Why do some Mexicans with psychosis risk symptoms seek mental health care and others do not?

Help-seeking barriers differ according to the sociocultural context and country-specific mental healthcare system. More research is needed in low-middle-income countries, where early psychosis programs are still scarce, and the mental health care gap is wide. This study aims to explore predisposing, enabling, and need factors associated with mental health service utilization in 481 Mexicans self-reporting psychosis risk symptoms, as well as differences between those who were currently mental health service users (MHSU) and those who were not (non-MHSU). Participants responded to self-reported measures through an online survey. The factors associated with an increased probability of using mental health services were having an occupation, having a medium/high socioeconomic status, an intention to seek help from a mental health professional, fewer help-seeking barriers, moderate/severe anxious symptoms, higher distress associated with psychosis risk symptoms and social functioning impairment. Findings provide relevant information for designing more effective strategies to improve help-seeking, early identification, and timely treatment delivery in Mexico. The need to generate strategies focused on reducing stigma, enhancing psychosis literacy in the community, and increasing the identification of emerging signs of psychosis in primary healthcare professionals is highlighted, mainly when co-occurring with other psychiatric symptoms.

Associations between rural/urban status, duration of untreated psychosis and mode of onset of psychosis: a mental health electronic clinical records analysis in the East of England, UK.

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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Early Intervention in the Treatment of Psychosis.

This article aims to: (1) describe the evolution of first episode of psychosis (FEP) approaches; (2) define a model of multidisciplinary care; (3) identify challenges and limitations; (4) discuss the unique challenges for those first experiencing psychosis; (5) identify strategies to expand early psychosis interventions. The authors take the medical standpoint and use the differential diagnosis and initial medical work-up as a context for assessment. The remainder of the article will be focused on treatment of FEP in those with schizophrenia-spectrum disorders.

Racial and Ethnic Disparities in the Diagnosis and Early Treatment of First-Episode Psychosis.

Background: Despite recognition that early intervention for first-episode psychosis (FEP) improves outcomes, Black youth with FEP continue to experience critical disparities in care. A historical lack of scientific focus on racial and ethnic factors in the study of psychosis and scant investigations among publicly insured (ie, Medicaid-enrolled) youth hinder our ability to understand and address factors that contribute to disparities in early FEP care. Strategies for improving FEP services for Black youth are reliant on more precise identification of who faces disparities and when during the early course of illness disparities are experienced. Study Design: A retrospective longitudinal analysis of Ohio Medicaid claims data was performed for 987 982 youth aged 15-24 years between 2010 and 2020 to examine: (1) the likelihood of FEP diagnosis, (2) the type of psychotic disorder diagnosis received, and (3) receipt of treatment following psychosis onset. Study Results: Non-Hispanic Black (NHB) youth, relative to non-Hispanic White (NHW) peers, were more likely to be diagnosed with a psychotic disorder and were further more likely to receive a diagnosis of schizophrenia relative to an affective psychotic disorder. In the first year following FEP diagnosis, NHB youth were also less likely to receive psychotherapy than NHW youth; this disparity was no longer present when examined at 2 years following FEP. Conclusions: In this study, Black youth experienced disparities in both the diagnosis and early treatment of FEP. Additional efforts are needed to understand and address these observed disparities and to promote equitable access to FEP care during the critical early illness phases.

