Early Psychosis Research Articles

Increased whole-brain functional heterogeneity in psychosis during rest and task

Past work has shown that people with schizophrenia exhibit more cross-subject heterogeneity in their functional connectivity patterns. However, it remains unclear whether specific brain networks are implicated, whether common confounds could explain the results, or whether task activations might also be more heterogeneous. Unambiguously establishing the existence and extent of functional heterogeneity constitutes a first step toward understanding why it emerges and what it means clinically. Methods. We first leveraged data from the HCP Early Psychosis project. Functional connectivity (FC) was extracted from 718 parcels via principal components regression. Networks were defined via a brain network partition (Ji et al., 2019). We also examined an independent data set with controls, later-stage schizophrenia patients, and ADHD patients during rest and during a working memory task. We quantified heterogeneity by averaging the Pearson correlation distance of each subject’s FC or task activity pattern to that of every other subject of the same cohort. Results. Affective and non-affective early psychosis patients exhibited more cross-subject whole-brain heterogeneity than healthy controls (ps < 0.001, Hedges’ g > 0.74). Increased heterogeneity could be found in up to seven networks. In-scanner motion, medication, nicotine, and comorbidities could not explain the results. Later-stage schizophrenia patients exhibited heterogeneous connectivity patterns and task activations compared to ADHD and control subjects. Interestingly, individual connection weights, parcel-wise task activations, and network averages thereof were not more variable in patients, suggesting that heterogeneity becomes most obvious over large-scale patterns. Conclusion. Whole-brain cross-subject functional heterogeneity characterizes psychosis during rest and task. Developmental and pathophysiological consequences are discussed.

Diverging functional connectivity timescales: Capturing distinct aspects of cognitive performance in early psychosis

BackgroundPsychosis spectrum disorders (PSDs) are marked by cognitive impairments, the neurobiological correlates of which remain poorly understood. Here, we investigate the entropy of time-varying functional connectivity (TVFC) patterns from resting-state functional magnetic resonance imaging (rs-fMRI) as potential biomarker for cognitive performance in PSDs. By combining our results with multimodal reference data, we hope to generate new insights into the mechanisms underlying cognitive dysfunction in PSDs. We hypothesized that low-entropy TVFC patterns (LEN) would be more behaviorally informative than high-entropy TVFC patterns (HEN), especially for tasks that require extensive integration across diverse cognitive subdomains. Methodsrs-fMRI and behavioral data from 97 patients in the early phases of psychosis and 53 controls were analyzed. Positron emission tomography (PET) and magnetoencephalography (MEG) data were taken from a public repository (Hansen et al., 2022). Multivariate analyses were conducted to examine relationships between TVFC patterns at multiple spatial scales and cognitive performance in patients. ResultsCompared to HEN, LEN explained significantly more cognitive variance on average in PSD patients, driven by superior encoding of information on psychometrically more integrated tasks. HEN better captured information in specific subdomains of executive functioning. Nodal HEN-LEN transitions were spatially aligned with neurobiological gradients reflecting monoaminergic transporter densities and MEG beta-power. Exploratory analyses revealed a close statistical relationship between LEN and positive symptom severity in patients. ConclusionOur entropy-based analysis of TVFC patterns dissociates distinct aspects of cognition in PSDs. By linking topographies of neurotransmission and oscillatory dynamics with cognitive performance, it enhances our understanding of the mechanisms underlying cognitive deficits in PSDs.

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

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. 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. 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. 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. https://osf.io/8mz7a.

Biological substrate of executive functions in infantile-youth population with early onset psychosis: N-acetyl aspartate

Biological substrate of executive functions in infantile-youth population with early onset psychosis: N-acetyl aspartate

The relationship between therapeutic alliance, frequency of consultation and uptake of telemedicine among patients seeking treatment for early psychosis: A moderated mediation model.

