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Purpose: Previous studies have investigated the role of gender in clinical symptoms, social functioning, and neuropsychological performance in people with first-episode psychosis (FEP). However, the evidence of gender differences for metacognition in subjects with FEP is still limited and controversial. The aim of the present study was to explore gender differences in cognitive insight and cognitive biases in this population. Methods: Cross-sectional study was carried out in a sample of 104 patients with FEP (35 females and 69 males) recruited from mental health services. Symptoms were assessed with the Positive and Negative Syndrome Scale, cognitive insight with the Beck Cognitive Insight Scale, and cognitive bias by the Cognitive Biases Questionnaire for Psychosis. The assessment also included clinical and sociodemographic characteristics. Results: After controlling for potential confounders (level of education, marital status, and duration of psychotic illness) analysis of covariance revealed that males presented greater self-reflectiveness (p = 0.004) when compared to females. However, no significant differences were found in self-certainty and composite index of the cognitive insight scale, as in the cognitive biases assessed. Conclusions: Gender was an independent influence factor for self-reflectiveness, being better for males. Self-reflectiveness, if shown to be relatively lacking in women, could contribute to the design of more gender-sensitive and effective psychotherapeutic treatments, as being able to self-reflect predicts to better treatment response in psychosis. [ABSTRACT FROM AUTHOR]

Background: There is strong evidence supporting the association between environmental factors and increased risk of non-affective psychotic disorders. However, the use of sound statistical methods to account for spatial variations associated with environmental risk factors, such as urbanicity, migration, or deprivation, is scarce in the literature. Methods: We studied the geographical distribution of non-affective first-episode psychosis (NA-FEP) in a northern region of Spain (Navarra) during a 54-month period considering area-level socioeconomic indicators as putative explanatory variables. We used several Bayesian hierarchical Poisson models to smooth the standardized incidence ratios (SIR). We included neighborhood-level variables in the spatial models as covariates. Results: We identified 430 NA-FEP cases over a 54-month period for a population at risk of 365,213 inhabitants per year. NA-FEP incidence risks showed spatial patterning and a significant ecological association with the migrant population, unemployment, and consumption of anxiolytics and antidepressants. The high-risk areas corresponded mostly to peripheral urban regions; very few basic health sectors of rural areas emerged as high-risk areas in the spatial models with covariates. Discussion: Increased rates of unemployment, the migrant population, and consumption of anxiolytics and antidepressants showed significant associations linked to the spatial-geographic incidence of NA-FEP. These results may allow targeting geographical areas to provide preventive interventions that potentially address modifiable environmental risk factors for NA-FEP. Further investigation is needed to understand the mechanisms underlying the associations between environmental risk factors and the incidence of NA-FEP. [ABSTRACT FROM AUTHOR]

The role of the complement system in schizophrenia (Sz) is inconclusive due to heterogeneity of the disease and study designs. Here, we assessed the levels of complement activation products and functionality of the classical pathway in acutely ill unmedicated Sz patients at baseline and after 6 weeks of treatment versus matched controls. The study included analyses of the terminal complement complex (sTCC) and C5a in plasma from 96 patients and 96 controls by enzyme-linked immunosorbent assay. Sub-group analysis of serum was conducted for measurement of C4 component and activity of the classical pathway (28 and 24 cases per cohort, respectively). We found no differences in levels of C5a, C4 and classical pathway function in patients versus controls. Plasma sTCC was significantly higher in patients [486 (392–659) ng/mL, n = 96] compared to controls [389 (304–612) ng/mL, n = 96] (p = 0.027, δ = 0.185), but not associated with clinical symptom ratings or treatment. The differences in sTCC between Sz and controls were confirmed using an Aligned Rank Transformation model considering the covariates age and sex (p = 0.040). Additional analysis showed that sTCC was significantly associated with C-reactive protein (CRP; p = 0.006). These findings suggest that sTCC plays a role in Sz as a trait marker of non-specific chronic immune activation, as previously described for CRP. Future longitudinal analyses with more sampling time points from early recognition centres for psychoses may be helpful to better understand the temporal dynamics of innate immune system changes during psychosis development. [ABSTRACT FROM AUTHOR]

Historically, the analysis of stimulus-dependent time–frequency patterns has been the cornerstone of most electroencephalography (EEG) studies. The abnormal oscillations in high-frequency waves associated with psychotic disorders during sensory and cognitive tasks have been studied many times. However, any significant dissimilarity in the resting-state low-frequency bands is yet to be established. Spectral analysis of the alpha and delta band waves shows the effectiveness of stimulus-independent EEG in identifying the abnormal activity patterns of pathological brains. A generalized model incorporating multiple frequency bands should be more efficient in associating potential EEG biomarkers with first-episode psychosis (FEP), leading to an accurate diagnosis. We explore multiple machine-learning methods, including random-forest, support vector machine, and Gaussian process classifier (GPC), to demonstrate the practicality of resting-state power spectral density (PSD) to distinguish patients of FEP from healthy controls. A comprehensive discussion of our preprocessing methods for PSD analysis and a detailed comparison of different models are included in this paper. The GPC model outperforms the other models with a specificity of 95.78% to show that PSD can be used as an effective feature extraction technique for analyzing and classifying resting-state EEG signals of psychiatric disorders. [ABSTRACT FROM AUTHOR]

Purpose: Service disengagement is a major concern for "Early Intervention in Psychosis" (EIP). Indeed, identifying predictors of engagement is crucial to maximize mental healthcare interventions in first-episode psychosis (FEP). No Italian study on this topic has been reported to date. Thus, the aims of this investigation were: (1) to examine short-term disengagement rate in an Italian population of FEP patients treated within an EIP service across a 1-year follow-up period, and (b) to assess the most relevant predictors of disengagement in the first year of treatment. Methods: All participants were young FEP help-seeking patients, aged 12–35 years, enrolled within the "Parma Early Psychosis" (Pr-EP) protocol. At baseline, they completed the Positive And Negative Syndrome Scale (PANSS), the Health of the Nation Outcome Scale (HoNOS) and the Global Assessment of Functioning (GAF) scale. Univariate and multivariate Cox regression analyses were used. Results: 496 FEP individuals were enrolled in this research. Across the follow-up, a 16.5% prevalence of short-term disengagement was found. Particularly robust predictors of service disengagement were poor baseline treatment non-adherence, living with parents and the presence of brief psychotic disorder or schizophreniform disorder at entry. Conclusion: About 16% of FEP patients disengaged the Pr-EP program within the first year of treatment. A solution to reduce disengagement and/or to favor re-engagement of these subjects might be to remain on EIP program caseloads allowing the option for low-intensity support and monitoring, also via remote technology. [ABSTRACT FROM AUTHOR]

Purpose: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Previous reviews of smoking prevalence among individuals with primary psychosis have largely been internationally focused, with little attention given to within- and among subgroup comparisons of U.S. individuals with such disorders. Nationally, smoking prevalence has been decreasing among the general population. We aimed to review national and divisional samples to determine if this downward trend is being reflected among individuals with primary psychotic disorders, if geographical differences exist, and which demographic characteristics are associated with reported rates. We conducted a systematic search of the PubMed, PsycINFO, and Cochrane databases using a floor of 2010. Studies found during a review of references, and studies previously known to the authors but not found during the initial search, were also reviewed. We found 7 papers which reported the prevalence of smoking among individuals with psychotic disorders, and 2 papers which reported the prevalence of general tobacco and/or vaped nicotine use in this population. One eligible paper was excluded due to the same authors publishing more recent data of the same sample. In all, 1 national and 7 divisional samples were included for analysis. Individuals with psychotic disorders still smoke at rates far higher than the general population. We did not find strong support for a downward trend in smoking in this population but did find support for geographical heterogeneity. Smoking interventions must be tested and implemented nationwide. [ABSTRACT FROM AUTHOR]