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

BACKGROUND: Early identification of treatment non-response in first-episode psychosis (FEP) is essential to outcome. Despite indications that exposure to childhood trauma (CT) can have adverse effects on illness severity, its impact on treatment non-response and the interplay with other pre-treatment characteristics is sparsely investigated. We use a lack of clinical recovery as an early indicator of treatment resistance to investigate the relationship between CT and treatment resistance status at one-year follow-up and the potential mediation of this effect by other pre-treatment characteristics. METHODS: This prospective one-year follow-up study involved 141 participants recruited in their first year of treatment for a schizophrenia-spectrum disorder. We investigated clinical status, childhood trauma (CT), premorbid adjustment (PA), and duration of untreated psychosis (DUP) at baseline and clinical status at one-year follow-up. Ordinal regression analyses were conducted to investigate how PA and DUP affected the relationship between CT and one-year outcome in FEP. RESULTS: 45 % of the FEP sample reported moderate to severe CT, with significantly higher levels of CT in the early treatment resistant group compared to participants with full or partial early recovery. Ordinal regression analysis showed that CT was a significant predictor of being in a more severe outcome group (OR = 4.59). There was a partial mediation effect of PA and a full mediation effect of DUP on the effect of CT on outcome group membership. DISCUSSION: Our findings indicate that reducing treatment delays may mitigate the adverse effects of CT on clinical outcomes and support the inclusion of broad trauma assessment in FEP services.

Corrigendum: Psychosocial stress moderates the relationship between cerebrospinal fluid lactate dehydrogenase and the duration of untreated psychosis in first-episode psychosis.

[This corrects the article DOI: 10.3389/fpsyt.2024.1327928.].

Factors associated with improved outcomes in the first psychotic episode at a specialized outpatient clinic in northeastern Brazil.

OBJECTIVES: The present study aimed to evaluate data from patients admitted to the first-episode psychotic (FEP) outpatient clinic at the Hospital of Clinics of the Federal University of Pernambuco from July 2018 to July 2021, seeking to identify factors related to better clinical outcomes. METHODS: This study was conducted using a convenience sample, including all patients between 15 and 65 years of age who were admitted to the FEP outpatient clinic from July 2018 to July 2021. Descriptive statistical analysis was performed using mean and standard deviation or median and interquartile range for continuous quantitative variables, and absolute number/percentage for qualitative variables. Paired T-test, a parametric test, was used to compare PANSS scores upon admission and after 6 months. Spearman's correlation test was employed to assess the correlation between duration of untreated psychosis (DUP) and treatment response with other variables. RESULTS: The sample consisted of 85.3% male individuals, with 50% of patients aged between 19 and 30 years, and 82% residing in the metropolitan area of Recife. Seventy percent of patients responded to the treatment implemented by the outpatient clinic, and only 30% required psychiatric hospitalization within 6 months of follow-up. The majority of patients had a history of psychoactive substance use (82.4%); however, the use of these substances did not impact the prognosis within the analysed sample. The median DUP was 4 weeks, and a shorter DUP was associated with a lower probability of psychiatric hospitalization and a greater treatment response (reduction >50% in PANSS). CONCLUSION: A shorter DUP was associated with a lower likelihood of psychiatric hospitalization and a greater treatment response. Furthermore, the specialized early psychosis outpatient clinic itself appears to yield positive outcomes, as 70% of the treated patients exhibited a positive treatment response.

Reduction of DUP in early intervention programmes: No pain almost no gain.

AIM: Considering the negative impact of long duration of untreated psychosis (DUP) on outcome, its reduction has become one of the aims of early intervention programmes. The TIPP programme (Treatment and early Intervention in Psychosis Program) was implemented in 2004 in Lausanne and hoped to reduce DUP, without any specific campaign in this regard, through the provision of accessible and specialized treatment. The aim of this study was to evaluate the evolution of patients' DUP over time and the characteristics of patients with extreme DUP. METHODS: Clinical follow-up data of 380 patients aged 18-35 years with a first psychotic episode who entered the TIPP programme between 2004 and 2017 were analysed. The evolution of DUP over time as well as referring entities and destination after the programme were assessed. The characteristics of patients with extreme DUPs (>percentile 90) were compared with that of other patients. RESULTS: The mean value of the DUP was 452.11 days with a median of 88 days. DUP decreased only moderately over time. We also observe a decrease in discharges to specialized outpatient care at our university hospital. The main characteristics of patients with extreme DUP were early age of onset of psychosis, diagnosis of schizophrenia and presence of history of psychiatric treatment for other conditions before onset of psychosis. CONCLUSIONS: These figures suggest that the DUP has reduced over time but that without specific interventions at this level, this reduction is only moderate.

