First-episode Non-affective Psychosis Research Articles

Antipsychotic discontinuation in nonaffective first-episode psychosis after clinical remission: Insights from the PEPsNa naturalistic study

The predictors of clinical evolution after nonaffective first-episode psychosis (NAFEP) have yet to be fully elucidated. It is important to weigh the long-term benefits of maintained antipsychotic (AP) treatment against the risks of relapse upon discontinuation. Between January 2017 and December 2022, we recruited 211 NAFEP patients from the Programa de Primeros Episodios Psicóticos de Navarra (PEPsNa) who achieved clinical remission within two years and continued follow-up. Clinicians recommended discontinuation of antipsychotics for 47 participants, resulting in significantly fewer relapses (10.6%, p≤ 0.05) and a longer relapse-free survival time (95% confidence interval= 16.9 to 18.2 months). For every four individuals out of 72 who voluntarily discontinued APs (in contrast to those who were advised to discontinue APs), there was one more relapse (number needed to harm= 4; p≤ 0.01). Moreover, one additional relapse was prevented for every seven individuals who continued APs instead of voluntarily discontinuing APs (number needed to treat= 7; p≤ 0.05). Lower premorbid risk factors and better clinical profiles, such as shorter DUP, shorter time to remission, good real-world performance, better neurocognitive functioning, lack of a schizophrenia spectrum diagnosis, and a lower average dose of APs led clinicians to recommend AP discontinuation after achieving remission from NAFEP. This guided discontinuation of APs did not lead to a higher risk of relapse, but participants who voluntarily withdrew from treatment had a higher risk of relapse.

Consistency of Delusion Themes Across First and Subsequent Episodes of Psychosis

Despite growing interest in the phenomenology of delusions in psychosis, at present little is known about their content and evolution over time, including whether delusion themes are consistent across episodes. To examine the course of delusions and thematic delusion content across relapse episodes in patients presenting to an early intervention service for psychosis. This longitudinal, observational study used clinical data systematically collected from January 2003 to March 2018 from a cohort of consenting patients with affective or nonaffective first-episode psychosis, followed up naturalistically for up to 2 years in an early intervention service for psychosis in Montréal, Quebec, Canada. Data included the thematic content and severity of delusions (scores ≥3 using the Scale for the Assessment of Positive Symptoms) and associated psychotic and nonpsychotic symptoms, both across an initial episode and, in the event of remission, a potential relapse. Data were analyzed from September 2021 to February 2023. An early intervention service for psychosis, organized around intensive case management and a multidisciplinary team approach, which observed each patient for up to 2 years of care. The primary outcome was positive symptom relapse and remission, including the presence and content of delusions, which was coded per the Scale for the Assessment of Positive Symptoms and accepted definitions. The main statistical measures included repeated paired-sample t tests and binary logistic regression analyses. Of 636 consenting patients, mean (SD) age was 23.8 (4.75) years; 191 patients were female, 444 were male, and 1 patient was nonbinary. Remission rates were high, and relapse rates were relatively low: 591 individuals had baseline delusions, of which 558 (94.4%) achieved remission. Of these 558 patients, only 182 (32.6%) had a subsequent relapse to a second or later episode of psychosis. Of the 182 patients who did relapse, however, a large proportion (115 [63.2%]) reported threshold-level delusions. Of these 115, 104 patients (90.4%) had thematic delusion content consistent with that reported during the index (first) episode. Those who relapsed with delusions had fewer delusion themes present during subsequent episodes of psychosis compared with the index episode and lower levels of other psychotic and nonpsychotic symptoms. Specialized early intervention services for psychosis can achieve high rates of sustained remission. However, in this study, the minority of individuals with delusions who later relapsed experienced similar delusion themes during subsequent episodes. These findings raise important considerations for the conceptualization of delusions and have clinical implications for trajectories of illness and care.