Vitamin deficiency syndromes and blood–brain barrier (BBB) dysfunction are frequent phenomena in psychiatric conditions. We analysed the largest available first-episode schizophrenia-spectrum psychosis (FEP) cohort to date regarding routine cerebrospinal fluid (CSF) and blood parameters to investigate the association between vitamin deficiencies (vitamin B12 and folate) and BBB impairments in FEP. We report a retrospective analysis of clinical data from all inpatients that were admitted to our tertiary care hospital with an ICD-10 diagnosis of a first-episode F2x (schizophrenia-spectrum) between January 1, 2008 and August 1, 2018 and underwent a lumbar puncture, blood-based vitamin status diagnostics and neuroimaging within the clinical routine. 222 FEP patients were included in our analyses. We report an increased CSF/serum albumin quotient (Qalb) as a sign of BBB dysfunction in 17.1% (38/222) of patients. White matter lesions (WML) were present in 29.3% of patients (62/212). 17.6% of patients (39/222) showed either decreased vitamin B12 levels or decreased folate levels. No statistically significant association was found between vitamin deficiencies and altered Qalb. This retrospective analysis contributes to the discussion on the impact of vitamin deficiency syndromes in FEP. Although decreased vitamin B12 or folate levels were found in approximately 17% of our cohort, we found no evidence for significant associations between BBB dysfunction and vitamin deficiencies. To strengthen the evidence regarding the clinical implications of vitamin deficiencies in FEP, prospective studies with standardized measurements of vitamin levels together with follow-up measurements and assessment of symptom severity in addition to CSF diagnostics are needed. [ABSTRACT FROM AUTHOR]

Background: Substance use remains a barrier to recovery for young people accessing early intervention services for psychosis. While correlates of use have been explored in populations experiencing a first episode of psychosis (FEP), sample sizes have been small and less research assesses cohorts at ultrahigh risk of psychosis (UHR). Methods: This study uses data from a naturalistic cohort including UHR and FEP participants (N = 1252) to elucidate clinical correlates of use in the past 3 months of any illicit substance, amphetamine-type stimulants (ATS), cannabis, and tobacco. Moreover, network analysis based on use of these substances and additionally alcohol, cocaine, hallucinogens, sedatives, inhalants, and opioids was completed. Results: Young people with FEP used substances at significantly higher rates than those at UHR. High concurrence of use was seen between substances. In the FEP group, participants who had used any illicit substance, ATS, and/or tobacco had increased positive symptoms and decreased negative symptoms. Young people with FEP who used cannabis had increased positive symptoms. In the UHR group, participants who had used any illicit substance, ATS, and/or cannabis in the past 3 months showed decreased negative symptoms compared to those who had not. Conclusion: A distinct clinical picture of more florid positive symptoms and alleviated negative symptoms seen in those who use substances in the FEP group appears muted in the UHR cohort. Treating young people at UHR in early intervention services represents the earliest opportunity to address substance use early to improve outcomes. [ABSTRACT FROM AUTHOR]

We determined cytokine levels in paired serum/CSF samples from first-episode schizophrenia (FES) participants (n = 20) and controls (n = 21) using a 13-plex immunoassay. Applying strictly-determined detection limits, 12 cytokines were found in serum and two in CSF. Higher serum MCP-1 levels (p = 0.007) were present in FES versus controls, which correlated with serum IgG (R = − 0.750; p = 0.013). Finally, IL-18 levels correlated with body weight in FES (R = 0.691; p = 0.041). This study demonstrates potential limitations in the sensitivity of multiplex cytokine assays for CSF studies in mental disorders and suggests that some published studies in this area should be re-evaluated. [ABSTRACT FROM AUTHOR]

Background: Some migrant and ethnic minority groups have a higher risk of coercive pathways to care; however, it is unclear whether differences in clinical presentation contribute to this risk. We sought to assess: (i) whether there were differences in clinician-rated symptoms and behaviours across first-generation immigrant and refugee groups at the first psychiatric hospitalization after psychosis diagnosis, and (ii) whether these differences accounted for disparities in involuntary admission. Methods: Using population-based health administrative data from Ontario, Canada, we constructed a sample (2009–2013) of incident cases of non-affective psychotic disorder followed for two years to identify first psychiatric hospitalization. We compared clinician-rated symptoms and behaviours at admission between first-generation immigrants and refugees and the general population, and adjusted for these variables to ascertain whether the elevated prevalence of involuntary admission persisted. Results: Immigrants and refugee groups tended to have lower ratings for affective symptoms, self-harm behaviours, and substance use, as well as higher levels of medication nonadherence and poor insight. Immigrant groups were more likely to be perceived as aggressive and a risk of harm to others, and both groups were perceived as having self-care issues. Adjustment for perceived differences in clinical presentation at admission did not attenuate the higher prevalence of involuntary admission for immigrant and refugee groups. Conclusions: First-generation migrant groups may differ in clinical presentation during the early course of psychotic illness, although these perceived differences did not explain the elevated rates of involuntary admission. Further research using outpatient samples and tools with established cross-cultural validity are warranted. [ABSTRACT FROM AUTHOR]

Primary care is an important part of the help-seeking pathway for young people experiencing early psychosis, but sex differences in clinical presentation in these settings are unexplored. We aimed to identify sex differences in clinical presentation to primary care services in the 1-year period prior to a first diagnosis of psychotic disorder. We identified first-onset cases of non-affective psychotic disorder over a 10-year period (2005–2015) using health administrative data linked with electronic medical records (EMRs) from primary care (n = 465). Detailed information on encounters in the year prior to first diagnosis was abstracted, including psychiatric symptoms, other relevant behaviours, and diagnoses recorded by the family physician (FP). We used modified Poisson regression models to examine sex differences in the signs, symptoms, and diagnoses recorded by the FP, adjusting for various clinical and sociodemographic factors. Positive symptoms (PR = 0.76, 95%CI: 0.58, 0.98) and substance use (PR = 0.54, 95%CI: 0.40, 0.72) were less prevalent in the medical records of women. Visits by women were more likely to be assigned a diagnosis of depression or anxiety (PR = 1.18, 95%CI: 1.00, 1.38), personality disorder (PR = 5.49, 95%CI: 1.22, 24.62), psychological distress (PR = 11.29, 95%CI: 1.23, 103.91), and other mental or behavioral disorders (PR = 3.49, 95%CI: 1.14, 10.66) and less likely to be assigned a diagnosis of addiction (PR = 0.33, 95%CI: 0.13, 0.87). We identified evidence of sex differences in the clinical presentation of early psychosis and recorded diagnoses in the primary care EMR. Further research is needed to better understand sex differences in clinical presentation in the primary care context, which can facilitate better understanding, detection, and intervention for first-episode psychotic disorders. [ABSTRACT FROM AUTHOR]

Purpose: First-episode psychosis (FEP) is characterised by wide heterogeneity in terms of symptom presentation and illness course. However, the heterogeneity of quality of life (QoL) in FEP is not well understood. We investigated whether subgroups can be identified using participants' responses on four QoL domains (physical health, psychological, social relationships, and environmental) 18-months into the recovery phase of FEP. We then examined the discriminant validity of these subgroups with respect to clinical, cognitive, and functioning features of FEP.Method: Demographic and clinical characteristics, QoL, cognition, and functioning were assessed in 100 people with FEP at the 18-month follow-up of a randomised controlled trial of Individual Placement Support, which aims to facilitate vocational recovery. QoL was measured using the World Health Organisation's QoL-BRIEF. A two-stage clustering approach using Ward's method and Squared Euclidean Distance with a k-means confirmation was conducted. Multinomial logistic regressions were used to establish external validity.Results: Three QoL subgroups emerged: a 'good' subgroup with relatively high QoL across all domains (31%), an 'intermediate' subgroup with relatively low psychological QoL (48%) and a 'poor' subgroup with markedly low social relationship QoL (21%). Negative symptoms, depressive symptoms, social/occupational functioning, and social inclusion at follow-up predicted subgroup membership. Sensitivity analysis found similar results.Conclusion: Although some individuals with FEP have QoL comparable to individuals without mental ill health, QoL can remain concerningly low despite treatment efforts. Future research on interventions that target factors associated with poor QoL, such as low social inclusion, is required to counteract prolonged poor QoL in FEP. [ABSTRACT FROM AUTHOR]

Access to evidence-based early intervention for adolescents with psychosis is critically important. The aim of this work was analysing the feasibility, acceptability and potential effects of a psychological intervention based on metacognitive interpersonal therapy (MIT) in adolescents presenting with early psychosis. Twenty-three participants (aged 14–18) experiencing first-episode psychosis or an at-risk mental state for psychosis were offered up to 40h of individual MIT over a 12-month period. Effect sizes were calculated for changes in subjective recovery experience (primary outcome), psychotic symptoms (secondary outcome), and metacognition (hypothetical mechanism of change) from baseline to treatment end. At study completion, 21 out of 23 (91.3%) participants had received twelve or more sessions of MIT. The average number of MIT treatment sessions received was 31 (range 12–40). Large effect sizes were observed for changes in subjective recovery, self-reflectivity, understanding others' minds, mastery, and emotional distress. Medium effect sizes were observed for changes in negative, positive, and disorganized symptoms. This is the first study to suggest that MIT is both acceptable to young people experiencing early psychosis and is associated with improvements in subjective recovery, symptoms, and metacognition. Despite study limitations, evidence of MIT feasibility, acceptability and potential effects was sufficient to warrant further investigation. [ABSTRACT FROM AUTHOR]

