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Lo Presti S, Bonavita M, Piga V, Lozito S, Doricchi F, Lasaponara S. "Don't stop believing" - Decoding belief dynamics in the brain: An ALE meta-analysis of neural correlates in belief formation and updating. Neurosci Biobehav Rev 2025; 173:106153. [PMID: 40228650 DOI: 10.1016/j.neubiorev.2025.106153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 03/18/2025] [Accepted: 04/03/2025] [Indexed: 04/16/2025]
Abstract
Understanding how individuals form and update their beliefs is a fundamental question in cognitive and social psychology. Belief formation (BF) refers to the initial development of an individual's belief, while belief updating (BU) pertains to the revision of existing beliefs in response to contradictory evidence. Although these two processes are often interwoven, they might operate through different neural mechanisms. This meta-analysis aims to synthesize the existing functional magnetic resonance imaging (fMRI) literature on BF and BU, with a particular focus on how BF is investigated. Approaches based on Theory of Mind paradigms, such as False Belief tasks, are often opposed to other approaches, emphasizing the role of individual or situational factors in belief formation. Notably, we propose that this differentiation might reflect the engagement of social and non-social dynamics within belief formation. Activation likelihood estimation (ALE) analysis revealed shared involvement of the Precuneus (PCu) in both BF and BU, while BF specifically engaged the bilateral activation of the Temporo-Parietal Junctions (TPJ). Additionally, social and non-social BF exhibited distinct neural correlates: social BF was associated with activity in the right TPJ, whereas non-social BF relied on the left dorsolateral prefrontal cortex (DLPFC). These findings support the hypothesis that BF and BU operate via partially dissociable neural networks and highlights the role of TPJ and PCu as essential hubs to build-up neural templates and enabling shifts in viewpoint necessary to adapt beliefs.
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Affiliation(s)
- S Lo Presti
- Psychology Department - "Sapienza" University of Rome, Via dei Marsi, 78, Rome 00185, Italy; Neuropsychology Department - IRCCS Fondazione Santa Lucia, Via Ardeatina, 306, Rome 00100, Italy
| | - M Bonavita
- Psychology Department - "Sapienza" University of Rome, Via dei Marsi, 78, Rome 00185, Italy
| | - V Piga
- Psychology Department - "Sapienza" University of Rome, Via dei Marsi, 78, Rome 00185, Italy; Neuropsychology Department - IRCCS Fondazione Santa Lucia, Via Ardeatina, 306, Rome 00100, Italy; PhD Program in behavioural neuroscience, "Sapienza" University of Rome, Rome, Italy
| | - S Lozito
- Psychology Department - "Sapienza" University of Rome, Via dei Marsi, 78, Rome 00185, Italy; Neuropsychology Department - IRCCS Fondazione Santa Lucia, Via Ardeatina, 306, Rome 00100, Italy; PhD Program in behavioural neuroscience, "Sapienza" University of Rome, Rome, Italy
| | - F Doricchi
- Psychology Department - "Sapienza" University of Rome, Via dei Marsi, 78, Rome 00185, Italy; Neuropsychology Department - IRCCS Fondazione Santa Lucia, Via Ardeatina, 306, Rome 00100, Italy
| | - S Lasaponara
- Psychology Department - "Sapienza" University of Rome, Via dei Marsi, 78, Rome 00185, Italy; Neuropsychology Department - IRCCS Fondazione Santa Lucia, Via Ardeatina, 306, Rome 00100, Italy.
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Sloan AF, Kittleson AR, Torregrossa LJ, Feola B, Rossi-Goldthorpe R, Corlett PR, Sheffield JM. Belief Updating, Childhood Maltreatment, and Paranoia in Schizophrenia-Spectrum Disorders. Schizophr Bull 2025; 51:646-657. [PMID: 38701234 PMCID: PMC12061658 DOI: 10.1093/schbul/sbae057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/05/2024]
Abstract
BACKGROUND AND HYPOTHESIS Exposure to childhood maltreatment-a risk factor for psychosis that is associated with paranoia-may impact one's beliefs about the world and how beliefs are updated. We hypothesized that increased exposure to childhood maltreatment is related to volatility-related belief updating, specifically higher expectations of volatility, and that these relationships are strongest for threat-related maltreatment. Additionally, we tested whether belief updating mediates the relationship between maltreatment and paranoia. STUDY DESIGN Belief updating was measured in 75 patients with schizophrenia-spectrum disorders and 76 nonpsychiatric controls using a 3-option probabilistic reversal learning (3PRL) task. A Hierarchical Gaussian Filter (HGF) was used to estimate computational parameters of belief updating, including prior expectations of volatility (μ03). The Childhood Trauma Questionnaire (CTQ) was used to assess cumulative maltreatment, threat, and deprivation exposure. Paranoia was measured using the Positive and Negative Syndrome Scale (PANSS) and the revised Green et al. Paranoid Thoughts Scale (R-GPTS). RESULTS Greater exposure to childhood maltreatment is associated with higher prior expectations of volatility in the whole sample and in individuals with schizophrenia-spectrum disorders. This was specific to threat-related maltreatment, rather than deprivation, in schizophrenia-spectrum disorders. Paranoia was associated with both exposure to childhood maltreatment and volatility priors, but we did not observe a significant indirect effect of volatility priors on the relationship between maltreatment and paranoia. CONCLUSIONS Our study suggests that individuals with schizophrenia-spectrum disorders who were exposed to threatening experiences during childhood expect their environment to be more volatile, potentially facilitating aberrant belief updating and conferring risk for paranoia.
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Affiliation(s)
- Ali F Sloan
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Andrew R Kittleson
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Lénie J Torregrossa
- Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, CA, USA
| | - Brandee Feola
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
| | | | - Philip R Corlett
- Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA
| | - Julia M Sheffield
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
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Chen YHE, Wong SM, So MM, Suen YN, Hui CL. Spurious autobiographical memories of psychosis: a dopamine-gated neuroplasticity account for relapse and treatment-resistant psychosis. Psychol Med 2025; 55:e14. [PMID: 40190096 PMCID: PMC12017373 DOI: 10.1017/s0033291724003027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Revised: 10/22/2024] [Accepted: 10/30/2024] [Indexed: 04/22/2025]
Abstract
Psychotic disorders are known to be associated with elevated dopamine synthesis; yet, nondopamine factors may underlie the manifestation of some psychotic symptoms that are nonresponsive to dopamine-blocking agents. One under-explored nondopamine mechanism is neuroplasticity. We propose an account of the course of psychotic symptoms based on the extensive evidence for dopamine facilitation of Hebbian synaptic plasticity in cortical and subcortical memory systems. The encoding of psychotic experiences in autobiographical memory (AM) is expected to be facilitated in the hyperdopaminergic state associated with acute psychosis. However, once such 'spurious AM of psychosis' (SAMP) is encoded, its persistence may become dependent more on synaptic factors than dopamine factors. Under this framework, the involuntary retrieval of residual SAMP is postulated to play a key role in mediating the reactivation of symptoms with similar contents, as often observed in patients during relapse. In contrast, with active new learning of normalizing experiences across diverse real-life contexts, supported by intact dopamine-mediated salience, well-integrated SAMP may undergo 'extinction', leading to remission. The key steps to the integration of SAMP across psychotic and nonpsychotic memories may correspond to one's 'recovery style', involving processes similar to the formation of 'non-believed memory' in nonclinical populations. The oversuppression of dopamine can compromise such processes. We synthesize this line of evidence into an updated dopamine-gated memory framework where neuroplasticity processes offer a parsimonious account for the recurrence, persistence, and progression of psychotic symptoms. This framework generates testable hypotheses relevant to clinical interventions.
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Affiliation(s)
- Yu Hai Eric Chen
- Centre for Youth Mental Health, University of Melbourne, Parkville, VIC 3052, Australia
- Orygen, Parkville, VIC 3052, Australia, 3 School of Clinical Medicine HKU
- School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR
| | - Stephanie M.Y. Wong
- Department of Social Work and Social Administration, The University of Hong Kong, Hong Kong SAR
| | - Melody M. So
- School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR
| | - Yi Nam Suen
- School of Nursing, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR
| | - Christy L.M. Hui
- School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR
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Castiello S, Rossi-Goldthorpe R, Fan S, Kenney J, Waltz JA, Erickson M, Bansal S, Gold JM, Corlett PR. Delusional Unreality and Predictive Processing. BIOLOGICAL PSYCHIATRY. COGNITIVE NEUROSCIENCE AND NEUROIMAGING 2024:S2451-9022(24)00382-3. [PMID: 39710316 DOI: 10.1016/j.bpsc.2024.12.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Revised: 10/30/2024] [Accepted: 12/12/2024] [Indexed: 12/24/2024]
Abstract
BACKGROUND Phenomenological psychopathologists have recently highlighted how people with delusions experience multiple realities (delusional and nondelusional) and have suggested that this double bookkeeping cannot be explained via predictive processing. Here, we present data from Kamin blocking and extinction learning that show how predictive processing might, in principle, explain a pervasive sense of dual reality. METHODS This cross-sectional study involved 3 participant groups: patients with schizophrenia (SZ) (n = 42), healthy participants with elevated esoteric beliefs (EEBs) (clairaudient psychics) (n = 31), and healthy control participants (HCs) with neither illness nor significant delusional ideation (n = 62). We examined belief formation using a Kamin blocking causal learning task with extinction and delusions with the 40-item Peters Delusion Inventory, specifically the unreality item "Do things around you ever feel unreal, as though it was all part of an experiment?" as a proxy for unreality experiences and beliefs. A clinician also assessed symptoms with a structured clinical interview. RESULTS Some people with SZ did not report a sense of unreality, and some people with elevated esoteric beliefs (but no psychotic illness) reported unreality experiences. No HCs reported them (despite reporting other delusion-like beliefs). Unreality experiences in clinical delusions and nonclinical delusion-like beliefs were associated with different types of aberrant prediction error processing. CONCLUSIONS These data suggest how predictive processing may explain the sense of unreality. They indicate that different prediction error dysfunctions are associated with delusions with different contents. In this case, we have used predictive processing to address a salient issue raised by our phenomenological colleagues, namely the impact of psychosis on experiences of and beliefs about reality.
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Affiliation(s)
| | | | - Siyan Fan
- Wu Tsai Institute, Yale University, New Haven, Connecticut
| | - Joshua Kenney
- Wu Tsai Institute, Yale University, New Haven, Connecticut
| | - James A Waltz
- School of Medicine, University of Maryland, Baltimore, Maryland
| | - Molly Erickson
- Division of the Biological Sciences, University of Chicago, Chicago, Illinois
| | - Sonia Bansal
- School of Medicine, University of Maryland, Baltimore, Maryland
| | - James M Gold
- School of Medicine, University of Maryland, Baltimore, Maryland
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Dewan M, Campbell Daniels E, Hunt JE, Bryant EA, Trikeriotis SI, Kelly DL, Adams HA, Hare SM, Waltz JA. Aberrant salience signaling in auditory processing in schizophrenia: Evidence for abnormalities in both sensory processing and emotional reactivity. Schizophr Res 2024; 274:329-336. [PMID: 39454324 PMCID: PMC11620929 DOI: 10.1016/j.schres.2024.09.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 08/06/2024] [Accepted: 09/20/2024] [Indexed: 10/28/2024]
Abstract
It has been long known that people with schizophrenia (SZ) have deficits in perceptual processing, including in the auditory domain. Furthermore, they often experience increased emotional responsivity and dysregulation, which further impacts overall functioning. Increased emotional responsivity to auditory stimuli is also seen in people with misophonia, a condition in which specific sounds elicit robust negative emotional responses. Given the role of emotional reactivity and dysregulation in the pathogenesis of SZ, our study investigated whether misophonia symptoms were elevated in SZ, or if people with SZ have a generalized increase in reactivity to sensory information. To explore the link between emotional reactivity to sound and more general aspects emotional reactivity and salience signaling in SZ, we used the Misophonia Questionnaire, the Sensory Processing Scale (SPS), and Aberrant Salience Inventory (ASI) in 30 people with SZ and 28 demographically-matched healthy volunteers (HVs). We found that people with SZ exhibited more emotional behavior associated with misophonia symptoms (specifically, distress in relation to sound) than HVs (t56 = 4.889, p < 0.001), but did not have elevated rates of misophonia overall. Also, sensory processing abnormalities and heightened emotional responses in people with SZ were not limited to the auditory domain but, rather, extended to all sensory modalities. Our results support the idea that SZ involves dysfunction in salience signaling, regarding auditory stimuli, but that abnormalities in salience signaling in SZ are more domain-general. These results highlight the importance of interventions designed to enhance emotion regulation in patients with SZ regarding stimuli in multiple modalities.
