Genetic variation of the catechol-O-methyltransferase (COMT) gene has long been thought to confer susceptibility to schizophrenia because of its catalytic activity for dopamine degradation. The negative symptom is a severe form of the illness related to prefrontal hypodopaminergia. In the present study, we attempted to perform a quantitative trait test for genetic association between the COMT gene and the negative symptoms in a Chinese population.

A total of 160 unrelated schizophrenic individuals were recruited for genetic analysis and their symptoms were assessed and scored by Positive and Negative Syndrome Scale (PANSS). The quantitative trait test was performed by the UNPHASED program to see the correlation between scored negative symptoms and some single nucleotide polymorphisms (SNPs) present in the COMT gene.

rs362204 (Del/Ins SNP) showed allelic association with four negative symptoms, including blunted affect (p=0.00008), poor rapport (p=0.00006), passive/apathetic social withdrawal (p=0.0003) and lack of spontaneity and flow of conversation (p=0.001). The rs165656(C)-rs6267(G)-rs4680 (G)-rs362204 (Del) haplotype was strongly associated with both blunted affect (p=0.0245) and poor rapport (p=0.0186).

The present study suggests that COMT may etiologically contribute to the severity of negative symptoms of schizophrenia but its precise mechanism needs further investigating.