Sex differences in prolactin levels and clinical outcomes in patients with a first psychotic episode

AimTo analyze the clinical, neurocognitive, and functional impact of prolactin levels according to sex in patients with a First Episode Psychosis (FEP). MethodsWe measured prolactin levels in 221 non-affective FEP patients treated with antipsychotics (AP) and 224 healthy controls, at baseline and 2-year follow-up. We examined whether the relationships between clinical and functional variables were mediated by prolactin, controlling for antipsychotic use, according to sex. ResultsProlactin levels were higher in patients when compared to controls at both time points. Baseline factors associated with prolactin were chlorpromazine equivalents, attention, and executive functioning. In the FEP group, prolactin levels were associated with functioning and diminished expression in males, and with working memory in females. Prolactin levels (p=0.0134) played a role as a mediator between negative symptomatology (p=0.086) and functional outcome (p=0.008) only in FEP male patients at baseline. ConclusionsProlactin plays a role in the functionality and clinical symptomatology of FEP patients. Our results suggest that pharmacological counselling in patients with hyperprolactinemia at baseline and negative symptomatology might improve their functional and clinical outcomes.

First episode psychoses in people over-35 years old: uncovering potential actionable targets for early intervention services

The traditional youth-oriented design of Early Intervention Services (EIS) may lead to the exclusion of patients who have their psychotic onset later in life. A retrospective study was conducted to compare first-episode psychosis (FEP) patients who accessed treatment when aged ≤ 35 years with those ≥36+. A total of 854 patients were identified among 46,222 individuals who had access to community psychiatric services from 1991 to 2021. FEP were aged 18–65, received care between 2012 and 2021 and had a diagnosis of affective or non-affective FEP. Two groups were identified (FEP diagnosed at age ≤ 35 vs ≥ 36) and compared for sociodemographic and clinical characteristics. Most patients were diagnosed when aged ≥ 36+ (61.8%). Compared to the ≤ 35 group, older patients were more likely to be women, married and diagnosed with affective psychosis, and they were less frequently hospitalized. Long-acting injectables antipsychotics (LAI) were less frequently prescribed in the ≥ 36+ group, whereas antidepressants were more frequently prescribed compared to those aged ≤ 35. In both age groups, women were less frequently prescribed LAIs compared to men. These findings highlight the need to reorient EIS to accommodate the needs of older FEP, especially women.

Antipsychotic Use and Psychiatric Hospitalization in First-Episode Non-affective Psychosis and Cannabis Use Disorder: A Swedish Nationwide Cohort Study.

There is a paucity of research on treatment outcomes of patients with psychosis and cannabis use disorder (CUD). We aimed to compare the effectiveness of antipsychotics in reducing the risk of hospitalization in patients with first-episode psychosis (FEP) and co-occurring CUD. We utilized a nationwide Swedish cohort of patients with longitudinal register data from the year 2006 to 2021. Participants were patients with FEP and co-occurring CUD (n = 1820, 84.73% men, mean age 26.80 years, SD 8.25 years). The main outcome was hospitalization due to psychotic relapse. Hospitalization due to any psychiatric disorder or substance use disorder (SUD) were examined as secondary outcomes. Within-individual Cox regression models were used to study these associations. Use of any antipsychotic was associated with a 33% risk reduction of psychotic relapse (aHR = 0.67; 95% CI 0.60-0.75). Clozapine (0.43; 0.29-0.64), long-acting injectable (LAI) formulations of risperidone (0.40; 0.22-0.71), aripiprazole (0.42; 0.27-0.65), and paliperidone (0.46; 0.30-0.69) were associated with the lowest risk of relapse. The association between the LAI formulation of olanzapine and hospitalization due to psychosis was statistically non-significant (0.61; 0.35-1.05). Clozapine was associated with an 86% risk reduction of hospitalization due to SUD (0.14; 0.05-0.44). Of oral non-clozapine antipsychotics, aripiprazole was associated with the lowest risk of hospitalization due to psychotic relapse (0.61; 0.45-0.83). These findings support the use of clozapine, LAI formulations of second-generation antipsychotics other than olanzapine, or oral aripiprazole to prevent hospitalization in FEP and co-occurring CUD.

