ARTICLE: "Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype"
AUTHORS: Norio Ozaki, David Goldman, Walter H Kaye, Katherine Plotnicov, Benjamin D Greenberg, Jaakko Lappalainen, Gary Rudnick, Dennis L Murphy
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan; Laboratory of Neurogenetics, NIAAA, NIH, Rockville, MD, USA; Department of Psychiatry, University of Pittsburgh Medical Center, Western Psychiatric Institute & Clinic, Iroquois Building, Pittsburgh, PA, USA; Butler Hospital, Providence, RI, USA; Department of Psychiatry, Brown University School of Medicine, USA; Yale University School of Medicine, VA Connecticut Healthcare System, Psychiatry 116A2, West Haven, CT, USA; Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA; Laboratory of Clinical Science, MSC 1264, NIMH, NIH, Bethesda, MD, USA
Prior research has shown that several gene variants are more common in individuals with obsessive-compulsive disorder (OCD) than other patient groups or controls, but the differences are not specific to OCD.
Investigations of a new, uncommon coding region variant, I425V, in the serotonin transporter gene in 112 OCD patients and 271 patients with other psychiatric disorders plus controls, found this new variant only in two families with OCD. In this multi-generational study, six of the seven family members who had the mutation had either OCD or obsessive-compulsive personality disorder. The seven other family members of the 14 total who did not have the mutation did not have OCD. The individuals in the two families who had OCD also had multiple other diagnoses including tic disorder (3), anorexia nervosa (2), Asperger's Syndrome (2), alcohol problems (4), social phobia (3), depression (3) plus ADHD and PTSD and were generally treatment resistant. This suggests that OCD in these two families is complicated and severe.
The mutation is rare, and thus far has been identified in a total of 7 of 833 individuals (in this study and a prior study) who have been genotyped for it. While more individuals need to be studied utilizing both clinical evaluations and DNA, it may be estimated that 2% or less of individuals with OCD may have it. The mutation is unusual in that in cell culture studies, the uptake of serotonin is markedly stimulated. This occurs by a change in the way the serotonin transporter is regulated by cell signals.
Citation source: Molecular Psychiatry 2003 Volume 8, number 11, pages 933-936.
For further information on this work, please contact Dr. Dennis Murphy, Laboratory of Clinical Science, Building 10, Room 3D41, 10 Center Drive, NIMH, NIH, Bethesda, MD, 20892-1264, USA; Phone: 301-496-2757; Fax: 301-402-0188; Email: email@example.com
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