Serotonin 5-HT<sub>2</sub> Receptors in Schizophrenia: A PET Study Using [<sup>18</sup>F]Setoperone in Neuroleptic-Naive Patients and Normal Subjects

Lewis, Roy Querejazu; Kapur, Shitij; Jones, Carl J.; DaSilva, Jean N.; Brown, Gregory M.; Wilson, Alan A.; Houle, Sylvain; Zipursky, Robert B.

doi:10.1176/ajp.156.1.72

Cited by 100 publications

(54 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…neither with regions-of-interest (ROI) based nor with a voxel-based analyses (Trichard et al, 1998;Lewis et al, 1999;Okubo et al, 2000;Verhoeff et al, 2000). However, both tracers suffer from a relatively low affinity for 5-HT 2A receptors and, thus, they have an insufficient signal-to-noise ratio in subcortical areas (Erritzoe et al, 2008).…”

Section: Included Cases Ofmentioning

confidence: 99%

Serotonin and Schizophrenia

Quednow

Geyer

Halberstadt

2010

Handbook of Behavioral Neuroscience

View full text Add to dashboard Cite

Although the serotonin hypothesis of schizophrenia is one of the oldest neurochemical hypotheses on the pathogenesis of this disease, it is still highly topical. The concept of how the serotonin system is involved in the origin and progress of schizophrenia has considerably changed over the past decades. Therefore, the present work will give an overview about the development and the current directions of the serotonin hypothesis of schizophrenia. In this regard, we will discuss the phenomenology of hallucinogenic drug action, model psychosis and translational research, post-mortem studies on receptors and transporters, imaging studies, antipsychotic drug action, neuroendocrine challenge studies, platelet and cerebrospinal fluid data, genetic association studies, developmental aspects, and the cross-talk between the glutamate and the serotonin system. In sum, there are several lines of evidence suggesting that the serotonin system plays a major role in the pathogenesis of at least a subpopulation of schizophrenia patients. Further studies are needed to better characterize patients whose psychotic symptoms are suspected to have a serotonergic origin. Serotonin and Schizophrenia AbstractAlthough the serotonin hypothesis of schizophrenia is one of the oldest neurochemical hypotheses on the pathogenesis of this disease, it is still highly topical. The concept of how the serotonin system is involved in the origin and progress of schizophrenia has considerably changed over the past decades.Therefore, the present work will give an overview about the development and the current directions of the serotonin hypothesis of schizophrenia. In this regard, we will discuss the phenomenology of hallucinogenic drug action, model psychosis and translational research, post-mortem studies on receptors and transporters, imaging studies, antipsychotic drug action, neuroendocrine challenge studies, platelet and cerebrospinal fluid data, genetic association studies, developmental aspects, and the cross-talk between the glutamate and the serotonin system. In sum, there are several lines of evidence suggesting that the serotonin system plays a major role in the pathogenesis of at least a subpopulation of schizophrenia patients. Further studies are needed to better characterize patients whose psychotic symptoms are suspected to have a serotonergic origin.3

show abstract

Section: Included Cases Ofmentioning

confidence: 99%

Serotonin and Schizophrenia

Quednow

Geyer

Halberstadt

2010

Handbook of Behavioral Neuroscience

View full text Add to dashboard Cite

show abstract

“…Three positron emission tomography (PET) studies showed no difference in 5-HT 2A/C receptor density between schizophrenic patients and controls (Lewis et al, 1999;Okubo et al, 2000;Trichard et al, 1998). Only one study revealed a decreased 5-HT 2A binding potential in the frontal cortex of six neuroleptic-naive schizophrenic subjects when compared to healthy controls (Ngan et al, 2000).…”

Section: Introductionmentioning

confidence: 98%

Cortical and Subcortical 5-HT2A Receptor Binding in Neuroleptic-Naive First-Episode Schizophrenic Patients

