An intersectional perspective on the sociodemographic and clinical factors influencing the status of not in Education, Employment, or training (NEET) in patients with first-episode psychosis (FEP).

PURPOSE: High rates of Not in Education, Employment or Training (NEET) are seen in people with first episode of psychosis (FEP). Sociodemographic and clinical factors were reported to be associated with NEET status in FEP patients. This study follows Intersectionality to examine the independent and additive effects, and most importantly the intersections of sociodemographic and clinical variables concerning NEET status in FEP patients. It was hypothesized that NEET status in FEP patients would be described by the intersection between at least two predictor variables. METHODS: Secondary analyses with chi-square tests, multiple logistic regression and Chi-squared Automatic Interaction Detection (CHAID) analyses were performed on 440 participants with FEP. RESULTS: Chi-square tests indicated that patient socioeconomic status and negative symptom severity were significantly and independently associated with their NEET status. Multiple logistic regression suggested additive effects of age (odds ratio = 1.61), patient socioeconomic status (odds ratio = 1.55) and negative symptom severity (odds ratio = 1.75) in predicting patients' NEET status. CHAID detected an intersection between patients' negative symptom severity and socioeconomic status in shaping their NEET status. CONCLUSION: This study explored how the NEET status of patients with FEP was explained not only by the separate effects of negative symptom severity and socioeconomic status but also by the unique intersections of their clinical and social identities. Findings indicated that functional outcomes of patients appear co-constructed by the intersections of multiple identities. Crucial clinical implications of complementing care for negative symptom severity with vocational resources to improve functional outcomes of patients are discussed.

Consistency of Delusion Themes Across First and Subsequent Episodes of Psychosis.

Importance: Despite growing interest in the phenomenology of delusions in psychosis, at present little is known about their content and evolution over time, including whether delusion themes are consistent across episodes. Objective: To examine the course of delusions and thematic delusion content across relapse episodes in patients presenting to an early intervention service for psychosis. Design, Setting, and Participants: This longitudinal, observational study used clinical data systematically collected from January 2003 to March 2018 from a cohort of consenting patients with affective or nonaffective first-episode psychosis, followed up naturalistically for up to 2 years in an early intervention service for psychosis in Montréal, Quebec, Canada. Data included the thematic content and severity of delusions (scores ≥3 using the Scale for the Assessment of Positive Symptoms) and associated psychotic and nonpsychotic symptoms, both across an initial episode and, in the event of remission, a potential relapse. Data were analyzed from September 2021 to February 2023. Exposure: An early intervention service for psychosis, organized around intensive case management and a multidisciplinary team approach, which observed each patient for up to 2 years of care. Main Outcomes and Measures: The primary outcome was positive symptom relapse and remission, including the presence and content of delusions, which was coded per the Scale for the Assessment of Positive Symptoms and accepted definitions. The main statistical measures included repeated paired-sample t tests and binary logistic regression analyses. Results: Of 636 consenting patients, mean (SD) age was 23.8 (4.75) years; 191 patients were female, 444 were male, and 1 patient was nonbinary. Remission rates were high, and relapse rates were relatively low: 591 individuals had baseline delusions, of which 558 (94.4%) achieved remission. Of these 558 patients, only 182 (32.6%) had a subsequent relapse to a second or later episode of psychosis. Of the 182 patients who did relapse, however, a large proportion (115 [63.2%]) reported threshold-level delusions. Of these 115, 104 patients (90.4%) had thematic delusion content consistent with that reported during the index (first) episode. Those who relapsed with delusions had fewer delusion themes present during subsequent episodes of psychosis compared with the index episode and lower levels of other psychotic and nonpsychotic symptoms. Conclusions and Relevance: Specialized early intervention services for psychosis can achieve high rates of sustained remission. However, in this study, the minority of individuals with delusions who later relapsed experienced similar delusion themes during subsequent episodes. These findings raise important considerations for the conceptualization of delusions and have clinical implications for trajectories of illness and care.

Overlap between individual differences in cognition and symptoms of schizophrenia.

