Mapping gray and white matter volume abnormalities in early-onset psychosis: an ENIGMA multicenter voxel-based morphometry study.

INTRODUCTION: Regional gray matter (GM) alterations have been reported in early-onset psychosis (EOP, onset before age 18), but previous studies have yielded conflicting results, likely due to small sample sizes and the different brain regions examined. In this study, we conducted a whole brain voxel-based morphometry (VBM) analysis in a large sample of individuals with EOP, using the newly developed ENIGMA-VBM tool. METHODS: 15 independent cohorts from the ENIGMA-EOP working group participated in the study. The overall sample comprised T1-weighted MRI data from 482 individuals with EOP and 469 healthy controls. Each site performed the VBM analysis locally using the standardized ENIGMA-VBM tool. Statistical parametric T-maps were generated from each cohort and meta-analyzed to reveal voxel-wise differences between EOP and healthy controls as well as the individual-based association between GM volume and age of onset, chlorpromazine (CPZ) equivalent dose, and other clinical variables. RESULTS: Compared with healthy controls, individuals with EOP showed widespread lower GM volume encompassing most of the cortex, with the most marked effect in the left median cingulate (Hedges' g = 0.55, p = 0.001 corrected), as well as small clusters of lower white matter (WM), whereas no regional GM or WM volumes were higher in EOP. Lower GM volume in the cerebellum, thalamus and left inferior parietal gyrus was associated with older age of onset. Deficits in GM in the left inferior frontal gyrus, right insula, right precentral gyrus and right superior frontal gyrus were also associated with higher CPZ equivalent doses. CONCLUSION: EOP is associated with widespread reductions in cortical GM volume, while WM is affected to a smaller extent. GM volume alterations are associated with age of onset and CPZ equivalent dose but these effects are small compared to case-control differences. Mapping anatomical abnormalities in EOP may lead to a better understanding of the role of psychosis in brain development during childhood and adolescence.

Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study.

Schizophrenia is a prototypical network disorder with widespread brain-morphological alterations, yet it remains unclear whether these distributed alterations robustly reflect the underlying network layout. We tested whether large-scale structural alterations in schizophrenia relate to normative structural and functional connectome architecture, and systematically evaluated robustness and generalizability of these network-level alterations. Leveraging anatomical MRI scans from 2439 adults with schizophrenia and 2867 healthy controls from 26 ENIGMA sites and normative data from the Human Connectome Project (n = 207), we evaluated structural alterations of schizophrenia against two network susceptibility models: (i) hub vulnerability, which examines associations between regional network centrality and magnitude of disease-related alterations; (ii) epicenter mapping, which identifies regions whose typical connectivity profile most closely resembles the disease-related morphological alterations. To assess generalizability and specificity, we contextualized the influence of site, disease stages, and individual clinical factors and compared network associations of schizophrenia with that found in affective disorders. Our findings show schizophrenia-related cortical thinning is spatially associated with functional and structural hubs, suggesting that highly interconnected regions are more vulnerable to morphological alterations. Predominantly temporo-paralimbic and frontal regions emerged as epicenters with connectivity profiles linked to schizophrenia's alteration patterns. Findings were robust across sites, disease stages, and related to individual symptoms. Moreover, transdiagnostic comparisons revealed overlapping epicenters in schizophrenia and bipolar, but not major depressive disorder, suggestive of a pathophysiological continuity within the schizophrenia-bipolar-spectrum. In sum, cortical alterations over the course of schizophrenia robustly follow brain network architecture, emphasizing marked hub susceptibility and temporo-frontal epicenters at both the level of the group and the individual. Subtle variations of epicenters across disease stages suggest interacting pathological processes, while associations with patient-specific symptoms support additional inter-individual variability of hub vulnerability and epicenters in schizophrenia. Our work outlines potential pathways to better understand macroscale structural alterations, and inter- individual variability in schizophrenia.

Precuneus and insular hypoactivation during cognitive processing in first-episode psychosis: Systematic review and meta-analysis of fMRI studies / Hipoactivación precúnea e insular durante el procesamiento cognitivo en el primer episodio psicótico: revisión sistemática y metaanálisis de estudios de fMRI

Introduction: The neural correlates of the cognitive dysfunction in first-episode psychosis (FEP) are still unclear. The present review and meta-analysis provide an update of the location of the abnormalities in the fMRI-measured brain response to cognitive processes in individuals with FEP.Methods: Systematic review and voxel-based meta-analysis of cross-sectional fMRI studies comparing neural responses to cognitive tasks between individuals with FEP and healthy controls (HC) according to PRISMA guidelines.Results: Twenty-six studies were included, comprising 598 individuals with FEP and 567 HC. Individual studies reported statistically significant hypoactivation in the dorsolateral prefrontal cortex (6 studies), frontal lobe (8 studies), cingulate (6 studies) and insula (5 studies). The meta-analysis showed statistically significant hypoactivation in the left anterior insula, precuneus and bilateral striatum.Conclusions: While the studies tend to highlight frontal hypoactivation during cognitive tasks in FEP, our meta-analytic results show that the left precuneus and insula primarily display aberrant activation in FEP that may be associated with salience attribution to external stimuli and related to deficits in perception and regulation. (AU)