Telehealth services ensure the delivery of healthcare services to a wider range of consumers through online platforms. Nonetheless, the acceptance and uptake of telehealth remain elusive. This study aims to understand the (a) uptake and (b) acceptability of telemedicine, (c) if therapeutic alliance mediates the relationship between the frequency of consultations with clinicians and the uptake of telemedicine in patients with early psychosis, and (d) role of education in moderating the relationship between therapeutic alliance and the uptake of telemedicine for their mental healthcare. A convenience sample of outpatients (n = 109) seeking treatment for early psychosis and their care providers (n = 106) were recruited from a tertiary psychiatric care centre. Sociodemographic and clinical characteristics, therapeutic alliance (Working Alliance Inventory), and telemedicine use were captured through self-administered surveys. The moderated mediation analysis was performed using PROCESS macro 3.4.1 with therapeutic alliance and level of education as the mediating and moderating factors, respectively. The acceptance of telemedicine was high (possibly will use: 47.7%; definitely will use: 26.6%) whilst the uptake was low (11%). Therapeutic alliance mediated the relationship between the frequency of consultation and the uptake of telemedicine (β: 0.326; CI: 0.042, 0.637). This effect was moderated by the level of education (β: -0.058; p < 0.05). Therapeutic alliance mediates the relationship between the frequency of consultations and the uptake of telemedicine services with the level of education moderating this mediation. Focusing on the patients with lower education to improve their telemedicine knowledge and therapeutic alliance might increase the uptake.

Brain texture as a marker of transdiagnostic clinical profiles in patients with recent-onset psychosis and depression

The inter-relationships of voxels can be captured by the radiomics texture features across multiple spatial scales. Prediction models of brain texture changes captured by the contrast texture feature in recent-onset psychosis (ROP) and recent-onset depression (ROD) have recently been proposed, although the validation of these models transdiagnostically at the individual level and the investigation of the variability in clinical profiles are lacking. Established prevention and treatment approaches focus on specific diagnoses and do not address the heterogeneity and manifold potential outcomes of patients. Here we aimed to investigate the cross-sectional utility of brain texture changes for (1) identification of the psychopathological state (ROP and ROD) and (2) the association of individualized brain texture maps with clinical symptom severity and outcome profiles. We developed transdiagnostic models based on structural magnetic resonance imaging data for 116 patients with ROD, 122 patients with ROP and 197 healthy control participants from the PRONIA (Personalized pROgNostic tools for early psychosIs mAnagement) study by applying a set of tools and frameworks to explain the classification decisions of the deep-learning algorithm (named explainable artificial intelligence) and clustering analysis. We investigated the contrast texture feature as the key feature for the identification of a general psychopathological state. The discrimination power of the trained prediction model was >72% and was validated in a second independent age- and sex-matched sample of 137 ROP, 94 ROD and 159 healthy control participants. Clustering analysis was implemented to map the changes in texture brain produced from an explainable artificial intelligence algorithm, in a group fashion. The explained individualized brain contrast map grouped into eight homogeneous clusters. In the clinical group, we investigated the association between the explained brain contrast texture map and clinical symptom severity as well as outcome profiles. Different patterns in the explained brain contrast texture map showed unique associations of brain alterations with clinical symptom severity and clinical outcomes, that is, age, positive, negative and depressive symptoms, and functionality. In some clusters, the mean explained brain contrast texture map values and/or brain contrast texture voxels that contributed significantly to the classification decision predicted accurately the PANSS (positive and negative symptom scale) scores, functionality and change in functionality over time. In conclusion, we created homogeneous clusters which predict the clinical severity and outcome profile in ROP and ROD patients.

Deslizamentos de posição subjetiva em enunciados tidos como ecolálicos de uma criança com Distúrbio de Linguagem: um estudo de caso

ABSTRACT Within a linguistic-discursive framework, subject markers in a chain of utterances considered to be echolalia based on the recurring linguistic structure does X want Y? were investigated. This chain was produced during a speech therapy session by J., a female child, 10-years-old at the time of data collection, and with a speech-language pathology diagnosis of language disorder and a medical diagnosis of early psychosis. A set of linguistic fluctuations indicated a sliding of the subject position in the analyzed chain. Such fluctuations involved syntactic, lexical, semantic, morphological and prosodic elements. Discursively, the fluctuations left traces of a sliding of the subject position in the chain formed by these utterances, from a spoken subject (do you want Y?) to a speaking/desiring one (I want Y.). In this way, utterances considered echolalia can provide clues, via their linguistic fluctuations and discursive slippages, about the subject's desire in their relationship with the O/other. Given this, although they do not emerge in a conventional way, such utterances can demonstrate possibilities for changes in subject position. A contribution of the present research for clinical practice involving language in therapeutic settings therefore, was to highlight a listening to utterances, which could be seen as connected/grounded in the speech of the other. In clinical practice involving language, it is possible to create space for new/other senses for utterances, to allow the constitution of the subject of/in language, based on utterances often interpreted as being devoid of subjectivity.

