Relationship of serotonin transporter gene polymorphism with depression and the curative effect of selective serotonin reuptake inhibitor antidepressants

Hong XIAO; Hui YAO; Suwan GUO; Qijun LI

ABSTRACT

BACKGROUND:

It has been reported tbat there are rich expressions of serotonin transporter (5-HTT) in the cortical and limbic regions related to emotion and behavior in cerebrum. Regulation of the intensity and persistence of serotonergic nerve response can change the serotonergic neurotransmission, meanwhile, 5-HTT is also an important target for selective serotonin reuptake inhibitors (SSRIs).

OBJECTIVE:

To observe whether there is a correlation of 5-HTT gene polymorphism with plasma level of 5-HT and the clinical response of SSRIs in the population of Nanjing area.

DESIGN:

A case-control observation.

SETTING:

Department of Psychiatry, Brain Hospital of Nanjing Medical University.

PARTICIPANTS:

Totally 132 inpatients with depression in the Department of Psychiatry, Brain Hospital of Nanjing Medical University and 100 volunteer healthy blood donors were taken as the observational subjects between January 2001 and December 2003.

METHODS:

The genotype was analyzed with polymerase chain reaction (PCR) polymorphism analysis in the patients with depression and healthy subjects; plasma level of 5-HT was analyzed with high performance liquid chromatography-electrical chemistry detector (HPLC-ECD); and the clinical response to the antidepressants were assessed with Hamilton depression rating scale (HAMD).MAIN OUTCOME

MEASURES:

The analytical results of 5-HTT genotype frequency and allele frequency in both groups, and the relationship between 5-HTT genotype and plasma level of 5-HT before and after SSRIs treatment were observed.

RESULTS:

Blood samples were collected from all the 132 patients with depression and 100 normal healthy subjects, and they all finished the scale test and entered the analysis of results. ① There were no significant differences between the depression group and normal control group in the 5-HTT gene genotype frequencies (LL 24.2%, LS 44.7%, SS31.1%; LL29.0%, LS 47.0%, SS 24.0%, x2=1.405 8, P ＞ 0.05) and allelefrequencies (L46.59%, S 53.41%; L 52.5%, S 47.5%, x2=0.696 2, P ＞ 0.05). ② The total score of HAMD had significant differences before treatment among the depressive patients of different genotypes (F=6.48, P=0.002 1). After 4-week treatment of SSRIs antidepressants, the total score of HAMD was significantly decreased, and there was significant difference in the decrease of score (F=3.38, P= 0.037). ③ The plasma level of 5-HT had significant differences before treatment among the depressive patients of different genotypes (F=5.38,P= 0.005 7). After 4-week treatment of SSRIs antidepressants, the plasma level of 5-HT was increased, and the increased level was significantly different among different genotypes (F=23.55, P ＜ 0.01).

CONCLUSION:

The 5-HTT polymorphism may be not associated with the attack of depression, but with the severity of depression and the clinical responses of SSRIs in the population of Nanjing area, and the genotype in this area may become a reference index for the realization of individualized treatment in patients with depression.