Tridimensional reconstruction of cerebral volumetry in schizophrenia

Address: 1Department of Medicine and Public Health, Section of Psychiatry and Clinical Psychology, University of Verona, Italy, 2Verona-Udine Brain Imaging Program, Inter-University Center for Behavioural Neurosciences, University of Udine and *University of Verona, Italy, 3Department of Morphological and Biomedical Sciences, Section of Radiology, University of Verona, Italy and 4Department of Pathology and Experimental and Clinical Medicine, Section of Psychiatry, University of Udine, Italy * Corresponding autho

Il ruolo dell'insight nelle psicosi: caratteristiche, fattori predittivi e variabili clinico-sociali associati

Molti pazienti affetti da psicosi non hanno consapevolezza o insight della natura del loro disturbo, dei sintomi che lo accompagnano, delle conseguenze della malattia e della necessità del trattamento. La mancanza di insight nel paziente affetto da psicosi comporta notevoli difficoltà nella gestione del paziente stesso sia da parte dei clinici sia da parte dei familiari (Amador & Kronengold, 2004). Per molti anni in letteratura l’insight è stata presentata in una prospettiva psicoanalitica e sono state offerte scarse linee-guida sulla fenomenologia o sul metodo di misurazione del processo psicologico che si ipotizzava alla base dell’insight (Amador et al., 1991). Negli ultimi 20 anni, l’insight nei pazienti affetti da psicosi ha suscitato l’interesse dei ricercatori che hanno esaminato questo fenomeno empiricamente. Da questi studi sono emersi alcuni importanti quesiti sulla fenomenologia, sui metodi di valutazione e sull’eziologia dell’insight. Negli anni ’90 sono stati messi a punto metodi validi e attendibili per la valutazione e misurazione dell’insight e ciò ha portato allo sviluppo di nuovi studi volti a chiarire il ruolo che la carenza di insight gioca nella prognosi, nel decorso e nel trattamento dei disturbi psicotici. Dallo studio dell'insight sono emersi dati interessanti per le implicazioni nella pratica clinica anche se spesso contrastanti. Evidenze cliniche suggeriscono che deficit nell’insight sono manifestazioni della malattia al pari degli altri sintomi (es. allucinazioni, deliri) e sono dovuti ad anomalie cerebrali. Queste ultime evidenze sono in contrasto con l’ipotesi che la carenza di insight sia una strategia di coping messa in atto dall’individuo per affrontare una situazione stressante (DSM IVTR, APA press, 2000). Inoltre è stato trovato che uno scarso insight è tra i predittori di non aderenza o di parziale aderenza al trattamento farmacologico (McEvoy, 2004). Quest’ultima evidenza ha accresciuto l’interesse verso lo studio dell’insight nelle psicosi per le sue importanti implicazioni nella pratica clinica. Una prima possibile spiegazione della controversia su quello che si può dire dell'insight sulla base dei risultati dei diversi studi è che l'insight è un costrutto complesso che esprime tale complessità anche nei tentativi di misurarlo. La consapevolezza della propria malattia e di ciò che ad essa è legato non è stabile e costante, ma presenta una certa variabilità intrasoggettiva e intersoggettiva. Alcuni pazienti possono riconoscere i propri sintomi ma non accettare la loro esistenza come parte di una malattia mentale, oppure possono attribuirli a cause diverse. L’eterogeneità dell’eziologia dell’insight fa aumentare l’interesse verso la conoscenza dei fattori che la determinano e di conseguenza verso gli strumenti per valutare tutte le sue caratteristiche. Nell’ultimo ventennio l’attenzione dei ricercatori, che hanno indagato l’insight nelle psicosi, si è rivolta in particolare alla schizofrenia.Non disponibil