Erritzoe

Rasmussen

Kristiansen

et al. 2008

Neuropsychopharmacol

View full text Add to dashboard Cite

The serotonin 5-HT 2A receptor is suspected to be involved in a number of psychiatric disorders, including schizophrenia. In particular, atypical antipsychotics have antagonistic effects on the 5-HT 2A receptors, supporting a specific role of the 5-HT 2A receptor in the pathophysiology of this disease. The aim of this study is to investigate cortical and subcortical 5-HT 2A binding in neuroleptic-naive schizophrenic patients. Fifteen neuroleptic-naive patients diagnosed with schizophrenia (age 27.5 ± 4.5 years), 11 men and 4 women, and 15 healthy control subjects matched for age (28.5 ± 5.7 years) and gender underwent a 40 min positron emission tomography (PET) study using the 5-HT 2A antagonist, [18 F]altanserin, as a radioligand. PET images were co-registered to 3 T magnetic resonance images (MRIs) for each individual subject, and ROIs were applied automatically onto the individual MRIs and PET images. The cerebellum was used as a reference region. The binding potential of specific tracer binding (BP p ) was used as the outcome measure. No significant difference was seen in cortical receptor distribution between patients and controls. An increase in 5-HT 2A receptor binding in the caudate nucleus was detected in the group of schizophrenic patients (0.7 ± 0.1) when compared to the healthy controls (0.5 ± 0.3) (p ¼ 0.02). Our results confirm other in vivo findings of no difference in cortical 5-HT 2A receptor binding between first-episode antipsychotic-naive schizophrenic patients and age-and gender-matched healthy control subjects. However, a preliminary finding of increased 5-HT 2A binding in the caudate nucleus requires further investigation to explore the relation of subcortical and cortical 5-HT 2A receptor binding.

show abstract

“…The relationship between genetic and epigenetic association is graphically represented in Figure 2. The idea of epigenetic dysregulation of HTR2A in SCZ is consistent with the decreased amounts of HTR2A mRNA (Burnet et al 1996) and serotonin receptor type 2 density (B max ) (Lewis et al 1999) in post-mortem brains of SCZ patients compared to controls.…”

Section: Epigenetic Interpretation Of Htr2a Studies With Sczmentioning

confidence: 64%

“…In this article, we further develop the epigenetic theory and re-analyze a number of experimental findings in psychiatric genetics that suggest a series of candidate genes and chromosomal loci that may become the targets for epigenetic studies. distributed throughout the central nervous system and that the hallucinogenic drug LSD demonstrates high affinity for serotonin receptors (reviewed in Lewis et al 1999). To our knowledge, association of HTR2A with SCZ was first detected in a Japanese sample when a higher frequency of C allele of the 102T/C polymorphism was documented (Inayama et al 1996).…”

mentioning

confidence: 99%

“…In HTR2A expression studies, post-mortem brains showed that amounts of HTR2A mRNA were roughly 50% lower in a number of cortical regions in SCZ patients compared to controls (Burnet et al 1996). In addition, a number of studies (although not all) detected decreased density of serotonin receptors (B max ) but no changes in receptor affinity (K d ) in the brains of SCZ patients compared to controls (reviewed in Lewis et al 1999). Changes in B max but not K d suggest that serotonergic dysfunction in SCZ is more likely to represent regulatory problems at the HTR2A rather than a structural mutation in the protein coding region…”

mentioning

confidence: 99%

See 1 more Smart Citation

The Genes for Major Psychosis Aberrant Sequence or Regulation?

Petronis

2000

Neuropsychopharmacology

View full text Add to dashboard Cite

Serotonin 5-HT₂ Receptors in Schizophrenia: A PET Study Using [¹⁸F]Setoperone in Neuroleptic-Naive Patients and Normal Subjects

Cited by 100 publications

References 49 publications

Serotonin and Schizophrenia

Serotonin and Schizophrenia

Cortical and Subcortical 5-HT2A Receptor Binding in Neuroleptic-Naive First-Episode Schizophrenic Patients

The Genes for Major Psychosis Aberrant Sequence or Regulation?

Contact Info

Product

Resources

About

Serotonin 5-HT2 Receptors in Schizophrenia: A PET Study Using [18F]Setoperone in Neuroleptic-Naive Patients and Normal Subjects

Cited by 100 publications

References 49 publications

Serotonin and Schizophrenia

Serotonin and Schizophrenia

Cortical and Subcortical 5-HT2A Receptor Binding in Neuroleptic-Naive First-Episode Schizophrenic Patients

The Genes for Major Psychosis Aberrant Sequence or Regulation?

Contact Info

Product

Resources

About

Serotonin 5-HT₂ Receptors in Schizophrenia: A PET Study Using [¹⁸F]Setoperone in Neuroleptic-Naive Patients and Normal Subjects