Predictors of transition to schizophrenia and other long-lasting non-affective psychoses in first-episode patients with acute and transient psychotic disorders: A validation study

Background and objectives Almost half of the individuals with a first-episode of psychosis who initially meet criteria for acute and transient psychotic disorder (ATPD) will have had a diagnostic revision during their follow-up, mostly toward schizophrenia. This study aimed to determine the proportion of diagnostic transitions to schizophrenia and other long-lasting non-affective psychoses in patients with first-episode ATPD, and to examine the validity of the existing predictors for diagnostic shift in this population. Methods We designed a prospective two-year follow-up study for subjects with first-episode ATPD. A multivariate logistic regression analysis was performed to identify independent variables associated with diagnostic transition to persistent non-affective psychoses. This prediction model was built by selecting variables on the basis of clinical knowledge. Results Sixty-eight patients with a first-episode ATPD completed the study and a diagnostic revision was necessary in 30 subjects at the end of follow-up, of whom 46.7% transited to long-lasting non-affective psychotic disorders. Poor premorbid adjustment and the presence of schizophreniform symptoms at onset of psychosis were the only variables independently significantly associated with diagnostic transition to persistent non-affective psychoses. Conclusion Our findings would enable early identification of those inidividuals with ATPD at most risk for developing long-lasting non-affective psychotic disorders, and who therefore should be targeted for intensive preventive interventions. (AU)

Proxy measures for the assessment of psychotic and affective symptoms in studies using electronic health records.

BACKGROUND: There is a lack of standardised psychometric data in electronic health record (EHR)-based research. Proxy measures of symptom severity based on patients' clinical records may be useful surrogates in mental health EHR research. AIMS: This study aimed to validate proxy tools for the short versions of the Positive and Negative Syndrome Scale (PANSS-6), Young Mania Rating Scale (YMRS-6) and Montgomery-Åsberg Depression Rating Scale (MADRS-6). METHOD: A cross-sectional, multicentre study was conducted in a sample of 116 patients with first-episode psychosis from 12 public hospitals in Spain. Concordance between PANSS-6, YMRS-6 and MADRS-6 scores and their respective proxies was evaluated based on information from EHR clinical notes, using a variety of statistical procedures, including multivariate tests to adjust for potential confounders. Bootstrapping techniques were used for internal validation, and an independent cohort from the Treatment and Early Intervention in Psychosis Program (TIPP-Lausanne, Switzerland) for external validation. RESULTS: The proxy versions correlated strongly with their respective standardised scales (partial correlations ranged from 0.75 to 0.84) and had good accuracy and discriminatory power in distinguishing between patients in and not in remission (percentage of patients correctly classified ranged from 83.9 to 91.4% and bootstrapped optimism-corrected area under the receiver operating characteristic curve ranged from 0.76 to 0.89), with high interrater reliability (intraclass correlation coefficient of 0.81). The findings remained robust in the external validation data-set. CONCLUSIONS: The proxy instruments proposed for assessing psychotic and affective symptoms by reviewing EHR provide a feasible and reliable alternative to traditional structured psychometric procedures, and a promising methodology for real-world practice settings.

Longitudinal trajectories in negative symptoms and changes in brain cortical thickness: 10-year follow-up study.

BACKGROUND: Understanding the evolution of negative symptoms in first-episode psychosis (FEP) requires long-term longitudinal study designs that capture the progression of this condition and the associated brain changes. AIMS: To explore the factors underlying negative symptoms and their association with long-term abnormal brain trajectories. METHOD: We followed up 357 people with FEP over a 10-year period. Factor analyses were conducted to explore negative symptom dimensionality. Latent growth mixture modelling (LGMM) was used to identify the latent classes. Analysis of variance (ANOVA) was conducted to investigate developmental trajectories of cortical thickness. Finally, the resulting ANOVA maps were correlated with a wide set of regional molecular profiles derived from public databases. RESULTS: Three trajectories (stable, decreasing and increasing) were found in each of the three factors (expressivity, experiential and attention) identified by the factor analyses. Patients with an increasing trajectory in the expressivity factor showed cortical thinning in caudal middle frontal, pars triangularis, rostral middle frontal and superior frontal regions from the third to the tenth year after the onset of the psychotic disorder. The F-statistic map of cortical thickness expressivity differences was associated with a receptor density map derived from positron emission tomography data. CONCLUSIONS: Stable and decreasing were the most common trajectories. Additionally, cortical thickness abnormalities found at relatively late stages of FEP onset could be exploited as a biomarker of poor symptom outcome in the expressivity dimension. Finally, the brain areas with less density of receptors spatially overlap areas that discriminate the trajectories of the expressivity dimension.