Hospitalization and help-seeking among first episode psychosis patients.

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.

Duration of untreated psychosis and its associated sociodemographic and clinical factors in first-episode psychosis: A study from Eastern Nepal.

OBJECTIVE: Duration of untreated psychosis (DUP) is considered an important factor in outcome. Individual, familial and illness factors may prolong DUP. Little data on this issue is available from the country of Nepal. The purpose of the present study was to assess DUP in patients with first-episode psychosis and identify associations with patients' socio-demographic and clinical factors. METHODS: A cross-sectional, descriptive study was conducted in the department of psychiatry, of Tertiary Hospital in the Eastern part of Nepal. Eighty-six patients were enrolled. ICD-10 was used to make the diagnosis. Nottingham Onset Schedule-DUP version (NOS-DUP) was used to assess DUP. Positive and Negative Syndrome Scale (PANSS) was used to assess patients' clinical symptoms. RESULTS: The mean (SD) DUP was 21.4 (42.1) months and median DUP was 3.0 months (IQR = 23.5). Participants from mountainous region, the unemployed, having an insidious onset of illness, and patients with a diagnosis of schizophrenia had significantly longer DUP (P < .005). Duration of untreated psychosis was also positively correlated with negative symptoms (r = .42, (P < .001) and total PANSS score (r = .42, P < .001). CONCLUSION: Duration of untreated psychosis in first-episode psychotic patients was relatively long (compared to studies in other countries), and was found to be positively associated with mountainous regions of Nepal, being unemployed, having an insidious onset of illness, and having a diagnosis of schizophrenia. Programs and educational efforts are needed to ensure early treatment of patients with first-episode psychosis, especially in the mountainous rural areas of Nepal.

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

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

Psychosocial stress moderates the relationship between cerebrospinal fluid lactate dehydrogenase and the duration of untreated psychosis in first-episode psychosis.

Introduction: Previous research has shown that lower lactate dehydrogenase (LDH) concentrations in cerebrospinal fluid (CSF) are associated with longer prodromal symptoms in first-episode psychosis (FEP). We aimed to study whether there is a relationship between the duration of untreated psychosis (DUP) and LDH and other CSF biomarkers in FEP and whether stressful life events moderate this association. Methods: Ninety-five inpatients with FEP and with less than 6 weeks of antipsychotic treatment were included in the study. All participants were informed about the nature of the study, which was approved by the local ethics committee, and signed an informed consent form. A lumbar puncture was performed at index admission (baseline) to measure CSF parameters (glucose, total protein, LDH). The DUP was assessed with the Quick Psychosis Onset and Prodromal Symptoms Inventory (Q-POPSI). Stressful life events (SLEs) in the previous 6 months were assessed with the List of Threatening Experiences. We dichotomized the SLE variable into having experienced at least one SLE or no experience of SLEs. Statistical analyses were performed with SPSS v. 25.0. Total protein and LDH concentrations were natural log transformed (ln) to reduce skewness. Multiple linear regression analyses were conducted to explore the association between the DUP and CSF parameters (considered the dependent variable). Age, sex, DUP and SLEs were considered independent variables. We tested the DUP by SLE interaction. Significant interactions were included in the final model. The threshold for significance was set at p<0.05. Results: Fifty-four FEP patients (56.8%) reported an SLE in the previous 6 months. There were no significant differences in the DUP between patients with or without SLEs. There were no significant differences in CSF biomarkers between the SLE groups. In the multiple linear regression analyses, we found a significant DUP by SLE interaction effect on CSF LDH concentrations (standardized beta= -0.320, t= -2.084, p= 0.040). In patients with SLEs, a shorter DUP was associated with higher CSF LDH concentrations and vice versa. No significant associations were found between the DUP or SLEs and other CSF biomarkers (glucose, total proteins). Conclusions: Our study suggests that psychosocial stress moderates the relationship between the onset of psychosis and CSF biomarkers related to bioenergetic systems.

