Gene variants in the dopamine receptor D2 expression network predict physiological and clinical features as well as treatment responses in schizophrenia.
Our results provide evidence that the <i>AKT1</i> gene modulates both striatal DRD2 availability and dopamine release in the human brain, which could account for its association with schizophrenia and psychosis.
RNA-sequencing analyses of cortical and striatal micropunches from Brd1<sup>+/-</sup> and wild-type mice revealed differential expression of genes enriched for schizophrenia risk, including several schizophrenia genome-wide association study risk genes (e.g., calcium channel subunits [Cacna1c and Cacnb2], cholinergic muscarinic receptor 4 [Chrm4)], dopamine receptor D<sub>2</sub> [Drd2], and transcription factor 4 [Tcf4]).
Using two independent post-mortem prefrontal messenger RNA (mRNA) data sets (total N=249), we identified a DRD2 co-expression pathway enriched for SCZ risk genes.
So, we attempted to evaluate the association between dopamine D2 (DRD2) receptor, serotonergic (5HT2A) receptor and CYP2D6 gene polymorphisms and response to treatment with risperidone in persons with schizophrenia from North India.
Previous research has indicated that variation in genes encoding catechol-O-methyltransferase (<i>COMT</i>) and dopamine receptor D2 (<i>DRD2</i>) may influence cognitive function and that this may confer vulnerability to the development of mental health disorders such as schizophrenia.
Altogether, the conditional Drd2 knockout model studied here revealed the overall fundamental contribution of D2R in motor functions and explains some of the side effects elicited by D2R blockers when used in neurological and psychiatric conditions, including schizophrenia, bipolar disorder, Tourette's syndrome, dementia, alcohol-induced delusions and obsessive-compulsive disorder.
In QUALIFY, a randomized study, aripiprazole once-monthly 400 mg (AOM 400), a dopamine D2 receptor partial agonist, showed noninferiority and subsequent superiority versus paliperidone palmitate (PP), a dopamine D2 receptor antagonist, on the Heinrichs-Carpenter Quality-of-Life Scale (QLS) in patients with schizophrenia aged 18-60 years.
Our findings indicate that GSTM1 may be a causal gene of both ATDH and SCZ, although further validation pertaining to other genes, such as CYP2E1 or DRD2, is necessary.
The phosphoinositide 3 kinase - protein kinase B (PI3K-Akt) signaling pathway plays an important role in the dopamine D2 receptor (DRD2) pathway and in the pathophysiology of schizophrenia.
A single nucleotide polymorphism, -141C insertion/deletion (Ins/Del) (rs1799732), in the promoter region of the dopamine D2 receptor gene has been linked to schizophrenia; however, the data are inconclusive.
Although there was no significant association between either DRD2 Taq1A genotype or DRD2 -141C Ins/Del genotype and PRL levels in all included patients, our results suggest that DRD2 Taq1A genotype may affect antipsychotic-related PRL levels in patients with schizophrenia.
Our meta-analysis suggests an association of the DRD2 gene and the risk for schizophrenia, given that TaqI and C957T polymorphisms presented a protective effect against schizophrenia, and in the sub-analyses the C957T variant increased the risk for this disorder in the Chinese population.
In a cross-sectional study, we examined 2 dopamine D2 receptor (DRD2) single-nucleotide polymorphisms (SNPs) previously associated with schizophrenia (C939 T, rs6275 and C957 T, rs6277) along with fasting blood glucose and body mass index (BMI) in 207 antipsychotic-treated patients with schizophrenia.
Here, we demonstrate that rs1076560(T) imparts a small but reliable risk for schizophrenia in a sample of 616 affected families and five independent replication samples totaling 4017 affected and 4704 unaffected individuals (odds ratio=1.1; P=0.004). rs1076560(T) was associated with impaired verbal fluency and comprehension in schizophrenia but improved performance among healthy comparison subjects. rs1076560(T) also associated with lower D2 short isoform expression in postmortem brain. rs1076560(T) disrupted a binding site for the splicing factor ZRANB2, diminished binding affinity between DRD2 pre-mRNA and ZRANB2 and abolished the ability of ZRANB2 to modulate short:long isoform-expression ratios of DRD2 minigenes in cell culture.