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.

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). 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. 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. 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.

A Matched Case-Control Study of the Serum Level and Gene Expression of IL-6 and IL-12 in Patients with Schizophrenia Spectrum Disorder: An Azeri Acute Phase/Recent-Onset Psychosis Survey (ARAS) Study

Background: The causes of schizophrenia spectrum disorders are believed to be multifactorial, with both genetic and environmental factors, as well as gene-environment interactions, influencing the course of this disorder. Research suggests that immunological factors may play a role in the development of psychotic disorders. Objectives: The aim of this study is to evaluate and compare the serum levels of interleukin-6 (IL-6) and interleukin-12 (IL-12), as well as the expression levels of IL-6 and IL-12 genes, between an Iranian Azeri population of patients with first-episode psychosis and healthy controls. Methods: Forty patients who had recently experienced first-episode non-affective psychosis were allocated to the patient group. Forty healthy volunteers, matched for age and gender, were also recruited as controls. The study was conducted in 2020 in Tabriz, Iran. Peripheral blood samples were collected (using the Ficoll-Paque process) and assessed to determine the expression levels of IL-6 and IL-12 mRNA (using real-time Polymerase Chain Reaction-PCR- system), as well as the serum levels of IL-6 and IL-12 (with a sandwich ELISA kit). GraphPad Prism Version 6.0 was used for all statistical analyses. Results: Each group consisted of 40 participants in this study. Patients had significantly higher levels of IL-6 mRNA expression compared to the healthy controls (P < 0.0001), while no significant difference was found between the two groups in terms of IL-12 mRNA expression (P = 0.5697). A similar pattern was reported for the serum levels of IL-6 (P < 0.0001) and IL-12 (P = 0.0777). The area under the curve (AUC), which indicates the accuracy of the predictive model, was 0.9669 for the level of IL-6 mRNA expression (P < 0.0001). This Area (AUC) was 0.9584 for the serum concentration of IL-6 (P < 0.0001). The levels of IL-6 or IL-12 were not correlated with the severity of symptoms, gender, or age of the patients. Conclusions: The expression level of IL-6 mRNA and the serum concentration of IL-6 were altered in patients with first-episode non-affective psychosis. This finding supports the role of inflammatory pathways in the pathogenesis of psychosis. According to our results, measurement of the circulating level of IL-6 may be useful in distinguishing patients with first-episode psychosis from healthy individuals.

Selected neuroendocrine factors as potential molecular biomarkers of early non-affective psychosis course in relation to treatment outcome: A pilot study

The aim of this pilot study was to find whether the dysregulation of neuroendocrine biomarker signaling pathways in the first episode of non-affective psychosis is a predictive factor of treatment outcome. Patients with the first episode of non-affective psychosis (N = 29) were examined at admission, at discharge, and at follow-up (N = 23). The biomarkers included serum aldosterone, cortisol, free thyroxine, thyroid stimulating hormone, and prolactin. We revealed lower baseline aldosterone and higher baseline cortisol concentrations in patients with very good outcome compared to those with good outcome after one year. We failed to reveal any significant association between treatment outcome and neurohumoral biomarkers in the whole sample at 1-year follow-up. However, baseline aldosterone concentrations negatively correlated with total PANSS scores at the discharge. Lower baseline aldosterone and higher baseline cortisol concentrations have the potential to predict a more favorable outcome for patients with the first episode of psychosis.

Small area variations in non-affective first-episode psychosis: the role of socioeconomic and environmental factors.

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. 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. 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. 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.

Cognitive subgroups and the relationships with symptoms, psychosocial functioning and quality of life in first-episode non-affective psychosis: a cluster-analysis approach.