Cerebral atrophy and white matter disruption in chronic schizophrenia

Several magnetic resonance imaging (MRI) studies have shown cerebral atrophy in established schizophrenia, although not in all reports. Discrepancies may mostly be due to population and postprocessing differences. Recently, disruption of cortical white matter integrity has also been reported in chronic patients with schizophrenia. In this study we explored tridimensional (3D) cerebral volumes and white matter microstructure in schizophrenia with structural and diffusion magnetic resonance. Twenty-five patients with established schizophrenia and 25 1:1 matched normal controls underwent a session of MRI using a Siemens 1.5T-scanner. 3D brain volume reconstruction was performed with the semi-automatic software Amira (TGS, San Diego, CA), whereas the apparent diffusion coefficients (ADCs) of cortical white matter water molecules were obtained with in-house developed softwares written in MatLab (The Mathworks-Inc., Natick, MA). Compared to controls, patients with schizophrenia had significantly smaller gray matter intracranium and total brain volumes, increased 4th ventricle volumes, and greater temporal and occipital ADCs. Patients treated with typical antipsychotic medication (N = 9) had significantly larger right lateral and 4th ventricles compared to those on atypical antipsychotic drugs. Intracranial volumes significantly inversely correlated with left temporal ADC in patients with schizophrenia. Also, age correlated directly with right, left, and 3rd ventricle volumes and inversely with gray matter intracranium volumes in individuals with schizophrenia. This study confirmed the presence of cortical atrophy in patients with schizophrenia, especially in those on typical antipsychotic drugs, and the existence of white matter disruption. It also suggested that physiological aging effects on brain anatomy may be abnormally pronounced in schizophrenia

Effect of COMT genotype on aggressive behaviour in a community cohort of schizophrenic patients

Although the etiology of aggression is multifactorial, many studies have associated the Val158Met polymorphism of the COMT with aggression in schizophrenia. This study tests the hypothesis that Met/Met patients display more episodes of aggression and violent behaviour than Val/Val patients in a 6 year follow-up cohort of subjects with schizophrenia in contact with the South-Verona Community-based Mental Health Service. Out of the 141 subjects with an ICD-10 SCAN-confirmed diagnosis of schizophrenia, 115 completed both baseline and follow-up assessments (81.6% of the baseline cohort). Of these, 80 subjects (70%) were genotyped and rated for aggression using the Overt Aggression Scale. Met/Met homozygous patients had higher aggressive behaviour compared to Val/Val homozygous subjects. Antipsychotic dosage, alcohol and drug abuse were taken into account as confounders. The Met/Met genotype of COMT may have an effect on aggressive behaviour in schizophrenia because norepinephrine is less effectively inactivated. \ua9 2011 Elsevier Ireland Ltd.Although the etiology of aggression is multifactorial, many studies have associated the Val158Met polymorphism of the COMT with aggression in schizophrenia. This study tests the hypothesis that Met/Met patients display more episodes of aggression and violent behaviour than Val/Val patients in a 6 year follow-up cohort of subjects with schizophrenia in contact with the South-Verona Community-based Mental Health Service. Out of the 141 subjects with an ICD-10 SCAN-confirmed diagnosis of schizophrenia, 115 completed both baseline and follow-up assessments (81.6% of the baseline cohort). Of these, 80 subjects (70%) were genotyped and rated for aggression using the Overt Aggression Scale.Met/Met homozygous patients had higher aggressive behaviour compared to Val/Val homozygous subjects. Antipsychotic dosage, alcohol and drug abuse were taken into account as confounders. The Met/Met genotype of COMT may have an effect on aggressive behaviour in schizophrenia because norepinephrine is less effectively inactivated

Cutaneous barrier leakage and gut inflammation drive skin disease in Omenn syndrome

BACKGROUND: Severe early-onset erythroderma and gut inflammation, with massive tissue infiltration of oligoclonal activated T cells are the hallmark of Omenn syndrome (OS). OBJECTIVE: The impact of altered gut homeostasis in the cutaneous manifestations of OS remains to be clarified. METHODS: We analyzed a cohort of 15 patients with OS and the 129Sv/C57BL/6 knock-in Rag2R229Q/R229Q (Rag2R229Q) mouse model. Homing phenotypes of circulating lymphocytes were analyzed by flow cytometry. Inflammatory cytokines and chemokines were examined in the sera by ELISA and in skin biopsies by immunohistochemistry and in situ RNA hybridization. Experimental colitis was induced in mice by dextran sulfate sodium salt. RESULTS: We show that memory/activated T cells from patients with OS and from the Rag2R229Q mouse model of OS abundantly express the skin homing receptors cutaneous lymphocyte associated antigen and CCR4 (Ccr4), associated with high levels of chemokine C-C motif ligands 17 and 22. Serum levels of LPS are also elevated. A broad Th1/Th2/Th17 inflammatory signature is detected in the periphery and in the skin. Increased Tlr4 expression in the skin of Rag2R229Q mice is associated with enhanced cutaneous inflammation on local and systemic administration of LPS. Likewise, boosting colitis in Rag2R229Q mice results in increased frequency of Ccr4+ splenic T cells and worsening of skin inflammation, as indicated by epidermal thickening, enhanced epithelial cell activation, and dermal infiltration by Th1 effector T cells. CONCLUSIONS: These results support the existence of an interplay between gut and skin that can sustain skin inflammation in OS.status: publishe