Background
Serotonergic abnormalities are hypothesized to contribute to obsessive-compulsive
disorder (OCD). This study used positron emission tomography with the radioligand
[11C]MDL 100907 to examine whether the distribution of serotonin 2A (5-HT2A) receptors is altered in OCD.
Methods
Nineteen OCD subjects, free of psychiatric medications and depression, and 19 matched
healthy subjects underwent positron emission tomography scans following injection
of [11C]MDL 100907. Total distribution volumes were derived by kinetic analysis using the
arterial input function. Two measures of 5-HT2A availability were computed: the ratio at equilibrium of specifically bound radiotracer
either to nondisplaceable radiotracer in tissue (BPND) or to unmetabolized tracer in arterial plasma (BPp). Groups were compared using a region of interest (ROI) analysis and voxelwise analysis
of spatially normalized parametric maps. ROIs included cortical (orbitofrontal, dorsolateral prefrontal, medial prefrontal,
anterior cingulate, temporal, parietal, occipital, and insular cortex) and limbic
(entorhinal cortex, parahippocampal gyrus, and medial temporal lobe) regions.
Results
No significant group differences were observed in [11C]MDL 100907 BPND or BPp in the ROIs or in the voxelwise analysis of BPND maps. There was a significant correlation in the orbitofrontal cortex between [11C]MDL 100907 binding and age of onset, with earlier age of onset associated with higher
binding.
Conclusions
Adults with OCD are not characterized as a group by major changes in 5-HT2A availability in cortical or limbic brain regions. Further research is warranted to
examine potential differences in 5-HT2A availability between early- and late-onset OCD and to assess 5-HT2A function in relation to other neurotransmitter systems implicated in OCD.
Key Words
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References
- Brain-behavior relationships in obsessive-compulsive disorder.Semin Clin Neuropsychiatry. 2001; 6: 82-101
- On the role of cortical glutamate in obsessive-compulsive disorder and attention-deficit hyperactivity disorder, two phenomenologically antithetical conditions.Acta Psychiatr Scand. 2000; 102: 401-413
- Glutamate-modulating drugs as novel pharmacotherapeutic agents in the treatment of obsessive-compulsive disorder.NeuroRx. 2006; 3: 69-81
- Brain imaging in pediatric obsessive-compulsive disorder.J Am Acad Child Adolesc Psychiatry. 2008; 47: 1262-1272
- Brain anatomy and chemistry may predict treatment response in paediatric obsessive-compulsive disorder.Int J Neuropsychopharmacol. 2001; 4: 179-190
- The serotonin hypothesis of obsessive compulsive disorder: Implications of pharmacologic challenge studies.J Clin Psychiatry. 1992; 53: 17-28
- Pathogenesis of obsessive-compulsive disorder.in: Stein D.J. Hollander E. Textbook of Anxiety Disorders. The American Psychiatric Publishing, Washington, DC2002: 191-205
- PET Imaging.in: Stolerman I. Encyclopedia of Psychopharmacology. Springer-Verlag, Berlin2010
- Serotonin transporters in obsessive-compulsive disorder: A positron emission tomography study with [(11)C]McN 5652.Biol Psychiatry. 2003; 54: 1414-1421
- Reduced serotonin transporter binding in the insular cortex in patients with obsessive-compulsive disorder: A [11C]DASB PET study.Neuroimage. 2010; 49: 121-126
- Segregation of serotonin 5-HT2A and 5-HT3 receptors in inhibitory circuits of the primate cerebral cortex.J Comp Neurol. 2000; 417: 337-348
- Serotonin 5-HT2A receptors are expressed on pyramidal cells and interneurons in the rat cortex.Synapse. 1997; 27: 79-82
- Mechanisms of action of current and potential pharmacotherapies of obsessive-compulsive disorder.Prog Neuropsychopharmacol Biol Psychiatry. 2006; 30: 362-373
- In vivo PET study of 5HT(2A) serotonin and D(2) dopamine dysfunction in drug-naive obsessive-compulsive disorder.Neuroimage. 2008; 42: 306-314
- Validation of a tracer kinetic model for the quantification of 5-HT(2A) receptors in human brain with [(11)C]MDL 100,907.J Cereb Blood Flow Metab. 2007; 27: 161-172
- Patients with obsessive-compulsive disorder have increased 5-HT2A receptor binding in the caudate nuclei.Int J Neuropsychopharmacol. 2005; 8: 391-401
- Characterization of radioactive metabolites of 5-HT2A receptor PET ligand [18F]altanserin in human and rodent.Nucl Med Biol. 1999; 26: 601-608
- Autoradiographic localization of 5-HT(2A) receptors in the human brain using [(3)H]M100907 and [(11)C]M100907.Synapse. 2000; 38: 421-431
Talbot PS, Slifstein M, Hwang D-R, Huang Y, Scher E, Abi-Dargham A, Laruelle M (in press): Extended characterization of the serotonin 2A (5-HT2A) receptor-selective PET radiotracer 11C-MDL100907 in healthy humans. NeuroImage. doi:10.1016/j.neuroimage.2011.07.001.
