Neural dysfunction underlying working memory processing at different stages of the illness course in schizophrenia: a comparative meta-analysis.

Schizophrenia, as a chronic and persistent disorder, exhibits working memory deficits across various stages of the disorder, yet the neural mechanisms underlying these deficits remain elusive with inconsistent neuroimaging findings. We aimed to compare the brain functional changes of working memory in patients at different stages: clinical high risk, first-episode psychosis, and long-term schizophrenia, using meta-analyses of functional magnetic resonance imaging studies. Following a systematic literature search, 56 whole-brain task-based functional magnetic resonance imaging studies (15 for clinical high risk, 16 for first-episode psychosis, and 25 for long-term schizophrenia) were included. The separate and pooled neurofunctional mechanisms among clinical high risk, first-episode psychosis, and long-term schizophrenia were generated by Seed-based d Mapping toolbox. The clinical high risk and first-episode psychosis groups exhibited overlapping hypoactivation in the right inferior parietal lobule, right middle frontal gyrus, and left superior parietal lobule, indicating key lesion sites in the early phase of schizophrenia. Individuals with first-episode psychosis showed lower activation in left inferior parietal lobule than those with long-term schizophrenia, reflecting a possible recovery process or more neural inefficiency. We concluded that SCZ represent as a continuum in the early stage of illness progression, while the neural bases are inversely changed with the development of illness course to long-term course.

Antipsychotic drugs in first-episode psychosis: A target trial emulation in the FEP-CAUSAL Collaboration.

Good adherence to antipsychotic therapy helps prevent relapses in First Episode Psychosis (FEP). We used data from the FEP-CAUSAL Collaboration, an international consortium of observational cohorts to emulate a target trial comparing antipsychotics with treatment discontinuation as the primary outcome. Other outcomes included all-cause hospitalization. We benchmarked our results to estimates from EUFEST, a randomized trial conducted in the 2000s. We included 1097 patients with a psychotic disorder and less than 2 years since psychosis onset. Inverse probability weighting was used to control for confounding. The estimated 12-month risks of discontinuation for aripiprazole, first-generation agents, olanzapine, paliperidone, quetiapine, and risperidone (95% CI) were: 61.5% (52.5-70.6), 73.5% (60.5-84.9), 76.8% (67.2-85.3), 58.4% (40.4-77.4), 76.5% (62.1-88.5), and 74.4% (67.0-81.2) respectively. Compared with aripiprazole, the 12-month risk differences (95% CI) were -15.3% (-30.0, 0.0) for olanzapine, -12.8% (-25.7, -1.0) for risperidone, and 3.0% (-21.5, 30.8) for paliperidone. The 12-month risks of hospitalization were similar between agents. Our estimates support use of aripiprazole and paliperidone as first-line therapies for FEP. Benchmarking yielded similar results for discontinuation and absolute risks of hospitalization as in the original trial, suggesting that data from the FEP-CAUSAL Collaboration data sufficed to approximately remove confounding for these clinical questions.

Ethnic density and first episode psychosis in the British Pakistani population: findings from the East Lancashire Early Intervention Service.

BACKGROUND: Elevated risk of psychosis for ethnic minority groups has generally been shown to be mitigated by high ethnic density. However, past survey studies examining UK Pakistani populations have shown an absence of protective ethnic density effects, which is not observed in other South Asian groups. AIMS: To assess the ethnic density effect at a local neighbourhood level, in the UK Pakistani population in East Lancashire. METHOD: Data was collected by the East Lancashire Early Intervention Service, identifying all cases of first episode psychosis (FEP) within their catchment area between 2012 and 2020. Multilevel Poisson regression analyses were used to compare incidence rates between Pakistani and White majority groups, while controlling for age, gender and area-level deprivation. The ethnic density effect was also examined by comparing incidence rates across high and low density areas. RESULTS: A total of 455 cases of FEP (364 White, 91 Pakistani) were identified. The Pakistani group had a higher incidence of FEP compared to the White majority population. A clear effect of ethnic density on rates of FEP was shown, with those in low density areas having higher incidence rates compared to the White majority, whereas incidence rates in high density areas did not significantly differ. Within the Pakistani group, a dose-response effect was also observed, with risk of FEP increasing incrementally as ethnic density decreased. CONCLUSIONS: Higher ethnic density related to lower risk of FEP within the Pakistani population in East Lancashire, highlighting the impact of local social context on psychosis incidence.

