Increased 5‐HT2A receptors in the temporal cortex of parkinsonian patients with visual hallucinations
Abstract
Well‐formed visual hallucinations (VH) are common in patients with Parkinson's disease (PD). The pathophysiology of VH in PD is unknown but may involve structures mediating visual processing such as the inferior temporal cortex. Serotonergic type 2A (5‐HT 2A) receptors have been linked to many psychiatric disorders, including psychosis. We hypothesized that enhanced 5‐HT 2A receptor levels may be involved in VH in PD. Autoradiographic binding using [3 H]‐ketanserin and spiperone, to define 5‐HT 2A receptors, was performed in 6 PD patients with VH, 6 PD patients without VH, and 5 healthy, age‐matched controls. The cerebral regions studied included the orbitofrontal cortex, inferolateral temporal cortex, motor cortex, striatum, and substantia nigra. There was a significant (45.6%) increase in the levels of [3 H]‐ketanserin binding in the inferolateral temporal cortex of PD patients with VH when compared with PD patients without VH (54.3 ± 5.2 fmol/mg vs. 37.3 ± 4.3 fmol/mg, P = 0.039). Additionally, there was a significant increase in the levels of 5‐HT 2A receptors in the motor cortex of all PD patients taken as a group when compared with controls (57.8 ± 5.7 fmol/mg vs. 41.2 ± 2.6 fmol/mg, P = 0.0297). These results suggest that enhanced 5‐HT 2A‐mediated neurotransmission in the inferolateral temporal cortex, a critical structure in visual processing, might be associated with the development of VH in PD. Our results provide new insights into the pathophysiology of VH in PD and provide an anatomical basis to explain why compounds with 5‐HT 2A antagonist activity are effective at alleviating this debilitating complication. © 2010 Movement Disorder Society
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The 5-HT2A receptor may be facilitating cortical disinhibition, consistent with previous proposals and studies showing 5-HT2A antagonists reducing psychosis-like symptoms.
“This finding may suggest that this receptor may be facilitating cortical disinhibition, consistent with previous proposals42,43 and studies showing 5-HT2A antagonists reducing psychosis-like symptoms20,42.”
From Deviations in effective connectivity explain different hallucination subtypes in Parkinson's disease psychosis (2026) · cites this paper as [42]
Exploratory analyses using PET receptor atlases revealed a positive correlation between cortical 5-HT2A receptor distribution and abnormal MMN source activity in PD-VH, consistent with the known role of serotonin in cortical disinhibition and psychosis.
“exploratory analyses using PET receptor atlases revealed a positive correlation between cortical 5-HT2A receptor distribution and abnormal MMN source activity in PD-VH, consistent with the known role of serotonin in cortical disinhibition53 and psychosis42,43”
From Deviations in effective connectivity explain different hallucination subtypes in Parkinson's disease psychosis (2026) · cites this paper as [42]
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- Authors
- Huot, P., Johnston, T. H., Darr, T., Hazrati, L., Visanji, N. P., Pires, D., Brotchie, J. M., & Fox, S. H.
- Affiliations
- University Health Network (CA)
- University of Toronto (CA)
- ORCID
- Venue
- Movement Disorders
- Publisher
- Wiley
- Published
- 2010-07-23
- Volume
- 25
- Issue
- 10
- Pages
- 1399-1408
- ISSN
- 0885-3185 (ISSN-L)
- 1531-8257
- OpenAlex
- W2086590261
- Cited by
- 153
- References
- 58
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 8 · 2023: 9 · 2022: 12 · 2021: 13 · 2020: 13 · 2019: 7 · 2018: 11 · 2017: 11 · 2016: 10 · 2015: 3 · 2014: 10 · 2013: 12 · 2012: 5
- FWCI
- 4.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Movement Disorders (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Dean's New Staff Award (SHF)
- Cure Parkinson's Trust
- Krembil Foundation (JMB)
- Edmond J. Safra Philanthropic Foundation
- Parkinson Society Canada
- United Kingdom Parkinson's Disease Society Tissue Bank at Imperial College
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Hallucinations in medical conditions
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- Parkinson's disease, visual hallucinations, 5-HT2A receptor, serotonin receptors, motor cortex, ketanserin binding, spiperone binding, receptor autoradiography, visual processing
- MeSH terms
- Aged, Aged, 80 and over, Analysis of Variance, Autoradiography, Female, Hallucinations, Humans, Ketanserin, Male, Middle Aged, Postmortem Changes, Protein Binding, Serotonin Antagonists, Temporal Lobe, Tritium, Parkinsonian Disorders, Receptor, Serotonin, 5-HT2A
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