Previous studies have suggested that naming and syntactic deficits in formal thought disorder may be related to global cognitive decline. This article reports the case of a patient, FM, with formal thought disorder schizophrenia who presents disproportionate deficits in receptive and expressive grammar with respect to his intellectual level of functioning. Syntactic and morphologic components of expressive grammar appeared equally impaired. Deficits in language comprehension were observed independently from working memory limitations. FM showed preserved grammaticality judgment, but defective sentence comprehension where semantic context does not provide heuristics for assigning thematic roles, but syntactic knowledge is essential. These atypical results are discussed within a neurodevelopmental aetiological model of formal thought disorder.

Although electroconvulsive therapy (ECT) is the most powerful treatment for depression, substantial variability in use has been described in Ireland. The Mental Health Commission collects usage data from approved centres but does not include home addresses or independent sector patients. Therefore, estimates of regional variation cannot be accurate, e.g. 145 (35% of total) independent sector patients were omitted from their 2008 analysis. When public and independent sector patients are combined inter-regional variation for 2008 is more than halved (chi-squared decreased from 83 to 30), with Western region contributing most to variation (chi-squared = 43). Ratio of ECT programmes to depressed admissions correlated negatively with rate for depressed admissions (r = -0.53, p = 0.01), while depressed admission numbers correlated with acute beds per area (r = 0.68, p = 0.001). Regional variation in ECT is less than previously reported; service factors probably account for much of this with smaller centres admitting severely ill patients more likely to require ECT.

Increased production and deposition of amyloid beta-protein (Abeta) are believed to be key pathogenic events in Alzheimer's disease. As such, routes for lowering cerebral Abeta levels represent potential therapeutic targets for Alzheimer's disease. X11beta is a neuronal adaptor protein that binds to the intracellular domain of the amyloid precursor protein (APP). Overexpression of X11beta inhibits Abeta production in a number of experimental systems. However, whether these changes to APP processing and Abeta production induced by X11beta overexpression also induce beneficial effects to memory and synaptic plasticity are not known. We report here that X11beta-mediated reduction in cerebral Abeta is associated with normalization of both cognition and in vivo long-term potentiation in aged APPswe Tg2576 transgenic mice that model the amyloid pathology of Alzheimer's disease. Overexpression of X11beta itself has no detectable adverse effects upon mouse behaviour. These findings support the notion that modulation of X11beta function represents a therapeutic target for Abeta-mediated neuronal dysfunction in Alzheimer's disease.

FE65 is a neuronal-enriched adaptor protein that binds to the Alzheimer's disease amyloid precursor protein (APP). FE65 forms a transcriptionally active complex with the APP intracellular domain (AICD). The precise gene targets for this complex are unclear but several Alzheimer's disease-linked genes have been proposed. Additionally, evidence suggests that FE65 influences APP metabolism. The mechanism by which FE65 expression is regulated is as yet unknown. To gain insight into the regulatory mechanism, we cloned a 1.6 kb fragment upstream of the human FE65 gene and found that it possesses particularly strong promoter activity in neurones. To delineate essential regions in the human FE65 promoter, a series of deletion mutants were generated. The minimal FE65 promoter was located between -100 and +5, which contains a functional Sp1 site. Overexpression of the transcription factor Sp1 potentiates the FE65 promoter activity. Conversely, suppression of the FE65 promoter was observed in cells either treated with an Sp1 inhibitor or in which Sp1 was knocked down. Furthermore, reduced levels of Sp1 resulted in downregulation of endogenous FE65 mRNA and protein. These findings reveal that Sp1 plays a crucial role in transcriptional control of the human FE65 gene.

Many studies have shown that rates of psychosis are elevated in the Black and minority ethnic (BME) population in the UK. One important, but relatively less researched explanation of these high rates may be social adversity associated with acculturation processes. Strong identification with an ethnic minority group subjected to social disadvantage may exert adverse effects on individuals from BME groups. Using data from a large epidemiological case-control study of first-episode psychosis, we aimed to investigate whether strong ethnic identification is a factor contributing to the excess of psychosis in BME groups compared with the White British, after adjustment for perceptions of disadvantage. All cases with a first episode of psychosis presenting to specialist mental health services within tightly defined catchment areas in London and Nottingham, UK, and geographically matched community controls were included in the study. Data were collected on socio-demographic and clinical characteristics, perceptions of disadvantage, and identification with one's own ethnic group. Analysis was performed on data from 139 cases and 234 controls. There was evidence that, as levels of ethnic identification increased, the odds of psychosis increased in the BME but not in the White British group, independent of potential confounders. However, the association between strong ethnic identity and psychosis in BME individuals was attenuated and non-significant when controlled for perceived disadvantage. Strong identification with an ethnic minority group may be a potential contributory factor of the high rates of psychosis in the BME population, the effects of which may be explained by perceptions of disadvantage.

Neurofilaments are the intermediate filaments of neurons and are synthesised in neuronal cell bodies and then transported through axons. Neurofilament light chain (NFL) is a principal component of neurofilaments, and phosphorylation of NFL head domain is believed to regulate the assembly of neurofilaments. However, the role that NFL phosphorylation has on transport of neurofilaments is poorly understood. To address this issue, we monitored axonal transport of phosphorylation mutants of NFL. We mutated four known phosphorylation sites in NFL head domain to either preclude phosphorylation, or mimic permanent phosphorylation. Mutation to preclude phosphorylation had no effect on transport but mutation of three sites to mimic permanent phosphorylation inhibited transport. Mutation of all four sites together to mimic permanent phosphorylation proved especially potent at inhibiting transport and also disrupted neurofilament assembly. Our results suggest that NFL head domain phosphorylation is a regulator of neurofilament axonal transport.

Several factors may predict adherence with psychiatric follow-up appointment for patients seen in the emergency department (ED) by liaison psychiatric teams. Awareness of these factors would allow for interventions targeted at vulnerable groups.

We sought to investigate the prevalence and social correlates of psychotic-like experiences in a general population sample of Black and White British subjects.