Am J Psychiatry
January 1, 2003
Shitij Kapur
2,813 citations
A framework is proposed in which psychosis in schizophrenia arises from a dysregulated, dopamine-driven process of aberrant salience. Normally, dopamine mediates the attribution of salience—the process by which stimuli and thoughts become noticeable and guide behavior. In schizophrenia, this system becomes dysfunctional, causing patients to experience heightened or inappropriate salience for ordinary events and internal thoughts. This aberrant salience leads to the formation of delusions as cognitive explanations for these strange experiences, and hallucinations as direct perceptual experiences of salience. The framework integrates biological, phenomenological, and pharmacological evidence, explaining how antipsychotics work by dampening salience, and how this model can guide future research and treatment.
Schizophr Res
November 1, 2005
Shitij Kapur, Romina Mizrahi, Ming Li
510 citations
Psychosis may arise from the brain incorrectly assigning novelty and importance to ordinary objects and associations, a process linked to dopamine's role in reward prediction and motivational salience. Antipsychotics block dopamine receptors, reducing this aberrant salience and creating a state of detachment from symptoms rather than eradicating them. Contrary to the idea of a delayed onset, improvement is evident within the first few days. The framework accounts for existing data and questions assumptions about antipsychotic action, including their effects in animal models, where they dampen both aberrant and normal motivational salience.
Journal of Psychopharmacology
October 5, 2012
Amir Englund, Paul D. Morrison, Judith Nottage et al.
463 citations
Pre-treatment with 600 mg of cannabidiol (CBD) reduced the likelihood of clinically significant psychotic symptoms and paranoia caused by intravenous delta-9-tetrahydrocannabinol (THC, 1.5 mg) in healthy volunteers. Participants who received CBD before THC had lower scores on the State Social Paranoia Scale and smaller declines in episodic memory compared with those who received placebo before THC. The odds of experiencing a clinically significant increase in positive psychotic symptoms were about 78% lower in the CBD group. These results support the view that cannabis products high in THC and low in CBD pose greater mental health risks.
Schizophrenia Research
May 1, 2015
T. Winton-Brown, V. Kumari, F. Windler et al.
Sensorimotor gating—measured by how a quieter sound modifies the eye-blink startle reflex to a loud noise—is altered in people with psychosis, their relatives, and those at high clinical risk. Cannabis use also alters gating, though less strongly, and is a known risk factor for psychosis in susceptible individuals. This study tested prepulse inhibition (PPI) and prepulse facilitation (PPF) in participants with an At Risk Mental State (ARMS) for psychosis and matched controls, some of whom had recently used cannabis (confirmed by urine drug screening). ARMS participants showed reduced PPF and PPI compared to controls; the PPI reduction was driven by an interaction with cannabis use, where recent use reduced PPI only in ARMS participants.