title: Dopamine receptor D2 and D4 genes, GABA(A) alpha-1 subunit genes and response to lithium prophylaxis in mood disorders.
abstract: Lithium is an effective prophylactic agent in mood disorders, and genetic factors are likely to modulate individual susceptibility to lithium treatment. The aim of this study is to investigate the influence of dopamine receptor D2 (DRD2), D4 exon 3 (DRD4), and gamma-aminobutyric acid type A (GABA(A)) receptor alpha-1 subunit (GABRA1) gene variants on the efficacy of lithium prophylaxis in mood disorders. Patients with mood disorders (N = 125: bipolar subtype, n = 100; major depressive disorder subtype, n = 25) were followed prospectively for an average of 53 months and were typed for DRD2 (Ser311/Cys311: n = 121, VNTR: n = 63), DRD4 (n = 125) and GABRA1 (n = 61) variants using polymerase chain reaction (PCR) techniques. DRD2, DRD4 and GABRA1 variants were not associated with response to lithium. A trend was observed toward a better outcome of DRD4* 2/4 subjects, but it was due to only two subjects. Consideration of possible stratification effects like gender, polarity, family history, age at onset and duration of lithium treatment did not reveal any association either. DRD2, DRD4 and GABRA1 variants therefore do not appear to be associated with the outcome of lithium prophylaxis in mood disorders.
authors.affiliation: Istituto Scientifico Ospedale San Raffaele, Department of Neuropsychiatric Sciences, University of Milan School of Medicine, Italy. serretti.alessandro@hsr.it
authors.forename: A
authors.initials: A
authors.lastname: Serretti
authors.forename: R
authors.initials: R
authors.lastname: Lilli
authors.forename: C
authors.initials: C
authors.lastname: Lorenzi
authors.forename: L
authors.initials: L
authors.lastname: Franchini
authors.forename: D
authors.initials: D
authors.lastname: Di Bella
authors.forename: M
authors.initials: M
authors.lastname: Catalano
authors.forename: E
authors.initials: E
authors.lastname: Smeraldi
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001714:Bipolar Disorder / Q000188:drug therapy / Q000235:genetics; D016009:Chi-Square Distribution; D003866:Depressive Disorder / Q000188:drug therapy / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008094:Lithium / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D011446:Prospective Studies; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050638:Receptors, Dopamine D4; D011963:Receptors, GABA-A / Q000235:genetics*; D055502:Secondary Prevention; D016896:Treatment Outcome
chemical_list: C493599:DRD4 protein, human; D005819:Genetic Markers; D017448:Receptors, Dopamine D2; D011963:Receptors, GABA-A; D050638:Receptors, Dopamine D4; D008094:Lithium