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Affiliation(s)
- Mahima Dewan
- University of Maryland School of Medicine, Baltimore, MD, USA
| | | | - Jared E Hunt
- University of Maryland School of Medicine, Baltimore, MD, USA; Maryland Psychiatric Research Center, Catonsville, MD, USA
| | - Emily A Bryant
- University of Maryland School of Medicine, Baltimore, MD, USA; Maryland Psychiatric Research Center, Catonsville, MD, USA
| | - Samantha I Trikeriotis
- University of Maryland School of Medicine, Baltimore, MD, USA; Maryland Psychiatric Research Center, Catonsville, MD, USA
| | - Deanna L Kelly
- University of Maryland School of Medicine, Baltimore, MD, USA; Maryland Psychiatric Research Center, Catonsville, MD, USA; Spring Grove Hospital Center, Catonsville, MD, USA
| | - Heather A Adams
- University of Maryland School of Medicine, Baltimore, MD, USA; Maryland Psychiatric Research Center, Catonsville, MD, USA; Spring Grove Hospital Center, Catonsville, MD, USA
| | - Stephanie M Hare
- University of Maryland School of Medicine, Baltimore, MD, USA; Maryland Psychiatric Research Center, Catonsville, MD, USA
| | - James A Waltz
- University of Maryland School of Medicine, Baltimore, MD, USA; Maryland Psychiatric Research Center, Catonsville, MD, USA.
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Slade M, Rennick-Egglestone S, Robinson C, Newby C, Elliott RA, Ali Y, Yeo C, Glover T, Gavan SP, Paterson L, Pollock K, Priebe S, Thornicroft G, Keppens J, Smuk M, Franklin D, Walcott R, Harrison J, Robotham D, Bradstreet S, Gillard S, Cuijpers P, Farkas M, Ben-Zeev D, Repper J, Kotera Y, Roe J, Llewellyn-Beardsley J, Ng F. Effectiveness and cost-effectiveness of online recorded recovery narratives in improving quality of life for people with psychosis experience (NEON Trial): a pragmatic randomised controlled trial. THE LANCET REGIONAL HEALTH. EUROPE 2024; 47:101101. [PMID: 39507771 PMCID: PMC11539663 DOI: 10.1016/j.lanepe.2024.101101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 10/03/2024] [Accepted: 10/04/2024] [Indexed: 11/08/2024]
Abstract
Background The Narrative Experiences Online (NEON) Intervention provides self-managed web-based access to mental health recovery narratives (n = 659). We evaluated effectiveness and cost-effectiveness in improving quality of life for adults resident in England with mental health problems and recent psychosis experience. Methods Prospectively registered pragmatic parallel-group randomised trial controlling for usual care, recruiting from statutory mental health services and through community engagement activities, with a 52-week primary endpoint (ISRCTN11152837). All trial procedures and the NEON Intervention were delivered by an integrated web-application. Randomisation was through an independently generated list (no stratification). Allocation was masked for statistical staff and the Chief Investigator but not participants. Intervention arm participants received immediate NEON Intervention access. Control arm participants received access after completing primary endpoint questionnaires. The primary outcome was quality of life through the Manchester Short Assessment (MANSA). Serious Adverse Events (SAEs) were collected through web-based safety report forms and identified from health service usage data. The primary analysis was by a prospectively described Intention To Treat principle excluding participants who had registered multiple times, with multiple imputation for missing data. Findings Between 9 March 2020 and 1 March 2021, 739 participants were randomised (intervention:370; control: 369), providing more than 90% power to detect a baseline-adjusted difference of 0.25 in the MANSA score. Mean age was 34.8 years (standard deviation (SD) 12.0), 561 (75.9%) were white British, 443 (59.9%) were female, 609 (82.4%) had accessed specialist care mental health services, and 698 (94.5%) had accessed primary care mental health services. Mean baseline MANSA score was 3.7 for control and intervention arms (SD 0.9 and 1.0). 565 (76.5%) participants provided primary endpoint MANSA data with a mean score of 4.1 (SD 1.0) for both arms. We found no significant difference in Quality of Life between the two arms at the primary endpoint (baseline-adjusted difference 0.07, 95% CI -0.07 to 0.21, p = 0.35). The incremental cost-effectiveness ratio (£110,501 per quality-adjusted life-year (QALY)) exceeded the prospectively defined cost-effectiveness threshold (£30,000 per QALY). 158 (42.8%) control arm and 194 (52.4%) intervention arm participants accessed narratives outside of the NEON Intervention. There were no related serious adverse events (SAEs). 116 unrelated SAEs were reported by control arm participants, and 107 by intervention arm participants. Interpretation Our findings do not indicate NEON Intervention access for all people with psychosis experience. Future research should consider a) evaluation with current mental health services users; b) optimisation to enable users to find hope-promoting narratives. Funding National Institute for Health and Care Research (NIHR).
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Affiliation(s)
- Mike Slade
- School of Health Sciences, Institute of Mental Health, University of Nottingham, Nottingham, UK
- Health and Community Participation Division, Faculty of Nursing and Health Sciences, Nord University, Namsos, Norway
| | | | - Clare Robinson
- Centre for Evaluation and Methods, Wolfson Institute of Population Health, Pragmatic Clinical Trials Unit, Queen Mary University of London, London, UK
| | - Chris Newby
- School of Medicine, University of Nottingham, Nottingham, UK
| | - Rachel A. Elliott
- Manchester Centre for Health Economics, Division of Population Health, Health Services Research & Primary Care, University of Manchester, Manchester, UK
| | - Yasmin Ali
- School of Health Sciences, Institute of Mental Health, University of Nottingham, Nottingham, UK
| | - Caroline Yeo
- School of Health Sciences, Institute of Mental Health, University of Nottingham, Nottingham, UK
- Department of Architecture and Built Environment, Faculty of Engineering, University of Nottingham, UK
| | | | - Sean P. Gavan
- Manchester Centre for Health Economics, Division of Population Health, Health Services Research & Primary Care, University of Manchester, Manchester, UK
| | - Luke Paterson
- Manchester Centre for Health Economics, Division of Population Health, Health Services Research & Primary Care, University of Manchester, Manchester, UK
| | - Kristian Pollock
- School of Health Sciences, University of Nottingham, Nottingham, UK
| | - Stefan Priebe
- Unit for Social and Community Psychiatry, East London NHS Foundation Trust, London, UK
| | - Graham Thornicroft
- Centre for Implementation Science and Centre for Global Mental Health, Health Service and Population Research Department, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - Jeroen Keppens
- Department of Informatics, King's College London, London, UK
| | - Melanie Smuk
- Centre for Genomics and Child Health, Blizard Institute, Queen Mary University of London, London, UK
| | - Donna Franklin
- NEON Lived Experience Advisory Panel, Nottingham, UK
- School of Health and Related Research, University of Sheffield, Sheffield, UK
| | - Rianna Walcott
- NEON Lived Experience Advisory Panel, Nottingham, UK
- Black Communication and Technology Lab, Department of Communication, University of Maryland, College Park, MD, USA
| | | | | | - Simon Bradstreet
- Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
| | - Steve Gillard
- School of Health Sciences, City, University of London, London, UK
| | - Pim Cuijpers
- Department of Clinical, Neuro and Developmental Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
- Babeș-Bolyai University, International Institute for Psychotherapy, Cluj-Napoca, Romania
| | - Marianne Farkas
- Center for Psychiatric Rehabilitation, College of Health and Rehabilitation Sciences, Boston University, Boston, MA, USA
| | - Dror Ben-Zeev
- Behavioral Research in Technology and Engineering (BRiTE) Center, School of Medicine, University of Washington, Seattle, WA, USA
| | | | - Yasuhiro Kotera
- School of Health Sciences, Institute of Mental Health, University of Nottingham, Nottingham, UK
- Center for Infectious Disease Education and Research, Osaka University, Osaka, Japan
| | - James Roe
- National Institute for Health and Care Research (NIHR) Applied Research Collaboration East Midlands, University of Nottingham, Nottingham, UK
| | - Joy Llewellyn-Beardsley
- School of Health Sciences, Institute of Mental Health, University of Nottingham, Nottingham, UK
| | - Fiona Ng
- School of Health Sciences, Institute of Mental Health, University of Nottingham, Nottingham, UK
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Grunfeld G, Lemonde AC, Gold I, Paquin V, Iyer SN, Lepage M, Joober R, Malla A, Shah JL. Consistency of Delusion Themes Across First and Subsequent Episodes of Psychosis. JAMA Psychiatry 2024; 81:1039-1046. [PMID: 39110444 PMCID: PMC11307164 DOI: 10.1001/jamapsychiatry.2024.2040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Accepted: 05/21/2024] [Indexed: 08/10/2024]
Abstract
Importance Despite growing interest in the phenomenology of delusions in psychosis, at present little is known about their content and evolution over time, including whether delusion themes are consistent across episodes. Objective To examine the course of delusions and thematic delusion content across relapse episodes in patients presenting to an early intervention service for psychosis. Design, Setting, and Participants This longitudinal, observational study used clinical data systematically collected from January 2003 to March 2018 from a cohort of consenting patients with affective or nonaffective first-episode psychosis, followed up naturalistically for up to 2 years in an early intervention service for psychosis in Montréal, Quebec, Canada. Data included the thematic content and severity of delusions (scores ≥3 using the Scale for the Assessment of Positive Symptoms) and associated psychotic and nonpsychotic symptoms, both across an initial episode and, in the event of remission, a potential relapse. Data were analyzed from September 2021 to February 2023. Exposure An early intervention service for psychosis, organized around intensive case management and a multidisciplinary team approach, which observed each patient for up to 2 years of care. Main Outcomes and Measures The primary outcome was positive symptom relapse and remission, including the presence and content of delusions, which was coded per the Scale for the Assessment of Positive Symptoms and accepted definitions. The main statistical measures included repeated paired-sample t tests and binary logistic regression analyses. Results Of 636 consenting patients, mean (SD) age was 23.8 (4.75) years; 191 patients were female, 444 were male, and 1 patient was nonbinary. Remission rates were high, and relapse rates were relatively low: 591 individuals had baseline delusions, of which 558 (94.4%) achieved remission. Of these 558 patients, only 182 (32.6%) had a subsequent relapse to a second or later episode of psychosis. Of the 182 patients who did relapse, however, a large proportion (115 [63.2%]) reported threshold-level delusions. Of these 115, 104 patients (90.4%) had thematic delusion content consistent with that reported during the index (first) episode. Those who relapsed with delusions had fewer delusion themes present during subsequent episodes of psychosis compared with the index episode and lower levels of other psychotic and nonpsychotic symptoms. Conclusions and Relevance Specialized early intervention services for psychosis can achieve high rates of sustained remission. However, in this study, the minority of individuals with delusions who later relapsed experienced similar delusion themes during subsequent episodes. These findings raise important considerations for the conceptualization of delusions and have clinical implications for trajectories of illness and care.