Purpose: In the US, Black people diagnosed with schizophrenia experience worse psychosocial and clinical outcomes than their White counterparts. While racism-related factors contribute to these disparities, an additional understudied explanation may be that psychosocial treatments for psychotic disorders are less effective for Black than White individuals. The purpose of this study is to examine the extent to which best treatment practices for first-episode psychosis (FEP) are effective for Black and White participants. Methods: We conducted a secondary data analysis of the Recovery After an Initial Schizophrenia Episode Early Treatment Program (RAISE-ETP), a two-year multisite trial that compared a coordinated specialty care intervention for FEP (NAVIGATE) to community care as usual (CC) in 34 sites across the US. Specifically, we compared interviewer-rated quality of life and symptoms, as well as self-reported mental health and stigma, between 139 Non-Latinx Black and 172 Non-Latinx White participants with FEP in NAVIGATE and CC. Results: We found few differences between Black and White participants over two-year outcomes, either overall or in terms of benefit from NAVIGATE. Across both treatment conditions, Black participants improved less than White participants on positive symptoms, an effect driven primarily by suspiciousness/persecution. In NAVIGATE, self-reported mental health stigma decreased for both Black and White participants, while in CC stigma decreased for White participants but increased for Black participants. This effect was driven primarily by experienced stigma rather than self-stigma. Conclusion: NAVIGATE benefits both Black and White individuals diagnosed with FEP. Mental health stigma and positive symptoms may be particularly important aspects of treatment for Black individuals diagnosed with FEP. [ABSTRACT FROM AUTHOR]

We investigated the level of hearing tolerance in patients with first-episode psychosis (FEP) and panic disorder (PD) as compared to two different groups of healthy controls (HC, HC2), one for each experiment, because we used two distinct psychophysical paradigms. We evaluated auditory discomfort of 28 volunteers (14 with FEP and 14 HC) in the first study and of 42 volunteers (21 with PD and 21 HC2) in the second study. We presented 20 sounds: 16 pure-tone frequency sweeps (specially designed for use with FEP) and 11 s or 13 s musical sequences from the very beginning of the music "Play the Game" (PLAY) from Queen and its reverses. The first procedure used a Likert-like 0–10 scale ranging from "nothing bad" to "too bad" where volunteers made vertical marks along a horizontal line according to their discomfort. The second procedure involved subjective magnitude estimation online due to the SARS-COV-19 pandemic. Sounds were placed online and played by PD and HC2 volunteers themselves after having listened to the standard (the first 8 s from RADIO, "Radio Ga Ga" by Queen). Then, PD and HC2 volunteers were asked to assign values equal to, or multiples of 10 that felt like, or proportional to, their hearing "discomfort" in comparison with Sound 00 (RADIO). Our findings showed that FEP volunteers assign more discomfort to the 16 specially designed frequency sweep stimuli that appear not to affect HC, HC2, and PD. On the other hand, musical sequences from PLAY caused strong discomfort to PD in the reverse mode, but did not seem to affect HC, HC2, and FEP. Further experiments using the exact same paradigm with FEP and PD are needed to explore these findings. [ABSTRACT FROM AUTHOR]

How people in long-term recovery (clinical and personal) in first-episode psychosis (schizophrenia and bipolar spectrum disorders) experience the mental health and welfare services they interact with is not frequently studied but has significant implications. We therefore aimed to explore which aspects of these services people with FEP evaluate as important for their long-term recovery. Twenty participants in clinical and/or personal recovery from two Norwegian long-term follow-up studies after FEP (TOP 10-year and TIPS 20-year) were sampled for this interview-based qualitative study. The research-team included service user experience. A deductive analysis based on personal accounts of recovery generated five service aspects. Few specific types of interventions were reported to promote recovery although medications, psychotherapy and employment support were mentioned. Participants valued services based in collaboration and that focused on their resources rather than limitations. The importance of long-term follow-up with a consistent aim was highlighted, as was the inclusion of caregivers and peers. Welfare services contributed to recovery by supporting basic needs and safety, but some experienced social exclusion when not participating in the labor market. This study is unique in exploring the role of services, including welfare, in long-term FEP recovery from service user perspectives. Participants evaluated that services played a more indirect role in long-term recovery by supporting their personal resources, although what they needed from services had frequently not been offered. Their expertise by experience contributes valuable knowledge. Better service coordination and consistent implementation of this knowledge are crucial to support recovery in FEP. [ABSTRACT FROM AUTHOR]

Purpose: The influence of rurality on the duration of untreated psychosis (DUP) in first-episode psychosis (FEP) is poorly understood. We investigated factors associated with FEP in rural/urban settings and whether there are rural/urban differences in DUP and the mode (speed) of onset of psychosis.We used the Cambridgeshire and Peterborough NHS Foundation Trust Research Database (CPFTRD) to identify all persons presenting to an early intervention for psychosis service with FEP between 2013 and 2015. We performed descriptive statistics and multivariable linear and multinomial regression to assess the relationships between the study outcomes and the independent variables.One hundred and fifty-five FEP patients were identified, with a mean age of 23.4 (SD, 5.3) years. The median DUP was 129.0 (IQR: 27.5–524.0) days. In rural areas, FEP patients were more likely to be employed and live with family than those in urban areas. A longer DUP was observed among patients with an insidious onset of psychosis compared with an acute onset (619.5 (IQR: 333.5–945.0)) vs. (17.0 (IQR: 8.0–30.5)) days respectively, p < 0.0001. We found evidence that the mode of onset of psychosis differed by employment status and living circumstances. There was insufficient evidence of rural/urban differences in DUP and mode of onset of psychosis.Our results suggest that the mode of onset of psychosis is an important indicator of treatment delay and could provide vital information for service planning and delivery. Sociodemographic variations in FEP exist in rural populations, and our findings are similar to those observed in urban settings.Methods: The influence of rurality on the duration of untreated psychosis (DUP) in first-episode psychosis (FEP) is poorly understood. We investigated factors associated with FEP in rural/urban settings and whether there are rural/urban differences in DUP and the mode (speed) of onset of psychosis.We used the Cambridgeshire and Peterborough NHS Foundation Trust Research Database (CPFTRD) to identify all persons presenting to an early intervention for psychosis service with FEP between 2013 and 2015. We performed descriptive statistics and multivariable linear and multinomial regression to assess the relationships between the study outcomes and the independent variables.One hundred and fifty-five FEP patients were identified, with a mean age of 23.4 (SD, 5.3) years. The median DUP was 129.0 (IQR: 27.5–524.0) days. In rural areas, FEP patients were more likely to be employed and live with family than those in urban areas. A longer DUP was observed among patients with an insidious onset of psychosis compared with an acute onset (619.5 (IQR: 333.5–945.0)) vs. (17.0 (IQR: 8.0–30.5)) days respectively, p < 0.0001. We found evidence that the mode of onset of psychosis differed by employment status and living circumstances. There was insufficient evidence of rural/urban differences in DUP and mode of onset of psychosis.Our results suggest that the mode of onset of psychosis is an important indicator of treatment delay and could provide vital information for service planning and delivery. Sociodemographic variations in FEP exist in rural populations, and our findings are similar to those observed in urban settings.Results: The influence of rurality on the duration of untreated psychosis (DUP) in first-episode psychosis (FEP) is poorly understood. We investigated factors associated with FEP in rural/urban settings and whether there are rural/urban differences in DUP and the mode (speed) of onset of psychosis.We used the Cambridgeshire and Peterborough NHS Foundation Trust Research Database (CPFTRD) to identify all persons presenting to an early intervention for psychosis service with FEP between 2013 and 2015. We performed descriptive statistics and multivariable linear and multinomial regression to assess the relationships between the study outcomes and the independent variables.One hundred and fifty-five FEP patients were identified, with a mean age of 23.4 (SD, 5.3) years. The median DUP was 129.0 (IQR: 27.5–524.0) days. In rural areas, FEP patients were more likely to be employed and live with family than those in urban areas. A longer DUP was observed among patients with an insidious onset of psychosis compared with an acute onset (619.5 (IQR: 333.5–945.0)) vs. (17.0 (IQR: 8.0–30.5)) days respectively, p < 0.0001. We found evidence that the mode of onset of psychosis differed by employment status and living circumstances. There was insufficient evidence of rural/urban differences in DUP and mode of onset of psychosis.Our results suggest that the mode of onset of psychosis is an important indicator of treatment delay and could provide vital information for service planning and delivery. Sociodemographic variations in FEP exist in rural populations, and our findings are similar to those observed in urban settings.Conclusions: The influence of rurality on the duration of untreated psychosis (DUP) in first-episode psychosis (FEP) is poorly understood. We investigated factors associated with FEP in rural/urban settings and whether there are rural/urban differences in DUP and the mode (speed) of onset of psychosis.We used the Cambridgeshire and Peterborough NHS Foundation Trust Research Database (CPFTRD) to identify all persons presenting to an early intervention for psychosis service with FEP between 2013 and 2015. We performed descriptive statistics and multivariable linear and multinomial regression to assess the relationships between the study outcomes and the independent variables.One hundred and fifty-five FEP patients were identified, with a mean age of 23.4 (SD, 5.3) years. The median DUP was 129.0 (IQR: 27.5–524.0) days. In rural areas, FEP patients were more likely to be employed and live with family than those in urban areas. A longer DUP was observed among patients with an insidious onset of psychosis compared with an acute onset (619.5 (IQR: 333.5–945.0)) vs. (17.0 (IQR: 8.0–30.5)) days respectively, p < 0.0001. We found evidence that the mode of onset of psychosis differed by employment status and living circumstances. There was insufficient evidence of rural/urban differences in DUP and mode of onset of psychosis.Our results suggest that the mode of onset of psychosis is an important indicator of treatment delay and could provide vital information for service planning and delivery. Sociodemographic variations in FEP exist in rural populations, and our findings are similar to those observed in urban settings. [ABSTRACT FROM AUTHOR]