Prior research examining cognitive heterogeneity in psychotic disorders primarily focused on chronic schizophrenia, with limited data on first-episode psychosis (FEP). We aimed to identify distinct cognitive subgroups in adult FEP patients using data-driven cluster-analytic approach, and examine relationships between cognitive subgroups and a comprehensive array of illness-related variables. Two-hundred-eighty-nine Chinese patients aged 26-55 years presenting with FEP to an early intervention program in Hong Kong were recruited. Assessments encompassing premorbid adjustment, illness-onset profile, symptom severity, psychosocial functioning, subjective quality-of-life, and a battery of cognitive tests were conducted. Hierarchical cluster-analysis was employed, optimized with k-means clustering and internally-validated by discriminant-functional analysis. Cognitive subgroup comparisons in illness-related variables, followed by multivariable multinominal-regression analyzes were performed to identify factors independently predictive of cluster membership. Three clusters were identified including patients with globally-impaired (n = 101, 34.9%), intermediately-impaired (n = 112, 38.8%) and relatively-intact (n = 76, 26.3%) cognition (GIC, IIC and RIC subgroups) compared to demographically-matched healthy-controls' performance (n = 50). GIC-subgroup was older, had lower educational attainment, greater positive, negative and disorganization symptom severity, poorer insight and quality-of-life than IIC- and RIC-subgroups, and higher antipsychotic-dose than RIC-subgroup. IIC-subgroup had lower education levels and more severe negative symptoms than RIC-subgroup, which had better psychosocial functioning than two cognitively-impaired subgroups. Educational attainment and disorganization symptoms were found to independently predict cluster membership. Our results affirmed cognitive heterogeneity in FEP and identified three subgroups, which were differentially associated with demographic and illness-related variables. Further research should clarify longitudinal relationships of cognitive subgroups with clinical and functional outcomes in FEP.

Altered neutrophil-to-lymphocyte ratio in patients with non-affective first episode psychosis and its relationship with symptom severity and cognitive impairment

Signatures of immune dysregulation as clinical biomarker for psychosis have remained unclear. We aimed to compare the Neutrophil-to-lymphocyte ratio (NLR) of patients with acute non-affective first-episode psychosis (FEP) with healthy controls after accounting for emotional states. We also explored the associations of NLR with symptom severity, onset profile and cognitive functions. The NLR was enumerated from complete blood count taken within a week of assessment. All FEP patients were rated on the Positive and Negative Syndrome Scale (PANSS) and the Clinician Global Impression-Severity (CGI-S) with verbal memory and executive functions assessed with the Cambridge Neuropsychological Test Automated Battery. Prevailing emotional state was measured with Beck Depression Inventory-II and Beck Anxiety Inventory. Out of seventy-nine consecutive FEP patients presenting to the study site, twenty-seven subjects were eligible and recruited. Twenty-seven age-/sex-matched controls were recruited. FEP patients had an NLR of 1.886 over the controls after accounting for scores on emotional states. The NLR of FEP patients was positively associated with CGI-S scores, PANSS positive symptom, disorganization and excitation scores. There was no significant correlation between NLR with the duration of untreated psychosis and cognitive performances. These findings support using NLR as a clinical biomarker in FEP, purporting further prospective study to measure NLR changes in the course of treatment.

Inflammatory cytokines and white matter microstructure in the acute phase of first-episode psychosis: A longitudinal study.

Schizophrenia-related psychosis is associated with abnormalities in white matter (WM) microstructure and structural brain dysconnectivity. However, the pathological process underlying such changes is unknown. We sought to investigate the potential association between peripheral cytokine levels and WM microstructure during the acute phase of first-episode psychosis (FEP) in a cohort of drug-naïve patients. Twenty-five non-affective FEP patients and 69 healthy controls underwent MRI scanning and blood collection at study entry. After achieving clinical remission, 21 FEP were reassessed; 38 age and biological sex-matched controls also had a second assessment. We measured fractional anisotropy (FA) of selected WM regions-of-interest (ROIs) and plasma levels of four cytokines (IL-6, IL-10, IFN-γ, and TNF-α). At baseline (acute psychosis), the FEP group showed reduced FA relative to controls in half the examined ROIs. Within the FEP group, IL-6 levels were negatively correlated with FA values. Longitudinally, patients showed increments of FA in several ROIs affected at baseline, and such changes were associated with reductions in IL-6 levels. A state-dependent process involving an interplay between a pro-inflammatory cytokine and brain WM might be associated with the clinical manifestation of FEP. This association suggests a deleterious effect of IL-6 on WM tracts during the acute phase of psychosis.