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Affiliation(s)
- Gil Grunfeld
- Department of Psychiatry, Faculty of Medicine and Health Sciences, McGill University, Montréal, Quebec, Canada
- Prevention and Early Intervention Program for Psychosis, Douglas Mental Health University Institute, Montréal, Quebec, Canada
| | - Ann-Catherine Lemonde
- Department of Psychiatry, Faculty of Medicine and Health Sciences, McGill University, Montréal, Quebec, Canada
- Prevention and Early Intervention Program for Psychosis, Douglas Mental Health University Institute, Montréal, Quebec, Canada
| | - Ian Gold
- Department of Psychiatry, Faculty of Medicine and Health Sciences, McGill University, Montréal, Quebec, Canada
- Department of Philosophy, Faculty of Arts, McGill University, Montréal, Quebec, Canada
| | - Vincent Paquin
- Department of Psychiatry, Faculty of Medicine and Health Sciences, McGill University, Montréal, Quebec, Canada
- Prevention and Early Intervention Program for Psychosis, Douglas Mental Health University Institute, Montréal, Quebec, Canada
| | - Srividya N. Iyer
- Department of Psychiatry, Faculty of Medicine and Health Sciences, McGill University, Montréal, Quebec, Canada
- Prevention and Early Intervention Program for Psychosis, Douglas Mental Health University Institute, Montréal, Quebec, Canada
| | - Martin Lepage
- Department of Psychiatry, Faculty of Medicine and Health Sciences, McGill University, Montréal, Quebec, Canada
- Prevention and Early Intervention Program for Psychosis, Douglas Mental Health University Institute, Montréal, Quebec, Canada
| | - Ridha Joober
- Department of Psychiatry, Faculty of Medicine and Health Sciences, McGill University, Montréal, Quebec, Canada
- Prevention and Early Intervention Program for Psychosis, Douglas Mental Health University Institute, Montréal, Quebec, Canada
| | - Ashok Malla
- Department of Psychiatry, Faculty of Medicine and Health Sciences, McGill University, Montréal, Quebec, Canada
- Prevention and Early Intervention Program for Psychosis, Douglas Mental Health University Institute, Montréal, Quebec, Canada
| | - Jai L. Shah
- Department of Psychiatry, Faculty of Medicine and Health Sciences, McGill University, Montréal, Quebec, Canada
- Prevention and Early Intervention Program for Psychosis, Douglas Mental Health University Institute, Montréal, Quebec, Canada
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Vaidya BP, Shenoy S, Praharaj SK. Aberrant salience in acute versus chronic schizophrenia: Do medication and positive symptoms make a difference? Indian J Psychiatry 2024; 66:788-795. [PMID: 39502592 PMCID: PMC11534132 DOI: 10.4103/indianjpsychiatry.indianjpsychiatry_521_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2024] [Revised: 08/22/2024] [Accepted: 08/23/2024] [Indexed: 11/08/2024] Open
Abstract
Background The nature of aberrant salience in schizophrenia, whether it is a state or a trait phenomenon, remains unclear. Aim To assess and compare aberrant salience in patients with schizophrenia at different stages of the illness and to explore its association with symptom severity and medication use. Methods A total of 113 subjects were included, comprising 83 patients with schizophrenia divided into three groups: group A (acute drug-free symptomatic stage, n = 23), group B (chronic-medicated symptomatic stage, n = 30), and group C (chronic-medicated asymptomatic stage, n = 30). These were compared with a healthy control group (group D, n = 30). Participants were assessed using the Aberrant Salience Inventory (ASI) and clinical rating scales, including Psychotic Symptom Rating Scales, Scale for Assessment of Positive Symptoms, and Scale for Assessment of Negative Symptoms (SANS). Results Significant differences were observed across almost all domains of aberrant salience. The most notable differences were between the symptomatic groups (A, B) and the healthy controls (D). Subgroup analysis showed no significant differences between the acute (A) and chronic groups (B, C), but significant differences were found between the symptomatic (A, B) and asymptomatic (C) groups in several domains and in the total ASI score. A highly significant positive correlation was noted between the total ASI score and the symptom rating scales, except for SANS. Conclusion Aberrant salience is significantly elevated in patients with prominent positive symptoms, particularly delusions and hallucinations. It appears comparable to the general population in chronic remitted patients, suggesting that aberrant salience is state-dependent. Medication did not significantly influence aberrant salience as both medicated and nonmedicated symptomatic patients continued to exhibit it. However, medication may contribute to reducing aberrant salience by alleviating positive psychotic symptoms.
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Affiliation(s)
| | - Sonia Shenoy
- Department of Psychiatry, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Samir Kumar Praharaj
- Department of Psychiatry, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
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9
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Dernbach MR, Carpenter JE. Case Files of the Emory University Medical Toxicology Fellowship: A Patient Presents to the Outpatient Toxicology Clinic with Delusions of Being Poisoned. J Med Toxicol 2024; 20:233-244. [PMID: 38378951 PMCID: PMC10959915 DOI: 10.1007/s13181-024-00995-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 02/05/2024] [Accepted: 02/08/2024] [Indexed: 02/22/2024] Open
Affiliation(s)
- Matthew Robert Dernbach
- Department of Emergency Medicine, Emory University, 50 Hurt Plaza SE, Suite 600, Atlanta, GA, 30303, USA.
- Georgia Poison Center, Atlanta, GA, USA.
| | - Joseph E Carpenter
- Department of Emergency Medicine, Emory University, 50 Hurt Plaza SE, Suite 600, Atlanta, GA, 30303, USA
- Georgia Poison Center, Atlanta, GA, USA
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10
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Abstract
According to the commonly accepted opinion, memory engrams are formed and stored at the level of neural networks due to a change in the strength of synaptic connections between neurons. This hypothesis of synaptic plasticity (HSP), formulated by Donald Hebb in the 1940s, continues to dominate the directions of experimental studies and the interpretations of experimental results in the field. The universal acceptance of the HSP has transformed it from a hypothesis into an incontrovertible theory. In this article, I show that the entire body of experimental and clinical data obtained in studies of long-term memory in mammals and humans is inconsistent with the HSP. Instead, these data suggest that long-term memory is formed and stored at the intracellular level where it is reliably protected from ongoing synaptic activity, including pathological epileptic activity. It seems that the generally accepted HSP became a serious obstacle to understanding the mechanisms of memory and that progress in this field requires rethinking this doctrine and shifting experimental efforts toward exploring the intracellular mechanisms.
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Affiliation(s)
- Yuri I Arshavsky
- BioCircuits Institute, University of California San Diego, La Jolla, CA, USA
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11
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Treviño M, Castiello S, De la Torre-Valdovinos B, Osuna Carrasco P, Medina-Coss Y León R, Arias-Carrión O. Two-stage reinforcement learning task predicts psychological traits. Psych J 2023. [PMID: 36740455 DOI: 10.1002/pchj.633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 12/20/2022] [Indexed: 02/07/2023]
Abstract
External sources of information influence human actions. However, psychological traits (PTs), considered internal variables, also play a crucial role in decision making. PTs are stable across time and contexts and define the set of behavioral repertoires that individuals express. Here, we explored how multiple metrics of adaptive behavior under uncertainty related to several PTs. Participants solved a reversal-learning task with volatile contingencies, from which we characterized a detailed behavioral profile based on their response sequences. We then tested the relationship between this multimetric behavioral profile and scores obtained from self-report psychological questionnaires. The PT measurements were based on the Hierarchical Taxonomy Of Psychopathology (HiTOP) model. By using multiple linear regression models (MLRMs), we found that the learning curves predicted important differences in the PTs and task response times. We confirmed the significance of these relationships by using random permutations of the predictors of the MLRM. Therefore, the behavioral profile configurations predicted the PTs and served as a "fingerprint" to identify participants with a high certainty level. We discuss briefly how this characterization and approach could contribute to better nosological classifications.
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Affiliation(s)
- Mario Treviño
- Laboratorio de Plasticidad Cortical y Aprendizaje Perceptual, Instituto de Neurociencias, Universidad de Guadalajara, Guadalajara, Mexico
| | | | | | - Paulina Osuna Carrasco
- Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Guadalajara, Mexico
| | - Ricardo Medina-Coss Y León
- Laboratorio de Plasticidad Cortical y Aprendizaje Perceptual, Instituto de Neurociencias, Universidad de Guadalajara, Guadalajara, Mexico
| | - Oscar Arias-Carrión
- Unidad de Trastornos del Movimiento y Sueño, Hospital General Dr. Manuel Gea González, Mexico City, Mexico
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12
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Peterson BS, Kaur T, Sawardekar S, Colibazzi T, Hao X, Wexler BE, Bansal R. Aberrant hippocampus and amygdala morphology associated with cognitive deficits in schizophrenia. Front Cell Neurosci 2023; 17:1126577. [PMID: 36909281 PMCID: PMC9996667 DOI: 10.3389/fncel.2023.1126577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2022] [Accepted: 02/06/2023] [Indexed: 02/25/2023] Open
Abstract
Background Working memory deficits are thought to be a primary disturbance in schizophrenia. We aimed to identify differences in morphology of the hippocampus and amygdala in patients with schizophrenia compared with healthy controls (HCs), and in patients who were either neuropsychologically near normal (NPNN) or neuropsychologically impaired (NPI). Morphological disturbances in the same subfields of the hippocampus and amygdala, but of greater magnitude in those with NPI, would strengthen evidence for the centrality of these limbic regions and working memory deficits in the pathogenesis of schizophrenia. Methods We acquired anatomical MRIs in 69 patients with schizophrenia (18 NPNN, 46 NPI) and 63 age-matched HC participants. We compared groups in hippocampus and amygdala surface morphologies and correlated morphological measures with clinical symptoms and working memory scores. Results Schizophrenia was associated with inward deformations of the head and tail of the hippocampus, protrusion of the hippocampal body, and widespread inward deformations of the amygdala. In the same regions where we detected the effects of schizophrenia, morphological measures correlated positively with the severity of symptoms and inversely with working memory performance. Patients with NPI displayed a similar pattern of anatomical abnormality compared to patients with NPNN. Conclusion Our findings indicate that anatomical abnormalities of the hippocampus relate to working memory performance and clinical symptoms in persons with schizophrenia. Moreover, NPNN and NPI patients may lie on a continuum of severity, both in terms of working memory abilities and altered brain structure, with NPI patients being more severe than NPNN patients in both domains.
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Affiliation(s)
- Bradley S. Peterson
- Children’s Hospital Los Angeles, Department of Psychiatry at the Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- *Correspondence: Bradley S. Peterson,
| | - Tejal Kaur
- Department of Psychiatry, Columbia College of Physicians and Surgeons, New York, NY, United States
| | - Siddhant Sawardekar
- Children’s Hospital Los Angeles, Department of Psychiatry at the Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Tiziano Colibazzi
- Department of Psychiatry, Columbia College of Physicians and Surgeons, New York, NY, United States
| | - Xuejun Hao
- Department of Psychiatry, Columbia College of Physicians and Surgeons, New York, NY, United States
| | - Bruce E. Wexler
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States
| | - Ravi Bansal
- Children’s Hospital Los Angeles, Department of Psychiatry at the Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
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13
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Relationships among subclinical psychotic symptoms in young adults over time. Psychiatry Res 2022; 314:114617. [PMID: 35749858 DOI: 10.1016/j.psychres.2022.114617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 04/11/2022] [Accepted: 04/16/2022] [Indexed: 11/20/2022]
Abstract
BACKGROUND Subclinical psychotic symptoms are common in the general population and are often benign. However, those that become distressing or persistent may increase risk for the development of a psychotic disorder. Cognitive models have proposed that certain appraisals of hallucinatory experiences can lead to delusional beliefs, particularly if an individual is experiencing negative mood. However, the dynamic relationships among these symptoms are poorly understood. This study examined the longitudinal relationships among subclincal hallucinations, delusional ideation, and depression in a sample of young adults. METHODS 677 college students completed baseline questionnaires to assess: delusional ideation (Peters Delusions Inventory), hallucinations (Launay-Slade Hallucinations Scale-Extended), and depression (Beck Depression Inventory). These measures were repeated 7, 13, 19, and 25 months later. RESULTS Higher baseline severity of hallucinations was strongly predictive of severity of delusions across all future follow-up timepoints, specifically when baseline depression was high. However, the severity of hallucinations did not change over time, nor were they predicted by baseline delusional ideation. CONCLUSIONS These findings support the proposal that hallucinations frequently precede more severe delusional ideation, rather than the reverse sequence, particularly when depressive symptoms are present. Such longitudinal relationships provide clues to the underlying mechanisms of psychosis, highlighting one pathway for intervention.