Cortical Network Disruption Is Minimal in Early Stages of Psychosis.

Schizophrenia is associated with white matter disruption and topological reorganization of cortical connectivity but the trajectory of these changes, from the first psychotic episode to established illness, is poorly understood. Current studies in first-episode psychosis (FEP) patients using diffusion magnetic resonance imaging (dMRI) suggest such disruption may be detectable at the onset of psychosis, but specific results vary widely, and few reports have contextualized their findings with direct comparison to young adults with established illness. Diffusion and T1-weighted 7T MR scans were obtained from N = 112 individuals (58 with untreated FEP, 17 with established schizophrenia, 37 healthy controls) recruited from London, Ontario. Voxel- and network-based analyses were used to detect changes in diffusion microstructural parameters. Graph theory metrics were used to probe changes in the cortical network hierarchy and to assess the vulnerability of hub regions to disruption. The analysis was replicated with N = 111 (57 patients, 54 controls) from the Human Connectome Project-Early Psychosis (HCP-EP) dataset. Widespread microstructural changes were found in people with established illness, but changes in FEP patients were minimal. Unlike the established illness group, no appreciable topological changes in the cortical network were observed in FEP patients. These results were replicated in the early psychosis patients of the HCP-EP datasets, which were indistinguishable from controls in most metrics. The white matter structural changes observed in established schizophrenia are not a prominent feature in the early stages of this illness.

A multiscale characterization of cortical shape asymmetries in early psychosis.

Psychosis has often been linked to abnormal cortical asymmetry, but prior results have been inconsistent. Here, we applied a novel spectral shape analysis to characterize cortical shape asymmetries in patients with early psychosis across different spatial scales. We used the Human Connectome Project for Early Psychosis dataset (aged 16-35), comprising 56 healthy controls (37 males, 19 females) and 112 patients with early psychosis (68 males, 44 females). We quantified shape variations of each hemisphere over different spatial frequencies and applied a general linear model to compare differences between healthy controls and patients with early psychosis. We further used canonical correlation analysis to examine associations between shape asymmetries and clinical symptoms. Cortical shape asymmetries, spanning wavelengths from about 22 to 75 mm, were significantly different between healthy controls and patients with early psychosis (Cohen's d = 0.28-0.51), with patients showing greater asymmetry in cortical shape than controls. A single canonical mode linked the asymmetry measures to symptoms (canonical correlation analysis r = 0.45), such that higher cortical asymmetry was correlated with more severe excitement symptoms and less severe emotional distress. Significant group differences in the asymmetries of traditional morphological measures of cortical thickness, surface area, and gyrification, at either global or regional levels, were not identified. Cortical shape asymmetries are more sensitive than other morphological asymmetries in capturing abnormalities in patients with early psychosis. These abnormalities are expressed at coarse spatial scales and are correlated with specific symptom domains.

The effect of using group-averaged or individualized brain parcellations when investigating connectome dysfunction in psychosis.

Functional magnetic resonance imaging (fMRI) is widely used to investigate functional coupling (FC) disturbances in a range of clinical disorders. Most analyses performed to date have used group-based parcellations for defining regions of interest (ROIs), in which a single parcellation is applied to each brain. This approach neglects individual differences in brain functional organization and may inaccurately delineate the true borders of functional regions. These inaccuracies could inflate or underestimate group differences in case-control analyses. We investigated how individual differences in brain organization influence group comparisons of FC using psychosis as a case study, drawing on fMRI data in 121 early psychosis patients and 57 controls. We defined FC networks using either a group-based parcellation or an individually tailored variant of the same parcellation. Individualized parcellations yielded more functionally homogeneous ROIs than did group-based parcellations. At the level of individual connections, case-control FC differences were widespread, but the group-based parcellation identified approximately 7.7% more connections as dysfunctional than the individualized parcellation. When considering differences at the level of functional networks, the results from both parcellations converged. Our results suggest that a substantial fraction of dysconnectivity previously observed in psychosis may be driven by the parcellation method, rather than by a pathophysiological process related to psychosis.

Confronting the dialectic between quality and access in early psychosis care in the United States: Finding the synthesis by leveraging psychological expertise.

