Reduced 3-O-methyl-dopa levels in OCD patients and their unaffected parents is associated with the low activity M158 COMT allele.
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.
Delorme
Richard
R
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.
Betancur
Catalina
C
INSERM U952, Paris, France.|Université Pierre et Marie Curie, Paris, France.
Chaste
Pauline
P
APHP, Hôpital Robert Debré, Child and Adolescent Psychiatry, Paris, France.|Pasteur Institute, Human Genetics and Cognitive Functions, Paris, France.
Kernéis
Solen
S
APHP, Groupe Hospitalier Cochin-Saint Vincent de Paul, Cochin-Pasteur Vaccinology Center, Paris, France.
Stopin
Astrid
A
INSERM U955, Institut Mondor de Recherche Biomedicale, Psychiatric Genetics, Créteil, France.|APHP, Groupe Hospitalier Henri Mondor-Albert Chenevier, Department of Psychiatry, Créteil, France.
Mouren
Marie-Christine
MC
Pasteur Institute, Human Genetics and Cognitive Functions, Paris, France.
Collet
Corinne
C
APHP, Hôpital Lariboisière, Department of Biochemistry, Paris, France.
Bourgeron
Thomas
T
Pasteur Institute, Human Genetics and Cognitive Functions, Paris, France.
Leboyer
Marion
M
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.
Launay
Jean-Marie
JM
APHP, Hôpital Lariboisière, Department of Biochemistry, Paris, France.
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
D002394:Catechol O-Methyltransferase
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