Up-regulation of the complement component 4A (C4A) in the brain has been associated with excessive synaptic pruning and increased schizophrenia (SZ) susceptibility. Over-expression of C4A has been observed in SZ postmortem brain tissue, and the gene encoding for a protein inhibitor of C4A activity, CUB and Sushi multiple domains 1 (CSMD1) gene, has been implicated in SZ risk and cognitive ability. Herein, we examined C4A and CSMD1 mRNA expression in peripheral blood from antipsychotic-naive individuals with first-episode psychosis (FEP; n = 73) and mentally healthy volunteers (n = 48). Imputed C4 locus structural alleles and C4A serum protein levels were investigated. Associations with symptom severity and cognitive domains performance were explored. A significant decrease in CSMD1 expression levels was noted among FEP patients compared to healthy volunteers, further indicating a positive correlation between C4A and CSMD1 mRNA levels in healthy volunteers but not in FEP cases. In addition, C4 copy number variants previously associated with SZ risk correlated with higher C4A mRNA levels in FEP cases, which confirms the regulatory effect of C4 structural variants on gene expression. Evidence also emerged for markedly elevated C4A serum concentrations in FEP cases. Within the FEP patient group, higher C4A mRNA levels correlated with more severe general psychopathology symptoms and lower CSMD1 mRNA levels predicted worse working memory performance. Overall, these findings suggest C4A complement pathway perturbations in individuals with FEP and corroborate the involvement of CSMD1 in prefrontal-mediated cognitive functioning. [ABSTRACT FROM AUTHOR]

First-episode psychosis (FEP) can be quite variable in clinical presentation, and both sex and gender may account for some of this variability. Prior literature on sex or gender differences in symptoms of psychosis have been inconclusive, and a comprehensive summary of evidence on the early course of illness is lacking. The objective of this study was to conduct a systematic review and meta-analysis of the literature to summarize prior evidence on the sex and gender differences in the symptoms of early psychosis. We conducted an electronic database search (MEDLINE, Scopus, PsycINFO, and CINAHL) from 1990 to present to identify quantitative studies focused on sex or gender differences in the symptoms of early psychosis. We used random effects models to compute pooled standardized mean differences (SMD) and risk ratios (RR), with 95% confidence intervals (CI), for a range of symptoms. Thirty-five studies met the inclusion criteria for the systematic review, and 30 studies were included in the meta-analysis. All studies examined sex differences. Men experienced more severe negative symptoms (SMD = − 0.15, 95%CI = − 0.21, − 0.09), whereas women experienced more severe depressive symptoms (SMD = 0.21, 95%CI = 0.14, 0.27) and had higher functioning (SMD = 0.16, 95%CI = 0.10, 0.23). Women also had a lower prevalence of substance use issues (RR = 0.65, 95%CI = 0.61, 0.69). Symptoms of early psychosis varied between men and women; however, we were limited in our ability to differentiate between biological sex and gender factors. These findings may help to inform early detection and intervention efforts to better account for sex and gender differences in early psychosis presentation. [ABSTRACT FROM AUTHOR]

This pilot study examined violence risk assessment among a sample of young adults receiving treatment for early psychosis. In this study, thirty participants were assessed for violence risk at baseline. Participants completed follow-up assessments at 3, 6, 9 and 12 months to ascertain prevalence of violent behavior. Individuals were on average 24.1 years old (SD = 3.3 years) and predominantly male (n = 24, 80%). In this sample, six people (20%) reported engaging in violence during the study period. Individuals who engaged in violence had higher levels of negative urgency (t(28) = 2.21, p = 0.035) This study sought to establish the feasibility, acceptability, and clinical utility of violence risk assessment for clients in treatment for early psychosis. Overall, this study found that most individuals with early psychosis in this study (who are in treatment) were not at risk of violence. Findings suggest that violent behavior among young adults with early psychosis is associated with increased negative urgency. [ABSTRACT FROM AUTHOR]

Rationale: How striatal dopamine synthesis capacity (DSC) contributes to the pathogenesis of negative symptoms in first-episode schizophrenia (SZ) and delusional disorder (DD) has seldom been explored. As negative symptoms during active psychotic episodes can be complicated by secondary influences, such as positive symptoms, longitudinal investigations may help to clarify the relationship between striatal DSC and negative symptoms and differentiate between primary and secondary negative symptoms. Objective: A longitudinal study was conducted to examine whether baseline striatal DSC would be related to negative symptoms at 3 months in first-episode SZ and DD patients. Methods: Twenty-three first-episode age- and gender-matched patients (11 DD and 12 SZ) were consecutively recruited through an early intervention service for psychosis in Hong Kong. Among them, 19 (82.6%) patients (9 DD and 10 SZ) were followed up at 3 months. All patients received an 18F-DOPA PET/MR scan at baseline. Results: Baseline striatal DSC (Kocc;30–60) was inversely associated with negative symptoms at 3 months in first-episode SZ patients (rs = − 0.80, p = 0.010). This association remained in SZ patients even when controlling for baseline negative, positive, and depressive symptoms, as well as cumulative antipsychotic dosage (β = − 0.69, p = 0.012). Such associations were not observed in first-episode DD patients. Meanwhile, the severity of negative symptoms at 3 months was associated with more positive symptoms in DD patients (rs = 0.74, p = 0.010) and not in SZ patients. Conclusions: These findings highlight the role of striatal DSC in negative symptoms upon resolution of active psychotic episodes among first-episode SZ patients. Baseline striatal dopamine activity may inform future symptom expression with important treatment implications. [ABSTRACT FROM AUTHOR]

The purpose of this program evaluation was to examine preliminary outcomes associated with a novel stepdown program for clients of early intervention in psychosis services (“Step Up”) that featured occupational therapy (OT) as a critical treatment component. Clients participated in Step Up for at least 6 months and were administered pre-post assessments of clinician-rated performance of daily living activities and self-perceived performance and satisfaction with daily occupational functioning. Paired samples Wilcoxon tests were used to compare outcomes across the two time points. Data from 23 participants of Step Up were analyzed. Clinician-rated performance of daily living (especially in the areas of money and time management and leisure engagement) and client-rated performance and satisfaction with daily occupational functioning improved significantly over time. Results demonstrate the promise of programs such as Step Up that capitalize on OT and promote functional outcomes during the transition from early intervention. [ABSTRACT FROM AUTHOR]