BACKGROUND: Neurocognitive impairment is a core feature of schizophrenia spectrum disorders (SSDs), and the relationship between cognition and symptoms in SSDs has been widely researched. Negative symptoms are related to a wide range of cognitive impairments; however, the aspects of negative symptoms that underpin this relationship have yet to be specified. STUDY DESIGN: We used iterative Constrained Principal Component Analysis (iCPCA) to explore the relationship between 18 cognitive measures (including processing speed, attention, working, spatial and verbal memory and executive functions) and 46 symptoms in schizophrenia at the individual item level while minimizing the risk of Type I errors. ICPCA was conducted on a sample of SSD patients in the early stages of psychiatric treatment (n = 121) to determine the components of cognition overlapping with symptoms measured by the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS). RESULTS: We found that a verbal memory component was associated with items from SANS and SAPS related to impoverished and disorganized emotional communication, language, and thought. In contrast, a working memory component was associated with SANS items related to motor system impoverishment. CONCLUSIONS: The iCPCA allowed us to explore the associations between individual items, optimized to understand the overlap between symptoms and cognition. The specific symptoms linked to verbal and working memory impairments imply distinct brain networks, which further investigation may lead to our deeper understanding of the illness and the development of treatment methods.

Patient- and family-reported experiences of their treating teams in early psychosis services in Chennai, India and Montreal, Canada.

BACKGROUND: Cross-cultural psychosis research has mostly focused on outcomes, rather than patient and family experiences. Therefore, our aim was to examine differences in patients' and families' experiences of their treating teams in early intervention services for psychosis in Chennai, India [low- and middle-income country] and Montreal, Canada [high-income country]. METHODS: Patients (165 in Chennai, 128 in Montreal) and their families (135 in Chennai, 110 in Montreal) completed Show me you care, a patient- and family-reported experience measure, after Months 3, 12, and 24 in treatment. The measure assesses the extent to which patients and families view treating teams as being supportive. A linear mixed model with longitudinal data from patient and family dyads was used to test the effect of site (Chennai, Montreal), stakeholder (patient, family), and time on Show me you care scores. This was followed by separate linear mixed effect models for patients and families with age and gender, as well as symptom severity and functioning as time-varying covariates. RESULTS: As hypothesized, Chennai patients and families reported more supportive behaviours from their treating teams (ß=4.04; ß= 9, respectively) than did Montreal patients (Intercept =49.6) and families (Intercept=42.45). Higher symptom severity over follow-up was associated with patients reporting lower supportive behaviours from treating teams. Higher levels of positive symptoms (but lower levels of negative symptoms) over follow-up were associated with families reporting lower supportive behaviours from treating teams. There was no effect of time, age, gender and functioning. CONCLUSIONS: The levels to which treating teams are perceived as supportive may reflect culturally shaped attitudes (e.g., warmer attitudes towards healthcare providers in India vis-à-vis Canada) and actual differences in how supportive treating teams are, which too may be culturally shaped. Being expected to be more involved in treatment, Chennai families may receive more attention and support, which may further reinforce their involvement. Across contexts, those who improve over follow-up may see their treating teams more positively.

Sociodemographic and clinical correlates of hallucinations in patients entering an early intervention program for first episode psychosis.

Hallucinations are a core feature of psychosis, and their severity during the acute phase of illness is associated with a range of poor outcomes. Various clinical and sociodemographic factors may predict hallucinations and other positive psychotic symptoms in first episode psychosis (FEP). Despite this, the precise factors associated with hallucinations at first presentation to an early intervention service have not been extensively researched. Through detailed interviews and chart reviews, we investigated sociodemographic and clinical predictors in 636 minimally-medicated patients who entered PEPP-Montréal, an early intervention service for FEP, between 2003 and 2018. Hallucinations were measured using the Scale for the Assessment of Positive Symptoms (SAPS), while negative symptoms were assessed using the Scale for the Assessment of Negative symptoms (SANS). Depressive symptoms were evaluated through the Calgary Depression Scale for Schizophrenia (CDSS), and anxiety symptoms via the Hamilton Rating Scale for Anxiety (HAS). A majority (n = 381, 59.9 %) of the sample presented with clinically significant hallucinations (SAPS global hallucinations score ≥ 3) at program entry. These patients had an earlier age at onset, fewer years of education, and a higher severity of delusions, depression and negative symptoms than those without clinical-level hallucinations. These results suggest that individuals with clinically significant hallucinations at admission tend to be younger and have a greater overall symptom burden. This makes it especially important to monitor hallucinations alongside delusions, depression and negative symptoms in order to identify who might benefit from targeted interventions. The implications of these findings for early intervention and person-centered care are discussed.