Coordinated specialty care (CSC) is the dominant model for early psychosis care in the United States, representing a proactive recovery-oriented approach to serious mental illness in its early stages. CSC involves broad multidisciplinary support for participants, including from psychologists in some CSC teams, encompassing educational and vocational support, medication management, psychotherapy, case management, peer support, and family interventions. CSC programs have proliferated in the last 20 years, leading to a quality-access dialectic, where increasing access to treatment simultaneously prompts concerns about care quality, particularly in the context of staffing shortages and funding limits. Evidence-based psychosocial treatment, including psychotherapy, is an integral part of CSC, yet workforce training deficits, workforce turnover, and CSC financing pose threats to intervention fidelity and thus CSC participants' ability to access high-quality care. We propose an enhanced role for psychologists as a way of resolving the quality-access dialectic in the area of psychosocial treatment, specifically evidence-based therapy. We describe the potential of psychologists' skills in clinical supervision, formulation, evidence-based interventions and measurement-based care, drawing on practice examples. After considering possible limitations, we outline implementation models, for example, drawing on Early Psychosis Intervention Network and Project Extension for Community Healthcare Outcomes. We conclude with four recommendations: Psychologists should be placed in CSC team or network-leadership roles; psychological expertise should be made available to CSC teams for training, consultation, and technical assistance; psychological expertise should be used to address CSC implementation challenges; and research is needed to demonstrate psychologists' value to stakeholders. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Remission with or without comorbid substance use disorders in early psychosis: long-term outcome in integrated care (ACCESS III study).

Schizophrenia-Spectrum-Disorders are associated with poor long-term outcome as well as disability and often severely affect the lives of patients and their families often from symptom onset. Up to 70% of first episode psychosis (FEP) patients suffer from comorbid substance use disorders (SUD). We aimed at studying the course of illness in FEP patients within evidence-based care, with and without comorbid SUD, to examine how decreased, remitted or persistent substance use impacted rates of a combined symptomatic and functional long-term recovery compared with patients without SUD. ACCESS III is an integrated care model for FEP or patients in the early phase of non-affective and affective psychotic disorders. Treatment trajectories of patients, who had been in ACCESS care for 1 year, with and without SUD were compared with regard to the course of illness and quality of life using Mixed Model Repeated Measures (MMRM) and recovery rates were compared using binary logistic regression. Change in substance use was coded as either persistent, decreased/remitted or no use. ACCESS III was a prospective 1-year study (N = 120) in patients aged 12-29 years. Of these, 74 (61.6%) had a comorbid SUD at admission. There were no group differences regarding the course of illness between patients with or without comorbid SUD or between patients with a substance abuse or substance dependence. The only outcome parameter that was affected by SUD was quality of life, with larger improvement found in the group without substance use (p = 0.05) compared to persistent and remitted users. Using LOCF, 44 patients (48.9%) fulfilled recovery criteria at the endpoint; recovery did not differ based on substance use status. SUD and especially substance dependence are common in psychotic disorders even in FEP patients. Evidence-based integrated care led to long-term improvement in patients with comorbid SUD and rate of recovery did not differ for patients with substance use.

DSM-5 conduct disorder and symptoms in youths at high risk of psychosis in Kenya with DSM-5 mental disorders and substance use: towards integrated management

Little is known about the prevalence of Conduct Disorder (CD) and symptoms of CD in high risk psychosis persons at both clinical and community populations in LMICs and in particular Kenya. This study aimed to document (1) the prevalence of CD diagnosis and symptoms in youth who screened positive for psychosis and (2) the associated mental disorders and substance use in the same cohort in LMIC. The sample size was 536 students who had screened positive on the Washington Early Recognition Center Affectivity and Psychosis (WERCAP) from a population of 9,742 high school, college and university students, but had not converted to a psychotic disorder. We collected data on socio-demographic characteristics and used the following tools: Economic indicators tool; the Diagnostic Interview Schedule (DIS) tool for DSM-5 diagnosis; World Health Organization (WHO) Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST). Basic descriptive statistics, chi-square test, Fisher's exact test, Pearson correlation and Poisson regression were conducted. Five percent (5%) of the respondents met the criteria for DSM-5 CD. Indeterminate CD comprised 10.1%. Male gender, all substances except hallucinogens lifetime, obsessive compulsive disorder, psychosis, agoraphobia, social phobia, drug abuse/dependence, antisocial personality disorder, oppositional defiant disorder, suicidality, WERCAP screen for bipolar disorder and WERCAP screen for schizophrenia were significantly (p < 0.05) associated with CD. Deceitfulness or theft criteria symptoms showed that CD had no significant gender difference. Criteria symptoms in aggression to people and animals, destruction of property and serious violations of rules were more common among males. Our findings suggest the need to screen for and diagnose CD, mental disorders and substance use in high risk psychosis youths in Kenya. This will inform integrated management.