The pharmacological interventions available for individuals in the early stages of psychosis are extremely limited. For those at clinical high risk for psychosis, there is no licensed treatment available. For those with first-episode psychosis, all licensed antipsychotic medications act via dopamine D2 receptors. While treatment with antipsychotics is transformative in some patients, in others, it is ineffective. In addition, these medications can often cause adverse effects which make patients reluctant to take them. This is a particular problem in the early phases of psychosis, when patients are being treated for the first time, as unpleasant experiences may colour their future attitude towards treatment. Recent research has suggested that cannabidiol (CBD), a compound found in the Cannabis sativa plant, may have antipsychotic effects and relatively few adverse effects and could therefore be an ideal treatment for the early phases of psychosis, when minimising adverse effects is a clinical priority. In this review, we consider CBD's potential as a treatment in the clinical high risk and first-episode stages of psychosis. First, we describe the limitations of existing treatments at these two stages. We then describe what is known of CBD's mechanisms of action, effectiveness as a treatment for psychosis, adverse effects and acceptability to patients. We discuss how some of the outstanding issues about the utility of CBD in the early phases of psychosis may be resolved through ongoing clinical trials. Finally, we consider the impact of recreational cannabis use and over-the-counter cannabinoids preparations and discuss the potential therapeutic role of other compounds that modulate the endocannabinoid system in psychosis. [ABSTRACT FROM AUTHOR]

Women present a second peak of incidence of psychosis during the menopausal transition, partially explained by the loss of estrogen protection conferred during the reproductive years. In view of the lack of studies comparing sociodemographic, biological, and clinical variables and neurocognitive performance between women with early onset of psychosis (EOP) and those with late onset of psychosis (LOP), our aim was to characterize both groups in a large sample of 294 first-episode psychosis (FEP) patients and 85 healthy controls (HC). In this cross-sectional study, the participants were interviewed to gather information on sociodemographic variables. We assessed laboratory features of interest and conducted a clinical assessment of psychopathological symptoms and neurocognitive abilities. From the latter, we derived a global cognitive functioning score. Analysis of covariance (ANCOVA) was used to compare EOP and LOP groups, and each group with age-comparable HC. EOP women were more frequently single and unemployed than HC age peers. While cholesterol levels in LOP women were higher than those in EOP women, no statistically significant differences were found in leptin levels. Women with LOP presented with less severe negative symptoms and higher cognitive processing speed scores than women with EOP. Cannabis and alcohol use was greater in EOP than in LOP women. Within the total FEP group, there was a history of significantly more recent traumatic events than in the HC group. Women with EOP and LOP show several sociodemographic and clinical differences, which may be valuable for planning personalized treatment. [ABSTRACT FROM AUTHOR]

Schizophrenia is characterised by cognitive impairments that are already present during early stages, including in the clinical high-risk for psychosis (CHR-P) state and first-episode psychosis (FEP). Moreover, data suggest the presence of distinct cognitive subtypes during early-stage psychosis, with evidence for spared vs. impaired cognitive profiles that may be differentially associated with symptomatic and functional outcomes. Using cluster analysis, we sought to determine whether cognitive subgroups were associated with clinical and functional outcomes in CHR-P individuals. Data were available for 146 CHR-P participants of whom 122 completed a 6- and/or 12-month follow-up; 15 FEP participants; 47 participants not fulfilling CHR-P criteria (CHR-Ns); and 53 healthy controls (HCs). We performed hierarchical cluster analysis on principal components derived from neurocognitive and social cognitive measures. Within the CHR-P group, clusters were compared on clinical and functional variables and examined for associations with global functioning, persistent attenuated psychotic symptoms and transition to psychosis. Two discrete cognitive subgroups emerged across all participants: 45.9% of CHR-P individuals were cognitively impaired compared to 93.3% of FEP, 29.8% of CHR-N and 30.2% of HC participants. Cognitively impaired CHR-P participants also had significantly poorer functioning at baseline and follow-up than their cognitively spared counterparts. Specifically, cluster membership predicted functional but not clinical outcome. Our findings support the existence of distinct cognitive subgroups in CHR-P individuals that are associated with functional outcomes, with implications for early intervention and the understanding of underlying developmental processes. [ABSTRACT FROM AUTHOR]

Purpose: Long-term data on recovery conceptualisation in psychotic illness are needed to support mental health services to organise themselves according to recovery-oriented frameworks. To our knowledge, no previous research has investigated how first-episode psychosis (FEP) service users (sampled across psychotic illness type) perceive recovery beyond 5 years after diagnosis. We aimed to explore personal recovery meaning with individuals 20 years after their FEP and examine the potential influence of clinical recovery status on how they defined recovery (i.e. personal recovery). Methods: Twenty participants were purposefully sampled from an epidemiologically representative FEP incidence cohort. At 20-year follow-up, semi-structured interviews were conducted with 10 cohort members who met full 'functional recovery criteria' (Clinically Recovered Group) and 10 who did not (Not Clinically Recovered Group). A thematic analysis was performed to develop shared themes and group-specific sub-themes to capture agreement and divergence between groups. Results: Five shared themes were produced: pursuing balance in conflict, generating meaning in life, experiencing a dynamic personal relationship with time, redressing inequality while managing added challenges/vulnerability, and directing life from resilience to flourishing. The five group-specific sub-themes developed illuminate differences in the meaning ascribed to personal recovery by each group. Conclusion: Findings emphasise the role of time in how personal recovery is conceptualised by service users and identify ways clinical recovery may influence personal recovery meaning in FEP at mid-later life. Mental health services failing to consider temporal changes in meaning-making and discounting clinical recovery risk ignoring key factors affecting personal recovery. [ABSTRACT FROM AUTHOR]

Background: Antipsychotics (APs) increase weight, metabolic syndrome, diabetes and cardiovascular disease. Guidelines recommend cardio-metabolic monitoring at initial assessment, at 3 months and then annually in people prescribed APs. Aim: To determine the rates of cardio-metabolic monitoring in AP treated early and chronic psychosis and to assess the impact of targeted improvement strategies. Methods: Medical records were reviewed in two cohorts of first-episode psychosis (FEP) patients before and after the implementation of a physical health parameter checklist and electronic laboratory order set. In a separate group of patients with chronic psychotic disorders, adherence to annual monitoring was assessed before and 3 months after an awareness-raising educational intervention. Results: In FEP, fasting glucose (39% vs 67%, p=0.05), HbA1c (0% vs 24%, p=0.005) and prolactin (18% vs 67%, p=0.001) monitoring improved. There were no significant differences in weight (67% vs 67%, p=1.0), BMI (3% vs 10%, p=0.54), waist circumference (3% vs 0%, p=1.0), fasting lipids (61% vs 76% p=0.22) or ECG monitoring (67% vs 67%, p=1.0). Blood pressure (BP) (88% vs 57%, p=0.04) and heart rate (91% vs 65%, p=0.03) monitoring dis-improved. Diet (0%) and exercise (<15%) assessment was poor. In chronic psychotic disorders, BP monitoring improved (20% vs 41.4%, p=0.05), whereas weight (17.0% vs 34.1%, p=0.12), BMI (9.7% vs 12.1%, p=1.0), fasting glucose (17% vs 24.3%, p=0.58) and fasting lipids remained unchanged (17% vs 24.3%, p=0.58). Conclusions: Targeted improvement strategies resulted in a significant improvement in a limited number of parameters in early and chronic psychotic disorders. Overall, monitoring remained suboptimal. [ABSTRACT FROM AUTHOR]

Supported by the 10% set-aside funds in the Community Mental Health Block grant, distributed at the state level, coordinated specialty care (CSC) have been widely disseminated throughout the U.S. This study explores variations in the geographical accessibility of CSC programs by neighborhood level characteristics in Washington State. CSC locations were geocoded. Socioeconomic neighborhood deprivation (i.e., Area deprivation index) and rurality (i.e., Rural–Urban Commuting Area codes) were neighborhood level characteristics extracted from the 2018 American Community Survey. Geographic accessibility of CSC was assessed using a two-step floating catchment area technique and multilevel linear models were used to examine the association between specific neighborhood characteristics and geographic accessibility. The association between access and socioeconomically deprived neighborhoods varied differentially by neighborhood rurality (an interaction effect). Model estimates indicated that the least deprived, metropolitan neighborhoods had the best access (M = 0.38; CI: 0.34, 0.42) and rural neighborhoods in the second most deprived quartile had the worst access (M = 0.16; CI: 0.11, 0.21) to CSC. There was a clear decrease in accessibility for more rural neighborhoods, regardless of other neighborhood characteristics. In conclusions, findings provide important insight into how resource distribution contributes to geographic disparities in access to CSC. The use of spatial analytic techniques has the potential to identify specific neighborhoods and populations where there is a need to expand and increase availability of CSC to ensure access to rural and socioeconomically deprived neighborhoods. [ABSTRACT FROM AUTHOR]