The relationship between human development and prevalence of deficit schizophrenia: Results from a systematic review and meta-analysis.

This study examined the relationship between the prevalence of deficit schizophrenia (DS) and a country's Human Development Index (HDI). A systematic review and meta-analysis of the literature published in the last decade were conducted to acquire data on the worldwide prevalence of deficit syndrome in schizophrenia cohorts and examine the correlation between DS prevalence and the HDI of the countries in the review. Twenty-six studies meeting our eligibility criteria provided prevalence data on DS in 14 countries with both low-to-middle and high-incomes, ranging from 14.34%-to 61.57%. The pooled prevalence of DS was 32.19% (95% CI = 26.17 to 38.52). Statistical analysis yielded a correlation coefficient (r) of -0.518 (95% CI = -0.754 to -0.164; p = 0.007), indicating a moderate inverse correlation between DS prevalence and HDI. This relationship remained significant in partial correlation analysis after controlling for potential sources of bias in the DS estimates (r = -0.489, p = 0.013). Our results show that schizophrenia cohorts from low-to-middle-income countries are more prone to primary and enduring negative symptoms, and contribute to the emerging evidence questioning the axiom that schizophrenia in the developing world has a better course than in high-income countries.

Clinical characterization of brief psychotic disorders triggered by the COVID-19 pandemic: a multicenter observational study.

This study aimed to characterize the clinical profile of patients with brief psychotic disorders (BPD) triggered by the psychosocial distress derived from the COVID-19 crisis. A multicenter study was conducted from March 14 to May 14, 2020 (the peak weeks of the pandemic in Europe). All consecutive patients presenting non-affective psychotic episodes with a duration of untreated psychosis of less than 1 month and whose onset was related to the COVID-19 crisis were recruited, but only those patients meeting Diagnostic Statistical Manual 5th edition (DSM-5) criteria for "BPD with marked stressors" (DSM-5 code: 298.8) during follow-up were finally included. Patients' sociodemographic and clinical characteristics were collected at baseline and summarized with descriptive statistics. During the study period, 57 individuals with short-lived psychotic episodes related to the emotional stress of the COVID-19 pandemic were identified, of whom 33 met DSM-5 criteria for "BPD with marked stressors". The mean age was 42.33 ± 14.04 years, the gender distribution was almost the same, and the majority were rated as having good premorbid adjustment. About a quarter of the patients exhibited suicidal symptoms and almost half presented first-rank schizophrenia symptoms. None of them were COVID-19 positive, but in more than half of the cases, the topic of their psychotic features was COVID-19-related. The coronavirus pandemic is triggering a significant number of BPD cases. Their risk of suicidal behavior, their high relapse rate, and their low temporal stability make it necessary to closely monitor these patients over time.

Diagnosis, prognosis, and treatment of brief psychotic episodes: a review and research agenda.

Brief psychotic episodes represent an intriguing paradox in clinical psychiatry because they elude the standard knowledge that applies to the persisting psychotic disorders such as schizophrenia. This Review describes key diagnostic considerations such as conceptual foundations, current psychiatric classification versus research-based operationalisations, epidemiology, and sociocultural variations; prognostic aspects including the risk of psychosis recurrence, types of psychotic recurrences, other clinical outcomes, prognostic factors; and therapeutic issues such as treatment guidelines and unmet need of care. The advances and challenges associated with the scientific evidence are used to set a research agenda in this area. We conclude that brief psychotic episodes can be reconceptualised within a clinical staging model to promote innovative translational research and improve our understanding and treatment of psychotic disorders.

Patterns of use, clinical efficacy, safety and tolerability of Ketamine and Esketamine in treatment-resistant depression: Towards registry-based surveillance systems.

More data on the long-term effects of Racemic Ketamine and Esketamine in TDR patients is needed. The implementation of centralized registries of their use for treatment of depression could be a tool of major importance for assessing their efficacy and safety in real-world clinical practice. This paper seeks to outline the rise and rationale behind these registry-based surveillance systems.

Examining the immune signatures of SARS-CoV-2 infection in pregnancy and the impact on neurodevelopment: Protocol of the SIGNATURE longitudinal study.