A Proxy Approach to Family Involvement and Neurocognitive Function in First Episode of Non-Affective Psychosis: Sex-Related Differences.

Schizophrenia spectrum disorders (SSD) often show cognitive deficits (CD) impacting daily life. Family support has been shown to be protective against CD, yet the relationship between these in psychotic patients remains complex and not fully understood. This study investigated the association between a subdomain of family support, namely, family involvement (estimated through a proxy measure), cognitive functioning, and sex in first-episode psychosis (FEP) patients. The sample included 308 patients enrolled in the Program for Early Phases of Psychosis (PAFIP), divided into 4 groups based on their estimated family involvement (eFI) level and sex, and compared on various variables. Women presented lower rates of eFI than men (37.1% and 48.8%). Higher eFI was associated with better cognitive functioning, particularly in verbal memory. This association was stronger in women. The findings suggest that eFI may be an important factor in FEP patients' cognitive functioning. This highlights the importance of including families in treatment plans for psychotic patients to prevent CD. Further research is needed to better understand the complex interplay between family support, sex, and cognitive functioning in psychotic patients and develop effective interventions that target these factors.

Antipsychotic treatment patterns in refugees and their Swedish-born peers with first-episode non-affective psychosis: findings from the REMAIN study

Previous studies suggest that migrants tend to utilise antipsychotics less often than their native-born peers. However, studies examining antipsychotic use among refugees with psychosis are lacking. To compare the prevalence of antipsychotic drug use during the first 5 years of illness among refugees and Swedish-born individuals with a newly diagnosed non-affective psychotic disorder, and to identify sociodemographic and clinical factors associated with antipsychotic use. The study population included refugees (n = 1656) and Swedish-born persons (n = 8908) aged 18-35 years during 2007-2018, with incident diagnosis of non-affective psychotic disorder recorded in the Swedish in-patient or specialised out-patient care register. Two-week point prevalence of antipsychotics use was assessed every 6 months in the 5 years following first diagnosis. Factors associated with antipsychotic use (versus non-use) at 1 year after diagnosis were examined with modified Poisson regression. Refugees were somewhat less likely to use antipsychotics at 1 year after first diagnosis compared with Swedish-born persons (37.1% v. 42.2%, age- and gender-adjusted risk ratio 0.88, 95% CI 0.82-0.95). However, at the 5-year follow-up, refugees and Swedish-born individuals showed similar patterns of antipsychotic use (41.1% v. 40.4%). Among refugees, higher educational level (>12 years), previous antidepressant use and being diagnosed with schizophrenia/schizoaffective disorder at baseline were associated with an increased risk of antipsychotics use, whereas being born in Afghanistan or Iraq (compared with former Yugoslavia) was associated with decreased risk. Our findings suggest that refugees with non-affective psychotic disorders may need targeted interventions to ensure antipsychotic use during the early phase of illness.

The trajectory of two negative symptom dimensions in first-episode psychosis and the role of cannabis use: A 10-year follow-up study