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14
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Leighton E, Garrett M, Beltrani A, Min JY, Schilder V. Capgras Syndrome and Other Delusions of Misidentification: a Summary of the Psychological, Psychiatric, and Neurophysiological Literature on DMI. Curr Behav Neurosci Rep 2022. [DOI: 10.1007/s40473-022-00248-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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15
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A generative framework for the study of delusions. Schizophr Res 2022; 245:42-49. [PMID: 33648810 DOI: 10.1016/j.schres.2020.11.048] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 11/28/2020] [Accepted: 11/30/2020] [Indexed: 11/20/2022]
Abstract
Despite the ubiquity of delusional information processing in psychopathology and everyday life, formal characterizations of such inferences are lacking. In this article, we propose a generative framework that entails a computational mechanism which, when implemented in a virtual agent and given new information, generates belief updates (i.e., inferences about the hidden causes of the information) that resemble those seen in individuals with delusions. We introduce a particular form of Dirichlet process mixture model with a sampling-based Bayesian inference algorithm. This procedure, depending on the setting of a single parameter, preferentially generates highly precise (i.e. over-fitting) explanations, which are compartmentalized and thus can co-exist despite being inconsistent with each other. Especially in ambiguous situations, this can provide the seed for delusional ideation. Further, we show by simulation how the excessive generation of such over-precise explanations leads to new information being integrated in a way that does not lead to a revision of established beliefs. In all configurations, whether delusional or not, the inference generated by our algorithm corresponds to Bayesian inference. Furthermore, the algorithm is fully compatible with hierarchical predictive coding. By virtue of these properties, the proposed model provides a basis for the empirical study and a step toward the characterization of the aberrant inferential processes underlying delusions.
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16
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Rethinking delusions: A selective review of delusion research through a computational lens. Schizophr Res 2022; 245:23-41. [PMID: 33676820 PMCID: PMC8413395 DOI: 10.1016/j.schres.2021.01.023] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Revised: 01/27/2021] [Accepted: 01/29/2021] [Indexed: 02/06/2023]
Abstract
Delusions are rigid beliefs held with high certainty despite contradictory evidence. Notwithstanding decades of research, we still have a limited understanding of the computational and neurobiological alterations giving rise to delusions. In this review, we highlight a selection of recent work in computational psychiatry aimed at developing quantitative models of inference and its alterations, with the goal of providing an explanatory account for the form of delusional beliefs in psychosis. First, we assess and evaluate the experimental paradigms most often used to study inferential alterations in delusions. Based on our review of the literature and theoretical considerations, we contend that classic draws-to-decision paradigms are not well-suited to isolate inferential processes, further arguing that the commonly cited 'jumping-to-conclusion' bias may reflect neither delusion-specific nor inferential alterations. Second, we discuss several enhancements to standard paradigms that show promise in more effectively isolating inferential processes and delusion-related alterations therein. We further draw on our recent work to build an argument for a specific failure mode for delusions consisting of prior overweighting in high-level causal inferences about partially observable hidden states. Finally, we assess plausible neurobiological implementations for this candidate failure mode of delusional beliefs and outline promising future directions in this area.
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17
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Waltz JA. From Childhood Trauma to Delusions: It's Complicated. BIOLOGICAL PSYCHIATRY. COGNITIVE NEUROSCIENCE AND NEUROIMAGING 2022; 7:633-634. [PMID: 35809987 DOI: 10.1016/j.bpsc.2022.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Accepted: 04/25/2022] [Indexed: 06/15/2023]
Affiliation(s)
- James A Waltz
- Maryland Psychiatric Research Center and Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland.
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18
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Affiliation(s)
- Awais Aftab
- Department of Psychiatry, Case Western Reserve University, Cleveland, Ohio
| | - Dan J Stein
- South African Medical Research Council Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry, University of Cape Town, Cape Town, South Africa
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19
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González-Rodríguez A, Seeman MV. Differences between delusional disorder and schizophrenia: A mini narrative review. World J Psychiatry 2022; 12:683-692. [PMID: 35663297 PMCID: PMC9150033 DOI: 10.5498/wjp.v12.i5.683] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Revised: 03/23/2022] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
Psychotic syndromes are divided into affective and non-affective forms. Even among the non-affective forms, substantial differences exist. The aim of this relatively brief review is to synthesize what is known about the differences between two non-affective psychoses, schizophrenia and delusional disorder (DD), with respect to clinical, epidemiological, sociodemographic, and treatment response characteristics. A PubMed literature search revealed the following: in schizophrenia, hallucinations, negative symptoms and cognitive symptoms are prominent. They are rare in DD. Compared to schizophrenia patients, individuals with DD maintain relatively good function, and their delusions are believable; many are beliefs that are widely held in the general population. Treatments are generally similar in these two forms of psychosis, with the exception that antidepressants are used more frequently in DD and, for acute treatment, effective antipsychotic doses are lower in DD than in schizophrenia. It is with the hope that the contrasts between these two conditions will aid in the provision of safe and effective treatment for both that this review has been conducted.
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Affiliation(s)
- Alexandre González-Rodríguez
- Department of Mental Health, Mutua Terrassa University Hospital, University of Barcelona, Barcelona 08280, Spain
| | - Mary V Seeman
- Department of Psychiatry, University of Toronto, Toronto M5P 3L6, Ontario, Canada
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20
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Dai ZH, Xu X, Chen WQ, Nie LN, Liu Y, Sui N, Liang J. The role of hippocampus in memory reactivation: an implication for a therapeutic target against opioid use disorder. CURRENT ADDICTION REPORTS 2022; 9:67-79. [PMID: 35223369 PMCID: PMC8857535 DOI: 10.1007/s40429-022-00407-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/16/2022] [Indexed: 12/29/2022]
Abstract
Purpose of the review The abuse of opioids induces many terrible problems in human health and social stability. For opioid-dependent individuals, withdrawal memory can be reactivated by context, which is then associated with extremely unpleasant physical and emotional feelings during opioid withdrawal. The reactivation of withdrawal memory is considered one of the most important reasons for opioid relapse, and it also allows for memory modulation based on the reconsolidation phenomenon. However, studies exploring withdrawal memory modulation during the reconsolidation window are lacking. By summarizing the previous findings about the reactivation of negative emotional memories, we are going to suggest potential neural regions and systems for modulating opioid withdrawal memory. Recent findings Here, we first present the role of memory reactivation in its modification, discuss how the hippocampus participates in memory reactivation, and discuss the importance of noradrenergic signaling in the hippocampus for memory reactivation. Then, we review the engagement of other limbic regions receiving noradrenergic signaling in memory reactivation. We suggest that noradrenergic signaling targeting hippocampus neurons might play a potential role in strengthening the disruptive effect of withdrawal memory extinction by facilitating the degree of memory reactivation. Summary This review will contribute to a better understanding of the mechanisms underlying reactivation-dependent memory malleability and will provide new therapeutic avenues for treating opioid use disorders.
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Affiliation(s)
- Zhong-hua Dai
- CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
- Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
| | - Xing Xu
- CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
- Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
| | - Wei-qi Chen
- CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
- Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
- Sino-Danish College, University of Chinese Academy of Sciences, Beijing, China
| | - Li-na Nie
- CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
- Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
| | - Ying Liu
- CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
- Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
| | - Nan Sui
- CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
- Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
| | - Jing Liang
- CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
- Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
- Sino-Danish College, University of Chinese Academy of Sciences, Beijing, China
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21
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Millard SJ, Bearden CE, Karlsgodt KH, Sharpe MJ. The prediction-error hypothesis of schizophrenia: new data point to circuit-specific changes in dopamine activity. Neuropsychopharmacology 2022; 47:628-640. [PMID: 34588607 PMCID: PMC8782867 DOI: 10.1038/s41386-021-01188-y] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 08/23/2021] [Accepted: 09/07/2021] [Indexed: 02/07/2023]
Abstract
Schizophrenia is a severe psychiatric disorder affecting 21 million people worldwide. People with schizophrenia suffer from symptoms including psychosis and delusions, apathy, anhedonia, and cognitive deficits. Strikingly, schizophrenia is characterised by a learning paradox involving difficulties learning from rewarding events, whilst simultaneously 'overlearning' about irrelevant or neutral information. While dysfunction in dopaminergic signalling has long been linked to the pathophysiology of schizophrenia, a cohesive framework that accounts for this learning paradox remains elusive. Recently, there has been an explosion of new research investigating how dopamine contributes to reinforcement learning, which illustrates that midbrain dopamine contributes in complex ways to reinforcement learning, not previously envisioned. This new data brings new possibilities for how dopamine signalling contributes to the symptomatology of schizophrenia. Building on recent work, we present a new neural framework for how we might envision specific dopamine circuits contributing to this learning paradox in schizophrenia in the context of models of reinforcement learning. Further, we discuss avenues of preclinical research with the use of cutting-edge neuroscience techniques where aspects of this model may be tested. Ultimately, it is hoped that this review will spur to action more research utilising specific reinforcement learning paradigms in preclinical models of schizophrenia, to reconcile seemingly disparate symptomatology and develop more efficient therapeutics.
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Affiliation(s)
- Samuel J Millard
- Department of Psychology, University of California, Los Angeles, CA, 90095, USA.
| | - Carrie E Bearden
- Department of Psychology, University of California, Los Angeles, CA, 90095, USA
- Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, 90095, USA
| | - Katherine H Karlsgodt
- Department of Psychology, University of California, Los Angeles, CA, 90095, USA
- Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, 90095, USA
| | - Melissa J Sharpe
- Department of Psychology, University of California, Los Angeles, CA, 90095, USA.
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22
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Katthagen T, Fromm S, Wieland L, Schlagenhauf F. Models of Dynamic Belief Updating in Psychosis-A Review Across Different Computational Approaches. Front Psychiatry 2022; 13:814111. [PMID: 35492702 PMCID: PMC9039658 DOI: 10.3389/fpsyt.2022.814111] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 02/18/2022] [Indexed: 11/20/2022] Open
Abstract
To understand the dysfunctional mechanisms underlying maladaptive reasoning of psychosis, computational models of decision making have widely been applied over the past decade. Thereby, a particular focus has been on the degree to which beliefs are updated based on new evidence, expressed by the learning rate in computational models. Higher order beliefs about the stability of the environment can determine the attribution of meaningfulness to events that deviate from existing beliefs by interpreting these either as noise or as true systematic changes (volatility). Both, the inappropriate downplaying of important changes as noise (belief update too low) as well as the overly flexible adaptation to random events (belief update too high) were theoretically and empirically linked to symptoms of psychosis. Whereas models with fixed learning rates fail to adjust learning in reaction to dynamic changes, increasingly complex learning models have been adopted in samples with clinical and subclinical psychosis lately. These ranged from advanced reinforcement learning models, over fully Bayesian belief updating models to approximations of fully Bayesian models with hierarchical learning or change point detection algorithms. It remains difficult to draw comparisons across findings of learning alterations in psychosis modeled by different approaches e.g., the Hierarchical Gaussian Filter and change point detection. Therefore, this review aims to summarize and compare computational definitions and findings of dynamic belief updating without perceptual ambiguity in (sub)clinical psychosis across these different mathematical approaches. There was strong heterogeneity in tasks and samples. Overall, individuals with schizophrenia and delusion-proneness showed lower behavioral performance linked to failed differentiation between uninformative noise and environmental change. This was indicated by increased belief updating and an overestimation of volatility, which was associated with cognitive deficits. Correlational evidence for computational mechanisms and positive symptoms is still sparse and might diverge from the group finding of instable beliefs. Based on the reviewed studies, we highlight some aspects to be considered to advance the field with regard to task design, modeling approach, and inclusion of participants across the psychosis spectrum. Taken together, our review shows that computational psychiatry offers powerful tools to advance our mechanistic insights into the cognitive anatomy of psychotic experiences.
