Accelerated brain aging is a possible mechanism of pathology in schizophrenia. Advances in MRI-based brain development algorithms allow for the calculation of predicted brain age (PBA) for individuals. Here, we assessed PBA in 70 first-episode schizophrenia-spectrum individuals (FESz) and 76 matched healthy neurotypical comparison individuals (HC) to determine if FESz showed advanced aging proximal to psychosis onset and whether PBA was associated with neurocognitive, social functioning, or symptom severity measures. PBA was calculated with BrainAgeR (v2.1) from T1-weighted MR scans. There were no differences in the PBAs between groups. After controlling for actual age, a \"younger\" PBA was associated with higher vocabulary scores among all individuals, while an \"older\" PBA was associated with more severe negative symptom \"Inexpressivity\" component scores among FESz. Female participants in both groups had an elevated PBA relative to male participants. These results suggest that a relatively younger brain age is associated with a better semantic memory performance. There is no evidence for accelerated aging in FESz with a late adolescent/early adult onset. Despite a normative PBA, FESz with a greater residual PBA showed impairments in a cluster of negative symptoms, which may indicate some underlying age-related pathology proximal to psychosis onset. Although a period of accelerated aging cannot be ruled out with disease course, it does not occur at the time of the first episode.

UNASSIGNED: Schizophrenia is most times a chronic and often debilitating illness associated with poor mental health outcomes. Early and effective treatment of schizophrenia in the most appropriate setting can make a significant difference in the long-term recovery. The aim of this narrative review was to provide suggestions and recommendations for effectively managing patients with schizophrenia during acute exacerbations and to enhance awareness and skills related to personalized medicine.
UNASSIGNED: A panel of academics and clinicians with experience in the field of psychosis met virtually on July 13th 2023 to narratively review and discuss the research evidence and their clinical experience about the most appropriate acute treatments for patients with schizophrenia. This manuscript represents a synthesis of the panel analysis and discussion.
UNASSIGNED: First contact is very important for service users, as is finding the most adequate treatment setting. If patients present to the emergency department, which may be a traumatic setting for service users, a dedicated environment with adequate space and specialized mental health support, including personnel trained in de-escalation techniques, is recommended. A well-connected continuum of care is strongly recommended, possibly with seamless links between inpatient units, day hospital services, outpatient facilities and rehabilitation services. Ideally, this should be structured as part of a coordinated step-down service line. Treatment challenges include suboptimal response, side effects, and nonadherence, which is reduced by the use of long-acting injectable antipsychotics.
UNASSIGNED: Individual circumstances, including age, gender, and presence of hostility/aggression or self-harm, cognitive impairment and negative symptoms, comorbidities (depression, substance use disorders) or associated symptoms (anxiety, insomnia), should be considered when selecting the most appropriate treatment for the acute phase of schizophrenia. Efficacy and feasibility, as well as acceptability and tolerability of treatments, require joint consideration from the early stages of schizophrenia, thereby enhancing the possibility of improved short- and long-term outcomes.

Paranoid delusions or unfounded beliefs that others intend to deliberately cause harm are a frequent and burdensome symptom in early psychosis, but their emergence and consolidation still remains opaque. Recent theories suggest that overly precise prediction errors lead to an unstable model of the world providing a breeding ground for delusions. Here, we employ a Bayesian approach to test for such an unstable model of the world and investigate the computational mechanisms underlying emerging paranoia. We modelled behaviour of 18 first-episode psychosis patients (FEP), 19 individuals at clinical high risk for psychosis (CHR-P), and 19 healthy controls (HC) during an advice-taking task designed to probe learning about others\' changing intentions. We formulated competing hypotheses comparing the standard Hierarchical Gaussian Filter (HGF), a Bayesian belief updating scheme, with a mean-reverting HGF to model an altered perception of volatility. There was a significant group-by-volatility interaction on advice-taking suggesting that CHR-P and FEP displayed reduced adaptability to environmental volatility. Model comparison favored the standard HGF in HC, but the mean-reverting HGF in CHR-P and FEP in line with perceiving increased volatility, although model attributions in CHR-P were heterogeneous. We observed correlations between perceiving increased volatility and positive symptoms generally as well as with frequency of paranoid delusions specifically. Our results suggest that FEP are characterised by a different computational mechanism - perceiving the environment as increasingly volatile - in line with Bayesian accounts of psychosis. This approach may prove useful to investigate heterogeneity in CHR-P and identify vulnerability for transition to psychosis.