Longitudinal inference of multiscale markers in psychosis: from hippocampal centrality to functional outcome.

Multiscale neuroscience conceptualizes mental illness as arising from aberrant interactions across and within multiple biopsychosocial scales. We leverage this framework to propose a multiscale disease progression model of psychosis, in which hippocampal-cortical dysconnectivity precedes impairments in episodic memory and social cognition, which lead to more severe negative symptoms and lower functional outcome. As psychosis represents a heterogeneous collection of biological and behavioral alterations that evolve over time, we further predict this disease progression for a subtype of the patient sample, with other patients showing normal-range performance on all variables. We sampled data from two cross-sectional datasets of first- and multi-episode psychosis, resulting in a sample of 163 patients and 119 non-clinical controls. To address our proposed disease progression model and evaluate potential heterogeneity, we applied a machine-learning algorithm, SuStaIn, to the patient data. SuStaIn uniquely integrates clustering and disease progression modeling and identified three patient subtypes. Subtype 0 showed normal-range performance on all variables. In comparison, Subtype 1 showed lower episodic memory, social cognition, functional outcome, and higher negative symptoms, while Subtype 2 showed lower hippocampal-cortical connectivity and episodic memory. Subtype 1 deteriorated from episodic memory to social cognition, negative symptoms, functional outcome to bilateral hippocampal-cortical dysconnectivity, while Subtype 2 deteriorated from bilateral hippocampal-cortical dysconnectivity to episodic memory and social cognition, functional outcome to negative symptoms. This first application of SuStaIn in a multiscale psychiatric model provides distinct disease trajectories of hippocampal-cortical connectivity, which might underlie the heterogeneous behavioral manifestations of psychosis.

The effects of intranasal oxytocin on the efficacy of psychotherapy for major depressive disorder: a pilot randomized controlled trial.

BACKGROUND: Although both pharmacotherapy and psychological treatments are considered to be efficacious in the treatment of major depressive disorder (MDD), one third of patients do not respond to treatment and many experience residual symptoms post-treatment. In this double-blind placebo-controlled randomized control trial (RCT), we assessed whether intranasal oxytocin (OT) augments the therapeutic efficacy of psychotherapy for MDD and improves the therapeutic alliance. METHODS: Twenty-three volunteers (12 female) with MDD underwent 16 sessions of interpersonal therapy. Prior to each session, volunteers self-administered 24 International Units of intranasal OT (n = 12; Syntocinon) or placebo (n = 11). Depressive symptoms were assessed with the Inventory of Depressive Symptomatology at pre- and post-treatment, and at a six month follow-up. RESULTS: Multilevel modeling found a significant effect of OT on the negative slope of depressive symptoms over time (p < 0.05), with medium-large effect sizes at post-treatment (Cohen's d = 0.75) and follow-up (Cohen's d = 0.82). Drug intervention also predicted the intercept when examining the weekly ratings of the therapeutic alliance (p < 0.05), such that volunteers receiving OT, relative to placebo, reported improved therapeutic alliance at session 1. The agreement of goals between therapists and participants, a facet of the therapeutic alliance, mediated the relationship between drug intervention and clinical outcome. CONCLUSION: In this pilot study, the administration of intranasal OT, relative to placebo, improved the therapeutic alliance at the beginning of therapy and therapeutic efficacy of psychotherapy in persons with MDD. Future RCTs should attempt to replicate these findings in larger samples with different therapeutic modalities (ClinicalTrials.gov: NCT02405715).

Speech markers to predict and prevent recurrent episodes of psychosis: A narrative overview and emerging opportunities.