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Affiliation(s)
- Teresa Katthagen
- Department of Psychiatry and Neurosciences, CCM, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
| | - Sophie Fromm
- Department of Psychiatry and Neurosciences, CCM, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.,Einstein Center for Neurosciences, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.,Bernstein Center for Computational Neuroscience, Berlin, Germany
| | - Lara Wieland
- Department of Psychiatry and Neurosciences, CCM, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.,Einstein Center for Neurosciences, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.,Bernstein Center for Computational Neuroscience, Berlin, Germany
| | - Florian Schlagenhauf
- Department of Psychiatry and Neurosciences, CCM, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.,Einstein Center for Neurosciences, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.,Bernstein Center for Computational Neuroscience, Berlin, Germany.,NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
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23
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Louzolo A, Lebedev AV, Björnsdotter M, Acar K, Ahrends C, Kringelbach ML, Ingvar M, Olsson A, Petrovic P. Resistance to Extinction of Evaluative Fear Conditioning in Delusion Proneness. SCHIZOPHRENIA BULLETIN OPEN 2022; 3:sgac033. [PMID: 39144763 PMCID: PMC11205979 DOI: 10.1093/schizbullopen/sgac033] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 08/16/2024]
Abstract
Delusional beliefs consist of strong priors characterized by resistance to change even when evidence supporting another view is overwhelming. Such bias against disconfirmatory evidence (BADE) has been experimentally demonstrated in patients with psychosis as well as in delusion proneness. In this fMRI-study, we tested for similar resistance to change and associated brain processes in extinction of fear learning, involving a well-described mechanism dependent of evidence updating. A social fear conditioning paradigm was used in which four faces had either been coupled to an unconditioned aversive stimulus (CS+) or not (CS-). For two of the faces, instructions had been given about the fear contingencies (iCS+/iCS-) while for two other faces no such instructions had been given (niCS+/niCS-). Interaction analysis suggested that individuals who score high on delusion-proneness (hDP; n = 20) displayed less extinction of evaluative fear compared to those with low delusion proneness (lDP; n = 23; n = 19 in fMRI-analysis) for non-instructed faces (F = 5.469, P = .024). The resistance to extinction was supported by a difference in extinction related activity between the two groups in medial prefrontal cortex and its connectivity with amygdala, as well as in a cortical network supporting fear processing. For instructed faces no extinction was noted, but there was a larger evaluative fear (F = 5.048, P = 0.03) and an increased functional connectivity between lateral orbitofrontal cortex and fear processing regions for hDP than lDP. Our study links previous explored BADE-effects in delusion associated phenotypes to fear extinction, and suggest that effects of instructions on evaluative fear learning are more pronounced in delusion prone subjects.
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Affiliation(s)
- Anaïs Louzolo
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Alexander V Lebedev
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
- Center for Cognitive and Computational Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Malin Björnsdotter
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
- Center for Cognitive and Computational Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Kasim Acar
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Christine Ahrends
- Center for Music in the Brain, Department of Clinical Medicine, Aarhus University and The Royal Academy of MusicAarhus/Aalborg, Aarhus, Denmark
| | - Morten L Kringelbach
- Center for Music in the Brain, Department of Clinical Medicine, Aarhus University and The Royal Academy of MusicAarhus/Aalborg, Aarhus, Denmark
- Hedonia Research Group, Department of Psychiatry, University of Oxford, Oxford, UK
| | - Martin Ingvar
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Andreas Olsson
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
- Center for Cognitive and Computational Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Predrag Petrovic
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
- Center for Cognitive and Computational Neuroscience, Karolinska Institutet, Stockholm, Sweden
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24
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Guinjoan SM, Bär KJ, Camprodon JA. Cognitive effects of rapid-acting treatments for resistant depression: Just adverse, or contributing to clinical efficacy? J Psychiatr Res 2021; 140:512-521. [PMID: 34157590 PMCID: PMC8319118 DOI: 10.1016/j.jpsychires.2021.06.026] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 06/07/2021] [Accepted: 06/13/2021] [Indexed: 12/28/2022]
Abstract
Major Depressive Disorder is a major public health problem and has a high rate of treatment resistance. Fear conditioning has been proposed as a potential mechanism sustaining negative affect in mood disorders. With the aim of exploring cognitive effects of rapid-acting antidepressant treatments as a potential mechanism of action that can be targeted by neuromodulation, we performed a narrative review of the extant literature on effects of electroconvulsive therapy, ketamine or esketamine, and sleep deprivation on emotional/fear memory retrieval-reconsolidation. We explore interference with reconsolidation as a potential common pathway that explains in part the efficacy of rapid-acting antidepressant treatments with disparate mechanisms of action. We propose the testable hypothesis that fear learning circuits can be specifically targeted by neuromodulation to attempt rapid amelioration of depressive symptoms (especially repetitive negative thinking) while limiting unspecific, untoward cognitive side effects.
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Affiliation(s)
- Salvador M. Guinjoan
- Principal Investigator, Laureate Institute for Brain Research, Tulsa, Oklahoma, United States of America,Schools of Medicine and Psychology, University of Buenos Aires, CONICET, Argentina,Mailing Address: Salvador M. Guinjoan, Laureate Institute for Brain Research, 6655 South Yale Avenue, Tulsa, Oklahoma 74136-3326, United States of America,
| | - Karl-Jürgen Bär
- Chief, Departments of Psychosomatic Medicine and Gerontopsychiatry and Psychotherapy, University Hospital Jena, Jena, Germany
| | - Joan A. Camprodon
- Director, Division of Neuropsychiatry, Massachusetts General Hospital and Harvard Medical School
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25
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Abstract
Introduction: Delusions demand an explanation in terms of their neural, psychological, and sociological mechanisms. We must bridge these levels of explanation in order to understand and ultimately treat delusions. To this end, debates continue as to the number of contributing factors, how those factors interact, and their underlying computational mechanisms.Methods: One popular family of models suggests that two separate insults are necessary, a problem with perception and an independent problem with belief. In particular, new work proposes that the belief problem entails a bias against disconfirmatory evidence - yielding the characteristic fixity of delusions. Here, we evaluate that claim, as well as explanations of delusions more broadly.Results: We suggest that such a bias may not explain enough of the variance in belief updating in delusional participants, and, more fundamentally, it might rule out specific accounts of delusions, since, such a bias might prevent them from forming in the first place, under particular assumptions about cognitive architectures.Conclusion: We suggest conceptualising delusions as an evolving uncertainty driven negotiation between beliefs and evidence, in which initial formation is fuelled by unexpected uncertainty, but, once formed, the delusion engenders new expectations about uncertainty that tune down updating but also facilitate the elastic assimilation of contradictory evidence.
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Affiliation(s)
- Philip R Corlett
- Department of Psychiatry, School of Medicine, Yale University, New Haven, CT, USA
| | - Paul Fletcher
- Department of Psychiatry, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.,Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK.,Wellcome Trust MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK
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Möller TJ, Georgie YK, Schillaci G, Voss M, Hafner VV, Kaltwasser L. Computational models of the "active self" and its disturbances in schizophrenia. Conscious Cogn 2021; 93:103155. [PMID: 34130210 DOI: 10.1016/j.concog.2021.103155] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 05/14/2021] [Accepted: 05/20/2021] [Indexed: 11/16/2022]
Abstract
The notion that self-disorders are at the root of the emergence of schizophrenia rather than a symptom of the disease, is getting more traction in the cognitive sciences. This is in line with philosophical approaches that consider an enactive self, constituted through action and interaction with the environment. We thereby analyze different definitions of the self and evaluate various computational theories lending to these ideas. Bayesian and predictive processing are promising approaches for computational modeling of the "active self". We evaluate their implementation and challenges in computational psychiatry and cognitive developmental robotics. We describe how and why embodied robotic systems provide a valuable tool in psychiatry to assess, validate, and simulate mechanisms of self-disorders. Specifically, mechanisms involving sensorimotor learning, prediction, and self-other distinction, can be assessed with artificial agents. This link can provide essential insights to the formation of the self and new avenues in the treatment of psychiatric disorders.
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Affiliation(s)
- Tim Julian Möller
- Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany; Department of Psychiatry and Psychotherapy, Charité University Medicine, Berlin, Germany.
| | - Yasmin Kim Georgie
- Department of Computer Science, Humboldt-Universität zu Berlin, Germany.
| | - Guido Schillaci
- The BioRobotics Institute and Dept. of Excellence in Robotics & AI, Scuola Superiore Sant'Anna, Pisa, Italy.
| | - Martin Voss
- Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany; Department of Psychiatry and Psychotherapy, Charité University Medicine and St. Hedwig Hospital, Berlin, Germany.
| | | | - Laura Kaltwasser
- Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany; Department of Psychiatry and Psychotherapy, Charité University Medicine, Berlin, Germany.
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27
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Lemonde AC, Joober R, Malla A, Iyer SN, Lepage M, Boksa P, Shah JL. Delusional content at initial presentation to a catchment-based early intervention service for psychosis. Br J Psychiatry 2021; 218:217-223. [PMID: 32900414 DOI: 10.1192/bjp.2020.157] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
BACKGROUND During a psychotic episode, patients frequently suffer from severe maladaptive beliefs known as delusions. Despite the abundant literature investigating the simple presence or absence of these beliefs, there exists little detailed knowledge regarding their actual content and severity at the onset of illness. AIMS This study reports on delusions during the initiation of indicated treatment for first-episode psychosis (FEP). METHOD Data were systematically collected from a sample of 636 patients entering a catchment-based early intervention service for FEP. The average severity and frequency of each delusional theme at baseline was reported with the Scale for the Assessment of Positive Symptoms. Delusional severity (globally and per theme) was examined across a number of sociodemographic and clinical variables. RESULTS Delusions were present in the vast majority of individuals experiencing onset of FEP (94%), with persecutory (77.7%) being the most common theme. Persecutory delusions remained consistent in severity across diagnoses, but were more severe with older age at onset of FEP. No meaningful differences in delusional severity were observed across gender, affective versus non-affective psychosis, or presence/absence of substance use disorder. Globally, delusion severity was associated with anxiety, but not depression. Delusions commonly referred to as passivity experiences were related to hallucinatory experiences. CONCLUSIONS This community sample offers a rare clinical lens into the severity and content of delusions in FEP. Although delusional severity was consistent across certain sociodemographic and clinical variables, this was not always the case. Future research should now consider the course of delusion themes over time.
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Affiliation(s)
| | - Ridha Joober
- Department of Psychiatry, McGill University; and Program for Early Intervention and Prevention of Psychoses (PEPP-Montreal), Douglas Mental Health University Institute, Quebec, Canada
| | - Ashok Malla
- Department of Psychiatry and Department of Epidemiology and Biostatistics, McGill University; and Program for Early Intervention and Prevention of Psychoses (PEPP-Montreal), Douglas Mental Health University Institute, Quebec, Canada
| | - Srividya N Iyer
- Department of Psychiatry, McGill University; and Program for Early Intervention and Prevention of Psychoses (PEPP-Montreal), Douglas Mental Health University Institute, Quebec, Canada
| | - Martin Lepage
- Department of Psychiatry, McGill University; and Douglas Mental Health University Institute, Quebec, Canada
| | - Patricia Boksa
- Department of Psychiatry, McGill University; and Douglas Mental Health University Institute, Quebec, Canada
| | - Jai L Shah
- Department of Psychiatry, McGill University; and Program for Early Intervention and Prevention of Psychoses (PEPP-Montreal), Douglas Mental Health University Institute, Quebec, Canada
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28
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Chan SKW, Liu T, Wong AOY, Wong GHY, Hsiao J, Hui CLM, Chang WC, Lee EHM, Chen EYH. Self-referential gaze perception of patients with schizophrenia and its relationship with symptomatology and cognitive functions. Schizophr Res 2021; 228:288-294. [PMID: 33493777 DOI: 10.1016/j.schres.2020.12.034] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 09/19/2020] [Accepted: 12/26/2020] [Indexed: 11/30/2022]
Abstract
Self-referential gaze perception (SRGP)-the perception that others' gaze is towards oneself-is a core experience in patients with schizophrenia, and may be related to common delusional themes such as delusions of reference. Studies exploring SRGP bias in schizophrenia are limited and results have been inconsistent, particularly regarding its relationship with symptomatology and cognition. Seventy-five patients with schizophrenia-spectrum disorders (25 with high level of reference delusion, 25 with low reference delusion and 25 in clinical remission) and 25 matched healthy controls were compared in a gaze perception task to judge whether averted gaze with varied ambiguity was directed at them. All subjects were assessed with delusion and reference ideations and cognitive functions. Psychotic symptoms were assessed in patients. Gaze perception analysis adopted both behavioural and psychophysical approaches. Group differences and predictors of SRGP in ambiguous and unambiguous conditions were investigated. Both groups of symptomatic patients displayed higher ambiguous SRGP rate, and the group with high reference delusions showed more unambiguous SRGP bias. Cognitive functions were negatively associated with SRGP rate while positive and negative symptoms were positively associated. Cognitive function was the only significant predictor for ambiguous-SRGP rate. Patients with psychotic symptoms have hypermentalization of gaze perception as towards oneself, whereas patients with delusions of reference have more profound bias in gaze perception. General cognition is implicated in SRGP rate. Future studies could investigate interventions with targeted psychopathological profiles by improving non-social cognitive functions to test the hypothesis that cognitive functioning is related to SRGP bias and delusional beliefs.