Introducción:Los correlatos neurales de la disfunción cognitiva en el primer episodio psicótico (PEP) aún no están claros. Esta revisión y este metaanálisis proporcionan una actualización de la localización de las anormalidades en la respuesta cerebral medida por fMRI a los procesos cognitivos en individuos con PEP.Métodos: Revisión sistemática y metaanálisis basado en vóxeles de estudios cros-seccionales de fMRI que comparen respuestas neuronales a tareas cognitivas entre individuos con PEP y controles sanos de acuerdo con las guías PRISMA.Resultados: Se incluyeron 26 estudios, que comprendían 598 individuos con PEP y 567 controles sanos. Los estudios individuales reportaban hipoactivación estadísticamente significativa en la corteza prefrontal dorsolateral (6 estudios), el lóbulo frontal (8 estudios), el cíngulo (6 estudios) y la ínsula (5 estudios). El metaanálisis mostró hipoactivación estadísticamente significativa en la ínsula anterior izquierda, el precúneo y el cuerpo estriado bilateral.Conclusiones: Si bien los estudios tienden a resaltar la hipoactivación frontal durante las tareas cognitivas en PEP, nuestros resultados metaanalíticos muestran que el precúneo izquierdo y la ínsula presentan principalmente una activación aberrante en PEP que puede estar asociada con la atribución de saliencia a estímulos externos y relacionada con déficits en la percepción y la regulación. (AU)

Neuroimaging correlates of insight in non-affective psychosis: A systematic review and meta-analysis / Revisión sistemática y metaanálisis en neuroimagen y conciencia de enfermedad en psicosis no afectivas

Objective: Neurological correlates of impaired insight in non-affective psychosis remain unclear. This study aimed to review and meta-analyze the studies assessing the grey matter volumetric correlates of impaired insight in non-affective psychosis.Methods: This study consisted of a systematic review of 23 studies, and a meta-analysis with SDM-PSI of the 11 studies that were whole-brain and reported maps or peaks of correlation of studies investigating the grey matter volumetric correlates of insight assessments of non-affective psychosis, PubMed and OVID datasets were independently reviewed for articles reporting neuroimaging correlates of insight in non-affective psychosis. Quality assessment was realized following previous methodological approaches for the ABC quality assessment test of imaging studies, based on two main criteria: the statistical power and the multidimensional assessment of insight. Study peaks of correlation between grey matter volume and insight were used to recreate brain correlation maps.Results: A total of 418 records were identified through database searching. Of these records, twenty-three magnetic resonance imaging (MRI) studies that used different insight scales were included. The quality of the evidence was high in 11 studies, moderate in nine, and low in three. Patients with reduced insight showed decreases in the frontal, temporal (specifically in superior temporal gyrus), precuneus, cingulate, insula, and occipital lobes cortical grey matter volume. The meta-analysis indicated a positive correlation between grey matter volume and insight in the right insula (i.e., the smaller the grey matter, the lower the insight). (AU)

Objetivo: Los correlatos neurológicos de la conciencia de enfermedad en psicosis no afectivas siguen sin estar claros. Este estudio tiene como objetivo revisar y metaanalizar los estudios que evalúan los correlatos volumétricos de la materia gris de la conciencia de enfermedad deficiente en la psicosis no afectiva.Métodos: Este estudio consistió en una revisión sistemática de 23 estudios y un metaanálisis con SDM-PSI de los 11 estudios que examinaron todo el cerebro y reportaron mapas o picos de correlación de estudios que investigan los correlatos volumétricos de materia gris de evaluaciones de insight de psicosis no afectiva. Los conjuntos de datos de PubMed y OVID se revisaron de forma independiente para los artículos que informaban sobre correlaciones de neuroimagen de insight en psicosis no afectiva. La evaluación de la calidad de los estudios de imagen se realizó siguiendo enfoques metodológicos previos usando la prueba de evaluación de la calidad ABC basados en dos criterios principales: el poder estadístico y la evaluación multidimensional del insight. Los picos de correlación del estudio entre el volumen de materia gris y la conciencia de enfermedad fueron utilizados para recrear mapas de correlación cerebral.Resultados: Se incluyeron veintitrés estudios de imágenes por resonancia magnética (IRM) que utilizaron diferentes escalas de conciencia de enfermedad. La calidad de los estudios revisados fue clasificada como alta en 11 estudios, moderada en 9 estudios y baja en 3 estudios. Los pacientes con insight reducido mostraron disminuciones en el volumen de materia gris cortical de los lóbulos frontal, temporal (específicamente en la circunvolución temporal superior), precúneo, cingulado, ínsula y lóbulo occipital. El metaanálisis mostró una correlación positiva entre el volumen de materia gris y la conciencia de enfermedad en la ínsula derecha (es decir, cuanto más pequeña es la materia gris, menor es el insight). (AU)

Comparison of aripiprazole and risperidone effectiveness in first episode non-affective psychosis: Rationale and design of a prospective, randomized, 3-phase, investigator-initiated study (PAFIP-3)

