ORCID Profile
0000-0002-4972-8786
Current Organisation
University of Oxford
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Publisher: Frontiers Media SA
Date: 11-07-2017
Publisher: Elsevier BV
Date: 2016
Publisher: Cambridge University Press (CUP)
Date: 23-12-2011
DOI: 10.1017/S0033291710002461
Abstract: Early Intervention in Psychosis Services (EIS) for young people in England experiencing first-episode psychosis (FEP) were commissioned in 2002, based on an expected incidence of 15 cases per 100 000 person-years, as reported by schizophrenia epidemiology in highly urban settings. Unconfirmed reports from EIS thereafter have suggested higher than anticipated rates. The aim of this study was to compare the observed with the expected incidence and delineate the clinical epidemiology of FEP using epidemiologically complete data from the CAMEO EIS, over a 6-year period in Cambridgeshire, for a mixed rural–urban population. A population-based study of FEP (ICD-10, F10–39) in people aged 17–35 years referred between 2002 and 2007 the denominator was estimated from mid-year census statistics. Sociodemographic variation was explored by Poisson regression. Crude and directly standardized rates (for age, sex and ethnicity) were compared with pre-EIS rates from two major epidemiological FEP studies conducted in urban English settings. A total of 285 cases met FEP diagnoses in CAMEO, yielding a crude incidence of 50 per 100 000 person-years [95% confidence interval (CI) 44.5–56.2]. Age- and sex-adjusted rates were raised for people from black ethnic groups compared with the white British [incidence rate ratio (IRR) 2.1, 95% CI 1.1–3.8]. Rates in our EIS were comparable with pre-EIS rates observed in more urban areas after age, sex and ethnicity standardization. Our findings suggest that the incidence observed in EIS is far higher than originally anticipated and is comparable to rates observed in more urban settings prior to the advent of EIS. Sociodemographic variation due to ethnicity and other factors extend beyond urban populations. Our results have implications for psychosis aetiology and service planning.
Publisher: Springer Science and Business Media LLC
Date: 31-03-2015
DOI: 10.1038/TP.2015.26
Abstract: Psychotic disorders such as schizophrenia are biologically complex and carry huge population morbidity due to their prevalence, persistence and associated disability. Defined by features such as delusions and hallucinations, they involve cognitive dysfunction and neurotransmitter dysregulations that appear mostly to involve the dopaminergic and glutamatergic systems. A number of genetic and environmental factors are associated with these disorders but it has been difficult to identify the biological pathways underlying the principal symptoms. The endophenotype concept of stable, heritable traits that form a mechanistic link between genes and an overt expression of the disorder has potential to reduce the complexity of psychiatric phenotypes. In this study, we used a genetically sensitive design with in iduals with a first episode of psychosis, their non-affected first-degree relatives and non-related healthy controls. Metabolomic analysis was combined with neurocognitive assessment to identify multilevel endophenotypic patterns: one concerned reaction times during the performance of cognitive and emotional tests that have previously been associated with the glutamate neurotransmission system, the other involved metabolites involved directly and indirectly in the co-activation of the N -methyl- D -aspartate receptor, a major receptor of the glutamate system. These cognitive and metabolic endophenotypes may comprise a single construct, such that genetically mediated dysfunction in the glutamate system may be responsible for delays in response to cognitive and emotional functions in psychotic disorders. This focus on glutamatergic neurotransmission should guide drug discovery and experimental medicine programmes in schizophrenia and related disorders.
Publisher: Elsevier BV
Date: 2017
Publisher: American Medical Association (AMA)
Date: 11-2013
DOI: 10.1001/JAMAPSYCHIATRY.2013.1976
Abstract: Dysregulation of corticostriatal circuitry has long been thought to be critical in the etiology of psychotic disorders, although the differential roles played by dorsal and ventral systems in mediating risk for psychosis have been contentious. To use resting-state functional magnetic resonance imaging to characterize disease-related, risk-related, and symptom-related changes of corticostriatal functional circuitry in patients with first-episode psychosis and their unaffected first-degree relatives. This case-control cross-sectional study was conducted at a specialist early psychosis clinic, GlaxoSmithKline Clinical Unit, and magnetic resonance imaging facility. Nineteen patients with first-episode psychosis, 25 of their unaffected first-degree relatives, and 26 healthy control subjects were included in this study. Voxelwise statistical parametric maps testing differences in the strength of functional connectivity between 6 striatal seed regions of interest (3 caudate and 3 putamen) per hemisphere and all other brain regions. Disease-related changes, reflecting differences between patients and control subjects, involved widespread dysregulation of corticostriatal systems characterized most prominently by a dorsal-to-ventral gradient of hypoconnectivity to hyperconnectivity between striatal and prefrontal regions. A similar gradient was evident in comparisons between relatives and control subjects, identifying it as a genetically inherited risk phenotype. In patients, functional connectivity in risk-affected and disease-affected dorsal frontostriatal circuitry correlated with the severity of both positive and negative symptoms. First-episode psychosis is associated with pronounced dysregulation of corticostriatal systems, characterized most prominently by hypoconnectivity of dorsal and hyperconnectivity of ventral frontostriatal circuits. These changes correlate with symptom severity and are also apparent in unaffected first-degree relatives, suggesting that they represent a putative risk phenotype for psychotic illness.
Publisher: Elsevier BV
Date: 03-2011
DOI: 10.1016/J.BIOPSYCH.2010.09.043
Abstract: Emotional impairments are important determinants of functional outcome in psychosis, and current treatments are not particularly effective. Modafinil is a wake-promoting drug that has been shown to improve emotion discrimination in healthy in iduals and attention and executive function in schizophrenia. We aimed to establish whether modafinil might have a role in the adjuvant treatment of emotional impairments in the first episode of psychosis, when therapeutic endeavor is arguably most vital. Forty patients with a first episode of psychosis participated in a randomized, double-blind, placebo-controlled crossover design study testing the effects of a single dose of 200 mg modafinil on neuropsychological performance. Emotional functions were evaluated with the emotional face recognition test, the affective go-no go task, and the reward and punishment learning test. Visual analogue scales were used throughout the study to assess subjective mood changes. Modafinil significantly improved the recognition of sad facial expressions (z = 2.98, p = .003). In contrast, there was no effect of modafinil on subjective mood ratings, on tasks measuring emotional sensitivity to reward or punishment, or on interference of emotional valence on cognitive function, as measured by the affective go-no go task. Modafinil improves the analysis of emotional face expressions. This might enhance social function in people with a first episode of psychosis.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Belinda Lennox.