Genotype of RGS4 (regulator of G protein signaling 4), which has been associated with schizophrenia, may predict severity of disease and likelihood of positive response to individual antipsychotic medications, according to an article in the January 1 issue of Biological Psychiatry.

Researchers genotyped and evaluated data for 678 patients with schizophrenia who had participated in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study. Among the 678 adults, inferred ancestries were 59 percent (397) "Europe Only,"29 percent (198) "Africa only," and 12 percent (83) "Other."

Eight single nucleotide polymorphisms (SNPs) spanning RGS4 were genotyped. Multiple linear regression was used to analyze association of RGS4 markers with Positive and Negative Symptoms Scale (PANSS) scores at baseline and throughout antipsychotic treatment.

The researchers found that two consecutive markers within the RGS4 gene, rs2661319 and rs2842030, were associated with more severe baseline total symptom score. Treatment with perphenazine was significantly more effective than treatment with quetiapine or ziprasidone in individuals of inferred African ancestry and homozygous for the rs951439 C allele.

Because RGS4 genotypes appear to predict both severity of baseline symptoms and relative responsiveness to antipsychotic treatment, further research should explore RSG4 genotype and function in patients of different ancestries to see whether genotype can prove useful in predicting severity of disease or likely response to antipsychotic medications.

Daniel Campbell, PhD, Vanderbilt University, lead author of the study, said the results, if replicated, would allow doctors to get a blood sample from a person with schizophrenia, genotype them at RGS4, and make a better prediction about which drug to use.

In 2000 researchers in the same lab used gene microarray technology to show that RGS4 was one of the most consistently altered genes in the frontal lobe of subjects with schizophrenia.

That was followed by human genetic studies, identifying variants in the RGS4 gene that showed association with schizophrenia.