The association of adverse childhood experiences with long-term outcomes of psychosis: a 21-year prospective cohort study after a first episode of psychosis.

BACKGROUND: Evidence suggests a possible relationship between exposure to childhood adversity (CA) and functional impairment in psychosis. However, the impact of CA on long-term outcomes of psychotic disorders remains poorly understood. METHODS: Two hundred and forty-three patients were assessed at their first episode of psychosis for CA and re-assessed after a mean of 21 years of follow-up for several outcome domains, including symptoms, functioning, quality of life, cognitive performance, neurological dysfunction, and comorbidity. The unique predictive ability of CA exposure for outcomes was examined using linear regression analysis controlling for relevant confounders, including socioeconomic status, family risk of schizophrenia, and obstetric complications. RESULTS: There were 54% of the patients with a documented history of CA at mild or higher levels. CA experiences were more prevalent and severe in schizophrenia than in other psychotic disorders (p < 0.001). Large to very large effect sizes were observed for CA predicting most role functioning variables and negative symptoms (ΔR2 between 0.105 and 0.181). Moderate effect sizes were observed for positive symptoms, personal functioning, impaired social cognition, impaired immediate verbal learning, poor global cognition, internalized stigma, poor personal recovery, and drug abuse severity (ΔR2 between 0.040 and 0.066). A dose-response relationship was observed between levels of CA and severity of outcome domains. CONCLUSION: Our results suggest a strong and widespread link between early adversity exposure and outcomes of psychotic disorders. Awareness of the serious long-term consequences of CA should encourage better identification of those at risk and the development of effective interventions.

Additive effects of a family history of schizophrenia spectrum disorders and an environmental risk score for the outcome of patients with non-affective first-episode psychosis.

BACKGROUND: First-episode psychotic disorders comprise a heterogeneous phenotype with a complex etiology involving numerous common small-effect genetic variations and a wide range of environmental exposures. We examined whether a family of schizophrenia spectrum disorder (FH-Sz) interacts with an environmental risk score (ERS-Sz) regarding the outcome of patients with non-affective first episode psychosis (NAFEP). METHODS: We included 288 patients with NAFEP who were evaluated after discharge from an intensive 2-year program. We evaluated three outcome measures: symptomatic remission, psychosocial functioning, and personal recovery. We analyzed the main and joint associations of a FH-Sz and the ERS-Sz on the outcomes by using the relative excess risk due to interaction (RERI) approach. RESULTS: A FH-Sz showed a significant association with poor symptomatic remission and psychosocial functioning outcomes, although there was no significant interaction between a FH-Sz and the ERS-Sz on these outcomes. The ERS-Sz did not show a significant association with poor symptomatic remission and psychosocial functioning outcomes, even though the magnitude of the interaction between ERS-Sz and FH-Sz with the later outcome was moderate (RERI = 6.89, 95% confidence interval -16.03 to 29.81). There was no association between a FH-Sz and the ERS-Sz and personal recovery. CONCLUSIONS: Our results provide further empirical support regarding the contribution of FH-Sz to poor symptomatic remission and poor psychosocial functioning outcomes in patients with NAFEP.

20-year neurocognitive development following a schizophrenia spectrum disorder and associations with symptom severity and functional outcomes.

