Polymorphisms within the DRD1, DRD2, DRD3, DAT1, 5-HTTLPR and HTR2A genes are being studied for association with lithium prophylaxis in a sample of 155 Sardinian unrelated probands affected by bipolar disorder (BP).
Various other protein products of genes associated with bipolar disorder either bind to or are affected by phosphatidyl-inositol phosphate products of this pathway (ADBRK2, HIP1R, KCNQ2, RGS4, WFS1), are associated with its constituent elements (BCR, DUSP6, FAT, GNAZ) or are downstream targets of this signalling cascade (DPYSL2, DRD3, GAD1, G6PD, GCH1, KCNQ2, NOS3, SLC6A3, SLC6A4, SST, TH, TIMELESS).
Functional polymorphisms in the serotonin transporter (5-HTTLPR), catechol-O-methyltransferase (Val158Met) and dopamine D3 receptor (Ser9Gly) genes have all been associated with bipolar disorder.
Our findings suggest that the expression of DRD3 mRNA is reduced in schizophrenia and bipolar disorder, supporting the hypothesis of distorted homeostasis of dopamine receptor subtypes in psychotic disorder.
One hundred twenty-four depressed inpatients affected by bipolar disorder (DSM-IV) were treated with TSD and were genotyped for DRD3 first exon Gly/Ser variants and DRD2 codon 311 Ser/Cys variants using polymerase chain reaction techniques.
In recent years, the BalI RFLP (restriction fragment length polymorphism) in the dopamine D3 receptor gene has been examined as a possible susceptibility factor for both schizophrenia and bipolar disorder.
We have performed a case-control analysis of dopamine D2-like receptor (DRD2, DRD3 and DRD4) gene polymorphisms in 118 Han Chinese cases with bipolar affective disorder and 196 control subjects, and replication analysis in 157 English cases and 143 control subjects.
Linkage of bipolar disorder and recurrent depression to the DRD3 gene was tested using a series of autosomal dominant and recessive models with varying penetrance levels.
Thus, this substitution, which is the first sequence variation identified in the dopamine D3 receptor gene altering the amino acid sequence of the protein, can be regarded as a protein variant with no major effect on the susceptibility to bipolar affective disorder.