From dopamine to salience to psychosis-linking biology, pharmacology and phenomenology of psychosis

Shitij Kapur, Romina Mizrahi, Ming Li

Research output: Contribution to journalArticle

323 Citations (Scopus)

Abstract

How does an excess in a neurochemical lead someone to being paranoid about the intentions of their neighbour? And why does blocking a dopamine receptor improve this symptom? In this article we present a heuristic framework which attempts to link the biology, phenomenology and pharmacology of psychosis. Focussing on dopamine's role in reward prediction and motivational salience we propose that psychosis arises from an aberrant assignment of novelty and salience to objects and associations. Antipsychotics block dopamine receptors and decrease dopamine transmission, which leads to the attenuation of aberrant novelty and salience. This 'salience' framework accounts for existing data and questions several current assumptions about the speed of onset phenomenological effects of antipsychotics and their behavioral effects in animal models. We review new data to show that in contrast to the prevailing idea of a "delayed onset" of antipsychotic action, the improvement is evident in the first few days. Antipsychotics do not eradicate symptoms, but create a state of "detachment" from them. And the actions of antipsychotics in the conditioned avoidance response model, one of the best established animal models for identifying antipsychotic action, are consistent with the idea that they dampen aberrant as well as normal motivational salience. The article discusses the caveats, limitations as well as the clinical implications of the salience framework.

Original languageEnglish (US)
Pages (from-to)59-68
Number of pages10
JournalSchizophrenia Research
Volume79
Issue number1
DOIs
StatePublished - Nov 1 2005

Fingerprint

Psychotic Disorders
Antipsychotic Agents
Dopamine
Pharmacology
Dopamine Receptors
Animal Models
Reward

Keywords

  • Antipsychotics
  • Dopamine
  • Motivation
  • Psychosis
  • Salience

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

From dopamine to salience to psychosis-linking biology, pharmacology and phenomenology of psychosis. / Kapur, Shitij; Mizrahi, Romina; Li, Ming.

In: Schizophrenia Research, Vol. 79, No. 1, 01.11.2005, p. 59-68.

Research output: Contribution to journalArticle

@article{8e56b59b34e8406ea41d3420eb211378,
title = "From dopamine to salience to psychosis-linking biology, pharmacology and phenomenology of psychosis",
abstract = "How does an excess in a neurochemical lead someone to being paranoid about the intentions of their neighbour? And why does blocking a dopamine receptor improve this symptom? In this article we present a heuristic framework which attempts to link the biology, phenomenology and pharmacology of psychosis. Focussing on dopamine's role in reward prediction and motivational salience we propose that psychosis arises from an aberrant assignment of novelty and salience to objects and associations. Antipsychotics block dopamine receptors and decrease dopamine transmission, which leads to the attenuation of aberrant novelty and salience. This 'salience' framework accounts for existing data and questions several current assumptions about the speed of onset phenomenological effects of antipsychotics and their behavioral effects in animal models. We review new data to show that in contrast to the prevailing idea of a {"}delayed onset{"} of antipsychotic action, the improvement is evident in the first few days. Antipsychotics do not eradicate symptoms, but create a state of {"}detachment{"} from them. And the actions of antipsychotics in the conditioned avoidance response model, one of the best established animal models for identifying antipsychotic action, are consistent with the idea that they dampen aberrant as well as normal motivational salience. The article discusses the caveats, limitations as well as the clinical implications of the salience framework.",
keywords = "Antipsychotics, Dopamine, Motivation, Psychosis, Salience",
author = "Shitij Kapur and Romina Mizrahi and Ming Li",
year = "2005",
month = "11",
day = "1",
doi = "10.1016/j.schres.2005.01.003",
language = "English (US)",
volume = "79",
pages = "59--68",
journal = "Schizophrenia Research",
issn = "0920-9964",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - From dopamine to salience to psychosis-linking biology, pharmacology and phenomenology of psychosis

AU - Kapur, Shitij

AU - Mizrahi, Romina

AU - Li, Ming

PY - 2005/11/1

Y1 - 2005/11/1

N2 - How does an excess in a neurochemical lead someone to being paranoid about the intentions of their neighbour? And why does blocking a dopamine receptor improve this symptom? In this article we present a heuristic framework which attempts to link the biology, phenomenology and pharmacology of psychosis. Focussing on dopamine's role in reward prediction and motivational salience we propose that psychosis arises from an aberrant assignment of novelty and salience to objects and associations. Antipsychotics block dopamine receptors and decrease dopamine transmission, which leads to the attenuation of aberrant novelty and salience. This 'salience' framework accounts for existing data and questions several current assumptions about the speed of onset phenomenological effects of antipsychotics and their behavioral effects in animal models. We review new data to show that in contrast to the prevailing idea of a "delayed onset" of antipsychotic action, the improvement is evident in the first few days. Antipsychotics do not eradicate symptoms, but create a state of "detachment" from them. And the actions of antipsychotics in the conditioned avoidance response model, one of the best established animal models for identifying antipsychotic action, are consistent with the idea that they dampen aberrant as well as normal motivational salience. The article discusses the caveats, limitations as well as the clinical implications of the salience framework.

AB - How does an excess in a neurochemical lead someone to being paranoid about the intentions of their neighbour? And why does blocking a dopamine receptor improve this symptom? In this article we present a heuristic framework which attempts to link the biology, phenomenology and pharmacology of psychosis. Focussing on dopamine's role in reward prediction and motivational salience we propose that psychosis arises from an aberrant assignment of novelty and salience to objects and associations. Antipsychotics block dopamine receptors and decrease dopamine transmission, which leads to the attenuation of aberrant novelty and salience. This 'salience' framework accounts for existing data and questions several current assumptions about the speed of onset phenomenological effects of antipsychotics and their behavioral effects in animal models. We review new data to show that in contrast to the prevailing idea of a "delayed onset" of antipsychotic action, the improvement is evident in the first few days. Antipsychotics do not eradicate symptoms, but create a state of "detachment" from them. And the actions of antipsychotics in the conditioned avoidance response model, one of the best established animal models for identifying antipsychotic action, are consistent with the idea that they dampen aberrant as well as normal motivational salience. The article discusses the caveats, limitations as well as the clinical implications of the salience framework.

KW - Antipsychotics

KW - Dopamine

KW - Motivation

KW - Psychosis

KW - Salience

UR - http://www.scopus.com/inward/record.url?scp=25444483073&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=25444483073&partnerID=8YFLogxK

U2 - 10.1016/j.schres.2005.01.003

DO - 10.1016/j.schres.2005.01.003

M3 - Article

C2 - 16005191

AN - SCOPUS:25444483073

VL - 79

SP - 59

EP - 68

JO - Schizophrenia Research

JF - Schizophrenia Research

SN - 0920-9964

IS - 1

ER -