UNASSIGNED: Metabolic syndrome (MetS) is common following first-episode psychosis (FEP), contributing to substantial morbidity and mortality. The Psychosis Metabolic Risk Calculator (PsyMetRiC), a risk prediction algorithm for MetS following a FEP diagnosis, was developed in the United Kingdom and has been validated in other European populations. However, the predictive accuracy of PsyMetRiC in Chinese populations is unknown.
UNASSIGNED: FEP patients aged 15-35 y, first presented to the Early Assessment Service for Young People with Early Psychosis (EASY) Programme in Hong Kong (HK) between 2012 and 2021 were included. A binary MetS outcome was determined based on the latest available follow-up clinical information between 1 and 12 years after baseline assessment. The PsyMetRiC Full and Partial algorithms were assessed for discrimination, calibration and clinical utility in the HK sample, and logistic calibration was conducted to account for population differences. Sensitivity analysis was performed in patients aged >35 years and using Chinese MetS criteria.
UNASSIGNED: The main analysis included 416 FEP patients (mean age = 23.8 y, male sex = 40.4%, 22.4% MetS prevalence at follow-up). PsyMetRiC showed adequate discriminative performance (full-model C = 0.76, 95% C.I. = 0.69-0.81; partial-model: C = 0.73, 95% C.I. = 0.65-0.8). Systematic risk underestimation in both models was corrected using logistic calibration to refine PsyMetRiC for HK Chinese FEP population (PsyMetRiC-HK). PsyMetRiC-HK provided a greater net benefit than competing strategies. Results remained robust with a Chinese MetS definition, but worse for the older age group.
UNASSIGNED: With good predictive performance for incident MetS, PsyMetRiC-HK presents a step forward for personalized preventative strategies of cardiometabolic morbidity and mortality in young Hong Kong Chinese FEP patients.
UNASSIGNED: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

OBJECTIVE: To examine hospitalization as part of a complex pathway to care in first episode psychosis (FEP), exploring help-seeking episodes (HSE) and their relationship to hospitalization.
METHODS: Data from 66 patients at the Early Psychosis Intervention Clinic New Orleans (EPIC-NOLA), a coordinated specialty care (CSC) clinic, was obtained from Pathways to Care (PTC) assessments, which documents elements of help seeking. A chart review was performed identifying hospitalizations.
RESULTS: Most patients were hospitalized multiple times (n = 37, M = 2.98, SD = 2.14). On average, patients had more hospitalizations prior to starting treatment at EPIC-NOLA (M = 1.72, SD = 1.35) than after (M = 1.27, SD = 1.79). Patients whose first HSE resulted in intake at EPIC-NOLA were significantly less likely to be hospitalized after intake than patients with multiple HSE (F(1,52.3) = 12.9, p < .001). There was a significant correlation (N = 42) between HSE and hospitalizations after intake (τb = .327 p < .05); patients seeking help more often were more likely to be hospitalized after intake. No significant correlations were found between duration of untreated psychosis (DUP) and hospitalization.
CONCLUSIONS: While results are correlational, several key relationships were noted. Fewer hospitalizations occurred after intake into EPIC-NOLA. Starting treatment after the first HSE was related to fewer future hospitalizations, compared to intake after multiple HSEs. Intake into a CSC clinic after a single HSE may reduce hospitalization. Additionally, increased HSE, not DUP, impacted patients\' likelihood of hospitalization. This prompts treatment engagement during a first HSE to reduce hospitalization.

