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      Cannabis Use, Schizotypy and Kamin Blocking Performance

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          Abstract

          Cannabis use has been associated with increased risk for a first episode of psychosis and inappropriate assignment of salience to extraneous stimuli has been proposed as a mechanism underlying this association. Psychosis-prone (especially schizotypal) personality traits are associated with deficits in associative learning tasks that measure salience allocation. The aim of this study was to examine the relationship between history of cannabis use and Kamin blocking (KB), a form of selective associative learning, in a non-clinical sample. Additionally, KB was examined in relation to self-reported schizotypy and aberrant salience scale profiles. A cross-sectional study was conducted in 307 healthy participants with no previous psychiatric or neurological history. Participants were recruited and tested using the Testable Minds behavioural testing platform. KB was calculated using Oades' “mouse in the house task”, performance of which is disrupted in schizophrenia patients. Schizotypy was measured using the Schizotypal Personality Questionnaire (SPQ), and the Aberrant Salience Inventory (ASI) was used to assess self-reported unusual or inappropriate salience. The modified Cannabis Experience Questionnaire (CEQm) was used to collect detailed history of use of cannabis and other recreational drugs. Regression models and Bayesian t-tests or ANOVA (or non-parametric equivalents) examined differences in KB based on lifetime or current cannabis use (frequent use during previous year), as well as frequency of use among those who had previously used cannabis. Neither lifetime nor current cannabis use was associated with any significant change in total or trial-specific KB scores. Current cannabis use was associated with higher Disorganised SPQ dimension scores and higher total and sub-scale values for the ASI. A modest positive association was observed between total KB score and Disorganised SPQ dimension scores, but no relationships were found between KB and other SPQ measures. Higher scores on “Senses Sharpening” ASI sub-scale predicted decreased KB score only in participants who have not engaged in recent cannabis use. These results are discussed in the context of our understanding of the effects of long-term cannabis exposure on salience attribution, as well as inconsistencies in the literature with respect to both the relationship between KB and schizotypy and the measurement of KB associative learning phenomena.

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            Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia.

            The clinical hallmark of schizophrenia is psychosis. The objective of this overview is to link the neurobiology (brain), the phenomenological experience (mind), and pharmacological aspects of psychosis-in-schizophrenia into a unitary framework. Current ideas regarding the neurobiology and phenomenology of psychosis and schizophrenia, the role of dopamine, and the mechanism of action of antipsychotic medication were integrated to develop this framework. A central role of dopamine is to mediate the "salience" of environmental events and internal representations. It is proposed that a dysregulated, hyperdopaminergic state, at a "brain" level of description and analysis, leads to an aberrant assignment of salience to the elements of one's experience, at a "mind" level. Delusions are a cognitive effort by the patient to make sense of these aberrantly salient experiences, whereas hallucinations reflect a direct experience of the aberrant salience of internal representations. Antipsychotics "dampen the salience" of these abnormal experiences and by doing so permit the resolution of symptoms. The antipsychotics do not erase the symptoms but provide the platform for a process of psychological resolution. However, if antipsychotic treatment is stopped, the dysregulated neurochemistry returns, the dormant ideas and experiences become reinvested with aberrant salience, and a relapse occurs. The article provides a heuristic framework for linking the psychological and biological in psychosis. Predictions of this hypothesis, particularly regarding the possibility of synergy between psychological and pharmacological therapies, are presented. The author describes how the hypothesis is complementary to other ideas about psychosis and also discusses its limitations.
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              The dopamine hypothesis of schizophrenia: version III--the final common pathway.

              The dopamine hypothesis of schizophrenia has been one of the most enduring ideas in psychiatry. Initially, the emphasis was on a role of hyperdopaminergia in the etiology of schizophrenia (version I), but it was subsequently reconceptualized to specify subcortical hyperdopaminergia with prefrontal hypodopaminergia (version II). However, these hypotheses focused too narrowly on dopamine itself, conflated psychosis and schizophrenia, and predated advances in the genetics, molecular biology, and imaging research in schizophrenia. Since version II, there have been over 6700 articles about dopamine and schizophrenia. We selectively review these data to provide an overview of the 5 critical streams of new evidence: neurochemical imaging studies, genetic evidence, findings on environmental risk factors, research into the extended phenotype, and animal studies. We synthesize this evidence into a new dopamine hypothesis of schizophrenia-version III: the final common pathway. This hypothesis seeks to be comprehensive in providing a framework that links risk factors, including pregnancy and obstetric complications, stress and trauma, drug use, and genes, to increased presynaptic striatal dopaminergic function. It explains how a complex array of pathological, positron emission tomography, magnetic resonance imaging, and other findings, such as frontotemporal structural and functional abnormalities and cognitive impairments, may converge neurochemically to cause psychosis through aberrant salience and lead to a diagnosis of schizophrenia. The hypothesis has one major implication for treatment approaches. Current treatments are acting downstream of the critical neurotransmitter abnormality. Future drug development and research into etiopathogenesis should focus on identifying and manipulating the upstream factors that converge on the dopaminergic funnel point.
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                Author and article information

                Contributors
                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                23 November 2021
                2021
                : 12
                : 633476
                Affiliations
                [1] 1School of Psychology, University Park, University of Nottingham , Nottingham, United Kingdom
                [2] 2Department of Sport, Leisure, and Childhood Studies, Munster Technological University , Cork, Ireland
                [3] 3Psychological Sciences Research Institute, Université Catholique de Louvain , Louvain-la-Neuve, Belgium
                [4] 4School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland , Dublin, Ireland
                [5] 5Medical Education Unit, School of Medicine, University College Cork , Cork, Ireland
                Author notes

                Edited by: Sinan Guloksuz, Maastricht University Medical Center, Netherlands

                Reviewed by: Emma Barkus, Northumbria University, United Kingdom; Preethi Premkumar, London South Bank University, United Kingdom

                *Correspondence: Colm M. P. O'Tuathaigh c.otuathaigh@ 123456ucc.ie

                This article was submitted to Psychopharmacology, a section of the journal Frontiers in Psychiatry

                Article
                10.3389/fpsyt.2021.633476
                8649723
                ab032520-8540-4e51-b008-730656623cee
                Copyright © 2021 Dawes, Bickerdike, O'Neill, Carneiro Pereira, Waddington, Moran and O'Tuathaigh.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 25 November 2020
                : 29 October 2021
                Page count
                Figures: 3, Tables: 3, Equations: 0, References: 79, Pages: 13, Words: 10794
                Categories
                Psychiatry
                Original Research

                Clinical Psychology & Psychiatry
                cannabis,schizotypy,kamin blocking effect,aberrant salience,psychosis

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