1,721,504 research outputs found

    Predicting the onset of psychosis in patients at clinical high risk: practical guide to probabilistic prognostic reasoning

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    Prediction of psychosis in patients at clinical high risk (CHR) has become a mainstream focus of clinical and research interest worldwide. When using CHR instruments for clinical purposes, the predicted outcome is but only a probability; and, consequently, any therapeutic action following the assessment is based on probabilistic prognostic reasoning. Yet, probabilistic reasoning makes considerable demands on the clinicians. We provide here a scholarly practical guide summarising the key concepts to support clinicians with probabilistic prognostic reasoning in the CHR state. We review risk or cumulative incidence of psychosis in, person-time rate of psychosis, Kaplan-Meier estimates of psychosis risk, measures of prognostic accuracy, sensitivity and specificity in receiver operator characteristic curves, positive and negative predictive values, Bayes’ theorem, likelihood ratios, potentials and limits of real-life applications of prognostic probabilistic reasoning in the CHR state. Understanding basic measures used for prognostic probabilistic reasoning is a prerequisite for successfully implementing the early detection and prevention of psychosis in clinical practice. Future refinement of these measures for CHR patients may actually influence risk management, especially as regards initiating or withholding treatment

    Third-generation neuroimaging in early schizophrenia: Translating research evidence into clinical utility

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    Psychiatric imaging needs to move away from simple investigations of the neurobiology underlying the early phases of schizophrenia to translate imaging findings in the clinical field, targeting clinical outcomes including transition, remission and response to preventive interventions

    Striatal presynaptic dopamine in schizophrenia, part i: Meta-analysis of dopamine active transporter (DAT) density

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    Background: Striatal dopaminergic neurotransmission has been postulated to be fundamental to the emergence of key symptoms of schizophrenia, such as psychotic symptoms, and is targeted by currently available dopaminergic drugs. A specific marker of the integrity of presynaptic dopamine neurons in the striatum, the density of striatal dopamine terminals, can be quantified through molecular neuroimaging of the dopamine active transporter (DAT). However, the currently available results using this approach in schizophrenia are inconsistent. Methods: Thirteen Single Photon Emission Tomography or Positron Emission Tomography (PET) studies investigating DAT density in the striatum of schizophrenic patients and matched controls were included in a quantitative meta-analysis. Binding potentials in the striatum, caudate, and putamen, as well as demographic, clinical, and methodological variables, were extracted from each publication. Hedges' g was used as a measure of effect size. Results: The overall database contained 202 subjects with schizophrenia and 147 controls, well matched with respect to sociodemographic variables. Striatal DAT density was not significantly different between patients and controls. Similar negative findings were regionally confirmed in the putamen and caudate. There was no moderating effect for external factors. Conclusions: Our meta-analysis uncovered no evidence indicating altered density of striatal dopamine terminals in schizophrenia. Moreover, striatal DAT density did not seem to be influenced by antipsychotic medication or illness duration. Our data suggest that altered integrity of striatal dopaminergic synapses is not critical for the emergence of schizophrenia or its treatment. These findings should be useful in further refining dopaminergic hypotheses of schizophrenia. © 2011 The Author

    Insular volume abnormalities associated with different transition probabilities to psychosis

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    Background Although individuals vulnerable to psychosis show brain volumetric abnormalities, structural alterations underlying different probabilities for later transition are unknown. The present study addresses this issue by means of voxel-based morphometry (VBM). Method We investigated grey matter volume (GMV) abnormalities by comparing four neuroleptic-free groups: individuals with first episode of psychosis (FEP) and with at-risk mental state (ARMS), with either long-term (ARMS-LT) or short-term ARMS (ARMS-ST), compared to the healthy control (HC) group. Using three-dimensional (3D) magnetic resonance imaging (MRI), we examined 16 FEP, 31 ARMS, clinically followed up for on average 3 months (ARMS-ST, n=18) and 4.5 years (ARMS-LT, n=13), and 19 HC. Results The ARMS-ST group showed less GMV in the right and left insula compared to the ARMS-LT (Cohen's d 1.67) and FEP groups (Cohen's d 1.81) respectively. These GMV differences were correlated positively with global functioning in the whole ARMS group. Insular alterations were associated with negative symptomatology in the whole ARMS group, and also with hallucinations in the ARMS-ST and ARMS-LT subgroups. We found a significant effect of previous antipsychotic medication use on GMV abnormalities in the FEP group. Conclusions GMV abnormalities in subjects at high clinical risk for psychosis are associated with negative and positive psychotic symptoms, and global functioning. Alterations in the right insula are associated with a higher risk for transition to psychosis, and thus may be related to different transition probabilities

    Striatal presynaptic dopamine in schizophrenia, part II: Meta-analysis of [18F/11C]-DOPA PET studies

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    Background: Alterations in striatal dopamine neurotransmission are central to the emergence of psychotic symptoms and to the mechanism of action of antipsychotics. Although the functional integrity of the presynaptic system can be assessed by measuring striatal dopamine synthesis capacity (DSC), no quantitative meta-analysis is available. Methods: Eleven striatal (caudate and putamen) [11C/18F]-DOPA positron emission tomography studies comparing 113 patients with schizophrenia and 131 healthy controls were included in a quantitative meta-analysis of DSC. Demographic, clinical, and methodological variables were extracted from each study or obtained from the authors and tested as covariates. Hedges' g was used as a measure of effect size in Comprehensive Meta-Analysis. Publication bias was assessed with funnel plots and Egger's intercept. Heterogeneity was addressed with the Q statistic and I2 index. Results: Patients and controls were well matched in sociodemographic variables (P >. 05). Quantitative evaluation of publication bias was nonsignificant (P =. 276). Heterogeneity across study was modest in magnitude and statistically nonsignificant (Q = 19.19; P =. 078; I2 = 39.17). Patients with schizophrenia showed increased striatal DSC as compared with controls (Hedges' g = 0.867, CI 95% from 0.594 to 1.140, Z = 6.222, P <. 001). The DSC schizophrenia/control ratio showed a relatively homogenous elevation of around 14% in schizophrenic patients as compared with controls. DSC elevation was regionally confirmed in both caudate and putamen. Controlling for potential confounders such as age, illness duration, gender, psychotic symptoms, and exposure to antipsychotics had no impact on the results. Sensitivity analysis confirmed robustness of meta-analytic findings. Conclusions: The present meta-analysis showed consistently increased striatal DSC in schizophrenia, with a 14% elevation in patients as compared with healthy controls. © 2011 The Author
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