OBJECTIVE: People with first-episode psychosis (FEP) in low- and lower-middle-income countries (LMIC) experience delays in receiving treatment, resulting in poorer outcomes and higher mortality. There is robust evidence for effective and cost-effective early intervention in psychosis (EIP) services for FEP, but the evidence for EIP in LMIC has not been reviewed. We aim to review the evidence on early intervention for the management of FEP in LMIC.
METHODS: We searched 4 electronic databases (Medline, Embase, PsycINFO, and CINAHL) to identify studies describing EIP services and interventions to treat FEP in LMIC published from 1980 onward. The bibliography of relevant articles was hand-searched. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed.
RESULTS: The search strategy produced 5074 records; we included 18 studies with 2294 participants from 6 LMIC countries. Thirteen studies (1553 participants) described different approaches for EIP. Pharmacological intervention studies (n = 4; 433 participants) found a high prevalence of metabolic syndrome among FEP receiving antipsychotics (P ≤ .005). One study found a better quality of life in patients using injectables compared to oral antipsychotics (P = .023). Among the non-pharmacological interventions (n = 3; 308 participants), SMS reminders improved treatment engagement (OR = 1.80, CI = 1.02-3.19). The methodological quality of studies evidence was relatively low.
CONCLUSIONS: The limited evidence showed that EIP can be provided in LMIC with adaptations for cultural factors and limited resources. Adaptations included collaboration with traditional healers, involving nonspecialist healthcare professionals, using mobile technology, considering the optimum use of long-acting antipsychotics, and monitoring antipsychotic side effects.

Evidence of elevated peripheral Neurofilament light-chain (NfL) as a biomarker of neuronal injury can be utilized to reveal nonspecific axonal damage, which could reflect altered neuroimmune function. To date, only a few studies have investigated NfL as a fluid biomarker in schizophrenia primarily, though none in its putative prodrome (Clinical High-Risk, CHR) or in untreated first-episode psychosis (FEP). Further, it is unknown whether peripheral NfL is associated with 18 kDa translocator protein (TSPO), a validated neuroimmune marker. In this secondary study, we investigated for the first time (1) serum NfL in early stages of psychosis including CHR and FEP as compared to healthy controls, and (2) examined its association with brain TSPO, using [18F]FEPPA positron emission tomography (PET). Further, in the exploratory analyses, we aimed to assess associations between serum NfL and symptom severity in patient group and cognitive impairment in the combined cohort. A large cohort of 84 participants including 27 FEP (24 antipsychotic-naive), 41 CHR (34 antipsychotic-naive) and 16 healthy controls underwent structural brain MRI and [18F]FEPPA PET scan and their blood samples were obtained and assessed for serum NfL concentrations. We found no significant differences in serum NfL levels across clinical groups, controlling for age. We also found no significant association between NfL levels and brain TSPO in the entire cohort. We observed a negative association between serum NfL and negative symptom severity in CHR. Our findings suggest that neither active neuroaxonal deterioration as measured with NfL nor associated neuroimmune activation (TSPO) is clearly identifiable in an early mostly untreated psychosis sample including its putative high-risk.

BACKGROUND: The intelligence quotient (IQ) of patients with first-episode psychosis (FEP) and their unaffected relatives may be related to the genetic burden of schizophrenia (SCZ). The polygenic score approach can be useful for testing this question.
OBJECTIVE: To assess the contribution of the polygenic risk scores for SCZ (PGS-SCZ) and polygenic scores for IQ (PGS-IQ) to the individual IQ and its difference from the mean IQ of the family (named family-IQ) through a family-based design in an FEP sample.
METHODS: The PAFIP-FAMILIES sample (Spain) consists of 122 FEP patients, 131 parents, 94 siblings, and 176 controls. They all completed the WAIS Vocabulary subtest for IQ estimation and provided a DNA sample. We calculated PGS-SCZ and PGS-IQ using the continuous shrinkage method. To account for relatedness in our sample, we performed linear mixed models. We controlled for covariates potentially related to IQ, including age, years of education, sex, and ancestry principal components.
RESULTS: FEP patients significantly deviated from their family-IQ. FEP patients had higher PGS-SCZ than other groups, whereas the relatives had intermediate scores between patients and controls. PGS-IQ did not differ between groups. PGS-SCZ significantly predicted the deviation from family-IQ, whereas PGS-IQ significantly predicted individual IQ.
CONCLUSIONS: PGS-SCZ discriminated between different levels of genetic risk for the disorder and was specifically related to patients\' lower IQ in relation to family-IQ. The genetic background of the disorder may affect neurocognition through complex pathological processes interacting with environmental factors that prevent the individual from reaching their familial cognitive potential.