BACKGROUND: Cognitive deficits are a core feature of schizophrenia and are closely associated with poor functional outcomes. It remains unclear if cognitive deficits progress over time or remain stable. Determining patients at increased risk of progressive worsening might help targeted neurocognitive remediation approaches. METHODS: This 20-year follow-up study examined neurocognitive outcomes of 156 participants from the OPUS I trial. Neurocognition was assessed using the brief assessment of cognition in schizophrenia at the 10- and 20-year follow-up, allowing us to examine changes in neurocognition over ten years. RESULTS: We found that 30.5% of patients had a declining course of neurocognition, 49.2% had a stable course of neurocognition and 20.3% experienced improvements in neurocognition. Good cognitive functioning at the 20-year follow-up was significantly associated with higher levels of social functioning (B 6.86, CI 4.71-9.02, p < 0.001) while increasing experiential negative symptoms were significantly correlated to cognitive worsening (PC-0.231, p = 0.029). Younger age at inclusion (B: 0.23 per 10-years, CI 0.00-0.045, p = 0.047) and low level of education (below ten years) (mean difference: -0.346, CI -0.616 to -0.076, p = 0.012) predicted declining neurocognition. CONCLUSION: Our findings support the notion of different schizophrenia subtypes with varying trajectories. Neurocognitive impairment at the 20-year follow-up was associated with other poor outcomes, highlighting the importance of treatments aimed at improving neurocognition in patients with schizophrenia spectrum disorders.

Long-term diagnostic stability, predictors of diagnostic change, and time until diagnostic change of first-episode psychosis: a 21-year follow-up study.

BACKGROUND: Although diagnostic instability in first-episode psychosis (FEP) is of major concern, little is known about its determinants. This very long-term follow-up study aimed to examine the diagnostic stability of FEP diagnoses, the baseline predictors of diagnostic change and the timing of diagnostic change. METHODS: This was a longitudinal and naturalistic study of 243 subjects with FEP who were assessed at baseline and reassessed after a mean follow-up of 21 years. The diagnostic stability of DSM-5 psychotic disorders was examined using prospective and retrospective consistencies, logistic regression was used to establish the predictors of diagnostic change, and survival analysis was used to compare time to diagnostic change across diagnostic categories. RESULTS: The overall diagnostic stability was 47.7%. Schizophrenia and bipolar disorder were the most stable diagnoses, with other categories having low stability. Predictors of diagnostic change to schizophrenia included a family history of schizophrenia, obstetric complications, developmental delay, poor premorbid functioning in several domains, long duration of untreated continuous psychosis, spontaneous dyskinesia, lack of psychosocial stressors, longer duration of index admission, and poor early treatment response. Most of these variables also predicted diagnostic change to bipolar disorder but in the opposite direction and with lesser effect sizes. There were no significant differences between specific diagnoses regarding time to diagnostic change. At 10-year follow-up, around 80% of the diagnoses had changed. CONCLUSIONS: FEP diagnoses other than schizophrenia or bipolar disorder should be considered as provisional. Considering baseline predictors of diagnostic change may help to enhance diagnostic accuracy and guide therapeutic interventions.

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.

Difficulties during delivery, brain ventricle enlargement and cognitive impairment in first episode psychosis.

BACKGROUND: Patients with a first episode of psychosis (FEP) display clinical, cognitive, and structural brain abnormalities at illness onset. Ventricular enlargement has been identified in schizophrenia since the initial development of neuroimaging techniques. Obstetric abnormalities have been associated with an increased risk of developing psychosis but also with cognitive impairment and brain structure abnormalities. Difficulties during delivery are associated with a higher risk of birth asphyxia leading to brain structural abnormalities, such as ventriculomegaly, which has been related to cognitive disturbances. METHODS: We examined differences in ventricular size between 142 FEP patients and 123 healthy control participants using magnetic resonance imaging. Obstetric complications were evaluated using the Lewis-Murray scale. We examined the impact of obstetric difficulties during delivery on ventricle size as well as the possible relationship between ventricle size and cognitive impairment in both groups. RESULTS: FEP patients displayed significantly larger third ventricle size compared with healthy controls. Third ventricle enlargement was associated with diagnosis (higher volume in patients), with difficulties during delivery (higher volume in subjects with difficulties), and was highest in patients with difficulties during delivery. Verbal memory was significantly associated with third ventricle to brain ratio. CONCLUSIONS: Our results suggest that difficulties during delivery might be significant contributors to the ventricular enlargement historically described in schizophrenia. Thus, obstetric complications may contribute to the development of psychosis through changes in brain architecture.

