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D4 dopamine receptor-mediated phospholipid methylation and its implications for
mental illnesses such as schizophrenia
A Sharma, ML Kramer, PF Wick, D Liu, S Chari, S Shim, W-B Tan, D Ouellette, M Nagata, CJ DuRand, M Kotb and RC Deth Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts, USA02115 ENRM VA Medical Center, Bedford, Massachusetts, USA University of Tennessee Medical School, Memphis, Tennessee, USA |
A team of researchers led by Northeastern University professor Richard C. Deth has discovered a link between dopamine receptors and cognition that could open new avenues for the treatment of conditions like schizophrenia and attention deficit/hyperactivity disorder. The findings are published in the May 1999 edition of Molecular Psychiatry.
The breakthrough centers around the brain's folate pathways and the D-4 dopamine receptor, which is thought to play a vital role in human attention and cognition. Deth's group found that dopamine's interaction with the D-4 receptor can cause local increases in the fluidity of nerve membranes which can influence synapse activity critical for normal cognition and attention.
While researchers have long suspected that dopamine and folate contribute to mental illness, they have not been able to show how. Deth's team has demonstrated that D-4 activity uses the folate pathway as a source of single-carbon methyl groups essential to affecting changes in nerve cell membranes. When this process is defective, it might contribute to schizophrenia or other psychiatric disorders.
Researchers from Northeastern University's Department of Pharmaceutical Sciences, the VA Medical Center in Bedford, MA and the University of Tennessee School of Medicine in Memphis contributed to the study.
For further information on this work, please contact Dr. Richard C. Deth, Department of Pharmaceutical Sciences-312 Mugar Hall, Northeastern University, 360 Huntington Avenue, Boston, MA 02115 Tel: 617-373-3224; FAX: 617-373-8886; e-mail: r.deth@nunet.neu.edu
Molecular Psychiatry is an independent, peer-reviewed journal published by the Nature Publishing Group. Editorial decisions and publication in Molecular Psychiatry do not constitute endorsement by the National Institute of Mental Health, the National Institutes of Health or any branch of the government of the United States of America.
Editor: Julio Licinio, M.D.; phone: 301-496-6885; FAX: 301-402-1561; e-mail: licinio@nih.gov
Pre-prints of this article can be obtained from Ms. Julie Vianello; (contact information above)
Journal
Molecular Psychiatry