Paola Dazzan

Reappraising the Long-term Course and Outcome of Psychotic Disorders: The ÆSOP-10 Study

BACKGROUND Studies of the long-term course and outcome of psychoses tend to focus on cohorts of prevalent cases. Such studies bias samples towards those with poor outcomes, which may distort our understanding of prognosis. Long-term follow-up studies of epidemiologically robust first-episode samples are rare. METHOD AESOP-10 is a 10-year follow-up study of 557 individuals with a first episode of psychosis initially identified in two areas in the UK (South East London and Nottingham). Detailed information was collated on course and outcome in three domains (clinical, social and service use) from case records, informants and follow-up interviews. RESULTS At follow-up, of 532 incident cases identified, at baseline 37 (7%) had died, 29 (6%) had emigrated and eight (2%) were excluded. Of the remaining 458, 412 (90%) were traced and some information on follow-up was collated for 387 (85%). Most cases (265, 77%) experienced at least one period of sustained remission; at follow-up, 141 (46%) had been symptom free for at least 2 years. A majority (208, 72%) of cases had been employed for less than 25% of the follow-up period. The median number of hospital admissions, including at first presentation, was 2 [interquartile range (IQR) 1-4]; a majority (299, 88%) were admitted a least once and a minority (21, 6%) had 10 or more admissions. Overall, outcomes were worse for those with a non-affective diagnosis, for men and for those from South East London. CONCLUSIONS Sustained periods of symptom remission are usual following first presentation to mental health services for psychosis, including for those with a non-affective disorder; almost half recover.

Duration of untreated psychosis and neuropsychological function in first episode psychosis.

PURPOSE We investigated whether duration of untreated psychosis (DUP) prior to first presentation was associated with cognitive function in first episode psychosis (FEP) subjects. We predicted that longer DUP would be associated with greater neurocognitive impairment. METHOD 180 subjects with schizophrenia (and 93 subjects with Other Psychoses) performed a neurocognitive battery assessing IQ, verbal learning, working memory, visual learning and speed of processing. DUP was defined as the number of days between first onset of psychotic symptoms and first contact with psychiatric services. RESULTS Longer DUP was associated with impaired performance in verbal IQ (p=0.04), verbal learning (p=0.02), and verbal working memory (p=0.04) in FEP subjects with schizophrenia. These associations remained significant for verbal IQ when scores were corrected for age, gender, educational level and ethnicity. CONCLUSIONS Longer DUP is associated with poorer neurocognitive ability in schizophrenia subjects at time of first presentation. Since this was a cross-sectional study we can not tell whether longer DUP was a cause or a consequence of the poorer performance.

Magnetic Resonance Imaging and the Prediction of Outcome in First-Episode Schizophrenia: A Review of Current Evidence and Directions for Future Research

UNLABELLED Magnetic Resonance Imaging (MRI) measures are promising outcome markers for schizophrenia, since regional frontal and temporal grey matter volumes reductions, and enlargement of the ventricles, have been associated with outcome in this disorder. However, a number of methodological issues have limited the potential clinical utility of these findings. This article reviewed studies that examined brain structure at illness onset as a predictor of outcome, discusses the limitations of the findings, and highlights the challenges that would need to be addressed if structural data are to inform the management of an individual patient. METHODS Using a set of a priori criteria, we systematically searched Medline and EMBASE databases for articles evaluating brain structure at the time of the first psychotic episode and assessed response to treatment, symptomatic outcome, or functional outcome at any point in the first 12 months of illness. RESULTS The 11 studies identified suggest that alterations in medial temporal and prefrontal cortical areas, and in the networks that connect them with subcortical structures, are promising neuroanatomical markers of poor symptomatic and functional outcomes. CONCLUSION Neuroimaging data, possibly in combination with other biomarkers of disease, could help stratifying patients with psychoses to generate patient clusters clinically meaningful, and useful to detect true therapeutic effects in clinical trials. Optimization of Treatment and Management of Schizophrenia in Europe (OPTiMiSE), a large multicenter study funded by the FP7 European Commission, could generate these much-needed findings.

Linear and non-linear associations of symptom dimensions and cognitive function in first-onset psychosis

BACKGROUND Associations between symptom dimensions and cognition have been mainly studied in non-affective psychosis. The present study investigated whether previously reported associations between cognition and four symptom dimensions (reality distortion, negative symptoms, disorganisation and depression) in non-affective psychosis generalise to a wider spectrum of psychoses. It also extended the research focus to mania, a less studied symptom dimension. METHODS Linear and non-linear (quadratic, curvilinear or inverted-U-shaped) associations between cognition and the above five symptom dimensions were examined in a population-based cohort of 166 patients with first-onset psychosis using regression analyses. RESULTS Negative symptoms showed statistically significant linear associations with IQ and processing speed, and a significant curvilinear association with verbal memory/learning. Significant quadratic associations emerged between mania and processing speed and mania and executive function. The contributions of mania and negative symptoms to processing speed were independent of each other. The findings did not differ between affective and non-affective psychoses, and survived correction for multiple testing. CONCLUSIONS Mania and negative symptoms are associated with distinct patterns of cerebral dysfunction in first-onset psychosis. A novel finding is that mania relates to cognitive performance by a complex response function (inverted-U-shaped relationship). The associations of negative symptoms with cognition include both linear and quadratic elements, suggesting that this dimension is not a unitary concept. These findings cut across affective and non-affective psychoses, suggesting that different diagnostic entities within the psychosis spectrum lie on a neurobiological continuum.

Letter to the Editor: are antipsychotics good or bad for the brain? A comment on Moncrieff & Leo (2010).

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