title: Reduced 3-O-methyl-dopa levels in OCD patients and their unaffected parents is associated with the low activity M158 COMT allele.
abstract: The catechol-O-methyltransferase (COMT) gene is considered as a candidate gene in obsessive-compulsive disorder (OCD). Specifically, the COMT low-activity M158 allele has been suggested to be associated with OCD. However, there is no study reporting that COMT activity is decreased in OCD patients and that the decrease is mediated by the V158M polymorphism. Therefore, the purpose of our study was to assess COMT activity in OCD by measuring plasma levels of 3-O-methyl-dopa (3-OMD), which result from the methylation of levodopa by COMT, and to investigate the relationship between 3-OMD levels and the V158M polymorphism. We also examined whether 3-OMD levels represented an endophenotype, associated with the genetic liability to OCD, by assessing unaffected relatives of OCD patients. We assessed plasma 3-OMD levels in a sample of drug-free OCD probands (n = 34) and their unaffected parents (n = 63), and compared them with controls (n = 85). The COMT V158M polymorphism was genotyped in all participants. Lower plasma 3-OMD levels were found in OCD probands and their unaffected parents compared to controls. The COMT M158 allele was associated with reduced plasma 3-OMD levels in a co-dominant manner, both in OCD probands and their relatives, but not in controls. Our results suggest that COMT activity could act as a limiting factor for the production of 3-OMD in OCD patients and in their relatives. These findings further support a role of COMT in the susceptibility to OCD and provide evidence that 3-OMD levels could represent an endophenotype in OCD.
authors.affiliation: INSERM U955, Institut Mondor de Recherche Biomedicale, Psychiatric Genetics, Créteil, France.|APHP, Hôpital Robert Debré, Child and Adolescent Psychiatry, Paris, France.|Pasteur Institute, Human Genetics and Cognitive Functions, Paris, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Delorme
authors.affiliation: INSERM U952, Paris, France.|Université Pierre et Marie Curie, Paris, France.
authors.forename: Catalina
authors.initials: C
authors.lastname: Betancur
authors.affiliation: APHP, Hôpital Robert Debré, Child and Adolescent Psychiatry, Paris, France.|Pasteur Institute, Human Genetics and Cognitive Functions, Paris, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Chaste
authors.affiliation: APHP, Groupe Hospitalier Cochin-Saint Vincent de Paul, Cochin-Pasteur Vaccinology Center, Paris, France.
authors.forename: Solen
authors.initials: S
authors.lastname: Kernéis
authors.affiliation: INSERM U955, Institut Mondor de Recherche Biomedicale, Psychiatric Genetics, Créteil, France.|APHP, Groupe Hospitalier Henri Mondor-Albert Chenevier, Department of Psychiatry, Créteil, France.
authors.forename: Astrid
authors.initials: A
authors.lastname: Stopin
authors.affiliation: Pasteur Institute, Human Genetics and Cognitive Functions, Paris, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Mouren
authors.affiliation: APHP, Hôpital Lariboisière, Department of Biochemistry, Paris, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Collet
authors.affiliation: Pasteur Institute, Human Genetics and Cognitive Functions, Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bourgeron
authors.affiliation: INSERM U955, Institut Mondor de Recherche Biomedicale, Psychiatric Genetics, Créteil, France.|APHP, Groupe Hospitalier Henri Mondor-Albert Chenevier, Department of Psychiatry, Créteil, France.|Université Paris 12, Medical School, Créteil, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Leboyer
authors.affiliation: APHP, Hôpital Lariboisière, Department of Biochemistry, Paris, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Launay
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001007:Anxiety / Q000235:genetics* / Q000378:metabolism*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000235:genetics* / Q000378:metabolism*; D010290:Parents; D020641:Polymorphism, Single Nucleotide
chemical_list: D002394:Catechol O-Methyltransferase
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