RESUMEN
Recent studies have identified neuregulin1 as a probable susceptibility gene for schizophrenia and bipolar disorder. However, little is known about how this gene may affect brain function to increase vulnerability to these disorders. The present investigation examined the impact of neuregulin1 genotype on brain function in patients with schizophrenia, patients with bipolar I disorder and healthy volunteers. We used functional magnetic resonance imaging to measure brain responses during a verbal fluency task in a total of 115 subjects comprising 41 patients with schizophrenia, 29 patients with bipolar disorder and 45 healthy volunteers. We then used statistical parametric mapping to estimate the main effects of diagnostic group, the main effect of genotype and their interaction. We tested the hypothesis that the high-risk variant of neuregulin1 would be associated with altered prefrontal function. In all three diagnostic groups, the high-risk variant of neuregulin1 was associated with greater deactivation in the left precuneus. In addition, there was an interaction between diagnosis and genotype in two regions of the prefrontal cortex. The right inferior frontal gyrus expressed increased activation in individuals with the high-risk variant, but only in patients with schizophrenia. Conversely, the right posterior orbital gyrus expressed increased activation in individuals with the high-risk variant, but only in patients with bipolar disorder. Our results suggest that genetic variation in neuregulin1 has a measurable impact on brain function and provide preliminary evidence for a disease-specific pattern of gene action in different regions of the prefrontal cortex.
Asunto(s)
Trastorno Bipolar/fisiopatología , Mapeo Encefálico/métodos , Encéfalo/fisiopatología , Imagen por Resonancia Magnética/métodos , Proteínas del Tejido Nervioso/genética , Esquizofrenia/fisiopatología , Adulto , Femenino , Predisposición Genética a la Enfermedad/genética , Humanos , Masculino , Neurregulina-1 , FenotipoRESUMEN
BACKGROUND: There are few evaluations of strategies to improve rates of early detection and treatment of patients with first-episode psychosis. AIMS: To evaluate the effectiveness of a general practitioner (GP) education programme and an early detection assessment team (the Lambeth Early Onset Crisis Assessment Team; LEO CAT) in reducing delays in accessing treatment for first-episode psychosis patients. METHOD: 46 clusters of GP practices randomised to GP education in early detection with direct access to LEO CAT v. care as usual. Primary outcome measures were GP referral rates, duration of untreated psychosis (DUP) and delays in receiving treatment. RESULTS: 150 patients with first-episode psychosis were recruited; 113 were registered with the study GPs, who referred 54 (47.7%) directly to mental health services. Significantly more intervention group GPs (86.1% v. 65.7%) referred their patients directly to mental health services and fewer patients experienced long delays in receiving treatment. However, their overall DUP was unaffected. CONCLUSIONS: Educating GPs improves detection and referral rates of first-episode psychosis patients. An early detection team reduces the long delays in initial assessment and treatment. However, these only impact on the later phases of the DUP. Broader measures, such as public health education, are needed to reduce the earlier delays in DUP.
Asunto(s)
Servicios Comunitarios de Salud Mental/organización & administración , Psiquiatría Comunitaria/educación , Educación Médica Continua/organización & administración , Medicina Familiar y Comunitaria/educación , Trastornos Psicóticos/diagnóstico , Esquizofrenia/diagnóstico , Adolescente , Adulto , Diagnóstico Precoz , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Londres , Masculino , Evaluación de Programas y Proyectos de Salud , Trastornos Psicóticos/terapia , Derivación y Consulta/estadística & datos numéricos , Esquizofrenia/terapia , Servicios Urbanos de Salud/organización & administraciónRESUMEN
Magnetic resonance imaging (MRI) studies have reported a variety of brain abnormalities in association with schizophrenia. These include a higher prevalence of an absent adhesio interthalamica (AI; also known massa intermedia), a gray matter junction that is present between the two thalami in approximately 80% of healthy subjects. In this meta-analytic review, we describe and discuss the main AI MRI findings in schizophrenia spectrum disorders (SSDs) to date. The MEDLINE and ISI Web of Knowledge databases were searched up to December 2010, for studies that used MRI to assess AI in patients with SSD and controls. From fourteen potential reports, eleven were eligible to be part of the current review. These studies included 822 patients with SSD and 718 healthy volunteers. There was a large degree of variability in the MRI methods they employed. Patients with SSD had a higher prevalence of absent AI than healthy volunteers (odds ratio = 1.98; 95% confidence interval 1.33-2.94; p = 0.0008). This association was evident in both male and female SSD subjects, and there was no evidence that the prevalence was related to age or duration of illness. The significance of the absence of an AI for SSD may be clarified by studies in large, longitudinal community-based samples using standardized methods.
Asunto(s)
Esquizofrenia/patología , Tálamo/patología , Antipsicóticos/efectos adversos , Antipsicóticos/uso terapéutico , Femenino , Humanos , Masculino , Sesgo de Publicación , Esquizofrenia/tratamiento farmacológico , Caracteres SexualesRESUMEN
Magnetic resonance imaging (MRI) studies have reported a variety of brain abnormalities in association with schizophrenia. These include a higher incidence of cavum septum pellucidum (CSP), which is consistent with a neurodevelopmental model for this disorder. In this meta-analytic review, we describe and discuss the main CSP MRI findings in schizophrenia spectrum disorders (SSDs) to date. We adopted as keywords cavum and schizophrenia or psychosis, and the inclusion criteria were articles in English, with samples of SSD patients compared to healthy subjects, which used MRI to assess CSP, without time limit. From 18 potential reports, fifteen were eligible to be part of the current review. These studies included 1054 patients with SSD and 866 healthy volunteers. Six out of 15 studies pointed to a higher prevalence of CSP of any size in SSD patients, while five out of 15 showed that subjects with SSD had a greater occurrence of a large CSP than healthy individuals. However, the meta-analysis demonstrated that only the incidence of a large CSP was significantly higher in SSD relative to healthy comparisons (odds ratio=1.59; 95%CI 1.07-2.38; p=0.02). Overall our results suggest that only a large CSP is associated with SSD while a small CSP may be considered a normal neuroanatomical variation. Our review revealed a large degree of variability in the methods employed across the MRI studies published to date, as well as evidence of publication bias. Studies in large, community-based samples with greater standardization of methods should clarify the true significance of CSP in SSD.
Asunto(s)
Esquizofrenia/patología , Tabique Pelúcido/patología , Bases de Datos Factuales/estadística & datos numéricos , Humanos , Imagen por Resonancia Magnética , Escalas de Valoración PsiquiátricaRESUMEN
We used functional magnetic resonance imaging to examine how brain activity associated with auditory verbal hallucinations in schizophrenia changed during hallucinatory events. Activation in the left inferior frontal and right middle temporal gyri was evident 6-9 s before the person signalled the onset of the hallucination, whereas activation in the bilateral temporal gyri and the left insula coincided with the perception of the hallucination. This supports the hypothesis that during hallucinations activation in cortical regions mediating the generation of inner speech may precede the engagement of areas implicated in the perception of auditory verbal material.