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Affiliation(s)
- Sherry Kit Wa Chan
- Department of Psychiatry, The University of Hong Kong, Hong Kong SAR; The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR.
| | - Tianyin Liu
- Department of Social Work and Social Administration, The University of Hong Kong, Hong Kong SAR
| | | | - Gloria Hoi Yan Wong
- Department of Social Work and Social Administration, The University of Hong Kong, Hong Kong SAR
| | - Janet Hsiao
- The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR; Department of Psychology, HKU, Hong Kong SAR
| | | | - Wing Chung Chang
- Department of Psychiatry, The University of Hong Kong, Hong Kong SAR; The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR
| | - Edwin Ho Ming Lee
- Department of Psychiatry, The University of Hong Kong, Hong Kong SAR
| | - Eric Yu Hai Chen
- Department of Psychiatry, The University of Hong Kong, Hong Kong SAR; The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR
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29
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Lyndon S, Corlett P. Hallucinations in posttraumatic stress disorder: Insights from predictive coding. JOURNAL OF ABNORMAL PSYCHOLOGY 2020; 129:534-543. [PMID: 32437205 PMCID: PMC10658640 DOI: 10.1037/abn0000531] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2023]
Abstract
Although hallucinations are not one of the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) criteria for posttraumatic stress disorder (PTSD), they are increasingly documented in PTSD. They are noted in the absence of clear delusions, formal thought disorganization, disorganized speech, or behavior, ruling out a comorbid psychotic disorder like schizophrenia as a better explanation for these hallucinations. Hallucinations in both PTSD and schizophrenia share phenomenological features. We propose that hallucinations in PTSD, like those in schizophrenia, might be explained in terms of aberrant predictive coding, specifically the misapplication of strong prior beliefs that vitiate perceptual inference. This approach highlights the broader relationship between trauma and psychosis. Under predictive coding, the nervous system organizes past sensory data into an internal model of the world. Under stress, the brain prioritizes speed over accurate encoding. However, memories for traumatic experiences are typically strongly consolidated, to avoid similar experiences in future. In PTSD, this could lead to a world model comprised of inaccurate but overly precise prior beliefs, that can be triggered by stimuli tangentially related to the index trauma, resulting in hallucinations. Crucially, this evidence accumulation depends upon the relative precision of prior beliefs and sensory evidence (supplied in the form of prediction errors). Our basic argument is that stressful situations induce belief updating, in terms of precise prior beliefs, that are difficult to undo. These unduly precise, trauma-related beliefs then constitute perceptual hypotheses, memories, or narratives that bias subsequent experience. This prior bias may be so severe that sensory evidence is effectively ignored; that is, treated as very imprecise, in relation to prior beliefs. Such an account may lead to cognitive therapies for hallucinations aimed at strong prior beliefs, and the exciting prospect of combining such therapies with drugs that modulate neuroplasticity and enhance the adaptive consolidation of more appropriate priors. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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Affiliation(s)
- S. Lyndon
- Yale University, Department of Psychiatry, Connecticut Mental Health Center, 34 Park Street, New Haven, CT, USA, 06511
| | - P.R. Corlett
- Yale University, Department of Psychiatry, Connecticut Mental Health Center, 34 Park Street, New Haven, CT, USA, 06511
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30
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Gold JM, Corlett PR, Strauss GP, Schiffman J, Ellman LM, Walker EF, Powers AR, Woods SW, Waltz JA, Silverstein SM, Mittal VA. Enhancing Psychosis Risk Prediction Through Computational Cognitive Neuroscience. Schizophr Bull 2020; 46:1346-1352. [PMID: 32648913 PMCID: PMC7707066 DOI: 10.1093/schbul/sbaa091] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Research suggests that early identification and intervention with individuals at clinical high risk (CHR) for psychosis may be able to improve the course of illness. The first generation of studies suggested that the identification of CHR through the use of specialized interviews evaluating attenuated psychosis symptoms is a promising strategy for exploring mechanisms associated with illness progression, etiology, and identifying new treatment targets. The next generation of research on psychosis risk must address two major limitations: (1) interview methods have limited specificity, as recent estimates indicate that only 15%-30% of individuals identified as CHR convert to psychosis and (2) the expertise needed to make CHR diagnosis is only accessible in a handful of academic centers. Here, we introduce a new approach to CHR assessment that has the potential to increase accessibility and positive predictive value. Recent advances in clinical and computational cognitive neuroscience have generated new behavioral measures that assay the cognitive mechanisms and neural systems that underlie the positive, negative, and disorganization symptoms that are characteristic of psychotic disorders. We hypothesize that measures tied to symptom generation will lead to enhanced sensitivity and specificity relative to interview methods and the cognitive intermediate phenotype measures that have been studied to date that are typically indicators of trait vulnerability and, therefore, have a high false positive rate for conversion to psychosis. These new behavioral measures have the potential to be implemented on the internet and at minimal expense, thereby increasing accessibility of assessments.
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Affiliation(s)
- James M Gold
- Department of Psychiatry and Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD,To whom correspondence should be addressed; Maryland Psychiatric Research Center, PO Box 21247, Baltimore, MD 21228; tel: +1-410-402-7871, fax: +1-410-401-7198, e-mail:
| | - Philip R Corlett
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT
| | | | | | - Lauren M Ellman
- Department of Psychology, Temple University, Philadelphia, PA
| | | | - Albert R Powers
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT
| | - Scott W Woods
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT
| | - James A Waltz
- Department of Psychiatry and Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD
| | - Steven M Silverstein
- Departments of Psychiatry, Neuroscience, and Ophthalmology, University of Rochester Medical Center, Rochester, NY
| | - Vijay A Mittal
- Departments of Psychology, Psychiatry, Medical Social Sciences, Institutes for Policy Research (IPR) and Innovations in Developmental Sciences (DevSci), Evanston and Chicago, IL
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31
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The Bayesian Brain and Psychoanalytic Dimensions of Hyper-salience in Psychosis. Curr Behav Neurosci Rep 2020. [DOI: 10.1007/s40473-020-00211-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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32
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Connors MH, Halligan PW. Delusions and theories of belief. Conscious Cogn 2020; 81:102935. [DOI: 10.1016/j.concog.2020.102935] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2019] [Revised: 03/28/2020] [Accepted: 04/08/2020] [Indexed: 02/01/2023]
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33
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Cole DM, Diaconescu AO, Pfeiffer UJ, Brodersen KH, Mathys CD, Julkowski D, Ruhrmann S, Schilbach L, Tittgemeyer M, Vogeley K, Stephan KE. Atypical processing of uncertainty in individuals at risk for psychosis. NEUROIMAGE-CLINICAL 2020; 26:102239. [PMID: 32182575 PMCID: PMC7076146 DOI: 10.1016/j.nicl.2020.102239] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Revised: 02/24/2020] [Accepted: 03/06/2020] [Indexed: 12/28/2022]
Abstract
Humans at psychosis clinical high risk (CHR) over-estimate environmental volatility. Low-level prediction error (PE) signals evoke increased frontal activity in CHR. Volatility-related PEs are associated with reduced frontal activity in CHR. Frontal cortical activation to low-level PEs reflects impaired clinical functioning. Atypical PE learning signal representations may promote delusion formation in CHR. Current theories of psychosis highlight the role of abnormal learning signals, i.e., prediction errors (PEs) and uncertainty, in the formation of delusional beliefs. We employed computational analyses of behaviour and functional magnetic resonance imaging (fMRI) to examine whether such abnormalities are evident in clinical high risk (CHR) individuals. Non-medicated CHR individuals (n = 13) and control participants (n = 13) performed a probabilistic learning paradigm during fMRI data acquisition. We used a hierarchical Bayesian model to infer subject-specific computations from behaviour – with a focus on PEs and uncertainty (or its inverse, precision) at different levels, including environmental ‘volatility’ – and used these computational quantities for analyses of fMRI data. Computational modelling of CHR individuals’ behaviour indicated volatility estimates converged to significantly higher levels than in controls. Model-based fMRI demonstrated increased activity in prefrontal and insular regions of CHR individuals in response to precision-weighted low-level outcome PEs, while activations of prefrontal, orbitofrontal and anterior insula cortex by higher-level PEs (that serve to update volatility estimates) were reduced. Additionally, prefrontal cortical activity in response to outcome PEs in CHR was negatively associated with clinical measures of global functioning. Our results suggest a multi-faceted learning abnormality in CHR individuals under conditions of environmental uncertainty, comprising higher levels of volatility estimates combined with reduced cortical activation, and abnormally high activations in prefrontal and insular areas by precision-weighted outcome PEs. This atypical representation of high- and low-level learning signals might reflect a predisposition to delusion formation.
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Affiliation(s)
- David M Cole
- Translational Neuromodeling Unit (TNU), Institute for Biomedical Engineering, University of Zurich and Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland; Department of Psychiatry, Psychotherapy and Psychosomatics, University of Zurich, Psychiatric Hospital of the University of Zurich, Zurich, Switzerland.
| | - Andreea O Diaconescu
- Translational Neuromodeling Unit (TNU), Institute for Biomedical Engineering, University of Zurich and Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland; Department of Psychiatry (UPK), University of Basel, Basel, Switzerland; Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, Canada
| | - Ulrich J Pfeiffer
- Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany
| | - Kay H Brodersen
- Translational Neuromodeling Unit (TNU), Institute for Biomedical Engineering, University of Zurich and Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland
| | - Christoph D Mathys
- Translational Neuromodeling Unit (TNU), Institute for Biomedical Engineering, University of Zurich and Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland; Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste, Italy; Interacting Minds Centre, Aarhus University, Aarhus, Denmark
| | - Dominika Julkowski
- Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany
| | - Stephan Ruhrmann
- Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany
| | - Leonhard Schilbach
- Independent Max Planck Research Group for Social Neuroscience, Max Planck Institute of Psychiatry, Munich, Germany; Graduate School for Systemic Neuroscience, Munich, Germany; International Max Planck Research School for Translational Psychiatry, Munich, Germany; Ludwig-Maximilians-Universität München, Munich, Germany; Kliniken der Heinrich-Heine-Universität/LVR-Klinik Düsseldorf, Düsseldorf, Germany
| | - Marc Tittgemeyer
- Max Planck Institute for Metabolism Research, Cologne, Germany; Cologne Cluster of Excellence in Cellular Stress and Aging associated Disease (CECAD), Germany
| | - Kai Vogeley
- Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany; Institute for Neuroscience and Medicine - Cognitive Neuroscience (INM3), Research Center Juelich, Juelich, Germany
| | - Klaas E Stephan
- Translational Neuromodeling Unit (TNU), Institute for Biomedical Engineering, University of Zurich and Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland; Max Planck Institute for Metabolism Research, Cologne, Germany; Wellcome Centre for Human Neuroimaging, University College London, London, United Kingdom
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McCutcheon RA, Krystal JH, Howes OD. Dopamine and glutamate in schizophrenia: biology, symptoms and treatment. World Psychiatry 2020; 19:15-33. [PMID: 31922684 PMCID: PMC6953551 DOI: 10.1002/wps.20693] [Citation(s) in RCA: 353] [Impact Index Per Article: 70.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Glutamate and dopamine systems play distinct roles in terms of neuronal signalling, yet both have been proposed to contribute significantly to the pathophysiology of schizophrenia. In this paper we assess research that has implicated both systems in the aetiology of this disorder. We examine evidence from post-mortem, preclinical, pharmacological and in vivo neuroimaging studies. Pharmacological and preclinical studies implicate both systems, and in vivo imaging of the dopamine system has consistently identified elevated striatal dopamine synthesis and release capacity in schizophrenia. Imaging of the glutamate system and other aspects of research on the dopamine system have produced less consistent findings, potentially due to methodological limitations and the heterogeneity of the disorder. Converging evidence indicates that genetic and environmental risk factors for schizophrenia underlie disruption of glutamatergic and dopaminergic function. However, while genetic influences may directly underlie glutamatergic dysfunction, few genetic risk variants directly implicate the dopamine system, indicating that aberrant dopamine signalling is likely to be predominantly due to other factors. We discuss the neural circuits through which the two systems interact, and how their disruption may cause psychotic symptoms. We also discuss mechanisms through which existing treatments operate, and how recent research has highlighted opportunities for the development of novel pharmacological therapies. Finally, we consider outstanding questions for the field, including what remains unknown regarding the nature of glutamate and dopamine function in schizophrenia, and what needs to be achieved to make progress in developing new treatments.