Exercise4Psychosis: A randomised control trial assessing the effect of moderate-to-vigorous exercise on inflammatory biomarkers and negative symptom profiles in men with first-episode psychosis.

INTRODUCTION: First-Episode Psychosis (FEP) is a devastating mental health condition that commonly emerges during early adulthood, and is characterised by a disconnect in perceptions of reality. Current evidence suggests that inflammation and perturbed immune responses are involved in the pathology of FEP and may be associated specifically with negative symptoms. Exercise training is a potent anti-inflammatory stimulus that can reduce persistent inflammation, and can improve mood profiles in general populations. Therefore, exercise may represent a novel adjunct therapy for FEP. The aim of this study was to assess the effect of exercise on biomarkers of inflammation, negative symptoms of psychosis, and physiological health markers in FEP. METHODS: Seventeen young males (26.67 ± 6.64 years) were recruited from Birmingham Early Intervention in Psychosis Services and randomised to a 6-week exercise programme consisting of two-to-three sessions per week that targeted 60-70 % heart-rate max (HRMax), or a treatment as usual (TAU) condition. Immune T-helper (Th-) cell phenotypes and cytokines, symptom severity, functional wellbeing, and cognition were assessed before and after 6-weeks of regular exercise. RESULTS: Participants in the exercise group (n = 10) achieved 81.11 % attendance to the intervention, with an average exercise intensity of 67.54 % ± 7.75 % HRMax. This led to favourable changes in immune cell phenotypes, and a significant reduction in the Th1:Th2 ratio (-3.86 %) compared to the TAU group (p = 0.014). After the exercise intervention, there was also a significant reduction in plasma IL-6 concentration (-22.17 %) when compared to the TAU group (p = 0.006). IL-8, and IL-10 did not show statistically significant differences between the groups after exercise. Symptomatically, there was a significant reduction in negative symptoms after exercise (-13.54 %, Positive and Negative Syndrome Scale, (PANSS) Negative) when compared to the TAU group (p = 0.008). There were no significant change in positive or general symptoms, functional outcomes, or cognition (all p > 0.05). DISCUSSION: Regular moderate-to-vigorous physical activity is feasible and attainable in clinical populations. Exercise represents a physiological tool that is capable of causing significant inflammatory biomarker change and concomitant symptom improvements in FEP cohorts, and may be useful for treatment of symptom profiles that are not targeted by currently prescribed antipsychotic medication.

Association of symptom severity and cerebrospinal fluid alterations in recent onset psychosis in schizophrenia-spectrum disorders - An individual patient data meta-analysis.

Neuroinflammation and blood-cerebrospinal fluid barrier (BCB) disruption could be key elements in schizophrenia-spectrum disorders(SSDs) etiology and symptom modulation. We present the largest two-stage individual patient data (IPD) meta-analysis, investigating the association of BCB disruption and cerebrospinal fluid (CSF) alterations with symptom severity in first-episode psychosis (FEP) and recent onset psychotic disorder (ROP) individuals, with a focus on sex-related differences. Data was collected from PubMed and EMBASE databases. FEP, ROP and high-risk syndromes for psychosis IPD were included if routine basic CSF-diagnostics were reported. Risk of bias of the included studies was evaluated. Random-effects meta-analyses and mixed-effects linear regression models were employed to assess the impact of BCB alterations on symptom severity. Published (6 studies) and unpublished IPD from n = 531 individuals was included in the analyses. CSF was altered in 38.8 % of individuals. No significant differences in symptom severity were found between individuals with and without CSF alterations (SMD = -0.17, 95 %CI -0.55-0.22, p = 0.341). However, males with elevated CSF/serum albumin ratios or any CSF alteration had significantly higher positive symptom scores than those without alterations (SMD = 0.34, 95 %CI 0.05-0.64, p = 0.037 and SMD = 0.29, 95 %CI 0.17-0.41p = 0.005, respectively). Mixed-effects and simple regression models showed no association (p > 0.1) between CSF parameters and symptomatic outcomes. No interaction between sex and CSF parameters was found (p > 0.1). BCB disruption appears highly prevalent in early psychosis and could be involved in positive symptoms severity in males, indicating potential difficult-to-treat states. This work highlights the need for considering BCB breakdownand sex-related differences in SSDs clinical trials and treatment strategies.