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

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

The effectiveness of public health interventions, initiatives, and campaigns designed to improve pathways to care for individuals with psychotic disorders: A systematic review.

PURPOSE: Lengthy duration of untreated psychosis (DUP) and duration of untreated illness (DUI) in people at clinical high-risk for psychosis (CHR-P) and first episode psychosis (FEP) is associated with poorer outcomes. However, individuals with FEP often experience negative pathways to care involving contacts with police, crisis services and requiring compulsory admissions, and evidence suggests individuals with both FEP and CHR-P often experience lengthy delays to treatment. Early detection interventions, such as public health interventions, may be one way to reduce delays. This systematic review aimed to synthesise the available evidence on such interventions. METHODS: The EMBASE, PsychINFO, CINAHL, and MEDLINE databases were searched. Studies were included if they compared an intervention designed to improve timely access to treatment for individuals with FEP or CHR-P to standard treatment provision. Interventions may be targeted at potential patients, their families, the general public, or non-healthcare professionals. Outcomes of interest were DUP or DUI, and/or characteristics of pathways to care. RESULTS: Nineteen studies met the inclusion criteria. All consisted of FEP populations, none of CHR-P populations. Employing narrative synthesis, we found mixed results about the effectiveness of interventions at reducing DUP and interventions appeared to differentially impact groups. Pathways to care information was limited and mixed. CONCLUSION: Findings on the effectiveness of interventions designed to improve timely access to treatment were inconclusive. More research is warranted to better understand where delays occur and factors which may influence this for both FEP and CHR-P populations which may help to develop targeted interventions to address delays.

Pre-onset subthreshold psychotic symptoms are associated with differential treatment delays before a first episode of psychosis: Initial evidence and implications.

BACKGROUND: Help-seeking and treatment delays are increasingly critical areas of study in mental health services. The duration of untreated psychosis (DUP), or the time between illness onset and initiation of treatment, is a predictor of symptom remission and functioning for a first episode of psychosis (FEP). The World Health Organization recommends that specialized treatment for psychosis be initiated within the first three months of FEP onset. As a result, research has focused on factors that are associated with threshold-level DUP, while the experience of subthreshold psychotic symptoms (STPS) prior to a FEP may also complicate and present barriers to accessing care for young people. We therefore examine the possibility that STPS can impact DUP and its components. METHOD: Using a follow-back cross-sectional design, we sought to describe duration of untreated illness, length of prodrome, DUP, help-seeking delay, referral delay, and number of help-seeking contacts among FEP patients who did and did not have STPS prior to psychosis onset. RESULTS: We found that patients who experienced STPS had a longer median duration of untreated illness, prodrome length, DUP, and help-seeking delay compared to patients who did not have such symptoms. Referral delay did not differ substantially between the two groups. Importantly, treatment delays were extremely lengthy for many participants. CONCLUSIONS: Pre-onset STPS are associated with help-seeking delays along the pathway to care even during a FEP. Examining early signs and symptoms may help to improve and tailor interventions aimed at reducing treatment delays and ultimately providing timely care when the need arises.

Role of Early Psychosis Detection in the Relationship Between Personal Income and Duration of Untreated Psychosis.

OBJECTIVE: Prolonged duration of untreated psychosis (DUP) predicts poor outcomes of first-episode psychosis (FEP) and is often linked to low socioeconomic status (SES). The authors sought to determine whether patients' personal income, used as a proxy for SES, predicts length of DUP and whether personal income influences the effect of an early psychosis detection campaign-called Mindmap-on DUP reduction. METHODS: Data were drawn from a trial that compared the effectiveness of early detection in reducing DUP across the catchment area of an FEP service (N=147 participants) compared with an FEP service with no early detection (N=75 participants). Hierarchical regression was used to determine whether personal income predicted DUP when analyses controlled for effects of age, race, and exposure to early psychosis detection. A group × personal income interaction term was used to assess whether the DUP difference between the early detection and control groups differed by personal income. RESULTS: Lower personal income was significantly associated with younger age, fewer years of education, Black race, and longer DUP. Personal income predicted DUP beyond the effects of age, race, and early psychosis detection. Although Mindmap significantly reduced DUP across all income levels, this effect was smaller for participants reporting lower personal income. CONCLUSIONS: Patients' personal income may be an important indicator of disparity in access to specialty care clinics across a wide range of settings. Early detection efforts should measure and target personal income and other SES indicators to improve access for all individuals who may benefit from FEP services.