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Affiliation(s)
- Robert A McCutcheon
- Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
- MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital, London, UK
- South London and Maudsley Foundation NHS Trust, Maudsley Hospital, London, UK
| | - John H Krystal
- Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
- VA National Center for PTSD, VA Connecticut Healthcare System, West Haven, CT, USA
| | - Oliver D Howes
- Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
- MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital, London, UK
- South London and Maudsley Foundation NHS Trust, Maudsley Hospital, London, UK
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35
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Dubovyk V, Manahan-Vaughan D. Distinct Time-Course of Alterations of Groups I and II Metabotropic Glutamate Receptor and GABAergic Receptor Expression Along the Dorsoventral Hippocampal Axis in an Animal Model of Psychosis. Front Behav Neurosci 2019; 13:98. [PMID: 31139061 PMCID: PMC6519509 DOI: 10.3389/fnbeh.2019.00098] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Accepted: 04/23/2019] [Indexed: 01/13/2023] Open
Abstract
Psychosis is a clinical state that encompasses a range of abnormal conditions, including distortions in sensory information processing and the resultant delusional thinking, emotional discordance and cognitive impairments. Upon developing this condition, the rate at which cognitive and behavioral deteriorations progress steadily increases suggesting an active contribution of the first psychotic event to the progression of structural and functional abnormalities and disease establishment in diagnosed patients. Changes in GABAergic and glutamatergic function, or expression, in the hippocampus have been proposed as a key factor in the pathophysiology of psychosis. However, little is known as to the time-point of onset of putative changes, to what extent they are progressive, and their relation to disease stabilization. Here, we characterized the expression and distribution patterns of groups I and II metabotropic glutamate (mGlu) receptors and GABA receptors 1 week and 3 months after systemic treatment with an N-methyl-D-aspartate receptor (NMDAR) antagonist (MK801) that is used to model a psychosis-like state in adult rats. We found an early alteration in the expression of mGlu1, mGlu2/3, and GABAB receptors across the hippocampal dorsoventral and transverse axes. This expanded to include an up-regulation of mGlu5 levels across the entire CA1 region and a reduction in GABAB expression, as well as GAD67-positive interneurons particularly in the dorsal hippocampus that appeared 3 months after treatment. Our findings indicate that a reduction of excitability may occur in the hippocampus soon after first-episode psychosis. This changes, over time, into increased excitability. These hippocampus-specific alterations are likely to contribute to the pathophysiology and stabilization of psychosis.
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Affiliation(s)
- Valentyna Dubovyk
- Department of Neurophysiology, Medical Faculty, Ruhr-University Bochum, Bochum, Germany.,International Graduate School of Neuroscience, Ruhr-University Bochum, Bochum, Germany
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Lancellotta E, Bortolotti L. Are clinical delusions adaptive? WILEY INTERDISCIPLINARY REVIEWS. COGNITIVE SCIENCE 2019; 10:e1502. [PMID: 31056862 PMCID: PMC6899558 DOI: 10.1002/wcs.1502] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/02/2018] [Revised: 04/06/2019] [Accepted: 04/08/2019] [Indexed: 12/31/2022]
Abstract
Delusions are symptoms of psychiatric disorders such as schizophrenia and dementia. By and large, delusions are characterized by their behavioral manifestations and defined as irrational beliefs that compromise good functioning. In this overview paper, we ask whether delusions can be adaptive notwithstanding their negative features. Can they be a response to a crisis rather than the source of the crisis? Can they be the beginning of a solution rather than the problem? Some of the psychological, psychiatric, and philosophical literature has recently suggested that they can. We consider different types of delusions and different ways in which they can be considered as adaptive: psychologically (e.g., by increasing wellbeing, purpose in life, intrapsychic coherence, or good functioning) and biologically (e.g., by enhancing genetic fitness). Although further research is needed to map the costs and benefits of adopting and maintaining delusional beliefs, a more nuanced picture of the role of delusions in people's lives has started to emerge. This article is categorized under:
Philosophy > Representation Philosophy > Knowledge and Belief Neuroscience > Cognition
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Affiliation(s)
- Eugenia Lancellotta
- Philosophy Department and Institute for Mental Health, University of Birmingham, Birmingham, UK
| | - Lisa Bortolotti
- Philosophy Department and Institute for Mental Health, University of Birmingham, Birmingham, UK
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Krawczyk MC, Millan J, Blake MG, Feld M, Boccia MM. Relevance of ERK1/2 Post-retrieval Participation on Memory Processes: Insights in Their Particular Role on Reconsolidation and Persistence of Memories. Front Mol Neurosci 2019; 12:95. [PMID: 31057366 PMCID: PMC6478671 DOI: 10.3389/fnmol.2019.00095] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Accepted: 03/29/2019] [Indexed: 12/12/2022] Open
Abstract
Back in 1968, Misanin and his group posited that reactivation of consolidated memories could support changes in that trace, similar to what might happen during the consolidation process. Not until 2000, when Nader et al. (2000) studied the behavioral effect of a protein synthesis inhibitor on retrieved memories, could this previous statement be taken under consideration once again; suggesting that consolidated memories can become labile after reactivation. The process of strengthening after memory labilization was named memory reconsolidation. In recent years, many studies pointed towards a critical participation of the extracellular signal-regulated kinase (ERK)/mitogen activated protein kinases (MAPKs) pathway in different memory processes (e.g., consolidation, extinction, reconsolidation, among others). In this review article, we will focus on how this system might be modulating the processes triggered after retrieval of well-consolidated memories in mice.
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Affiliation(s)
- Maria C Krawczyk
- Laboratorio de Neurofarmacología de los Procesos de Memoria, Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina
| | - Julieta Millan
- Laboratorio de Neurofarmacología de los Procesos de Memoria, Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina
| | - Mariano G Blake
- Instituto de Fisiología y Biofísica (IFIBIO UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina
| | - Mariana Feld
- CONICET-Universidad de Buenos Aires, Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), CABA, Argentina
| | - Mariano M Boccia
- Laboratorio de Neurofarmacología de los Procesos de Memoria, Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina
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38
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Abstract
The 2016 U.S. presidential election brought considerable attention to the phenomenon of "fake news": entirely fabricated and often partisan content that is presented as factual. Here we demonstrate one mechanism that contributes to the believability of fake news: fluency via prior exposure. Using actual fake-news headlines presented as they were seen on Facebook, we show that even a single exposure increases subsequent perceptions of accuracy, both within the same session and after a week. Moreover, this "illusory truth effect" for fake-news headlines occurs despite a low level of overall believability and even when the stories are labeled as contested by fact checkers or are inconsistent with the reader's political ideology. These results suggest that social media platforms help to incubate belief in blatantly false news stories and that tagging such stories as disputed is not an effective solution to this problem. It is interesting, however, that we also found that prior exposure does not impact entirely implausible statements (e.g., "The earth is a perfect square"). These observations indicate that although extreme implausibility is a boundary condition of the illusory truth effect, only a small degree of potential plausibility is sufficient for repetition to increase perceived accuracy. As a consequence, the scope and impact of repetition on beliefs is greater than has been previously assumed. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
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Affiliation(s)
- Gordon Pennycook
- Department of Psychology, Yale University, 1 Prospect Street, New Haven, CT 06511, USA
| | - Tyrone D. Cannon
- Department of Psychology, Yale University, 1 Prospect Street, New Haven, CT 06511, USA
| | - David G. Rand
- Department of Psychology, Yale University, 1 Prospect Street, New Haven, CT 06511, USA
- Department of Economics, Yale University, 1 Prospect Street, New Haven, CT 06511, USA
- School of Management, Yale University, 1 Prospect Street, New Haven, CT 06511, USA
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Sterzer P, Adams RA, Fletcher P, Frith C, Lawrie SM, Muckli L, Petrovic P, Uhlhaas P, Voss M, Corlett PR. The Predictive Coding Account of Psychosis. Biol Psychiatry 2018; 84:634-643. [PMID: 30007575 PMCID: PMC6169400 DOI: 10.1016/j.biopsych.2018.05.015] [Citation(s) in RCA: 434] [Impact Index Per Article: 62.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2017] [Revised: 05/14/2018] [Accepted: 05/15/2018] [Indexed: 01/12/2023]
Abstract
Fueled by developments in computational neuroscience, there has been increasing interest in the underlying neurocomputational mechanisms of psychosis. One successful approach involves predictive coding and Bayesian inference. Here, inferences regarding the current state of the world are made by combining prior beliefs with incoming sensory signals. Mismatches between prior beliefs and incoming signals constitute prediction errors that drive new learning. Psychosis has been suggested to result from a decreased precision in the encoding of prior beliefs relative to the sensory data, thereby garnering maladaptive inferences. Here, we review the current evidence for aberrant predictive coding and discuss challenges for this canonical predictive coding account of psychosis. For example, hallucinations and delusions may relate to distinct alterations in predictive coding, despite their common co-occurrence. More broadly, some studies implicate weakened prior beliefs in psychosis, and others find stronger priors. These challenges might be answered with a more nuanced view of predictive coding. Different priors may be specified for different sensory modalities and their integration, and deficits in each modality need not be uniform. Furthermore, hierarchical organization may be critical. Altered processes at lower levels of a hierarchy need not be linearly related to processes at higher levels (and vice versa). Finally, canonical theories do not highlight active inference-the process through which the effects of our actions on our sensations are anticipated and minimized. It is possible that conflicting findings might be reconciled by considering these complexities, portending a framework for psychosis more equipped to deal with its many manifestations.
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Affiliation(s)
- Philipp Sterzer
- Department of Psychiatry, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Rick A Adams
- Division of Psychiatry, University College London, London, United Kingdom
| | - Paul Fletcher
- Department of Psychiatry, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Wellcome-MRC Behavioral and Clinical Neuroscience Institute, Cambridge and Peterborough Foundation Trust, Cambridge, United Kingdom
| | - Chris Frith
- Wellcome Trust Centre for Neuroimaging, University College London, London, United Kingdom
| | - Stephen M Lawrie
- Center for Clinical and Brain Sciences, Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh, United Kingdom
| | - Lars Muckli
- Centre for Cognitive Neuroimaging, Institute of Neuroscience & Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
| | - Predrag Petrovic
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Peter Uhlhaas
- Centre for Cognitive Neuroimaging, Institute of Neuroscience & Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
| | - Martin Voss
- Department of Psychiatry and Psychotherapy, Charité University Medicine and St. Hedwig Hospital, Berlin Center for Advanced Neuroimaging, Humboldt University Berlin, Berlin, Germany
| | - Philip R Corlett
- Department of Psychiatry, Yale University, New Haven, Connecticut.
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40
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Dubovyk V, Manahan-Vaughan D. Time-Dependent Alterations in the Expression of NMDA Receptor Subunits along the Dorsoventral Hippocampal Axis in an Animal Model of Nascent Psychosis. ACS Chem Neurosci 2018; 9:2241-2251. [PMID: 29634239 DOI: 10.1021/acschemneuro.8b00017] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Psychosis is a mental condition that is characterized by hallucinations, delusions, disordered thought, as well as socio-emotional and cognitive impairments. Once developed, it tends to progress into a chronic psychotic illness. Here, the duration of untreated psychosis plays a crucial role: the earlier the treatment begins, relative to the first episode of the disease, the better the patient's functional prognosis. To what extent the success of early interventions relate to progressive changes at the neurotransmitter receptor level is as yet unclear. In fact, very little is known as to how molecular changes develop, transform, and become established following the first psychotic event. One neurotransmitter receptor for which a specific role in psychosis has been discussed is the N-methyl-d-aspartate receptor (NMDAR). This receptor is especially important for information encoding in the hippocampus. The hippocampus is one of the loci of functional change in psychosis, to which a role in the pathophysiology of psychosis has been ascribed. Here, we examined whether changes in NMDAR subunit expression occur along the dorsoventral axis of the hippocampus 1 week and 3 months after systemic treatment with an NMDAR antagonist (MK801) that initiates a psychosis-like state in adult rats. We found early (1 week) upregulation of the GluN2B levels in the dorso-intermediate hippocampus and late (3 month) downregulation of GluN2A expression across the entire CA1 region. The ventral hippocampus did not exhibit subunit expression changes. These data suggest that a differing vulnerability of the hippocampal longitudinal axis may occur in response to MK801-treatment and provide a time-resolved view of the putative development of pathological changes of NMDAR subunit expression in the hippocampus that initiate with an emulated first episode and progress through to the chronic stabilization of a psychosis-like state in rodents.