Soluble terminal complement complex blood levels are elevated in schizophrenia.

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.

Neuropsychological profiles in first-episodes psychosis and their relationship with clinical, metacognition and social cognition variables.

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.

Patients with first-episode psychosis in northern Taiwan: neurocognitive performance and niacin response profile in comparison with schizophrenia patients of different familial loadings and relationship with clinical features.

BACKGROUND: Examining patients with first-episode psychosis (FEP) provides opportunities to better understand the mechanism underlying these illnesses. By incorporating quantitative measures in FEP patients, we aimed to (1) determine the baseline distribution of clinical features; (2) examine the impairment magnitude of the quantitative measures by comparing with external controls and then the counterparts of schizophrenia patients of different familial loadings; and (3) evaluate whether these quantitative measures were associated with the baseline clinical features. METHODS: Patients with FEP were recruited from one medical center, two regional psychiatric centers, and two private clinics in northern Taiwan with clinical features rated using the Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance (PSP) scale. Quantitative measurements included the Continuous Performance Test (CPT), Wisconsin Card Sorting Test (WCST), niacin response abnormality (NRA), and minor physical anomalies and craniofacial features (MPAs). To evaluate the relative performance of the quantitative measures in our FEP patients, four external comparison groups from previous studies were used, including three independent healthy controls for the CPT, WCST, and NRA, respectively, and one group of treatment-resistant schizophrenia patients for the MPAs. Additionally, patients from simplex families and patients from multiplex families were used to assess the magnitude of FEP patients' impairment on the CPT, WCST, and NRA. RESULTS: Among the 80 patients with FEP recruited in this study (58% female, mean age = 25.6 years, mean duration of untreated psychosis = 132 days), the clinical severity was mild to moderate (mean PANSS score = 67.3; mean PSP score = 61.8). Patients exhibited both neurocognitive and niacin response impairments (mean Z-scores: -1.24 for NRA, - 1.06 for undegraded d', - 0.70 for degraded d', - 0.32 for categories achieved, and 0.44 for perseverative errors) but did not show MPAs indicative of treatment resistance. Among these quantitative measures, three of the four neurocognitive indices were correlated with the baseline clinical features, whereas NRA did not show such correlation. CONCLUSIONS: This FEP study of Taiwanese patients revealed the presence of neurocognitive performance and niacin response and their different relationships with clinical features, rendering this sample useful for future follow-up and incorporation of multiomics investigation.

Prevalence and risk factors for psychotic symptoms in young, first-episode and drug-naïve patients with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a common psychiatric disorder worldwide. Psychotic depression has been reported to be frequently under-diagnosed due to poor recognition of psychotic features. Therefore, the purpose of this study was to reveal the rate and risk factors of psychotic symptoms in young, drug-naïve patients with major depressive disorder at the time of their first episode. METHODS: A total of 917 patients were recruited and divided into psychotic and non-psychotic subgroups based on the Positive and Negative Syndrome Scale (PANSS) positive subscale score. Anxiety symptoms and depressive symptoms were measured by the Hamilton Anxiety Rating Scale (HAMA) and the 17-item Hamilton Depression Rating Scale (HAMD-17), respectively. Several biochemical indicators such as total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were also measured. RESULTS: The rate of psychotic symptoms among young adult MDD patients was 9.1%. There were significant differences in TSH (p<0.001), FBG (p<0.001), TC (p<0.0001), TG (p = 0.001), HDL-C (p = 0.049), LDL-C (p = 0.010), diastolic blood pressure (DP) (p<0.001), systolic blood pressure (SP) (p<0.001), and HAMD total score (p<0.001) between young MDD patients with and without psychotic depression. HAMD, TSH, TC, and severe anxiety were independently associated with psychotic symptoms in young adult MDD patients. In addition, among young MDD patients, the rate of suicide attempts in the psychotic subgroup was much higher than in the non-psychotic subgroup (45.8% vs. 16.9%). CONCLUSIONS: Our findings suggest that psychotic symptoms are common in young MDD patients. Several clinical variables and biochemical indicators are associated with the occurrence of psychotic symptoms in young MDD patients.