Time is the enemy: Negative symptoms are related to even slight differences in the duration of untreated psychosis.

BACKGROUND: Negative symptoms (NS) represent a detrimental symptomatic domain in schizophrenia affecting social and occupational outcomes. AIMS: We aimed to identify factors from the baseline visit (V1) - with a mean illness duration of 0.47 years (SD = 0.45) - that predict the magnitude of NS at the follow-up visit (V3), occurring 4.4 years later (mean +/- 0.45). METHOD: Using longitudinal data from 77 first-episode schizophrenia spectrum patients, we analysed eight predictors of NS severity at V3: (1) the age at disease onset, (2) age at V1, (3) sex, (4) diagnosis, (5) NS severity at V1, (6) the dose of antipsychotic medication at V3, (7) hospitalisation days before V1 and; (8) the duration of untreated psychosis /DUP/). Secondly, using a multiple linear regression model, we studied the longitudinal relationship between such identified predictors and NS severity at V3 using a multiple linear regression model. RESULTS: DUP (Pearson's r = 0.37, p = 0.001) and NS severity at V1 (Pearson's r = 0.49, p < 0.001) survived correction for multiple comparisons. The logarithmic-like relationship between DUP and NS was responsible for the initial stunning incremental contribution of DUP to the severity of NS. For DUP < 6 months, with the sharpest DUP/NS correlation, prolonging DUP by five days resulted in a measurable one-point increase in the 6-item negative symptoms PANSS domain assessed 4.9 (+/- 0.6) years after the illness onset. Prolongation of DUP to 14.7 days doubled this NS gain, whereas 39 days longer DUP tripled NS increase. CONCLUSION: The results suggest the petrification of NS during the early stages of the schizophrenia spectrum and a crucial dependence of this symptom domain on DUP. These findings are clinically significant and highlight the need for primary preventive actions.

What is the duration of untreated psychosis worldwide? - A meta-analysis of pooled mean and median time and regional trends and other correlates across 369 studies.

Duration of untreated psychosis (DUP) has been associated with poor mental health outcomes. We aimed to meta-analytically estimate the mean and median DUP worldwide, evaluating also the influence of several moderating factors. This PRISMA/MOOSE-compliant meta-analysis searched for non-overlapping individual studies from inception until 9/12/2022, reporting mean ± s.d. or median DUP in patients with first episode psychosis (FEP), without language restrictions. We conducted random-effect meta-analyses, stratified analyses, heterogeneity analyses, meta-regression analyses, and quality assessment (PROSPERO:CRD42020163640). From 12 461 citations, 369 studies were included. The mean DUP was 42.6 weeks (95% confidence interval (CI) 40.6-44.6, k = 283, n = 41 320), varying significantly across continents (p < 0.001). DUP was (in descending order) 70.0 weeks (95% CI 51.6-88.4, k = 11, n = 1508) in Africa; 48.8 weeks (95% CI 43.8-53.9, k = 73, n = 12 223) in Asia; 48.7 weeks (95% CI 43.0-54.4, k = 36, n = 5838) in North America; 38.6 weeks (95% CI 36.0-41.3, k = 145, n = 19 389) in Europe; 34.9 weeks (95% CI 23.0-46.9, k = 11, n = 1159) in South America and 28.0 weeks (95% CI 20.9-35.0, k = 6, n = 1203) in Australasia. There were differences depending on the income of countries: DUP was 48.4 weeks (95% CI 43.0-48.4, k = 58, n = 5635) in middle-low income countries and 41.2 weeks (95% CI 39.0-43.4, k = 222, n = 35 685) in high income countries. Longer DUP was significantly associated with older age (ß = 0.836, p < 0.001), older publication year (ß = 0.404, p = 0.038) and higher proportion of non-White FEP patients (ß = 0.232, p < 0.001). Median DUP was 14 weeks (Interquartile range = 8.8-28.0, k = 206, n = 37 215). In conclusion, DUP is high throughout the world, with marked variation. Efforts to identify and intervene sooner in patients with FEP, and to promote global mental health and access to early intervention services (EIS) are critical, especially in developing countries.