ObjectiveTo investigate the trajectories of diminished expression and apathy over 10 years. Further, to explore the effects of baseline- and persistent cannabis use on the development of diminished expression and apathy during follow-up, while controlling other potential sources and predictors of secondary negative symptoms. Methods351 participants with a first episode of non-affective psychosis were examined at baseline and invited to follow-up at one year and 10 years. The trajectories of diminished expression and apathy were investigated using linear mixed models. Subsequently, cannabis use and other potential predictors and sources of secondary negative symptoms were added to the model to investigate the respective impact on their trajectories. ResultsThe severity of both diminished expression and apathy decreased during the follow-up period after the first episode of psychosis, with the most improvement observed from baseline to 1-year follow-up. Cannabis use at baseline was associated with a long-lasting higher symptom load for diminished expression, but not apathy. Introducing persistent cannabis use to the model further strengthened the association with diminished expression. ConclusionBoth cannabis use at baseline and persistent cannabis use after a first episode of psychosis were associated with more severe symptoms of diminished expression. Our results imply a causal relationship between cannabis use and diminished expression and suggest that measures to reduce cannabis use both before and after psychosis onset may reduce expressive negative symptoms.

Processing speed and psychomotor speed in first-episode of non-affective psychosis and first-degree relatives: a candidate endophenotype for schizophrenia

Processing speed and psychomotor speed in first-episode of non-affective psychosis and first-degree relatives: a candidate endophenotype for schizophrenia

Effectiveness of Antipsychotic Use for Reducing Risk of Work Disability: Results From a Within-Subject Analysis of a Swedish National Cohort of 21,551 Patients With First-Episode Nonaffective Psychosis.

The authors sought to determine whether antipsychotic use, compared with nonuse, is associated with lower work disability in first-episode nonaffective psychosis, and if so, for how long. A within-subject design was used to study the risk of sickness absence or disability pension during antipsychotic use compared with nonuse during a maximum of 11 years of follow-up (2006-2016) in a Swedish nationwide cohort of patients with first-episode nonaffective psychosis (N=21,551; age range, 16-45 years). The within-subject analyses were conducted with stratified Cox regression models, adjusted for time-varying factors, using each individual as her or his own control to eliminate selection bias. The primary outcome was work disability (sickness absence or disability pension). Overall, 45.9% of first-episode patients had work disability during the median length of follow-up of 4.8 years. The risk of work disability was lower during use compared with nonuse of any antipsychotic (adjusted hazard ratio [aHR]=0.65, 95% CI=0.59-0.72). The lowest adjusted hazard ratios emerged for long-acting injectable antipsychotics (aHR=0.46, 95% CI=0.34-0.62), oral aripiprazole (aHR=0.68, 95% CI=0.56-0.82), and oral olanzapine (aHR=0.68, 95% CI=0.59-0.78). Long-acting injectables were associated with lower risk than olanzapine, the most commonly used oral antipsychotic (aHR=0.68, 95% CI=0.50-0.94). Adjusted hazard ratios were similar during the periods of <2 years, 2-5 years, and >5 years since diagnosis. Among individuals with first-episode nonaffective psychosis, antipsychotic treatment (with long-acting injectables in particular) was associated with about 30%-50% lower risk of work disability compared with nonuse of antipsychotics in the same individuals, which held true beyond 5 years after first diagnosis. These findings are informative regarding the important topic of early discontinuation of antipsychotic treatment after a first episode of nonaffective psychosis, but they need replication.

Influence of clinical and neurocognitive factors in psychosocial functioning after a first episode non-affective psychosis: Differences between males and females.

Deficits in psychosocial functioning are present in the early stages of psychosis. Several factors, such as premorbid adjustment, neurocognitive performance, and cognitive reserve (CR), potentially influence functionality. Sex differences are observed in individuals with psychosis in multiple domains. Nonetheless, few studies have explored the predictive factors of poor functioning according to sex in first-episode psychosis (FEP). This study aimed to explore sex differences, examine changes, and identify predictors of functioning according to sex after onset. The initial sample comprised 588 individuals. However, only adults with non-affective FEP (n = 247, 161 males and 86 females) and healthy controls (n = 224, 142 males and 82 females) were included. A comprehensive assessment including functional, neuropsychological, and clinical scales was performed at baseline and at 2-year follow-up. A linear regression model was used to determine the predictors of functioning at 2-year follow-up. FEP improved their functionality at follow-up (67.4% of both males and females). In males, longer duration of untreated psychosis (β = 0.328, p = 0.003) and worse premorbid adjustment (β = 0.256, p = 0.023) were associated with impaired functioning at 2-year follow-up, while in females processing speed (β = 0.403, p = 0.003), executive function (β = 0.299, p = 0.020) and CR (β = -0.307, p = 0.012) were significantly associated with functioning. Our data indicate that predictors of functioning at 2-year follow-up in the FEP group differ according to sex. Therefore, treatment and preventative efforts may be adjusted taking sex into account. Males may benefit from functional remediation at early stages. Conversely, in females, early interventions centered on CR enhancement and cognitive rehabilitation may be recommended.