Subjective quality of life (SQoL) represents an important outcome of psychotic disorders. However, determinants of SQoL and their complex inter-relationships in the early course of illness remain to be clarified. Association between neurocognitive impairment and SQoL in first-episode psychosis (FEP) is understudied. This study employed structural equation modeling (SEM) to examine relationships among SQoL, depressive, positive and negative symptoms, neurocognition, and psychosocial functioning in FEP patients. Three hundred and forty-seven patients aged 25–55 years presenting with FEP to early intervention program in Hong Kong were recruited. Assessment encompassing symptom profiles, psychosocial functioning and a battery of neurocognitive tests were conducted. SF-12 mental component summary scores were computed as the primary measure of SQoL. Our correlation analyses revealed differential relationships between negative symptom subdomains and SQoL, with amotivation, but not diminished expression, being related to SQoL. Final SEM model yielded a good model fit (comparative fix index = 0.94; root mean square error of approximation = 0.05; standardized root mean square residuals = 0.07) and demonstrated that depression, positive symptoms and psychosocial functioning were directly associated with SQoL, with depression showing the strongest effect. Amotivation, neurocognition and positive symptoms had an indirect effect on SQoL via the mediation of psychosocial functioning. This study affirms depression as a critical determinant of subjective mental wellbeing, and underscores an intermediary role of psychosocial functioning in linking amotivation, neurocognitive impairment and positive symptoms to SQoL in FEP patients. Depression and functional impairment thus constitute as crucial therapeutic targets for improvement of SQoL in the early illness stage. [ABSTRACT FROM AUTHOR]

Purposes: To better assess and reduce suicidal risk in first-episode psychosis (FEP), we aimed to investigate the evolution of suicidal thoughts and behaviors (STBs) and associated factors in FEP.Method: This systematic review (PROSPERO-CRD42020168050) meets PRISMA guidelines. PubMed, Medline, PsycINFO, Embase, EBM Reviews and references lists of relevant articles were searched (February 2020) to identify longitudinal studies, published in English or in French, that assessed the prevalence of STBs at entry to services and over follow-up, and examined factors associated with STBs among all persons with affective and non-affective FEP from a defined catchment area. Screening, data extraction and quality assessment using the adapted Newcastle Ottawa Scale were done independently by two reviewers. Results on prevalence and associated factors are presented by type of STB.Results: Of 3,177 references, 17 studies of 11 non-overlapping samples (n = 14,907) with varying lengths of follow-up (1-41.7 years) were included. The prevalence of STBs decreased over follow-up. Up to 21.6% made at least one suicide attempt, 27% had suicidal ideation, and 1-4.3% died by suicide during follow-up. Of 53 factors assessed across studies, only male sex, depressive symptoms, and STBs occurring early during follow-up were associated with subsequent STBs. Early intervention for psychosis decreased STBs in the first three years. Other factors were assessed in a single study, yielded conflicting results, or were not associated with STBs.Conclusions: The high prevalence of STBs following onset of psychosis highlights the need for early detection and intervention and ongoing assessment of suicidal risk throughout follow-up, with attention to identified risk factors. The heterogeneity of the studies precluded a meta-analysis and several factors were each assessed by a single study. Additional well-designed longitudinal studies of STBs and associated factors are warranted. [ABSTRACT FROM AUTHOR]

Impacts of comorbid severe substance use disorders (SUD) on first-episode psychosis (FEP) patients can, in some cases, be extremely serious (dangerousness, suicidality, homelessness). Traditional treatment approaches for SUD may unfortunately fail or not be acceptable to them. Impacts of mandatory residential SUD treatment (RT) are sometimes integrated to community treatment orders (CTO) but have not been studied. This is a retrospective longitudinal study by medical file review of 16 FEP patients with serious consequences of severe comorbid FEP and substance use disorders, who attended mandatory RT prescribed within a CTO. Outcomes were compared before and after mandatory RT. The mean follow-up was 4.4 years (2.3 years before RT, 2.2 years thereafter). After the mandatory RT, increased likelihood of alcohol, cannabis, amphetamines and cocaine abstinence was observed. The number of patients needing hospitalizations, presenting dangerous behaviours or employment and housing instability, decreased. Further research must be conducted to gain a more in-depth understanding of the clinical and ethical impacts of this legal approach, as well as potential pitfalls. [ABSTRACT FROM AUTHOR]

Purpose: Delay in receiving effective treatment for psychosis adversely impacts outcomes. We investigated the timing of the first help-seeking attempt in individuals with recent onset non-affective psychosis by comparing those who sought help during the prodrome to those who sought help after psychosis onset across sociodemographic and clinical characteristics, overall functioning, and occurrence of aversive events during their pathways to care. Methods: Patients were admitted from February 1st, 2014 to January 31st, 2019 to the Program for Specialized Treatment Early in Psychosis (STEP) in New Haven, CT. Psychosis-onset date was ascertained using the Structured Interview for Psychosis-risk Syndromes. Key dates before and after psychosis onset, along with initiators and aversive events, were collected via semi-structured interview. Results: Within 168 individuals, 82% had their first help-seeking episode after psychosis onset and did not differ in terms of sociodemographic characteristics from prodrome help seekers. When the first help-seeking episode started before (i.e., during prodrome) vs after psychosis onset it was mostly initiated by patients vs family members (Cramer's V = 0.23, p = 0.031) and led to a faster prescription of an antipsychotic once full-blown psychosis emerged (time to antipsychotic since psychosis onset = 21 vs 56 days, p = 0.03). No difference in aversive events before STEP enrollment was detected across groups. Conclusion: Help seeking during the prodrome is associated with faster initiation of antipsychotic treatment and is more likely to be self-initiated, compared to help seeking after psychosis onset. Early detection efforts that target prodromal samples may improve the length and experience of pathways to care. [ABSTRACT FROM AUTHOR]

The review summarizes the results of our own studies and published data on the biological markers of psychiatric disorders, with special emphasis on the activity of platelet monoamine oxidase. Pharmacotherapy studies in patients with the mixed anxiety-depressive disorder and first episode of schizophrenia have shown that the activity of platelet monoamine oxidase could serve as a potential biomarker of the efficacy of therapeutic interventions in these diseases. [ABSTRACT FROM AUTHOR]

Background: Migrants present high rates of psychosis. A better understanding of this phenomenon is needed. Methods: We conducted a multicentre First-Episode Psychosis (FEP) prospective study over two years (January 2012–December 2013) to evaluate first-generation migrants presenting with FEP at the participating Community Mental Health Centers (CMHCs). Results: 109 FEP migrants were identified. Almost half of them were highly educated, employed and in a stable affective relationship. The average age was 32.8 (± 9.8) years, and the average length of stay in Italy was 8.6 (± 8.8) years. About 2/3 of patients were referred to CMHCs following Emergency Department access or psychiatric admission. Conclusions: Our finding of a "high functioning portrait" of FEP migrants allow us to hypothesize that a high burden of negative psychosocial factors is likely to be needed for the FEP onset. Furtherly, mental health services should implement more appropriate resources and organizational methods to respond to migrants' health needs. [ABSTRACT FROM AUTHOR]

An increasing interest in the assessment of neuropsychological performance variability in people with first-episode psychosis (FEP) has emerged. However, its association with clinical and functional outcomes requires further study. Furthermore, FEP neuropsychological subgroups have not been characterized by clinical insight or metacognition and social cognition domains. The aim of this exploratory study was to identify specific groups of patients with FEP based on neuropsychological variables and to compare their sociodemographic, clinical, metacognition and social cognition profiles. A sample of 149 FEP was recruited from adult mental health services. Neuropsychological performance was assessed by a neuropsychological battery (WAIS-III; TMT; WSCT; Stroop Test; TAVEC). The assessment also included sociodemographic characteristics, clinical, functional, metacognition and social cognition variables. Two distinct neuropsychological profiles emerged: one neuropsychological impaired cluster (N = 56) and one relatively intact cluster (N = 93). Significant differences were found between both profiles in terms of sociodemographic characteristics (age and level of education) (p = 0.001), clinical symptoms (negative, positive, disorganized, excitement and anxiety) (p = 0.041–0.001), clinical insight (p = 0.038–0.017), global functioning (p = 0.014), as well as in social cognition domains (emotional processing and theory of mind) (p = 0.001; p = 0.002). No significant differences were found in metacognitive variables (cognitive insight and ‘jumping to conclusions’ bias). Relationship between neurocognitive impairment, social cognition and metacognition deficits are discussed. Early identifying of neuropsychological profiles in FEP, characterized by significant differences in clinical and social cognition variables, could provide insight into the prognosis and guide the implementation of tailored early-intervention. [ABSTRACT FROM AUTHOR]