Risk of unemployment and work disability among refugee and non-refugee migrants with incident psychotic disorders in Sweden and Denmark.

Unemployment and work disability are common among individuals with non-affective psychotic disorders (NAPDs) but it is unknown whether rates differ among migrants and native-born individuals. The present study aimed to compare the risk of these outcomes during the first 5 years of illness in non-refugee migrants, refugees and native-born individuals with NAPDs in Sweden and Denmark-two countries with different immigration policies and models of early psychosis care. Using national registers, we identified all individuals aged 18-35 years in Sweden and Denmark who received an incident NAPD diagnosis between 2006 and 2013 (N = 6750 and 8320, respectively). Cohorts were followed for 5 years to determine the days of unemployment and sickness absence (analyzed using zero-inflated negative binomial models) and the time to receipt of disability pension (analyzed using complementary log-log models). Relative to their native-born peers, refugees and non-refugee migrants in Sweden and non-refugee migrants in Denmark were significantly less likely to have zero unemployment days (OR range: 0.54-0.72) and all migrant groups experienced more unemployment days (IRR range: 1.26-1.37). Results were largely unchanged after adjustment for sociodemographic and clinical factors. In the adjusted model, both Swedish migrant groups and refugees in Denmark were more likely to experience zero sickness absence days than native-born individuals (OR range: 1.48-1.56). Only refugees in Denmark were at greater risk of disability pension. Non-refugee migrants and refugees with NAPDs in both Sweden and Denmark are particularly vulnerable to experiencing unemployment. Targeted interventions may help to reduce these disparities and promote long-term work ability among migrant groups.

Evaluation of a Cannabis Harm Reduction Intervention for People With First-Episode Psychosis: Protocol for a Pilot Multicentric Randomized Trial.

Cannabis use is highly prevalent in young people with first-episode psychosis (FEP). Most report cannabis use and are often diagnosed with a cannabis use disorder upon admission to specialized services for psychosis. Cannabis use in this population is associated with worse clinical and psychosocial outcomes, rendering it an important clinical target. Despite this, few cannabis-specific interventions have been developed for FEP and empirically evaluated through randomized controlled trials. Most evaluated interventions have targeted cannabis abstinence, with limited efficacy, but none have centered on harm reduction outcomes for people with FEP who use cannabis. Early intervention services (EIS), the standard of care for FEP, have not successfully addressed problematic cannabis use in people with FEP either. Clinical trials are needed to explore the potential of harm reduction strategies, although these should be preceded by robust pilot studies to establish optimal design and approaches. Recognizing the need for harm reduction strategies for individuals with FEP who use cannabis and based on research on patients' preferences supporting harm reduction interventions, we developed a mobile app-based cannabis harm reduction intervention for this population. This intervention is called Cannabis Harm-reducing Application to Manage Practices Safely (CHAMPS). Here, we describe the protocol for a multicenter, 2-arm, parallel group, randomized pilot trial evaluating the acceptability of CHAMPS for people with FEP who use cannabis and the feasibility of conducting a full-scale trial in this population using CHAMPS. The impact on key clinical outcomes will also be explored. This pilot trial aims to recruit 100 young people with FEP using cannabis from 6 Canadian EIS clinics. Participants will be randomized in a 1:1 ratio to CHAMPS+EIS or EIS-only. CHAMPS acceptability will be assessed using completion rates for the intervention arm. Trial feasibility will be assessed using a retention rate for randomized participants. Secondary outcomes will explore tendencies of change in the use of protective behavioral strategies and in motivation to change strategies. Exploratory outcomes include cannabis use-related problems, other substance use, the severity of dependence, psychotic symptoms, and health care service use. Recruitment began in December 2021. Data collection and analysis are expected to be completed in early 2024. Study results describing CHAMPS acceptability and trial feasibility will then be submitted for publication in a peer-reviewed journal. CHAMPS uniquely combines evidence-based approaches, patient perspectives, and mobile health technology to support harm reduction in people with FEP who use cannabis. Attaining adequate acceptability and feasibility through this trial may justify further exploration of harm reduction tools, particularly within the context of conducting a larger-scale randomized controlled trial. This pilot trial has the potential to advance knowledge for researchers and clinicians regarding a feasible and user-acceptable research design in the cannabis and early psychosis fields. ClinicalTrials.gov NCT04968275, https://clinicaltrials.gov/ct2/show/NCT04968275. DERR1-10.2196/53094.

