RESUMEN
Impaired functional capacity is a core feature of schizophrenia and presents even in first-episode psychosis (FEP) patients. Impairments in daily functioning tend to persist despite antipsychotic therapy but their neural basis is less clear. Previous studies suggest that volume loss in frontal cortex might be an important contributor, but findings are inconsistent. We aimed to comprehensively investigate the brain structural correlates of functional capacity in FEP using MRI and a reliable objective measure of functioning [University of California, San Diego Performance-Based Skills Assessment (UPSA)]. In a sample of FEP (n = 39) and a well-matched control group (n = 21), we measured cortical thickness, gray matter volume, and white matter tract integrity (fractional anisotropy, FA) within brain regions implicated by previous work. The FEP group had thinner cortex in various frontal regions and fusiform, and reduced FA in inferior longitudinal fasciculus (ILF). In FEP, poorer functional capacity correlated with reduced superior frontal volume and lower FA in left ILF. Importantly, frontal brain volumes and integrity of the ILF were identified as the structural correlates of functional capacity in FEP, controlling for other relevant factors. These findings enhance mechanistic understanding of functional capacity deficits in schizophrenia by specifying the underlying neural correlates. In future, this could help inform intervention strategies.
Asunto(s)
Lóbulo Frontal/patología , Lóbulo Frontal/fisiopatología , Trastornos Psicóticos/patología , Adulto , Anisotropía , Femenino , Lóbulo Frontal/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Tamaño de los Órganos , Trastornos Psicóticos/diagnóstico por imagen , Trastornos Psicóticos/fisiopatología , Adulto JovenRESUMEN
BACKGROUND: Glioblastoma (GBM) is the most common and most lethal primary brain tumor in adults. Clinical trials in older patients with GBM have explored the use of single and multimodality treatment regimens with modest survival benefits; however, trial criteria are commonly based on chronological age and do not reflect the heterogeneity of this cohort. Geriatric assessment (GA) techniques predict survival and treatment tolerance in other tumor sites and thus may objectively guide the decision-making process, but data are lacking in the neuro-oncology cohort. METHODS: We performed a prospective, multicenter feasibility study involving patients age 65 years or older with newly diagnosed GBM. A modified GA was undertaken in the outpatient setting prior to starting treatment. Feasibility was determined primarily by recruitment rate, alongside data completeness, impact on clinic time, and acceptability to patients and staff. Factors associated with survival were explored using Cox regression models. RESULTS: Fifty patients were recruited within a prespecified time period with a recruitment rate of 82% (target 80%). Data completeness was greater than 80% in all except one assessment. Median overall survival was 9.5 months (95% confidence interval [CI] 5.0-14.0 months). Among the GA screening factors analyzed, a baseline impaired Montreal Cognitive Assessment (hazard ratio [HR] = 2.7, 95% CI 1.128-6.530) and impairment in instrumental activities of daily living (HR = 2.9 95% CI 0.983-8.541) were associated with poorer survival. CONCLUSION: In the first study of this kind among elderly GBM patients, we have shown that undertaking a neurologically focused GA screen is feasible and may provide useful prognostic information.
RESUMEN
BACKGROUND: Cognitive problems in people with schizophrenia predict poor functional recovery even with the best possible rehabilitation opportunities and optimal medication. A psychological treatment known as cognitive remediation therapy (CRT) aims to improve cognition in neuropsychiatric disorders, with the ultimate goal of improving functional recovery. Studies suggest that intervening early in the course of the disorder will have the most benefit, so this study will be based in early intervention services, which treat individuals in the first few years following the onset of the disorder. The overall aim is to investigate different methods of CRT. METHODS: This is a multicentre, randomised, single-blinded, controlled trial based in early intervention services in National Health Service Mental Health Trusts in six English research sites. Three different methods of providing CRT (intensive, group, and independent) will be compared with treatment as usual. We will recruit 720 service users aged between 16 and 45 over 3 years who have a research diagnosis of non-affective psychosis and will be at least 3 months from the onset of the first episode of psychosis. The primary outcome measure will be the degree to which participants have achieved their stated goals using the Goal Attainment Scale. Secondary outcome measures will include improvements in cognitive function, social function, self-esteem, and clinical symptoms. DISCUSSION: It has already been established that cognitive remediation improves cognitive function in people with schizophrenia. Successful implementation in mental health services has the potential to change the recovery trajectory of individuals with schizophrenia-spectrum disorders. However, the best mode of implementation, in terms of efficacy, service user and team preference, and cost-effectiveness is still unclear. The CIRCuiTS trial will provide guidance for a large-scale roll-out of CRT to mental health services where cognitive difficulties impact recovery and resilience. TRIAL REGISTRATION: ISRCTN, ISRCTN14678860 , Registered on 6 June 2016.