Monthly engagement with EIP keyworkers was associated with a five-fold increase in the odds of engagement with psychosocial interventions.

BACKGROUND: Early intervention in psychosis (EIP) supports people who are experiencing their first episode of psychosis (FEP). A new Model of Care (MoC) for EIP services was launched in Ireland in 2019. Three EIP demonstration sites were chosen to test this MoC through a 'hub and spoke' approach. These services were a new way of organising care for people experiencing FEP, based upon a recovery model of care, and which sought to standardise care, improve access by clinically led multidisciplinary teams. This included newly created EIP keyworker roles whereby keyworkers assumed responsibilities regarding assessment, comprehensive individual care planning and coordination of care. METHODS: A mixed methods design utilising the UK Medical Research Council's process evaluation framework. Purposive sampling techniques were utilised. Descriptive analyses and logistic regression were performed to examine how increased keyworker engagement influenced the use of other psychosocial interventions within the EIP demonstration sites. Thematic analyses was used for qualitative data. RESULTS: There was a strong positive relationship between keyworker contacts and psychosocial interventions offered. Specifically, the odds of achieving at least monthly engagement with cognitive behavioural therapy for psychosis (CBTp; (5.76 (2.43-13.64), p < 0.001), and behavioural family therapy (BFT; (5.52(1.63-18.69, p < 0.006)) increased by fivefold with each additional monthly keyworker contact. For individual placement support (IPS) each additional monthly keyworker contact was associated with a three-fold increase in the odds of achieving monthly attendance with IPS (3.73 (1.64-8.48), p < 0.002). Qualitative results found that the EIP keyworker role as viewed by both service users and staff as a valuable nodal point, with a particular emphasis on care coordination and effective communication. CONCLUSIONS: This study advances the understanding of keyworker effects through qualitative evidence of keyworkers functioning as a "linchpin" to the service, while the positive response association between keyworker contacts and engagement with other services provides quantitative support for keyworkers reducing the organisational or structural barriers to service access. Given the importance of these positions, health systems should ensure that EIP programmes identify qualified and experienced staff to fill these roles, as well as allocate the appropriate funding and protected time to support keyworker engagement and impact.

Experiences of Sexual and Reproductive Health Care Access for Women and Nonbinary People With Early Psychosis: Towards an Integrated Perspective of Service Users and Clinicians.

OBJECTIVE: Individuals with psychosis are at elevated risk of adverse sexual and reproductive health (SRH) outcomes, and not receiving adequate SRH care. SRH is important for youth, yet little is known about SRH care access and experiences among those with early psychosis. This study explored SRH care experiences among women and nonbinary individuals with early psychosis. METHOD: We conducted semistructured qualitative interviews with 19 service users (cisgender and transgender women, nonbinary individuals) receiving care in 2 early psychosis programs in Ontario, Canada. We also conducted semistructured interviews and focus groups with 36 clinicians providing SRH or mental health care to this population. Participants were asked about SRH care access/provision experiences and the interplay with psychosis. Using a social interactionist orientation, a thematic analysis described and explained service user and clinician perspectives regarding SRH care. RESULTS: Amongst both service users and clinician groups, common themes developed: (a) diversity of settings: SRH services are accessed in a large range of spaces across the health care system, (b) barriers in nonpsychiatric SRH care settings: psychosis impacts the ability to engage with existing SRH services, (c) invisibility of SRH in psychiatric settings: SRH is rarely addressed in psychiatric care, (d) variability of informal SRH-related conversations and supports, and cutting across all of the above themes, (e) intersecting social and cultural factors impacted SRH services access. CONCLUSIONS: SRH is important for health and wellbeing; improvements are urgently needed across the healthcare system and within early psychosis programs to meet this population's multifaceted SRH needs.