Peripheral and central biomarkers associated with inflammation in antipsychotic naïve first episode psychosis: Pilot studies

BackgroundElevated serum pro-inflammatory molecules have been reported in early psychosis. What is not known is whether peripheral inflammatory biomarkers are associated with CNS biomarkers. In the brain, release of pro-inflammatory molecules by microglial hyperactivity may lead to neuronal apoptosis seen in neurodegenerative disorders and account for loss of brain tissue observed in psychotic disorders. Neurochemical changes, including elevated glutamate levels, are also associated with neuroinflammation, present in early psychosis and change with antipsychotic treatment. MethodsAntipsychotic naïve patients with first episode psychosis (FEP) were studied as part of a collaborative project of neuroinflammation. In Study 1 we explored associations between plasma inflammatory molecules and neurometabolites in the dorsal caudate using magnetic resonance spectroscopy (1H-MRS) in N = 13 FEP participants. Study 2 examined the relationship between inflammatory molecules in the Plasma and CSF in N = 20 FEP participants. ResultsIn Study 1, the proinflammatory chemokine MDC/CCL22 and IL10 were significantly positively correlated with Glutamate and Glx (glutamate + glutamine) levels in the dorsal caudate. In Study 2, plasma inflammatory molecules (MIP1β/CCL4, MCP1/CCL2, Eotaxin-1/CCL11 and TNFα) were significantly correlated with CSF MIP1β/CCL4, IL10, MCP1/CCL2 and Fractalkine/CX3CL1 and symptoms ratings. DiscussionPlasma inflammatory biomarkers are elevated in early psychosis, associated with neurochemical markers as well as CSF inflammatory molecules found in neurodegenerative disorders. Future studies are needed that combine both peripheral and central biomarkers in both FEP and HC to better understand a potential neuroinflammatory subtype of psychosis likely to respond to targeted interventions.

Patient-reported outcome measures in early psychosis: Evaluating the psychometric properties of the single-item self-reported health and self-reported mental health measures in Chennai, India and Montreal, Canada.

Patient-reported outcome measures (PROMs) provide valuable information and promote shared decision-making but are infrequently used in psychosis. Self-rated Health (SRH) and Self-rated Mental Health (SRMH) are single-item PROMs in which respondents rate their health and mental health from 'poor' to 'excellent'. We examined the psychometric properties of the SRH and SRMH in early psychosis services in Chennai, India and Montreal, Canada. Assessments were completed in Tamil/English in Chennai and French/English in Montreal. Test-retest reliability included data from 59 patients in Chennai and Montreal. Criterion validity was examined against clinician-rated measures of depression, anxiety, positive and negative symptoms, and a quality-of-life PROM for 261 patients in Chennai and Montreal. SRH and SRMH had good to excellent test-retest reliability (ICC >0.63) at both sites and in English and Tamil (but not French). Results for criterion validity were mixed. In Montreal, low SRH was associated with not being in positive symptom remission, and poorer functioning and quality of life. SRH was associated only with functioning in Chennai. No associations were found for SRMH in Montreal. In Chennai, low SRMH was associated with not being in positive symptom remission and poorer functioning. Patient-reported outcome measures may perform differently across contexts as a potential function of variations in sociodemographics, illness characteristics/course, understandings of health/mental health, and so forth. More work is needed to understand if discrepancies between PROMs and CROMs indicate poor validity of PROMs or 'valid' differences between patient and clinician perceptions. Our work suggests that single-item PROMs can be feasibly integrated into clinical settings.

NAVIGATE Program Directors' perspectives on treatment for early psychosis.