Preventing relapse in schizophrenia improves long-term health outcomes. Repeated episodes of psychotic symptoms shape the trajectory of this illness and can be a detriment to functional recovery. Despite early intervention programs, high relapse rates persist, calling for alternative approaches in relapse prevention. Predicting imminent relapse at an individual level is critical for effective intervention. While clinical profiles are often used to foresee relapse, they lack the specificity and sensitivity needed for timely prediction. Here, we review the use of speech through Natural Language Processing (NLP) to predict a recurrent psychotic episode. Recent advancements in NLP of speech have shown the ability to detect linguistic markers related to thought disorder and other language disruptions within 2-4 weeks preceding a relapse. This approach has shown to be able to capture individual speech patterns, showing promise in its use as a prediction tool. We outline current developments in remote monitoring for psychotic relapses, discuss the challenges and limitations and present the speech-NLP based approach as an alternative to detect relapses with sufficient accuracy, construct validity and lead time to generate clinical actions towards prevention.

Patient-reported outcome measures in early psychosis: A cross-cultural, longitudinal examination of the self-reported health and self-reported mental health measures in Chennai, India and Montreal, Canada.

OBJECTIVE: Despite their acknowledged value, patient-reported outcome measures (PROMs) are infrequently used in psychosis, particularly in low-and middle-income countries. We compared ratings on two single-item PROMs, Self-Rated Health (SRH) and Self-Rated Mental Health (SRMH), of persons receiving similar early psychosis services in Chennai, India and Montreal, Canada. We hypothesized greater improvements in SRH and SRMH in the Chennai (compared to the Montreal) sample. METHODS: Participants (Chennai N = 159/168 who participated in the larger study; Montreal N = 74/165 who participated in the larger study) completed the SRH and SRMH during at least two out of three timepoints (entry, months 12 and 24). Repeated measures proportional odds logistic regressions examined the effects of time (baseline to month 24), site, and relevant baseline (e.g., gender) and time-varying covariates (i.e., symptoms) on SRH and SRMH scores. RESULTS: SRH (but not SRMH) scores significantly differed between the sites at baseline, with Chennai patients reporting poorer health (OR: 0.33; CI: 0.18, 0.63). While Chennai patients reported similar significant improvements in their SRH (OR: 7.03; CI: 3.13; 15.78) and SRMH (OR: 2.29, CI: 1.03, 5.11) over time, Montreal patients only reported significant improvements in their SRMH. Women in Chennai (but not Montreal) reported lower mental health than men. Higher anxiety and longer durations of untreated psychosis were associated with poorer SRH and SRMH, while negative symptoms were associated with SRH. CONCLUSIONS: As hypothesized, Chennai patients reported greater improvements in health and mental health. The marked differences between health and mental health in Montreal, in contrast to the overlap between the two in Chennai, aligns with previous findings of clearer distinctions between mind and body in Western societies. Cross-context (e.g., anxiety) and context-specific (e.g., gender) factors influence patients' health perceptions. Our results highlight the value of integrating simple PROMs in early psychosis.

Genetic and phenotypic similarity across major psychiatric disorders: a systematic review and quantitative assessment.

There is widespread overlap across major psychiatric disorders, and this is the case at different levels of observations, from genetic variants to brain structures and function and to symptoms. However, it remains unknown to what extent these commonalities at different levels of observation map onto each other. Here, we systematically review and compare the degree of similarity between psychiatric disorders at all available levels of observation. We searched PubMed and EMBASE between January 1, 2009 and September 8, 2022. We included original studies comparing at least four of the following five diagnostic groups: Schizophrenia, Bipolar Disorder, Major Depressive Disorder, Autism Spectrum Disorder, and Attention Deficit Hyperactivity Disorder, with measures of similarities between all disorder pairs. Data extraction and synthesis were performed by two independent researchers, following the PRISMA guidelines. As main outcome measure, we assessed the Pearson correlation measuring the degree of similarity across disorders pairs between studies and biological levels of observation. We identified 2975 studies, of which 28 were eligible for analysis, featuring similarity measures based on single-nucleotide polymorphisms, gene-based analyses, gene expression, structural and functional connectivity neuroimaging measures. The majority of correlations (88.6%) across disorders between studies, within and between levels of observation, were positive. To identify a consensus ranking of similarities between disorders, we performed a principal component analysis. Its first dimension explained 51.4% (95% CI: 43.2, 65.4) of the variance in disorder similarities across studies and levels of observation. Based on levels of genetic correlation, we estimated the probability of another psychiatric diagnosis in first-degree relatives and showed that they were systematically lower than those observed in population studies. Our findings highlight that genetic and brain factors may underlie a large proportion, but not all of the diagnostic overlaps observed in the clinic.

