limitations identified included a lack of appropriate validation, small sample sizes, poor handling of missing data and inadequate reporting of calibration and discrimination measures. To date, no model has been applied to clinical practice. Future prediction studies in psychosis should prioritise methodological rigour and external validation in larger samples. The potential for prediction modelling in FEP is yet to be realised.