The influence of gender in cognitive insight and cognitive bias in people with first-episode psychosis: an uncontrolled exploratory analysis.

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.

Comprehensive spatial distribution of patients with first-episode psychosis (FEP) and its relation to socio-economic factors.

BACKGROUND: The functional-cognitive impact of first-episode psychosis (FEP) is extremely relevant and implies dysfunction from early life stages like adolescence and youth. Like other illnesses, FEP incidence is also influenced by environmental factors. It is necessary to attend to this age group with early interventions and to act on the environmental factors that the literature correlates with increased FEP incidence: socio-economic aspects, social adversity, bullying at school or cannabis use. In this context, identifying the areas of cities where FEP patients concentrate is important to perform early interventions. The spatial analysis of patient distribution in a whole city is one way to identify the most vulnerable areas and to propose psycho-social interventions for the possible prevention and/or early detection of FEP by improving urban mental health. METHODS: An epidemiological study of point patterns to determine the areas of a city with a higher incidence of patients with FEP. To do so, the addresses of FEP cases were georeferenced from 1 January 2016 to 31 October 2022, and 109 FEP patients were analysed. Data from a random sample of 383 controls, comprising their addresses, age, and sex, were randomly obtained from the official city council database. By GIS, the areas with higher FEP incidence were analysed to see if they coincided with the zones where inhabitants with lower incomes lived. RESULTS: The risk ratio of the FEP patients was compatible with the constant risk ratio in Albacete (p = 0.22). When performing the process separately with cases and controls only in men and women, the results were not significant for both distributions (p value: 0.12 and 0.57, respectively). Nonetheless, areas within the city had a significantly higher risk. These groups of cases coincided with those who had lower income and more inequality for women, but this pattern was not clear for men. CONCLUSIONS: Classifying city areas per income can help to determine the zones at higher risk of FEP, which would allow early healthcare and preventive measures for these zones.

Sociodemographic and clinical predictors of delay to and length of stay with early intervention for psychosis service: findings from the CRIS-FEP study.

PURPOSE: We investigated the influence of sociodemographic and clinical characteristics on delay to early intervention service (EIS) and the length of stay (LOS) with EIS. METHODS: We used incidence data linked to the Clinical Record Interactive Search-First Episode Psychosis (CRIS-FEP) study. We followed the patients from May 2010 to March 2016. We performed multivariable Cox regression to estimate hazard ratios of delay to EIS. Negative binomial regression was used to determine LOS with EIS by sociodemographic and clinical characteristics, controlling for confounders. RESULTS: 343 patients were eligible for an EIS, 34.1% of whom did not receive the service. Overall, the median delay to EIS was 120 days (IQR; 15-1668); and the median LOS was 130.5 days (IQR 0-663). We found that women (adj.HR 0.58; 95%C I 0.42-0.78), living alone (adj.HR: 0.63; 95% CI 0.43-0.92) and ethnicity ('Other': adj.HR 0.47; 95% CI 0.23-0.98) were associated with prolonged delay to EIS. However, family involvement in help-seeking for psychosis (adj.HR 1.37; 95% CI 1.01-1.85) was strongly associated with a shorter delay to EIS. Patients who have used mental health services previously also experienced long delays to EIS. CONCLUSIONS: Our analyses highlight the link between sociodemographic status, help-seeking behaviours, and delay to EIS. Our findings also show the vulnerability faced by those with a previous mental health problem who later develop psychosis in receiving specialist treatment for psychosis. Initiatives that ameliorate indicators of social disadvantage are urgently needed to reduce health inequalities and improve clinical outcomes.