Introduction: The role of Olanzapine therapeutic drug monitoring is controversial. The present study explores the associations of Olanzapine plasma concentrations with clinical response and metabolic side effects in first episode psychosis (FEP) after 2 months of treatment. Methods: Forty-seven patients were included. Improvement in clinical symptomatology was assessed using the PANSS. Metabolic assessment included weight, blood pressure, waist circumference, blood glucose, total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides. Results: The Olanzapine plasma concentrations after 2 months of treatment were positively correlated with weight gain (r = 0.49, p = 0.003), and a concentration > 23.28 ng/mL was identified as a positive predictor of weight gain (≥ 7%). The Olanzapine concentration to dose (C/D) ratio was positively correlated with the percentage of improvement in the total PANSS (r = 0.46, p = 0.004), and a C/D ratio > 2.12 was identified as a positive predictor of a good response (percentage of improvement > 30%) after 2 months of treatment. We also identified several factors that could alter Olanzapine pharmacokinetics: gender (p = 0.03), diagnosis (p = 0.05), smoking habit (p = 0.05), and co-medications such as valproic acid (p = 0.05) and anxiolytics (p = 0.01). Discussion: In conclusion, our results suggest that therapeutic drug monitoring of Olanzapine could be helpful to evaluate therapeutic efficacy and metabolic dysfunction in FEP patients treated with Olanzapine. [ABSTRACT FROM AUTHOR]

Advance statements represent a promising but relatively unexplored means to empower young people with first-episode psychosis to actively participate in their own mental health care. This qualitative study explored the use of advance statement's for young people with first-episode psychosis, as well as their carers and clinicians, and provided actionable feedback on how to better meet the needs and preferences of these key stakeholders and more effectively implement advance statements in clinical settings. [ABSTRACT FROM AUTHOR]

Introduction: Diminished motivation (e.g., low drive, curiosity, and engagement in activities) is associated with robust impairment in psychosocial functioning in schizophrenia, yet even the most effective evidence-based interventions rarely effect meaningful change in motivation. Individual Resiliency Training (IRT) is a psychosocial treatment for individuals following a first episode of psychosis, supporting motivation through recovery goal setting and pursuit. The extent to which such an approach might improve motivation over time is unknown. Method: We tested the impact of exposure to IRT modules focused on goal setting and attainment on motivation and functional outcomes among participants in the Recovery After an Initial Schizophrenia Episode-Early Treatment Program (RAISE-ETP). In the sample of 404 individuals with a first episode of psychosis receiving treatment across 34 community sites, we ran mixed-effect models with group (exposed to four or more goal-focused IRT sessions vs. Community Care (CC)), time (baseline, six- and 12-month follow-up), and the group-by-time interaction as predictors of motivation, role and social functioning. We also ran these analyses with those exposed to three or fewer goal-focused IRT sessions compared to CC. Results: Controlling for gender, ethnicity, baseline cognition, and total number of outpatient mental health visits, exposure to four or more goal-focused IRT sessions was associated with greater improvements in motivation and role functioning compared to CC; effects were not observed for social functioning. Participants receiving three or fewer goal-focused IRT sessions did not differ from those in CC in these outcomes. Further, sensitivity analysis showed that general exposure to IRT was not associated with differential outcomes. Conclusions: Findings suggest that sufficient focus on recovery goal setting and support in psychosocial intervention for first-episode psychosis may have specific impact on motivation. [ABSTRACT FROM AUTHOR]

Early-psychosis researchers have documented that duration of untreated psychosis (DUP) is an important predictor of outcomes in first-episode psychosis. Very few cross-national studies have been conducted, and none have been carried out involving patients from both Mexico and the U.S. We collaborated to answer three questions: (1) Are DUP estimates similar in two very different settings and samples? (2) Are demographic variables, premorbid adjustment, and symptom severity similarly related to DUP in the two different settings? (3) Does the same set of variables account for a similar proportion of variance in DUP in the two settings? Data on sociodemographic characteristics, premorbid adjustment, symptom severity, and DUP were available for 145 Mexican and 247 U.S. first-episode psychosis patients. DUP was compared, and bivariate analyses and multiple linear regressions were carried out in each sample. DUP estimates were similar (medians of 35 weeks in Mexico and 38 weeks in the U.S.). In the Mexican sample, DUP was associated with gender, employment status, premorbid social adjustment, and positive symptom severity (explaining 18% of variance). In the U.S. sample, DUP was associated with age, employment status, premorbid social adjustment, and positive symptom severity (but in the opposite direction of that observed in the Mexican sample), accounting for 25% of variance. Additional cross-national collaborations examining key facets of early-course psychotic disorders, including DUP, will clarify the extent of generalizability of findings, strengthen partnerships for more internationally relevant studies, and support the global movement to help young people struggling with first-episode psychosis and their families. [ABSTRACT FROM AUTHOR]

Apathy is prevalent in first-episode psychosis (FEP) and associated with reduced global functioning. Investigations of the trajectory of apathy and its early predictors are needed to develop new treatment interventions. We here measured the levels of apathy over the first 10 years of treatment in FEP and in healthy controls (HC). We recruited 198 HC and 198 FEP participants. We measured apathy with the Apathy Evaluation Scale, self-report version, psychotic symptoms with the Positive and Negative Syndrome Scale, depression with the Calgary Depression Scale for Schizophrenia, functioning with the Global Assessment of Functioning Scale, and also estimated the duration of untreated psychosis (DUP). The longitudinal development of apathy and its predictors were explored using linear mixed models analyses. Associations to functioning at 10 years were investigated using multiple hierarchical linear regression analyses. In HC, mean apathy levels were low and stable. In FEP, apathy levels decreased significantly during the first year of treatment, followed by long-term stability. High individual levels of apathy at baseline were associated with higher apathy levels during the follow-up. Long DUP and high baseline levels of depression predicted higher apathy levels at follow-ups. The effect of DUP was persistent, while the effect of baseline depression decreased over time. At 10 years, apathy was statistically significantly associated with reduced functioning. The early phase of the disorder may be critical to the development of apathy in FEP. [ABSTRACT FROM AUTHOR]

Purpose: The EUropean Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study contains an unparalleled wealth of comprehensive data that allows for testing hypotheses about (1) variations in incidence within and between countries, including by urbanicity and minority ethnic groups; and (2) the role of multiple environmental and genetic risk factors, and their interactions, in the development of psychotic disorders.Methods: Between 2010 and 2015, we identified 2774 incident cases of psychotic disorders during 12.9 million person-years at risk, across 17 sites in 6 countries (UK, The Netherlands, France, Spain, Italy, and Brazil). Of the 2774 incident cases, 1130 cases were assessed in detail and form the case sample for case-control analyses. Across all sites, 1497 controls were recruited and assessed. We collected data on an extensive range of exposures and outcomes, including demographic, clinical (e.g. premorbid adjustment), social (e.g. childhood and adult adversity, cannabis use, migration, discrimination), cognitive (e.g. IQ, facial affect processing, attributional biases), and biological (DNA via blood sample/cheek swab). We describe the methodology of the study and some descriptive results, including representativeness of the cohort.Conclusions: This resource constitutes the largest and most extensive incidence and case-control study of psychosis ever conducted. [ABSTRACT FROM AUTHOR]

Acute and transient psychotic disorders (ATPD) have moderate prospective diagnostic stability. Female gender, older age at onset, good premorbid adjustment, abrupt onset, shifting polymorphic symptomatology and absence of schizophrenic features have been found to be predictive factors of diagnostic stability in ATPDs. Nevertheless, most of these findings need to be replicated. The purpose of this study was to evaluate the diagnostic stability of patients with ATPD, and to determine whether previously accepted predictors of diagnostic stability for ATPD could be externally validated in our cohort. To that end, a prospective 2-year observational study was conducted on patients with first-episode ATPD. Multivariate analysis was performed to determine factors associated with ATPD diagnostic stability at the end of the follow-up period. The following prior knowledge variables were analyzed: female gender, older age at onset, good premorbid adjustment, abrupt onset, shifting polymorphic symptomatology and absence of schizophrenic features. Sixty-eight patients with first-episode ATPD completed the follow-up, of whom 55.9% (n = 38) retained their diagnosis of ATPD at the end of the study. Multivariate analysis revealed that diagnostic stability was independently significantly associated with the presence of shifting polymorphic symptomatology (OR = 7.42, 95% CI 1.65–33.30; p = 0.009) and the absence of schizophrenic features (OR = 6.37, 95% CI 1.47–27.54; p = 0.013) at the onset of the psychotic disorder. Our findings provide empirical support for the ICD-11 proposal restricting the new ATPD category to the acute polymorphic disorder without schizophrenia symptoms. [ABSTRACT FROM AUTHOR]