Elevated risk of liver steatosis in first-episode psychosis patients: Results from a 3-year prospective study

BackgroundCardiometabolic disorders are largely responsible for excess mortality in schizophrenia. Non-alcoholic fatty liver disease (NAFLD) is increasingly relevant in the development of metabolic risk factors that have been associated with antipsychotic treatment.We aimed to assess the incidence of NAFLD and metabolic disturbances during the first 3 years of antipsychotic treatment in patients with first episode of psychosis (FEP), and compare it with the incidence in a control group. MethodsData were obtained from patients with psychosis (n = 160) and healthy controls (n = 66) included in the Cantabria's clinical and research program on FEP (PAFIP) from 2012 to 2018. Fatty Liver Index (FLI) was used to estimate the amount of fat in the liver. FLI has been validated for the diagnosis of NAFLD against different standards such as liver ultrasound and biopsy. FLI and metabolic parameters were registered at baseline, 3 months and then yearly for 3 years. ResultsAt the end of the follow-up (3-years), 21.9 % of patients with psychosis developed a FLI ≥ 60, suggestive of liver steatosis, compared to only a 3 % of subjects within the control group (X2 = 12.120; p < 0.001). In the FEP patients group, developing a FLI ≥ 60 was statistically associated with significant increments in metabolic parameters, and with Metabolic Syndrome (MetS) (X2 = 16.151; p < 0.001) and high blood pressure (X2 = 10.654; p = 0.001). ConclusionsHaving a first episode of non-affective psychosis was significantly associated with developing liver steatosis (FLI ≥ 60) in the first three years after initiating antipsychotic treatment. The results highlight the importance of early screening the emergence of NAFLD in schizophrenia patients.

Guidelines for Discontinuation of Antipsychotics in Patients Who Recover From First-Episode Schizophrenia Spectrum Disorders: Derived From the Aggregated Opinions of Asian Network of Early Psychosis Experts and Literature Review.

ObjectiveAntipsychotic discontinuation has been a long-standing clinical and medicolegal issue. The Asian Network of Early Psychosis developed guidelines for antipsychotic discontinuation in patients who recover from first-episode non-affective psychosis. We reviewed the existing studies and guidelines on antipsychotic discontinuation to develop guidelines for antipsychotic discontinuation in such patients.MethodsWe reviewed the relevant studies, reviews, guidelines, and ongoing trials related to antipsychotic discontinuation in patients with first-episode psychosis or schizophrenia. The quality of randomized controlled trials was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach.ResultsMost studies had low to very low quality, and 2 had moderate quality. All studies, except 1, advised against antipsychotic discontinuation because of higher relapse rates in the antipsychotic discontinuation group (19%–82% at 1-year follow-up) than the treatment maintenance group compared with the maintenance group. Based on expert opinion and Grading of Recommendations Assessment, Development, and Evaluation evidence of trials, guidelines have been recommended for future discontinuation studies on patients with first-episode schizophrenia spectrum disorders.ConclusionsCurrently, there are no recommendations for antipsychotic discontinuation in patients with first-episode schizophrenia spectrum disorders. However, there is a pressing need to conduct more rigorous research in remitted patients using more stringent criteria of full recovery, which can form the basis of guidelines on when and how antipsychotics should be tapered and discontinued. Studies that evaluate the patient characteristics and biomarkers that predict successful antipsychotic discontinuation are also needed.