Increased 5‐HT2A receptors in the temporal cortex of parkinsonian patients with visual hallucinations
Identifieur interne : 002063 ( Main/Merge ); précédent : 002062; suivant : 002064Increased 5‐HT2A receptors in the temporal cortex of parkinsonian patients with visual hallucinations
Auteurs : Philippe Huot [Canada] ; Tom H. Johnston [Canada] ; Tayyeba Darr [Canada] ; Lili-Naz Hazrati [Canada] ; Naomi P. Visanji [Canada] ; Donna Pires [Canada] ; Jonathan M. Brotchie [Canada] ; Susan H. Fox [Canada]Source :
- Movement Disorders [ 0885-3185 ] ; 2010-07-30.
English descriptors
- KwdEn :
- 5‐HT2A receptors, Aged, Aged, 80 and over, Analysis of Variance, Autoradiography (methods), Female, Hallucinations (etiology), Humans, Ketanserin (pharmacokinetics), Male, Middle Aged, Parkinson's disease, Parkinsonian Disorders (complications), Parkinsonian Disorders (pathology), Postmortem Changes, Protein Binding (drug effects), Receptor, Serotonin, 5-HT2A (metabolism), Serotonin Antagonists (pharmacokinetics), Temporal Lobe (metabolism), Tritium (pharmacokinetics), autoradiography, serotonin, visual hallucinations.
- MESH :
- chemical , metabolism : Receptor, Serotonin, 5-HT2A.
- chemical , pharmacokinetics : Ketanserin, Serotonin Antagonists, Tritium.
- complications : Parkinsonian Disorders.
- drug effects : Protein Binding.
- etiology : Hallucinations.
- metabolism : Temporal Lobe.
- methods : Autoradiography.
- pathology : Parkinsonian Disorders.
- Aged, Aged, 80 and over, Analysis of Variance, Female, Humans, Male, Middle Aged, Postmortem Changes.
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‐HT2A) receptors have been linked to many psychiatric disorders, including psychosis. We hypothesized that enhanced 5‐HT2A receptor levels may be involved in VH in PD. Autoradiographic binding using [3H]‐ketanserin and spiperone, to define 5‐HT2A 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 [3H]‐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‐HT2A 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‐HT2A‐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‐HT2A antagonist activity are effective at alleviating this debilitating complication. © 2010 Movement Disorder Society
Url:
DOI: 10.1002/mds.23083
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<front><div type="abstract" xml:lang="en">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‐HT2A) receptors have been linked to many psychiatric disorders, including psychosis. We hypothesized that enhanced 5‐HT2A receptor levels may be involved in VH in PD. Autoradiographic binding using [3H]‐ketanserin and spiperone, to define 5‐HT2A 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 [3H]‐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‐HT2A 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‐HT2A‐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‐HT2A antagonist activity are effective at alleviating this debilitating complication. © 2010 Movement Disorder Society</div>
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<front><div type="abstract" xml:lang="en">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‐HT2A) receptors have been linked to many psychiatric disorders, including psychosis. We hypothesized that enhanced 5‐HT2A receptor levels may be involved in VH in PD. Autoradiographic binding using [3H]‐ketanserin and spiperone, to define 5‐HT2A 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 [3H]‐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‐HT2A 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‐HT2A‐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‐HT2A antagonist activity are effective at alleviating this debilitating complication. © 2010 Movement Disorder Society</div>
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<PubMed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Increased 5-HT2A receptors in the temporal cortex of parkinsonian patients with visual hallucinations.</title>
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<author><name sortKey="Johnston, Tom H" sort="Johnston, Tom H" uniqKey="Johnston T" first="Tom H" last="Johnston">Tom H. Johnston</name>
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<author><name sortKey="Darr, Tayyeba" sort="Darr, Tayyeba" uniqKey="Darr T" first="Tayyeba" last="Darr">Tayyeba Darr</name>
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<author><name sortKey="Hazrati, Lili Naz" sort="Hazrati, Lili Naz" uniqKey="Hazrati L" first="Lili-Naz" last="Hazrati">Lili-Naz Hazrati</name>
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<author><name sortKey="Visanji, Naomi P" sort="Visanji, Naomi P" uniqKey="Visanji N" first="Naomi P" last="Visanji">Naomi P. Visanji</name>
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<author><name sortKey="Pires, Donna" sort="Pires, Donna" uniqKey="Pires D" first="Donna" last="Pires">Donna Pires</name>
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<author><name sortKey="Brotchie, Jonathan M" sort="Brotchie, Jonathan M" uniqKey="Brotchie J" first="Jonathan M" last="Brotchie">Jonathan M. Brotchie</name>
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<author><name sortKey="Fox, Susan H" sort="Fox, Susan H" uniqKey="Fox S" first="Susan H" last="Fox">Susan H. Fox</name>
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<author><name sortKey="Darr, Tayyeba" sort="Darr, Tayyeba" uniqKey="Darr T" first="Tayyeba" last="Darr">Tayyeba Darr</name>
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<author><name sortKey="Hazrati, Lili Naz" sort="Hazrati, Lili Naz" uniqKey="Hazrati L" first="Lili-Naz" last="Hazrati">Lili-Naz Hazrati</name>
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<author><name sortKey="Pires, Donna" sort="Pires, Donna" uniqKey="Pires D" first="Donna" last="Pires">Donna Pires</name>
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<author><name sortKey="Brotchie, Jonathan M" sort="Brotchie, Jonathan M" uniqKey="Brotchie J" first="Jonathan M" last="Brotchie">Jonathan M. Brotchie</name>
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<series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title>
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<term>Female</term>
<term>Hallucinations (etiology)</term>
<term>Humans</term>
<term>Ketanserin (pharmacokinetics)</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Parkinsonian Disorders (complications)</term>
<term>Parkinsonian Disorders (pathology)</term>
<term>Postmortem Changes</term>
<term>Protein Binding (drug effects)</term>
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<term>Serotonin Antagonists (pharmacokinetics)</term>
<term>Temporal Lobe (metabolism)</term>
<term>Tritium (pharmacokinetics)</term>
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<term>Serotonin Antagonists</term>
<term>Tritium</term>
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<term>Aged, 80 and over</term>
<term>Analysis of Variance</term>
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<front><div type="abstract" xml:lang="en">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.</div>
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