Paranoia as a deficit in non-social belief updating

  1. Erin J Reed
  2. Stefan Uddenberg
  3. Praveen Suthaharan
  4. Christoph D Mathys
  5. Jane R Taylor
  6. Stephanie Mary Groman
  7. Philip R Corlett  Is a corresponding author
  1. Yale University, United States
  2. Princeton University, United States
  3. Scuola Internazionale Superiore di Studi Avanzati (SISSA), Italy

Abstract

Paranoia is the belief that harm is intended by others. It may arise from selective pressures to infer and avoid social threats, particularly in ambiguous or changing circumstances. We propose that uncertainty may be sufficient to elicit learning differences in paranoid individuals, without social threat. We used reversal learning behavior and computational modeling to estimate belief updating across individuals with and without mental illness, online participants, and rats chronically exposed to methamphetamine, an elicitor of paranoia in humans. Paranoia is associated with a stronger prior on volatility, accompanied by elevated sensitivity to perceived changes in the task environment. Methamphetamine exposure in rats recapitulates this impaired uncertainty-driven belief updating and rigid anticipation of a volatile environment. Our work provides evidence of fundamental, domain-general learning differences in paranoid individuals. This paradigm enables further assessment of the interplay between uncertainty and belief-updating across individuals and species.

Data availability

Data are available on ModelDB83 (http://modeldb.yale.edu/258631) with accession code p2c8q74m. Figures 2-10 have associated raw data available. Code for the HGF toolbox v5.3.1 is freely available at https://translationalneuromodeling.github.io/tapas/.

Article and author information

Author details

  1. Erin J Reed

    Psychiatry, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Stefan Uddenberg

    Neuroscience Institute, Princeton University, New Jersey, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Praveen Suthaharan

    Psychiatry, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Christoph D Mathys

    Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste, Italy
    Competing interests
    The authors declare that no competing interests exist.
  5. Jane R Taylor

    Psychiatry, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Stephanie Mary Groman

    Psychiatry, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5231-0612
  7. Philip R Corlett

    Psychiatry, Yale University, New Haven, United States
    For correspondence
    philip.corlett@yale.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5368-1992

Funding

NIMH (R01MH12887)

  • Philip R Corlett

NIMH (R21MH120799-01)

  • Stephanie Mary Groman
  • Philip R Corlett

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) at Yale University

Human subjects: Experiments were conducted at Yale University and the Connecticut Mental Health Center (New Haven, CT) in strict accordance with Yale University's Human Investigation Committee and Institutional Animal Care and Use Committee. Informed consent was provided by all research participants (Yale HIC# 2000022111: Beliefs and Personality Traits)

Reviewing Editor

  1. Geoffrey Schoenbaum, National Institute on Drug Abuse, National Institutes of Health, United States

Version history

  1. Received: February 24, 2020
  2. Accepted: May 22, 2020
  3. Accepted Manuscript published: May 26, 2020 (version 1)
  4. Accepted Manuscript updated: May 27, 2020 (version 2)
  5. Version of Record published: June 30, 2020 (version 3)
  6. Version of Record updated: July 7, 2020 (version 4)

Copyright

© 2020, Reed et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 6,832
    Page views
  • 711
    Downloads
  • 47
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Erin J Reed
  2. Stefan Uddenberg
  3. Praveen Suthaharan
  4. Christoph D Mathys
  5. Jane R Taylor
  6. Stephanie Mary Groman
  7. Philip R Corlett
(2020)
Paranoia as a deficit in non-social belief updating
eLife 9:e56345.
https://doi.org/10.7554/eLife.56345

Further reading

    1. Neuroscience
    Stijn A Nuiten, Jan Willem de Gee ... Simon van Gaal
    Research Article

    Perceptual decisions about sensory input are influenced by fluctuations in ongoing neural activity, most prominently driven by attention and neuromodulator systems. It is currently unknown if neuromodulator activity and attention differentially modulate perceptual decision-making and/or whether neuromodulatory systems in fact control attentional processes. To investigate the effects of two distinct neuromodulatory systems and spatial attention on perceptual decisions, we pharmacologically elevated cholinergic (through donepezil) and catecholaminergic (through atomoxetine) levels in humans performing a visuo-spatial attention task, while we measured electroencephalography (EEG). Both attention and catecholaminergic enhancement improved decision-making at the behavioral and algorithmic level, as reflected in increased perceptual sensitivity and the modulation of the drift rate parameter derived from drift diffusion modeling. Univariate analyses of EEG data time-locked to the attentional cue, the target stimulus, and the motor response further revealed that attention and catecholaminergic enhancement both modulated pre-stimulus cortical excitability, cue- and stimulus-evoked sensory activity, as well as parietal evidence accumulation signals. Interestingly, we observed both similar, unique, and interactive effects of attention and catecholaminergic neuromodulation on these behavioral, algorithmic, and neural markers of the decision-making process. Thereby, this study reveals an intricate relationship between attentional and catecholaminergic systems and advances our understanding about how these systems jointly shape various stages of perceptual decision-making.

    1. Neuroscience
    Manfred G Kitzbichler, Daniel Martins ... Neil A Harrison
    Research Article Updated

    The relationship between obesity and human brain structure is incompletely understood. Using diffusion-weighted MRI from ∼30,000 UK Biobank participants, we test the hypothesis that obesity (waist-to-hip ratio, WHR) is associated with regional differences in two micro-structural MRI metrics: isotropic volume fraction (ISOVF), an index of free water, and intra-cellular volume fraction (ICVF), an index of neurite density. We observed significant associations with obesity in two coupled but distinct brain systems: a prefrontal/temporal/striatal system associated with ISOVF and a medial temporal/occipital/striatal system associated with ICVF. The ISOVF~WHR system colocated with expression of genes enriched for innate immune functions, decreased glial density, and high mu opioid (MOR) and other neurotransmitter receptor density. Conversely, the ICVF~WHR system co-located with expression of genes enriched for G-protein coupled receptors and decreased density of MOR and other receptors. To test whether these distinct brain phenotypes might differ in terms of their underlying shared genetics or relationship to maps of the inflammatory marker C-reactive Protein (CRP), we estimated the genetic correlations between WHR and ISOVF (rg = 0.026, P = 0.36) and ICVF (rg = 0.112, P < 9×10−4) as well as comparing correlations between WHR maps and equivalent CRP maps for ISOVF and ICVF (P<0.05). These correlational results are consistent with a two-way mechanistic model whereby genetically determined differences in neurite density in the medial temporal system may contribute to obesity, whereas water content in the prefrontal system could reflect a consequence of obesity mediated by innate immune system activation.