Maternal smoking during pregnancy and cortical structure in children with attention-deficit/hyperactivity disorder.

Maternal smoking during pregnancy (MSDP) is considered a risk factor for ADHD. While the mechanisms underlying this association are not well understood, MSDP may impact the developing brain in ways that lead to ADHD. Here, we investigated the effect of prenatal smoking exposure on cortical brain structures in children with ADHD using two methods of assessing prenatal exposure: maternal recall and epigenetic typing. Exposure groups were defined according to: (1) maternal recall (+MSDP: n = 24; -MSDP: n = 85) and (2) epigenetic markers (EM) (+EM: n = 14 -EM: n = 21). CIVET-1.1.12 and RMINC were used to acquire cortical brain measurements and perform statistical analyses, respectively. The vertex with highest significance was tested for association with Continuous Performance Test (CPT) dimensions. While no differences of brain structures were identified between +MSDP and -MSDP, +EM children (n = 10) had significantly smaller surface area in the right orbitofrontal cortex (ROFc), middle temporal cortex (RTc) and parahippocampal gyrus (RPHg) (15% FDR) compared to -EM children (n = 20). Cortical surface area in the RPHg significantly correlated with CPT commission errors T-scores. This study suggests that molecular markers may better define exposure to environmental risks, as compared to human recall.

Similar and different? A cross-cultural comparison of the prevalence, course of and factors associated with suicidal thoughts and behaviors in first-episode psychosis in Chennai, India and Montreal, Canada.

BACKGROUND: Data from high-income countries (HICs) show a high risk of suicidal thoughts and behaviors (STBs) in first-episode psychosis (FEP). It is unknown, however, whether rates and associated factors differ in low- and middle-income countries (LMICs). AIMS: We therefore aimed to compare the 2-year course of STBs and associated factors in persons with FEP treated in two similarly structured early intervention services in Chennai, India and Montreal, Canada. METHOD: To ensure fit to the data that included persons without STBs and with varying STBs' severity, a hurdle model was conducted by site, including known predictors of STBs. The 2-year evolution of STBs was compared by site with mixed-effects ordered logistic regression. RESULTS: The study included 333 FEP patients (168 in Chennai, 165 in Montreal). A significant decrease in STBs was observed at both sites (OR = 0.87; 95% CI [0.84, 0.90]), with the greatest decline in the first 2 months of follow-up. Although three Chennai women died by suicide in the first 4 months (none in Montreal), Chennai patients had a lower risk of STBs over follow-up (OR = 0.44; 95% CI [0.23, 0.81]). Some factors (depression, history of suicide attempts) were consistently associated with STBs across contexts, while others (gender, history of suicidal ideation, relationship status) were associated at only one of the two sites. CONCLUSIONS: This is the first study to compare STBs in FEP between two distinct geo-sociocultural contexts (an HIC and an LMIC). At both sites, STBs reduced after treatment initiation, suggesting that early intervention reduces STBs across contexts. At both sites, for some patients, STBs persisted or first appeared during follow-up, indicating need for suicide prevention throughout follow-up. Our study demonstrates contextual variations in rates and factors associated with STBs. This has implications for tailoring suicide prevention and makes the case for more research on STBs in FEP in diverse contexts.

Manualized Group Cognitive-Behavioral Therapy for Social Anxiety in At-Risk Mental State and First Episode Psychosis: A Pilot Study of Feasibility and Outcomes.