- Brief screening for family psychiatric history: The family history screen.Arch Gen Psychiatry. 2000; 57: 675-682
- Structured Clinical Interview for DSM-IV Axis I Disorders-Patient Edition.Biometrics Research Department, New York State Psychiatric Institute, New York1996
- The Yale-Brown Obsessive Compulsive Scale.Arch Gen Psychiatry. 1989; 46: 1006-1011
- The Yale-Brown Obsessive Compulsive Scale.Arch Gen Psychiatry. 1989; 46: 1012-1016
- A rating scale for depression.J Neurol Neurosurg Psychiatry. 1960; 23: 56-62
- Taboo thoughts and doubt/checking: a refinement of the factor structure for obsessive-compulsive disorder symptoms.Psychiatry Res. 2007; 151: 255-258
- Using individual items to clarify OCD symptom structure: The case for five factors.Am J Psychiatry. 2009; 166 (author reply 729–731): 728-729
- Further development of YBOCS dimensions in the OCD Collaborative Genetics study: Symptoms vs. categories.Psychiatry Res. 2008; 160: 83-93
- [11C]MDL 100907, a radioligand for selective imaging of 5-HT(2A) receptors with positron emission tomography.Life Sci. 1996; 58: 187-192
- Prefrontal dopamine D1 receptors and working memory in schizophrenia.J Neurosci. 2002; 22: 3708-3719
- Measurement of striatal and extrastriatal dopamine D1 receptor binding potential with [11C]NNC 112 in humans: Validation and reproducibility.J Cereb Blood Flow Metab. 2000; 20: 225-243
- SPECT measurement of benzodiazepine receptors in human brain with iodine-123-iomazenil: kinetic and equilibrium paradigms.J Nucl Med. 1994; 35: 228-238
- Effects of reduced endogenous 5-HT on the in vivo binding of the serotonin transporter radioligand 11C-DASB in healthy humans.Synapse. 2005; 55: 164-175
- Dose-occupancy study of striatal and extrastriatal dopamine D2 receptors by aripiprazole in schizophrenia with PET and [18F]fallypride.Neuropsychopharmacology. 2008; 33: 3111-3125
- Multimodal image coregistration and partitioning—a unified framework.Neuroimage. 1997; 6: 209-217
- Automated three-dimensional registration of magnetic resonance and positron emission tomography brain images by multiresolution optimization of voxel similarity measures.Med Phys. 1997; 24: 25-35
- Relationships between radiotracer properties and image quality in molecular imaging of the brain with positron emission tomography.Mol Imaging Biol. 2003; 5: 363-375
- Consensus nomenclature for in vivo imaging of reversibly binding radioligands.J Cereb Blood Flow Metab. 2007; 27: 1533-1539
- A quantitative model for the in vivo assessment of drug binding sites with positron emission tomography.Ann Neurol. 1984; 15: 217-227
- Cognitive dysfunction in obsessive-compulsive disorder.Acta Psychiatr Scand. 2000; 101: 281-285
- Consensus nomenclature for in vivo imaging of reversibly binding radioligands.J Cereb Blood Flow Metab. 2007; 27: 1533-1539
- Controlling the false discovery rate—a practical and powerful approach to multiple testing.J R Stat Soc Series B Stat Methodol. 1995; 57: 289-300
- Regional cerebral blood flow abnormalities in early-onset obsessive-compulsive disorder: An exploratory SPECT study.J Am Acad Child Adolesc Psychiatry. 2001; 40: 347-354
- Paediatric obsessive-compulsive disorder, a neurodevelopmental disorder?.Neurosci Biobehav Rev. 2009; 33: 818-830
- Association studies of serotonin system candidate genes in early-onset obsessive-compulsive disorder.Biol Psychiatry. 2007; 61: 322-329
- Association testing of the positional and functional candidate gene SLC1A1/EAAC1 in early-onset obsessive-compulsive disorder.Arch Gen Psychiatry. 2006; 63: 778-785
- Increased 5-HT(2A) receptor binding in euthymic, medication-free patients recovered from depression: A positron emission study with [(11)C]MDL 100,907.Am J Psychiatry. 2006; 163: 1580-1587
- Dysfunctional attitudes and 5-HT2 receptors during depression and self-harm.Am J Psychiatry. 2003; 160: 90-99
Article info
Publication history
Published online: August 22, 2011
Accepted:
June 21,
2011
Received in revised form:
June 20,
2011
Received:
January 14,
2011
Identification
Copyright
© 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