The COVID-19 pandemic represents a valuable opportunity to carry out cohort studies that allow us to advance our knowledge on pathophysiological mechanisms of neuropsychiatric diseases. One of these opportunities is the study of the relationships between inflammation, brain development and an increased risk of suffering neuropsychiatric disorders. Based on the hypothesis that neuroinflammation during early stages of life is associated with neurodevelopmental disorders and confers a greater risk of developing neuropsychiatric disorders, we propose a cohort study of SARS-CoV-2-infected pregnant women and their newborns. The main objective of SIGNATURE project is to explore how the presence of prenatal SARS-CoV-2 infection and other non-infectious stressors generates an abnormal inflammatory activity in the newborn. The cohort of women during the COVID-19 pandemic will be psychological and biological monitored during their pregnancy, delivery, childbirth and postpartum. The biological information of the umbilical cord (foetus blood) and peripheral blood from the mother will be obtained after childbirth. These samples and the clinical characterisation of the cohort of mothers and newborns, are tremendously valuable at this time. This is a protocol report and no analyses have been conducted yet, being currently at, our study is in the recruitment process step. At the time of this publication, we have identified 1,060 SARS-CoV-2 infected mothers and all have already given birth. From the total of identified mothers, we have recruited 537 SARS-COV-2 infected women and all of them have completed the mental health assessment during pregnancy. We have collected biological samples from 119 mothers and babies. Additionally, we have recruited 390 non-infected pregnant women.

Predictors of diagnostic stability in brief psychotic disorders: Findings from a 3-year longitudinal study.

INTRODUCTION: Brief psychotic disorder (BPD) is a relatively uncommon and underexplored psychotic condition. Even though BPD has been related to a more favorable outcome than other schizophrenia spectrum disorders (SSD), current knowledge of its predictive factors remains scant. This study aimed to examine its prevalence and find early predictors of BPD diagnostic stability. METHODS: SSD diagnosis following Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria was explored in a large epidemiological cohort (n = 569) of non-affective first-episode psychosis (FEP) patients enrolled in a three-year longitudinal intervention program (PAFIP). Premorbid, sociodemographic, and clinical information was collected to characterize BPD patients and determine factors predictive of diagnostic stability. Multivariate analysis included predictors selected from clinical knowledge and also those that had achieved marginal significance (p ≤ 0.1) in univariate analysis. RESULTS: A total of 59 patients enrolled in the PAFIP program (10.4% of the whole cohort) met DSM-IV criteria for BPD, of whom 40 completed the three-year follow-up. The temporal stability of BPD in our sample was as high as 40% (n = 16). Transition from BPD to schizophrenia occurred in 37% (n = 15) of patients. Fewer hallucinations at baseline and better insight independently significantly predicted BPD diagnostic stability over time. CONCLUSION: Our findings confirm that BPD is a clinical condition with moderate-to-low temporal stability and demonstrate that approximately two-thirds of FEP individuals experiencing BPD will develop a long-lasting psychotic disorder during follow-up, mainly schizophrenia.

Prognostic significance of psychotic relapse in patients with first-episode acute and transient psychosis: New empirical support for ICD-11.

This study examined the impact of psychotic relapse on the diagnostic stability of acute and transient psychotic disorders (ATPD), and how this potential risk factor could differentiate 'acute polymorphic psychotic disorder without symptoms of schizophrenia' (APPD; ICD-10 code F23.0) from the remaining non-APPD subtypes (F23.1-9). A two-year cohort study was performed on 68 patients with first-episode ATPD. At the end of follow-up, the diagnostic stability of ATPD was 55.9% and the overall rate of psychotic relapse was 61.8%. Statistical analysis showed that recurrence was an independent risk factor for diagnostic shift in ATPDs (relative risk [RR] = 1.67, 95% confidence interval [CI] = 1.17-2.39; p = 0.005) and that this risk differed among their subtypes insofar as its appearance significantly increased the likelihood of diagnostic change in patients with non-APPD subtypes (RR = 2.52, 95% CI = 1.56-4.07; p < 0.001), but not in those with APPD (RR = 0.95, 95% CI = 0.57-1.57; p = 0.844). Our findings confirm the negative implications of recurrence in patients with ATPD, encourage long-term intervention targeting relapse prevention in this population, and provide new empirical evidence in support of narrowing the ATPD category to APPD in the upcoming ICD-11.