Since the release of the Recovery After Initial Schizophrenia Episode-Early Treatment Program results in 2015, the United States Congress expanded funding for early intervention programs and these programs now exist in every state. The purpose of the present study was to understand the real-world experience of NAVIGATE Program Directors with respect to identifying and recruiting patients with early psychosis and engaging families in treatment. Utilizing a mixed-methods sequential explanatory design, researchers surveyed 32 program directors in 13 states and engaged in 22 follow-up interviews to explore how NAVIGATE is being translated to serve individuals experiencing early psychosis and their families. We found that program directors using the NAVIGATE model encountered difficulty identifying diagnosis at admission and that supporting families of individuals experiencing psychosis was an important aspect of the program with unique complexity. These findings have important implications for future mental health research on early intervention programs and may serve to stimulate future research on how early intervention mental health programs can better serve individuals recovering from psychosis and support their families. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Elevated Tau burden in Amygdala and Hippocampus amongst older participants with psychosis

AbstractBackgroundPsychosis is a debilitating cluster of symptoms occurring in some Alzheimer’s Disease (AD) patients, and is defined by the presence of delusions and/or hallucinations. Previous studies suggest that psychosis in AD patients is associated with increased tau burden and accelerated cognitive decline. We sought to assess differences in tau burden between cognitively impaired patients with psychosis(+P) and those without psychosis(‐P).MethodTwenty‐six ADNI participants with psychosis (+P; 11.5% CDR0, 42.3% CDR0.5, 30.7% CDR1, 11.5% CDR2, 4% CDR3, 77±7yr old, 50% women, 16±3yr education, 92% White) and 26 without psychosis were matched by CDR, age, sex, education, and race (‐P; 11.5% CDR0, 42.3% CDR0.5, 30.7% CDR1, 11.5% CDR2, 4% CDR3, 77±6yr old, 54% women, 15±3yr education, 92% White). The +P group was defined based on any endorsement of hallucinations or delusions on Neuropsychiatric Inventory. Flortaucipir PET data were processed according to ADNI methods. Difference in tau burden was assessed using a paired t‐test on the ROI and voxel‐level between +P and ‐P groups in Braak regions as well as the amygdala, hippocampus, and frontal, temporal, and parietal lobes A follow‐up voxelwise t‐test was performed within the +P group between those with and without concurrent symptoms at the time of their scan. Analyses were corrected for amyloid‐level and voxel‐wise analyses were evaluated at p&lt;0.001 without multiple comparisons correction.ResultDescriptively, participant‐level scans demonstrated a variety of tau patterns, often with right laterality. Tau was elevated for +P participants compared to ‐P in the amygdala (0.6 [0.25, 0.96]; p = 0.003) and the hippocampus (0.3 [0.04, 0.55]; p = 0.03), while marginally elevated in the frontal cortex (0.09 [‐0.002, 0.189]; p = 0.06) [Figure1]. Voxel‐wise, elevated tau was localized to the amygdala, hippocampus, thalamus, and right frontal lobe [Figure2]. Additionally, with concurrent delusion symptomatology, elevated tau was localized to Braak III/IV regions [Figure3].ConclusionTau burden in the amygdala may be a potential biomarker of psychosis across the AD continuum. Right‐sided laterality is consistent with psychosis‐related structural changes and psychosis‐related tau binding needs to be assessed further. Given that early psychosis in AD is associated with faster cognitive decline, these results could inform the development of prognostic biomarkers.

Models of shared care for the management of psychotic disorder after first diagnosis in Ontario.

To describe the provision of care for young people following first diagnosis of psychotic disorder. Retrospective cohort study using health administrative data. Ontario. People aged 14 to 35 years with a first diagnosis of nonaffective psychotic disorder in Ontario between 2005 and 2015 (N=39,449). Models of care, defined by psychosis-related service contacts with primary care physicians and psychiatrists during the 2 years after first diagnosis of psychotic disorder. During the 2-year follow-up period, 29% of the cohort received only primary care, 30% received only psychiatric care, and 32% received both primary and psychiatric care (shared care). Among the shared care group, 72% received care predominantly from psychiatrists, 20% received care predominantly from primary care physicians, and 9% received approximately equal care from psychiatry and primary care. Variation in patient and physician characteristics was observed across the different models of care. One in 3 young people with psychotic disorder received shared care during the 2-year period after first diagnosis. The findings highlight opportunities for increasing collaboration between primary care physicians and psychiatrists to enhance the quality of care for those with early psychosis.