Background: Selecting the most effective treatment represents a critical challenge with the potential of modifying the long-term prognosis of individuals suffering a first break of psychosis. Head-to-head clinical trials comparing effectiveness among antipsychotic drugs in individuals with a first-episode of non-affective psychosis (FEP) are scarce.MethodsThe rationale and design of a 3 phases clinical trial (PAFIP-3, NCT02305823) comparing the effectiveness of aripiprazole and risperidone, and to additionally assess the benefits of an early use of clozapine in primary treatment-resistant patients is reported. The design encompasses of 5 work packages (medication algorithm, cognitive functioning, psychoeducation/vocational functioning, imaging and biological markers) addressing critical issues and needs of first episode psychosis individuals and their cares. The primary outcome measure was treatment effectiveness assessed by all-cause treatment discontinuation rate.Results266 individuals have been included in the randomization study phase I (risperidone vs. aripiprazole). At 3 months, the retention rate was of 94% (249/266), 48(19.3%) patients have gone through phase II (olanzapine treatment), and 7(2.8%) entered the clozapine phase (phase III).DiscussionThe PAFIP 3 clinical trial may provide relevant information about clinical guidelines to optimally treat patients with a first episode of non-affective psychosis and the benefits and risks of an early use of clozapine in treatment resistant patients. (AU)

Diferencias en la efectividad clínica y funcional, entre trastornos psiquiátricos, de un hospital de día psiquiátrico de agudos para pacientes con enfermedad mental aguda / Differences between psychiatric disorders in the clinical and functional effectiveness of an acute psychiatric day hospital, for acutely ill psychiatric patients

Introducción: El tratamiento intensivo y agudo en unidades psiquiátricas de ingreso a tiempo parcial puede representar una alternativa eficaz a los ingresos hospitalarios a tiempo completo. Sin embargo, existe evidencia que indica que estos dispositivos podrían no ser igualmente eficaces para todos los trastornos psiquiátricos.El objetivo primario del estudio fue explorar las diferencias entre los principales grupos de diagnóstico psiquiátrico en la efectividad de un programa de hospitalización parcial aguda, así como identificar predictores de respuesta al tratamiento.Material y métodosEl estudio se realizó en un hospital psiquiátrico de día. La gravedad clínica se evaluó mediante las escalas BPRS, CGI y HoNOS. También se recogieron variables sociodemográficas. Los pacientes se agruparon en 4grupos diagnósticos amplios (psicosis no afectiva, bipolar, depresión, trastornos de la personalidad).ResultadosSe seleccionó a 331 participantes, 115 de los cuales (34,7%) fueron diagnosticados de psicosis no afectiva, 97 (28,3%) de trastorno bipolar, 92 (27,8%) de trastorno afectivo y 27 (8,2%) de trastorno de personalidad. Los pacientes con trastorno bipolar mostraron una mayor mejoría BPRS (F = 5,30; p = 0,001) y CGI (F = 8,78; p < 0,001) que aquellos que presentaban psicosis o trastorno depresivo. Estancias más prolongadas en el hospital de día y una mayor gravedad inicial (BPRS) fueron factores predictores de buena respuesta. La tasa de reingreso en unidad psiquiátrica a los 30 días del alta fue del 3% y del 11,8% en los siguientes 6 meses.ConclusionesEl cuidado intensivo en una unidad psiquiátrica de día es factible y eficaz para los pacientes con un trastorno mental agudo. Sin embargo, esta eficacia difiere entre los grupos de diagnóstico. (AU)

Introduction: Intensive treatment in acute day-care psychiatric units may represent an efficient alternative to inpatient care. However, there is evidence suggesting that this clinical resource may not be equally effective for every psychiatric disorder.The primary aim of this study was to explore differences between main psychiatric diagnostic groups, in the effectiveness of an acute partial hospitalization program. And, to identify predictors of treatment response.Material and methodsThe study was conducted at an acute psychiatric day hospital. Clinical severity was assessed using BPRS, CGI, and the HoNOS scales. Main socio-demographic variables were also recorded. Patients were clustered into 4wide diagnostic groups (i.e.: non-affective psychosis; bipolar; depressive; and personality disorders) to facilitate statistical analyses.ResultsA total of 331 participants were recruited, 115 of whom (34.7%) were diagnosed with non-affective psychosis, 97 (28.3%) with bipolar disorder, 92 (27.8%) with affective disorder, and 27 (8.2%) with personality disorder. Patients with a diagnosis of bipolar disorder showed greater improvement in BPRS (F=5.30; P=0.001) and CGI (F=8.78; P<0.001) than those suffering from psychosis or depressive disorder. Longer length of stay in the day-hospital, and greater baseline BPRS severity, were identified as predictors of good clinical response. Thirty-day readmission rate was 3%; at long-term (6 months after discharge) only 11.8% (N=39) of patients were re-admitted to a psychiatric hospitalization unit, and no differences were observed between diagnostic groups.ConclusionsIntensive care in an acute psychiatric day hospital is feasible and effective for patients suffering from an acute mental disorder. However, this effectiveness differs between diagnostic groups. (AU)