Dopamine D1 Receptor Gene Polymorphism is Associated with Prophylactic Lithium Response in Bipolar Disorder

Abstract

Background: Previously, we have found an association between the −48 A/G polymorphism of the dopamine receptor D1 (DRD1) gene and bipolar disorder. The aim of the present study was to investigate a possible association of this polymorphism with the quality of the prophylactic lithium response in bipolar patients.

Methods: Ninety-two patients (39 male, 53 female), aged 30–77 (mean: 54 years) were studied. They have received lithium for prophylactic purposes for 5–27 years (mean: 15 years). Twenty-four patients were identified as excellent lithium responders (ER), 48 patients as partial responders (PR), and 20 patients were non-responders (NR). They all were genotyped for −48 A/G polymorphism of the DRD1 gene.

Results: The frequency of G/G genotype in ER, PR, and NR patients was 21%, 48%, and 60%, respectively, and the frequency of G allele was 58%, 76%, and 80%, respectively.

Discussion: The results obtained suggest that the higher frequency of G allele, and G/G genotype, which has been associated with a predisposition to bipolar illness, is also connected with a poorer prophylactic effect of lithium.

References

• 1 Berk M, Dodd S, Kauer-Sant’anna M. et al . Dopamine dysregulation syndrome: implications for a dopamine hypothesis of bipolar disorder.  Acta Psychiatr Scand. 2007;  434 ((Suppl)) 41-49
• 2 Carli M, Morissette M, Hébert C. et al . Effects of a chronic lithium treatment on central dopamine neurotransporters.  Biochem Pharmacol. 1997;  54 391-397
• 3 Cichon S, Nothen MM, Erdmann J. et al . Detection of four polymorphic sites in the human dopamine D₁ receptor gene.  Hum Mol Genet. 1994;  3 209
• 4 Cichon S, Nothen MM, Stober G. et al . Systematic screening for mutations in the 5′-regulatory region of the human dopamine D1 receptor (DRD1) gene in patients with schizophrenia and bipolar affective disorder.  Am J Med Genet. 1996;  67 424-428
• 5 Dmitrzak-Weglarz M, Rybakowski JK, Slopien A. et al . Dopamine receptor D1 gene −48A/G polymorphism is associated with bipolar illness but nor with schizophrenia in a Polish population.  Neuropsychobiology. 2006;  53 51-56
• 6 First MB, Spitzer RL, Gibbon M. et al . Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version (SCID-CV). American Psychiatric Press, Washington, D.C 1996
• 7 Goldman-Rakic PS, Muly EC, Williams GV. D₁ receptors in prefrontal cells and circuits.  Brain Res Rev. 2000;  31 295-301
• 8 Grandy DK, Zhou QY, Allen L. et al . A human D₁ dopamine receptor gene is located on chromosome 5 at q35.1 and identifies and EcoRi RFLP.  Am J Hum Genet. 1990;  47 828-834
• 9 Kojima H, Ohmori O, Shinkai T. et al . Dopamine D₁ receptor gene polymoprhism and schizophrenia in Japan.  Am J Med Genet. 1999;  88 116-119
• 10 Miller SA, Dykaes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells.  Nucleic Acid Res. 1988;  16 1215
• 11 Permoda-Osip A, Rybakowski J, Suwalska A. et al . Polymorphism of catechol-O-methyltransferase gene and prophylactic effect of lithium in bipolar affective illness (in Polish).  Farmakoter Psychiatr Neurol. 2008;  24 19-24
• 12 Rybakowski JK, Borkowska A, Czerski PM. et al . An association study of dopamine receptors polymorphisms and the Wisconsin card sorting test in schizophrenia.  J Neural Transm. 2005;  112 1575-1582
• 13 Rybakowski JK, Borkowska A, Czerski PM. et al . Polymorphism of the brain-derived neurotrophic factor gene and performance on a cognitive prefrontal test in bipolar patients.  Bipolar Disord. 2003;  5 468-472
• 14 Rybakowski JK, Suwalska A, Czerski PM. et al . Prophylactic effect of lithium in bipolar affective illness may be related to serotonin transporter genotype.  Pharmacol Rep. 2005;  57 124-127
• 15 Rybakowski JK, Suwalska A, Skibinska M. et al . Prophylactic lithium response and polymorphism of the brain-derived neurotrophic factor gene.  Pharmacopsychiatry. 2005;  38 166-170
• 16 Serretti A, Lilli R, Mandelli L. et al . Serotonin transporter gene associated with lithium prophylaxis in mood disorders.  Pharmacogenomics J. 2001;  1 71-77
• 17 Serretti A, Lorenzi C, Lilli R. et al . Pharmacogenetics of lithium prophylaxis in mood disorders: analysis of COMT, MAO-A, and Gbeta3 variants.  Am J Med Genet. 2002;  114 370-379
• 18 Severino G, Congiu D, Serelli C. et al . A48G polymorphism in the D1 receptor genes associated with bipolar I disorder.  Am J Med Genet. 2005;  134B 37-38
• 19 Suwalska A, Rybakowski J, Dmitrzak-Weglarz M. et al . Prophylactic efficacy of lithium in patients with bipolar affective disorder and polymorphism of dopamine receptors genes type D2 (in Polish).  Farmakoter Psychiatr Neurol. 2006;  22 79-85
• 20 Turecki G, Grof P, Grof E. et al . Mapping susceptibility genes for bipolar disorder: a pharmacogenetic approach based on excellent response to lithium.  Mol Psychiatry. 2001;  6 570-578
• 21 Ulrich S, Heimke C, Laux G. et al . Value and actuality of the prescription information for therapeutic drug monitoring of psychopharmaceuticals: a comparison with the medico-scientific evidence.  Pharmacopsychiatry. 2007;  40 121-127

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