UNASSIGNED: The early stages of psychotic disorders correspond to the early phases of the disease and include the prodromal phase and first-episode psychosis; they constitute a period at high risk of suicidal behaviour. A long duration of untreated psychosis (DUP) is among the risk factors of suicidal behaviour identified in this early period. Many studies have shown the effectiveness of early interventions on the overall prognosis of psychotic disorders in the early stages, and early intervention strategies have been developed and tested worldwide. Several authors reported an improvement in suicidal behaviours; however, all these data have not been systematically analysed yet. The main objective of this systematic review was to collect evidence on the effect on suicidal behaviour of early interventions for patients in the early stages of psychotic disorders.
UNASSIGNED: We will carry out a systematic review of the literature according to the PRISMA criteria by searching articles in five databases (PubMed, Cochrane, PsycINFO, Scopus, EMBASE), without restriction on the publication date. The selection criteria are: articles (any type; e.g. prospective, retrospective, controlled or uncontrolled, and literature reviews) on early interventions for psychotic disorders in the early stages with data on suicide attempts, death by suicide, suicidal ideation; articles written in English or French. Exclusion criteria are: articles on suicidal behaviours in patients with psychotic disorders in the early stages, but without early intervention, and articles on early-stage psychotic disorders without data on suicidal behaviours.
UNASSIGNED: If this review confirms the effectiveness on suicidal behaviours of early interventions for young patients with psychotic disorders, the development/implementation of such intervention programmes should be better promoted.
UNASSIGNED: https://www.crd.york.ac.uk/prospero/, identifier CRD42021237833.

UNASSIGNED: Psychiatric patients are at high risk of readmission, and a high body mass index has previously been shown as a risk factor. We sought to replicate this finding and 1) to prospectively assess the association of metabolic syndrome and its five components with readmission in psychiatric hospitals and 2) to identify other clinical and sociodemographic predictors of readmission.
UNASSIGNED: Between 2007 and 2019, data on 16727 admissions of 7786 adult and elderly patients admitted to the Department of Psychiatry of the Lausanne University Hospital, were collected. Metabolic syndrome was defined according to the International Diabetes Federation definition. Cox frailty models were used to investigate the associations between readmission and metabolic disturbances.
UNASSIGNED: A total of 2697 (35%) patients were readmitted to our psychiatric hospital. Novel risk factors for readmission in non-smokers were identified, including being overweight (HR=1.26; 95%CI=[1.05; 1.51]) or obese (HR=1.33; 95%CI=[1.08; 1.62]), displaying hypertriglyceridemia (HR=1.21; 95%CI=[1.04; 1.40]) and metabolic syndrome (HR=1.26; 95%CI=[1.02; 1.55]). Central obesity and hyperglycemia increased the risk of readmission when considering the Health of the Nation Outcome Scales variable. In first-episode psychosis patients, obesity (HR=2.23; 95%CI=[1.14; 4.30]) and high-density lipoprotein hypocholesterolemia (HR=1.90; 95%CI=[1.14; 3.20]) doubled the risk of readmission.
UNASSIGNED: The observed interaction between smoking and metabolic variables are compatible with a ceiling effect; metabolic variables increase the risk of readmission in non-smokers but not in smokers who are already at higher risk. Future studies should determine whether better metabolic monitoring and treatment can reduce readmission risk.