Functional and structural connectivity correlates of semantic verbal fluency deficits in first-episode psychosis.

INTRODUCTION: Semantic verbal fluency (SVF) impairments are debilitating and present early in the course of psychotic illness. Deficits within frontal, parietal, and temporal brain regions contribute to this deficit, as long-range communication across this functionally integrated network is critical to SVF. This study sought to isolate disruptions in functional and structural connectivity contributing to SVF deficits during first-episode psychosis in the schizophrenia spectrum (FESz). METHODS: Thirty-three FESz and 34 matched healthy controls (HC) completed the Animal Naming Task to assess SVF. Magnetoencephalography was recorded during an analogous covert SVF task, and phase-locking value (PLV) used to measure functional connectivity between inferior frontal and temporoparietal structures bilaterally. Diffusion imaging was collected to measure fractional anisotropy (FA) of the arcuate fasciculus, the major tract connecting frontal and temporoparietal language areas. RESULTS: SVF scores were lower among FESz compared to HC. While PLV and FA did not differ between groups overall, FESz exhibited an absence of the left-lateralized nature of both measures observed in HC. Among FESz, larger right-hemisphere PLV was associated with worse SVF performance (ρ = -0.51) and longer DUP (ρ = -0.50). DISCUSSION: In addition to worse SVF, FESz exhibited diminished leftward asymmetry of structural and functional connectivity in fronto-temporoparietal SVF network. The relationship between theta-band hyperconnectivity and poorer performance suggests a disorganized executive network and may reflect dysfunction of frontal cognitive control centers. These findings illustrate an aberrant pattern across the distributed SVF network at disease onset and merit further investigation into development of asymmetrical hemispheric connectivity and its failure among high-risk populations.

Duration of the psychosis prodrome and its relationship to duration of untreated psychosis across all 12 DSM-IV psychotic diagnoses: Evidence for a trans-diagnostic process associated with resilience.

While duration of the psychosis prodrome (DPP) attracts attention in relation to the developmental trajectory of psychotic illness and service models, fundamental issues endure in the context of dimensional-spectrum models of psychosis. Among 205 epidemiologically representative subjects in the Cavan-Monaghan First Episode Psychosis Study, DPP was systematically quantified and compared, for the first time, across all 12 DSM-IV psychotic diagnoses. DPP was also compared with duration of untreated psychosis (DUP) and each was then analysed in relation to premorbid features across three age ranges: <12, 12-15 and 16-18 years. For each diagnosis, medians for both DPP and DUP were shorter than means, indicating common right-skewed distributions. Rank orders for both DPP and DUP were longest for schizophrenia, intermediate for other schizophrenia-spectrum psychoses, psychotic depression and psychotic disorder not otherwise specified, and shortest for brief psychotic disorder, bipolar disorder and substance-induced psychotic disorder, though with overlapping right-skewed distributions. DPP was longer than DUP for all diagnoses except substance-induced psychotic disorder. Across functional psychotic diagnoses, longer DPP was predicted by higher premorbid intelligence and better premorbid adjustment during age 16-18 years. These findings indicate that, trans-diagnostically, DPP and DUP share right-skewed continuities, in accordance with a dimensional-spectrum model of psychotic illness, and may reflect a unitary process that has been dichotomized at a subjective threshold along its trajectory. Better premorbid functioning during age 16-18 years appears to confer resilience by delaying progression to overt psychotic symptoms and may constitute a particular target period for psychosocial interventions.