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      Anhedonia across borders: Transdiagnostic relevance of reward dysfunction for noninvasive brain stimulation endophenotypes

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          Abstract

          Introduction

          Anhedonia is a transdiagnostic psychopathological dimension, consisting in the impaired ability to experience pleasure. In order to further our understanding of its neural correlates and to explore its potential relevance as a predictor of treatment response, in this article we systematically reviewed studies involving anhedonia and neuromodulation interventions, across different disorders.

          Methods

          We included seven studies fulfilling inclusion/exclusion criteria and involving different measures of anticipatory and consummatory anhedonia, as well as different noninvasive brain stimulation interventions (transcranial magnetic stimulation and transcranial direct current stimulation). Studies not exploring hedonic measures or not involving neuromodulation intervention were excluded.

          Results

          All the included studies entailed the use of rTMS protocols in one of the diverse prefrontal targets. The limited amount of studies and the heterogeneity of stimulation protocols did not allow to draw any conclusion with regard to the efficacy of rTMS in the treatment of transnosographic anhedonia. A potential for anhedonia in dissecting possible endophenotypes of different psychopathological conditions preliminarily emerged.

          Conclusions

          Anhedonia is an underexplored condition in neuromodulation trials. It may represent a valuable transdiagnostic dimension that requires further examination in order to discover new clinical predictors for treatment response.

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          Most cited references59

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          Time-related predictors of suicide in major affective disorder.

          The authors studied 954 psychiatric patients with major affective disorders and found that nine clinical features were associated with suicide. Six of these--panic attacks, severe psychic anxiety, diminished concentration, global insomnia, moderate alcohol abuse, and severe loss of interest or pleasure (anhedonia)--were associated with suicide within 1 year, and three others--severe hopelessness, suicidal ideation, and history of previous suicide attempts--were associated with suicide occurring after 1 year. These findings draw attention to the importance of 1) standardized prospective data for studies of suicide, 2) assessment of short-term suicide risk factors, and 3) anxiety symptoms as modifiable suicide risk factors within a clinically relevant period.
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            Assessing anhedonia in depression: Potentials and pitfalls.

            The resurgence of interest in anhedonia within major depression has been fuelled by clinical trials demonstrating its utility in predicting antidepressant response as well as recent conceptualizations focused on the role and manifestation of anhedonia in depression. Historically, anhedonia has been understood as a "loss of pleasure", yet neuropsychological and neurobiological studies reveal a multifaceted reconceptualization that emphasizes different facets of hedonic function, including desire, effort/motivation, anticipation and consummatory pleasure. To ensure generalizability across studies, evaluation of the available subjective and objective methods to assess anhedonia is necessary. The majority of research regarding anhedonia and its neurobiological underpinnings comes from preclinical research, which uses primary reward (e.g. food) to probe hedonic responding. In contrast, behavioural studies in humans primarily use secondary reward (e.g. money) to measure many aspects of reward responding, including delay discounting, response bias, prediction error, probabilistic reversal learning, effort, anticipation and consummatory pleasure. The development of subjective scales to measure anhedonia has also increased in the last decade. This review will assess the current methodology to measure anhedonia, with a focus on scales and behavioural tasks in humans. Limitations of current work and recommendations for future studies are discussed.
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              Transdiagnostic psychiatry: a systematic review

              The usefulness of current psychiatric classification, which is based on ICD/DSM categorical diagnoses, remains questionable. A promising alternative has been put forward as the “transdiagnostic” approach. This is expected to cut across existing categorical diagnoses and go beyond them, to improve the way we classify and treat mental disorders. This systematic review explores whether self‐defining transdiagnostic research meets such high expectations. A multi‐step Web of Science literature search was performed according to an a priori protocol, to identify all studies that used the word “transdiagnostic” in their title, up to May 5, 2018. Empirical variables which indexed core characteristics were extracted, complemented by a bibliometric and conceptual analysis. A total of 111 studies were included. Most studies were investigating interventions, followed by cognition and psychological processes, and neuroscientific topics. Their samples ranged from 15 to 91,199 (median 148) participants, with a mean age from 10 to more than 60 (median 33) years. There were several methodological inconsistencies relating to the definition of the gold standard (DSM/ICD diagnoses), of the outcome measures and of the transdiagnostic approach. The quality of the studies was generally low and only a few findings were externally replicated. The majority of studies tested transdiagnostic features cutting across different diagnoses, and only a few tested new classification systems beyond the existing diagnoses. About one fifth of the studies were not transdiagnostic at all, because they investigated symptoms and not disorders, a single disorder, or because there was no diagnostic information. The bibliometric analysis revealed that transdiagnostic research largely restricted its focus to anxiety and depressive disorders. The conceptual analysis showed that transdiagnostic research is grounded more on rediscoveries than on true innovations, and that it is affected by some conceptual biases. To date, transdiagnostic approaches have not delivered a credible paradigm shift that can impact classification and clinical care. Practical “TRANSD”iagnostic recommendations are proposed here to guide future research in this field.
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                Author and article information

                Contributors
                mauro.pettorruso@hotmail.it
                Journal
                CNS Neurosci Ther
                CNS Neurosci Ther
                10.1111/(ISSN)1755-5949
                CNS
                CNS Neuroscience & Therapeutics
                John Wiley and Sons Inc. (Hoboken )
                1755-5930
                1755-5949
                22 October 2019
                November 2019
                : 25
                : 11 , Special Issue on Personalized Brain Stimulation ( doiID: 10.1111/cns.v25.11 )
                : 1229-1236
                Affiliations
                [ 1 ] Department of Neuroscience, Imaging and Clinical Sciences University “G. d’Annunzio” of Chieti‐Pescara Chieti Italy
                [ 2 ] Reference Centre for Behavioural Sciences and Mental Health Istituto Superiore di Sanità Rome Italy
                [ 3 ] Fondazione Policlinico Universitario A. Gemelli IRCCS Roma Italy
                [ 4 ] Università Cattolica del Sacro Cuore Roma Italy
                [ 5 ] Department of Pharmacy, Pharmacology and Clinical Science University of Hertfordshire Herts UK
                Author notes
                [*] [* ] Correspondence

                Mauro Pettorruso, Department of Neuroscience, Imaging and Clinical Sciences, University “G. d’Annunzio” of Chieti‐Pescara, Via Luigi Polacchi, 11 – Chieti, Italy.

                Email: mauro.pettorruso@ 123456hotmail.it

                Author information
                https://orcid.org/0000-0002-4164-3040
                https://orcid.org/0000-0002-3626-8928
                https://orcid.org/0000-0002-5758-3986
                Article
                CNS13230
                10.1111/cns.13230
                6834920
                31638332
                dc8baa2b-340b-46aa-9e43-2d664c3710e5
                © 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 May 2019
                : 15 September 2019
                : 29 September 2019
                Page count
                Figures: 1, Tables: 1, Pages: 8, Words: 5618
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                cns13230
                November 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.7.1 mode:remove_FC converted:06.11.2019

                Neurosciences
                addiction,depression,hedonic tone dysfunction,neuromodulation,schizophrenia,shaps,transcranial direct current stimulation,transcranial magnetic stimulation

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