COVID-19 natural herd immunity and risk of neuropsychiatric disorders / Inmunidad natural de grupo y riesgo de trastornos neuropsiquiátricos de la COVID-19

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Reactive psychoses in the context of the COVID-19 pandemic: clinical perspectives from a case series / Psicosis reactivas en el contexto de la pandemia del COVID-19: perspectivas clínicas de una serie de casos

INTRODUCTION: The world is currently undergoing an extremely stressful scenario due to the COVID-19 pandemic. This unexpected and dramatic situation could increase the incidence of mental health problems, among them, psychotic disorders. The aim of this paper was to describe a case series of brief reactive psychosis due to the psychological distress from the current coronavirus pandemic. MATERIALS AND METHODS: We report on a case series including all the patients with reactive psychoses in the context of the COVID-19 crisis who were admitted to the Virgen del Rocío and Virgen Macarena University Hospitals (Seville, Spain) during the first two weeks of compulsory nationwide quarantine. RESULTS: In that short period, four patients met the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for a brief reactive psychotic disorder. All of the episodes were directly triggered by stress derived from the COVID-19 pandemic and half of the patients presented severe suicidal behavior at admission. CONCLUSIONS: We may now be witnessing an increasing number of brief reactive psychotic disorders as a result of the COVID-19 pandemic. This type of psychosis has a high risk of suicidal behavior and, although short-lived, has a high rate of psychotic recurrence and low diagnostic stability over time. Therefore, we advocate close monitoring in both the acute phase and long-term follow-up of these patients

INTRODUCCIÓN: El mundo está experimentando un escenario extremadamente estresante a causa de la pandemia del COVID-19. Esta situación inesperada y dramática podría incrementar la incidencia de los problemas de salud mental y, entre estos, los trastornos psicóticos. El objetivo de este documento es describir una serie de casos de psicosis reactiva breve, debidos al distrés psicológico debido a la pandemia actual de coronavirus. MATERIALES Y MÉTODOS: Reportamos una serie de casos que incluye a todos los pacientes con psicosis reactiva en el contexto de la crisis del COVID-19, ingresados en los Hospitales Universitarios Virgen del Rocío y Virgen Macarena (Sevilla, España) durante las 2 primeras semanas de la cuarentena obligatoria a nivel nacional. RESULTADOS: En este breve espacio de tiempo, 4 pacientes cumplieron los criterios de trastorno psicótico breve del manual diagnóstico y estadístico de trastornos mentales (DSM-5). Todos los episodios fueron desencadenados por el estrés derivado de la pandemia del COVID-19, y la mitad de los pacientes presentaron un comportamiento suicida grave a su ingreso. CONCLUSIONES: Actualmente podemos estar asistiendo a un incremento del número de trastornos psicóticos reactivos breves, como resultado de la pandemia del COVID-19. Este tipo de psicosis tiene un elevado riesgo de comportamiento suicida y, aunque es transitorio, tiene una elevada tasa de recurrencia psicótica y baja estabilidad diagnóstica a lo largo del tiempo. Por tanto, somos partidarios de una supervisión estrecha tanto en la fase aguda como en el seguimiento a largo plazo de estos pacientes

Reactive psychoses in the context of the COVID-19 pandemic: Clinical perspectives from a case series.

INTRODUCTION: The world is currently undergoing an extremely stressful scenario due to the COVID-19 pandemic. This unexpected and dramatic situation could increase the incidence of mental health problems, among them, psychotic disorders. The aim of this paper was to describe a case series of brief reactive psychosis due to the psychological distress from the current coronavirus pandemic. MATERIALS AND METHODS: We report on a case series including all the patients with reactive psychoses in the context of the COVID-19 crisis who were admitted to the Virgen del Rocío and Virgen Macarena University Hospitals (Seville, Spain) during the first two weeks of compulsory nationwide quarantine. RESULTS: In that short period, four patients met the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for a brief reactive psychotic disorder. All of the episodes were directly triggered by stress derived from the COVID-19 pandemic and half of the patients presented severe suicidal behavior at admission. CONCLUSIONS: We may now be witnessing an increasing number of brief reactive psychotic disorders as a result of the COVID-19 pandemic. This type of psychosis has a high risk of suicidal behavior and, although short-lived, has a high rate of psychotic recurrence and low diagnostic stability over time. Therefore, we advocate close monitoring in both the acute phase and long-term follow-up of these patients.