What is the pathophysiology of delusions?

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Last updated: March 11, 2025View editorial policy

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From the Guidelines

Delusions arise from complex neurobiological abnormalities affecting multiple brain regions and neurotransmitter systems, primarily involving dysfunction in dopaminergic pathways, particularly hyperactivity in the mesolimbic pathway and hypoactivity in the mesocortical pathway, as noted in the most recent study 1. The pathophysiology of delusions is multifaceted, involving:

  • Dysfunction in dopaminergic pathways, leading to aberrant salience attribution, where neutral stimuli are incorrectly assigned emotional significance 1
  • Structural and functional abnormalities in the prefrontal cortex, temporal lobe, and limbic structures, contributing to impaired reality testing and cognitive processing 1
  • Glutamate dysfunction, particularly NMDA receptor hypofunction, interacting with dopamine systems to further disrupt neural signaling 1
  • Genetic factors predisposing individuals to these neurochemical imbalances, while environmental stressors can trigger or exacerbate delusion formation 1
  • Neuroinflammatory processes and disrupted neural connectivity patterns also playing important roles 1 The most recent study 1 highlights the importance of understanding the underlying pathophysiology of delusions, which is crucial for developing effective treatment strategies. Key points to consider:
  • Delusions are a cardinal feature of psychotic symptomatology, often presenting with hallucinations, disorganized speech or thought, and disorganized or abnormal motor behavior 1
  • The economic impact of delirium, a condition often associated with delusions, is profound, with total costs estimated at $38 to $152 billion each year in the United States 1
  • Treatment of delusions typically targets the underlying mechanisms, using antipsychotic medications that block dopamine D2 receptors, with second-generation antipsychotics like risperidone or olanzapine often prescribed at individualized doses 1

From the Research

Pathophysiology of Delusions

The pathophysiology of delusions is a complex and multifaceted phenomenon that has been studied extensively in various psychiatric and neurological disorders.

  • Delusions are marked by fixed beliefs that are incongruent with reality and can present transdiagnostically in disorders such as schizophrenia, bipolar disorder, Alzheimer's disease, and Parkinson's disease 2.
  • Studies have found that delusions are associated with gray matter reductions in various brain regions, including the dorsolateral prefrontal cortex, left claustrum, hippocampus, insula, amygdala, thalamus, superior temporal gyrus, and middle frontal gyrus 2.
  • The current dopaminergic hypothesis of psychosis suggests that delusions may arise from dysregulated dopamine release from ascending midbrain pathways and reasoning bias 3.
  • Other theories propose that delusions may be related to cognitive biases and abnormalities in the belief formation network 2, 4.

Neural Correlates of Delusions

  • Neuroimaging studies have found that delusions are associated with structural and functional abnormalities in various brain regions, including the prefrontal cortex, temporal lobe, and basal ganglia 2, 5.
  • These abnormalities may contribute to the development and maintenance of delusions, and may also be related to other symptoms of psychiatric and neurological disorders 2, 5.
  • Further research is needed to fully understand the neural correlates of delusions and to develop effective treatments for these symptoms 2, 3.

Theoretical Models of Delusions

  • Various theoretical models have been proposed to explain the development and maintenance of delusions, including the dopaminergic hypothesis, cognitive bias models, and neuroanatomical models 4, 3.
  • These models suggest that delusions may arise from a combination of genetic, environmental, and neurobiological factors, and may be influenced by cognitive, emotional, and motivational processes 4, 3.
  • Further research is needed to test and refine these models, and to develop a more comprehensive understanding of the pathophysiology of delusions 2, 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

The emerging biology of delusions.

Psychological medicine, 2011

Research

Neuroanatomy and neurophysiology in schizophrenia.

Neuroscience research, 2002

Research

Understanding delusions.

Industrial psychiatry journal, 2009

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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