Social anxiety has received scant attention in studies of schizophrenia and related psychoses. However, some data suggest it may be an obstacle to vocational and functional outcome. This pilot study investigated the feasibility of a group-based cognitive behavioral therapy (CBGT) to reduce social anxiety in those at risk for developing psychosis or in the early phase. Twenty-nine patients with first-episode psychosis (FEP) or at ultra high risk for developing psychosis or often referred to as at-risk mental state (ARMS) with comorbid social anxiety attended a CBGT intervention weekly for 14 weeks in 90-minute sessions. Baseline, post-treatment, and follow-up ratings of social anxiety were measured using the Social Interaction Anxiety Scale, the Social Phobia Inventory, and the Brief Social Phobia Scale. Psychotic symptoms and general psychopathology were also measured before and after the intervention. Results suggest that the proposed CBGT is feasible and beneficial for socially anxious patients at risk, or with experience of, psychosis. Participants significantly improved on three outcome measures of social anxiety after completing this intervention (all p's < .002). Participants who completed treatment also showed a significant reduction on measures of depression and negative symptoms. Future research should examine the relative efficacy of this brief manualized CBGT intervention for the treatment of social anxiety and psychotic symptoms in a larger randomized controlled trial.

Estrés y factores protectores en individuos en riesgo ultra-alto de psicosis, pacientes con un primer episodio de psicosis e individuos de control sanos / Stress and protective factors in individuals at ultra-high risk for psychosis, first episode psychosis and healthy controls

Los modelos de esquizofrenia de vulnerabilidad al estrés consideran que el estrés psicosocial es un importante factor en el inicio y la agravación de los síntomas psicóticos, pero en los estadios iniciales de la psicosis dicha investigación es limitada. Los factores protectores frente a los efectos del estrés podrían ser la clave para entender algunos hallazgos poco concluyentes y para el establecimiento de intervenciones psicosociales óptimas. En el presente estudio se compararon los niveles de estrés autorreferido, la autoestima, el apoyo social y el afrontamiento activo en 32 pacientes con un primer episodio de psicosis (PEP), en 30 individuos en riesgo ultra-alto (RUA) de psicosis y en 30 individuos de control sanos. En ambos grupos de pacientes se evaluaron las asociaciones con los síntomas de psicosis. Los individuos en RUA refirieron niveles de estrés significativamente mayores, comparados con los pacientes PEP. En ambos grupos de pacientes fue evidente una menor autoestima comparado con los individuos de control, y el grupo RUA mencionó un menor apoyo social y afrontamiento activo que los individuos de control. En el grupo de pacientes PEP estas diferencias de grupo no pudieron explicarse por la edad ni por la dosis de medicación antipsicótica. En el grupo RUA, los mayores niveles de estrés y la menor autoestima se asociaron a síntomas positivos y depresivos más graves en la escala breve de valoración psiquiátrica (Brief Psychiatric Rating Scale). En los análisis de regresión múltiple se puso de manifiesto que el estrés fue la única variable predictora significativa de la valoración de ambos síntomas y que la autoestima no moderó la relación. Los hallazgos del presente estudio ponen de relieve que los individuos en RUA de psicosis experimentan niveles elevados de estrés psicosocial y deficiencias destacadas en los factores de protección. Los resultados sugieren que las intervenciones psicosociales destinadas a reducir los niveles de estrés y a mejorar la resistencia y la capacidad de recuperación en esta población podrían ser beneficiosas para mejorar los desenlaces (AU)

Stress-vulnerability models of schizophrenia regard psychosocial stress as an important factor in the onset and aggravation of psychotic symptoms, but such research in the early phases of psychosis is limited. Protective factors against the effects of stress might be the key to understanding some inconclusive findings and to the development of optimal psychosocial interventions. The present study compared self-reported levels of stress, self-esteem, social support and active coping in 32 patients with a first episode of psychosis (FEP), 30 individuals at ultra-high risk for psychosis (UHR) and 30 healthy controls. Associations with symptoms of psychosis were assessed in both patient groups. Individuals at UHR reported significantly higher stress levels compared to FEP patients. Both patient groups showed lower self-esteem compared to controls, and the UHR group reported lower social support and active coping than controls. These group differences could not be explained by age and dose of antipsychotic medication in the FEP group. In the UHR group, higher stress levels and lower self-esteem were associated with more severe positive and depressive symptoms on the Brief Psychiatric Rating Scale. Multiple regression analyses revealed that stress was the only significant predictor for both symptom measures and that the relationship was not moderated by self-esteem. Our findings show that individuals at UHR for psychosis experience high levels of psychosocial stress and marked deficits in protective factors. The results suggest that psychosocial interventions targeted at reducing stress levels and improving resilience in this population may be beneficial in improving outcomes (AU)