Alterations in complex lipids may be involved in pathophysiology of schizophrenia spectrum disorders. Previously, we demonstrated importance of detecting lipid metabolism dysregulation by acylcarnitine (ACs) profile analysis in patients with first-episode psychosis (FEP). The aim of this study was to adopt lipidomics to identify serum glycerophospholipids (GPLs) and sphingomyelins (SMs) for describing FEP status before and after 7-month antipsychotic treatment. Using mass spectrometry and liquid chromatography technique, we profiled 105 individual lipids [14 lysophosphatidylcholines (LysoPCs), 76 phosphatidylcholines (PCs) and 15 SMs] in serum samples from 53 antipsychotic-naïve FEP patients, 44 of them were studied longitudinally and from 37 control subjects (CSs). Among the identified and quantified metabolites one LysoPC was elevated, and contrary the levels of 16 PCs as well as the level of one SM were significantly (p ≤ 0.0005) reduced in antipsychotic-naïve FEP patients compared to CSs. Comparison of serum lipids profiles of FEP patients before and after 7-month antipsychotic treatment revealed that 11 GPLs (2 LysoPCs, 9 PCs), and 2 SMs were found to be significantly changed (p ≤ 0.0005) in which GPLs were up-regulated, and SMs were down-regulated. However, no significant differences were noted when treated patient's serum lipid profiles were compared with CSs. Our findings suggest that complex lipid profile abnormalities are specifically associated with FEP and these discrepancies reflect two different disease-related pathways. Our findings provide insight into lipidomic information that may be used for monitoring FEP status and impact of the treatment in the early stage of the schizophrenia spectrum disorder. [ABSTRACT FROM AUTHOR]

Working memory (WM) deficits constitute a core symptom of schizophrenia. Inadequacy of WM maintenance in schizophrenia has been reported to reflect abnormalities in the excitation/inhibition (E/I) balance between pyramidal neurons and parvalbumin basket cells, which may explain alterations of the dynamics of gamma and delta oscillations. To address this issue, we assessed event-related gamma (35–45 Hz) and delta (0.5–4 Hz) oscillatory responses in a visual n-back WM task in patients with first-episode psychosis (FEP) and healthy controls (HC). Periodicity analyses of oscillations were computed to explore the relationship between the psychiatric status and the WM load-related processes reflected by each frequency range. The correspondence between nested delta–gamma oscillations was estimated to assess the strength of the frontal E/I balance. In HC, gamma oscillations were synchronized by the stimulus in a 50–150 ms time range for all tasks, and periodicity of the delta cycle was comparable between the tasks. In addition, synchronization of gamma oscillations in HC occurred at the maximal descending phase of the delta cycle half-period, supporting the coexistence of delta-nested gamma oscillations. Compared with controls, FEP patients showed a lack of gamma synchronization independently of the nature of the task, and the period of delta oscillation increased significantly with the difficulty of the WM task. We thus demonstrated in FEP an inability to encode multiple items in short-term memory associated with abnormalities in the relationship between oscillations related to the difficulty of the WM task. These results argue in favor of a dysfunction of the E/I balance in psychosis. [ABSTRACT FROM AUTHOR]

Purpose: Ethnic minority groups with early psychosis may have longer treatment delays, potentially leading to poorer outcomes. We updated a previous systematic review of the literature on racial and ethnic differences in duration of untreated psychosis (DUP) among people with first-episode psychosis.Results: Six of 17 studies described significant differences across aggregated racial groups; however, the pooled estimates did not show differences across groups. Additional data from this update allowed for disaggregated analyses, finding that Black-African groups have a shorter DUP, whereas Black-Caribbean groups have longer DUP, relative to White groups.Conclusions: These findings highlight the importance of in-depth research on disaggregated ethnic groups to inform targeted early intervention strategies for minority populations. [ABSTRACT FROM AUTHOR]

Background: A core component of treatment provided by early intervention for psychosis (EI) services is ensuring individuals remain successfully engaged with the service. This ensures they can receive the care they may need at this critical early stage of illness. Unfortunately, rates of disengagement are high in individuals with a first episode of psychosis (FEP), representing a major barrier to effective treatment. This study aimed to ascertain the rates and determinants of disengagement and subsequent re-engagement of young people with FEP in a well-established EI service in Melbourne, Australia.Method: This cohort study involved all young people, aged 15-24, who presented to the Early Psychosis Prevention and Intervention Centre (EPPIC) service with FEP between 1st January 2011 and 1st September 2014. Data were collected retrospectively from clinical files and electronic records. Cox regression analysis was used to identify determinants of disengagement and re-engagement.Results: A total of 707 young people presented with FEP during the study period, of which complete data were available for 700. Over half of the cohort (56.3%, N = 394) disengaged at least once during their treatment period, however, the majority of these individuals (85.5%, N = 337) subsequently re-engaged following the initial episode of disengagement. Of those who disengaged from the service, 54 never re-engaged, representing 7.6% of the total cohort. Not being in employment, education or training, not having a family history of psychosis in second degree relatives and using cannabis were found to be significant predictors of disengagement. No significant predictors of re-engagement were identified.Conclusion: In this study, the rate of disengagement in young people with first-episode psychosis was higher than found previously. Encouragingly, rates of re-engagement were also high. The concept of disengagement from services might be more complex than previously thought with individuals disengaging and re-engaging a number of times during their episode of care. What prompts individuals to re-engage with services needs to be better understood. [ABSTRACT FROM AUTHOR]

Patients with schizophrenia frequently present hyperprolactinemia as a consequence of antipsychotic treatment. However, an increase in circulating prolactin levels has also been shown in patients without previous treatment. Our objective was to compare prolactin levels between antipsychotic-naive first-episode psychosis (AN-FEP) patients and healthy controls (HC). As part of an FEP program (Programa Asistencial Fases Iniciales de Psicosis [PAFIP]), 270 AN-FEP patients and 153 HC were eligible for this study. Serum prolactin levels were measured by an automated immunochemiluminescent assay. Subjects' sex and having an AN-FEP diagnosis both had an effect on prolactin levels, with higher levels in women than in men, and in AN-FEP patients than in HC. Moreover, plasma prolactin levels showed a negative correlation with the SAPS scores in AN-FEP female patients. AN-FEP patients have increased levels of prolactin, which might be stress-induced. This, together with the association of higher prolactin with a lower severity of the disease, suggests that prolactin might play a neuroprotective role, especially in women. [ABSTRACT FROM AUTHOR]

Recruitment of immigrants and racial and ethnic minorities with first-episode psychosis (FEP) for research studies presents numerous challenges. We describe methods used to recruit 43 U.S. Latinos with FEP and their family caregivers (n = 41) participating in a study to reduce duration of untreated psychosis. A key challenge was that patients were not continuing treatment at an outpatient clinic, as initially expected. To facilitate identification of patients prior to outpatient care, we collaborated with clinic and hospital administrators. Many patients and families were grappling with the aftermath of a hospitalization or adjusting to a diagnosis of a serious mental illness. A considerable amount of time was devoted to addressing participants' concerns and when possible, facilitating needed services. Our experience underscores the importance of establishing long-term relationships through multiple contacts with patients, families, and stakeholders to address recruitment barriers among underserved groups with FEP. [ABSTRACT FROM AUTHOR]

Purpose: Prevention of mental disorders is a rapidly growing area of research with substantial potential benefits for population health. This paper reviews the evidence base for prevention of depression, anxiety, and schizophrenia.Methods: We synthesized evidence from recent systematic reviews and meta-analyses published between 2013 and 2018 on prevention of depression, anxiety, and first-episode psychosis. We included reviews of randomized controlled trials testing psychological, psychosocial, and pharmacological preventive interventions.Results: There is good evidence that depression and anxiety can be prevented, although effect sizes are generally small. Indicated prevention of first-episode psychosis appears promising. Economic evaluations provide support for prevention of depression, anxiety, and first-episode psychosis, but more studies evaluating costs and benefits are needed to strengthen the knowledge base, particularly regarding long-term outcomes, which include chronicity of the prevented disorder, as well as later occurence of important comorbid mental and physical health problems. Promising areas for further development include internet- or computer-based prevention strategies, mindfulness-based interventions, and integration of prevention programs within occupational settings.Conclusions: A number of interventions to prevent mental disorders are efficacious. While intervention effect sizes are generally small for prevention of depression and anxiety, they may nonetheless be of significant population benefit. Using the growing evidence base to inform policy and dissemination of evidence-based prevention programs is critical for moving prevention science into real-world settings. [ABSTRACT FROM AUTHOR]