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Abstract
Ketamine, principally an antagonist of N-methyl-ᴅ-aspartate receptors, induces schizophrenia-like symptoms in adult humans, warranting its use in the investigation of psychosis-related phenotypes in animal models. Genomic studies further implicate N-methyl-ᴅ-aspartate receptor-mediated processes in schizophrenia pathology, together with more broadly-defined synaptic plasticity and associative learning processes. Strong pathophysiological links have been demonstrated between fear learning and psychiatric disorders such as schizophrenia. To further investigate the impact of ketamine on associative fear learning, we studied the effects of pre- and post-training ketamine on the consolidation and extinction of contextual fear memory in rats. Administration of 25 mg/kg ketamine prior to fear conditioning did not affect consolidation when potentially confounding effects of state dependency were controlled for. Pre-training ketamine (25 mg/kg) impaired the extinction of the conditioned fear response, which was mirrored with the use of a lower dose (8 mg/kg). Post-training ketamine (25 mg/kg) had no effect on the consolidation or extinction of conditioned fear. These observations implicate processes relating to the extinction of contextual fear memory in the manifestation of ketamine-induced phenotypes, and are consistent with existing hypotheses surrounding abnormal associative learning in schizophrenia.
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Affiliation(s)
- Nicholas E Clifton
- Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK
| | - Kerrie L Thomas
- Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK
- School of Biosciences, Cardiff University, Cardiff, UK
| | - Jeremy Hall
- Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK
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42
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Adams RA. Bayesian Inference, Predictive Coding, and Computational Models of Psychosis. COMPUTATIONAL PSYCHIATRY 2018. [DOI: 10.1016/b978-0-12-809825-7.00007-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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43
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Parlikar R, Dinakaran D, Bose A, Rao NP, Venkatasubramanian G. Neural Basis of Delusions in Schizophrenia: Translational Implications for Therapeutic Neuromodulation. J Indian Inst Sci 2017. [DOI: 10.1007/s41745-017-0058-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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44
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Fernández RS, Pedreira ME, Boccia MM. Does reconsolidation occur in natural settings? Memory reconsolidation and anxiety disorders. Clin Psychol Rev 2017; 57:45-58. [DOI: 10.1016/j.cpr.2017.08.004] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Revised: 07/28/2017] [Accepted: 08/07/2017] [Indexed: 12/11/2022]
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45
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Comprehensive review: Computational modelling of schizophrenia. Neurosci Biobehav Rev 2017; 83:631-646. [PMID: 28867653 DOI: 10.1016/j.neubiorev.2017.08.022] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Revised: 07/08/2017] [Accepted: 08/30/2017] [Indexed: 12/21/2022]
Abstract
Computational modelling has been used to address: (1) the variety of symptoms observed in schizophrenia using abstract models of behavior (e.g. Bayesian models - top-down descriptive models of psychopathology); (2) the causes of these symptoms using biologically realistic models involving abnormal neuromodulation and/or receptor imbalance (e.g. connectionist and neural networks - bottom-up realistic models of neural processes). These different levels of analysis have been used to answer different questions (i.e. understanding behavioral vs. neurobiological anomalies) about the nature of the disorder. As such, these computational studies have mostly supported diverging hypotheses of schizophrenia's pathophysiology, resulting in a literature that is not always expanding coherently. Some of these hypotheses are however ripe for revision using novel empirical evidence. Here we present a review that first synthesizes the literature of computational modelling for schizophrenia and psychotic symptoms into categories supporting the dopamine, glutamate, GABA, dysconnection and Bayesian inference hypotheses respectively. Secondly, we compare model predictions against the accumulated empirical evidence and finally we identify specific hypotheses that have been left relatively under-investigated.
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46
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A conditioning model of delusion. Neurosci Biobehav Rev 2017; 80:223-239. [PMID: 28601666 DOI: 10.1016/j.neubiorev.2017.05.024] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2016] [Revised: 05/14/2017] [Accepted: 05/29/2017] [Indexed: 11/22/2022]
Abstract
"Delusions" are beliefs that are false and persistent. It is suggested here that these characteristics can emerge from interplays between two fundamental learning processes: (1) the allocation of attentional resources among stimuli; and (2) the effects of feedback on learning. The former of these has been operationalized in the learned irrelevance and latent inhibition paradigms; the latter in studies of the effects of persistence-training. Normally, the attentional process functions to constrain persistence-training effects so that only valid associations acquire persistence. But when persistence-training is less influenced in this way, its mechanisms can interact with a noisy environment to gradually insulate maladaptive associations from disconfirming feedback. When unchecked, these dynamics likely lead to a systematic distortion of beliefs that can become increasingly persistent regardless of their validity. Delusions are therefore predicted to tend to arise whenever the balance of (1) is weakened in favour of (2), whether by experimental manipulation, trait-related factors, cultural causes or evolutionary history. Existing evidence is consistent with the model and further implications are discussed.
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47
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Vyazovskiy VV, Walton ME, Peirson SN, Bannerman DM. Sleep homeostasis, habits and habituation. Curr Opin Neurobiol 2017; 44:202-211. [PMID: 28575718 DOI: 10.1016/j.conb.2017.05.002] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Revised: 04/06/2017] [Accepted: 05/01/2017] [Indexed: 02/08/2023]
Abstract
The importance of sleep for behavioural performance during waking is long-established, but the underlying reasons and mechanisms remain elusive. Waking and sleep are associated with changes in the levels of GluA1 AMPAR subunit in synaptic membranes, while studies using genetically-modified mice have identified an important role for GluA1-dependent synaptic plasticity in a non-associative form of memory that underlies short-term habituation to recently experienced stimuli. Here we posit that sleep may play a role in dishabituation, which restores attentional capacity and maximises the readiness of the animal for learning and goal-directed behaviour during subsequent wakefulness. Furthermore we suggest that sleep disturbance may fundamentally change the nature of behaviour, making it more model-free and habitual as a result of reduced attentional capacity.
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Affiliation(s)
- Vladyslav V Vyazovskiy
- Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford, OX1 3PT, United Kingdom; Sleep and Circadian Neuroscience Institute, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, United Kingdom.
| | - Mark E Walton
- Department of Experimental Psychology, University of Oxford,South Parks Road, Oxford OX1 3UD, United Kingdom
| | - Stuart N Peirson
- Sleep and Circadian Neuroscience Institute, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, United Kingdom
| | - David M Bannerman
- Sleep and Circadian Neuroscience Institute, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, United Kingdom; Department of Experimental Psychology, University of Oxford,South Parks Road, Oxford OX1 3UD, United Kingdom
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48
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Neural coding of prior expectations in hierarchical intention inference. Sci Rep 2017; 7:1278. [PMID: 28455527 PMCID: PMC5430911 DOI: 10.1038/s41598-017-01414-y] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2016] [Accepted: 03/28/2017] [Indexed: 11/22/2022] Open
Abstract
The ability to infer other people’s intentions is crucial for successful human social interactions. Such inference relies on an adaptive interplay of sensory evidence and prior expectations. Crucially, this interplay would also depend on the type of intention inferred, i.e., on how abstract the intention is. However, what neural mechanisms adjust the interplay of prior and sensory evidence to the abstractness of the intention remains conjecture. We addressed this question in two separate fMRI experiments, which exploited action scenes depicting different types of intentions (Superordinate vs. Basic; Social vs. Non-social), and manipulated both prior and sensory evidence. We found that participants increasingly relied on priors as sensory evidence became scarcer. Activity in the medial prefrontal cortex (mPFC) reflected this interplay between the two sources of information. Moreover, the more abstract the intention to infer (Superordinate > Basic, Social > Non-Social), the greater the modulation of backward connectivity between the mPFC and the temporo-parietal junction (TPJ), resulting in an increased influence of priors over the intention inference. These results suggest a critical role for the fronto-parietal network in adjusting the relative weight of prior and sensory evidence during hierarchical intention inference.
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49
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Feeney EJ, Groman SM, Taylor JR, Corlett PR. Explaining Delusions: Reducing Uncertainty Through Basic and Computational Neuroscience. Schizophr Bull 2017; 43:263-272. [PMID: 28177090 PMCID: PMC5605246 DOI: 10.1093/schbul/sbw194] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Delusions, the fixed false beliefs characteristic of psychotic illness, have long defied understanding despite their response to pharmacological treatments (e.g., D2 receptor antagonists). However, it can be challenging to discern what makes beliefs delusional compared with other unusual or erroneous beliefs. We suggest mapping the putative biology to clinical phenomenology with a cognitive psychology of belief, culminating in a teleological approach to beliefs and brain function supported by animal and computational models. We argue that organisms strive to minimize uncertainty about their future states by forming and maintaining a set of beliefs (about the organism and the world) that are robust, but flexible. If uncertainty is generated endogenously, beliefs begin to depart from consensual reality and can manifest into delusions. Central to this scheme is the notion that formal associative learning theory can provide an explanation for the development and persistence of delusions. Beliefs, in animals and humans, may be associations between representations (e.g., of cause and effect) that are formed by minimizing uncertainty via new learning and attentional allocation. Animal research has equipped us with a deep mechanistic basis of these processes, which is now being applied to delusions. This work offers the exciting possibility of completing revolutions of translation, from the bedside to the bench and back again. The more we learn about animal beliefs, the more we may be able to apply to human beliefs and their aberrations, enabling a deeper mechanistic understanding.
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Affiliation(s)
- Erin J Feeney
- Department of Psychiatry, Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University, Park Street, New Haven, CT, USA
- Interdepartmental Neuroscience Program, Yale University, New Haven, CT, USA
| | - Stephanie M Groman
- Department of Psychiatry, Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University, Park Street, New Haven, CT, USA
| | - Jane R Taylor
- Department of Psychiatry, Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University, Park Street, New Haven, CT, USA
| | - Philip R Corlett
- Department of Psychiatry, Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University, Park Street, New Haven, CT, USA
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50
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Clifton NE, Pocklington AJ, Scholz B, Rees E, Walters JTR, Kirov G, O'Donovan MC, Owen MJ, Wilkinson LS, Thomas KL, Hall J. Schizophrenia copy number variants and associative learning. Mol Psychiatry 2017; 22:178-182. [PMID: 27956746 PMCID: PMC5285462 DOI: 10.1038/mp.2016.227] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2016] [Revised: 09/13/2016] [Accepted: 10/11/2016] [Indexed: 12/21/2022]
Abstract
Large-scale genomic studies have made major progress in identifying genetic risk variants for schizophrenia. A key finding from these studies is that there is an increased burden of genomic copy number variants (CNVs) in schizophrenia cases compared with controls. The mechanism through which these CNVs confer risk for the symptoms of schizophrenia, however, remains unclear. One possibility is that schizophrenia risk CNVs impact basic associative learning processes, abnormalities of which have long been associated with the disorder. To investigate whether genes in schizophrenia CNVs impact on specific phases of associative learning we combined human genetics with experimental gene expression studies in animals. In a sample of 11 917 schizophrenia cases and 16 416 controls, we investigated whether CNVs from patients with schizophrenia are enriched for genes expressed during the consolidation, retrieval or extinction of associative memories. We show that CNVs from cases are enriched for genes expressed during fear extinction in the hippocampus, but not genes expressed following consolidation or retrieval. These results suggest that CNVs act to impair inhibitory learning in schizophrenia, potentially contributing to the development of core symptoms of the disorder.
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Affiliation(s)
- N E Clifton
- Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK
| | - A J Pocklington
- Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK
- MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK
| | - B Scholz
- Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK
| | - E Rees
- MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK
| | - J T R Walters
- MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK
| | - G Kirov
- MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK
| | - M C O'Donovan
- Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK
- MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK
| | - M J Owen
- Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK
- MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK
| | - L S Wilkinson
- Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK
- MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK
- School of Psychology, Cardiff University, Cardiff, UK
| | - K L Thomas
- Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK
- School of Biosciences, Cardiff University, Cardiff, UK
| | - J Hall
- Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK
- MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK
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