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      Computational Nosology and Precision Psychiatry

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          Abstract

          This article provides an illustrative treatment of psychiatric morbidity that offers an alternative to the standard nosological model in psychiatry. It considers what would happen if we treated diagnostic categories not as causes of signs and symptoms, but as diagnostic consequences of psychopathology and pathophysiology. This reformulation (of the standard nosological model) opens the door to a more natural description of how patients present—and of their likely responses to therapeutic interventions. In brief, we describe a model that generates symptoms, signs, and diagnostic outcomes from latent psychopathological states. In turn, psychopathology is caused by pathophysiological processes that are perturbed by (etiological) causes such as predisposing factors, life events, and therapeutic interventions. The key advantages of this nosological formulation include (i) the formal integration of diagnostic (e.g., DSM) categories and latent psychopathological constructs (e.g., the dimensions of the Research Domain Criteria); (ii) the provision of a hypothesis or model space that accommodates formal, evidence-based hypothesis testing (using Bayesian model comparison); and (iii) the ability to predict therapeutic responses (using a posterior predictive density), as in precision medicine. These and other advantages are largely promissory at present: The purpose of this article is to show what might be possible, through the use of idealized simulations.

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          The positive and negative syndrome scale (PANSS) for schizophrenia.

          The variable results of positive-negative research with schizophrenics underscore the importance of well-characterized, standardized measurement techniques. We report on the development and initial standardization of the Positive and Negative Syndrome Scale (PANSS) for typological and dimensional assessment. Based on two established psychiatric rating systems, the 30-item PANSS was conceived as an operationalized, drug-sensitive instrument that provides balanced representation of positive and negative symptoms and gauges their relationship to one another and to global psychopathology. It thus constitutes four scales measuring positive and negative syndromes, their differential, and general severity of illness. Study of 101 schizophrenics found the four scales to be normally distributed and supported their reliability and stability. Positive and negative scores were inversely correlated once their common association with general psychopathology was extracted, suggesting that they represent mutually exclusive constructs. Review of five studies involving the PANSS provided evidence of its criterion-related validity with antecedent, genealogical, and concurrent measures, its predictive validity, its drug sensitivity, and its utility for both typological and dimensional assessment.
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            Dynamic causal modelling.

            In this paper we present an approach to the identification of nonlinear input-state-output systems. By using a bilinear approximation to the dynamics of interactions among states, the parameters of the implicit causal model reduce to three sets. These comprise (1) parameters that mediate the influence of extrinsic inputs on the states, (2) parameters that mediate intrinsic coupling among the states, and (3) [bilinear] parameters that allow the inputs to modulate that coupling. Identification proceeds in a Bayesian framework given known, deterministic inputs and the observed responses of the system. We developed this approach for the analysis of effective connectivity using experimentally designed inputs and fMRI responses. In this context, the coupling parameters correspond to effective connectivity and the bilinear parameters reflect the changes in connectivity induced by inputs. The ensuing framework allows one to characterise fMRI experiments, conceptually, as an experimental manipulation of integration among brain regions (by contextual or trial-free inputs, like time or attentional set) that is revealed using evoked responses (to perturbations or trial-bound inputs, like stimuli). As with previous analyses of effective connectivity, the focus is on experimentally induced changes in coupling (cf., psychophysiologic interactions). However, unlike previous approaches in neuroimaging, the causal model ascribes responses to designed deterministic inputs, as opposed to treating inputs as unknown and stochastic.
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              Applications of Centre Manifold Theory

              Jack Carr (1981)
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                Author and article information

                Journal
                101719151
                47223
                Comput Psychiatr
                Comput Psychiatr
                Computational psychiatry (Cambridge, Mass.)
                2379-6227
                27 January 2018
                8 September 2017
                2017
                02 February 2018
                : 1
                : 2-23
                Affiliations
                [1 ]The Wellcome Trust Centre for Neuroimaging, Institute of Neurology, UCL, London WC1N 3BG, UK
                [2 ]Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455
                [3 ]Department of Psychiatry, Columbia University, New York, NY 10032
                [4 ]Director: National Institute of Mental Health (NIMH), Bethesda MD 20814
                Author notes
                Corresponding Author: K. J. Friston, k.friston@ 123456ucl.ac.uk
                Article
                EMS75596
                10.1162/CPSY_a_00001
                5774181
                29400354
                7ece3658-e875-4c63-8934-e201f7a52d1f

                Published under a Creative Commons Attribution 4.0 International (CC BY 4.0) license ( http://creativecommons.org/licenses/by/4.0/)

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                Article

                nosology,psychiatry,psychopathology,pathophysiology,bayesian,model selection,dynamics,therapy

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