5-HTTLPR与卒中后抑郁及单相抑郁病因和疗效的关联分析

目的 探讨我国汉族人群卒中后抑郁（post-stroke depression,PSD）及单相抑郁（unipolar depression,UD）患者病因和疗效与5-羟色胺转运蛋白启动子区基因多态性（serotonin transporter gene-linked polymorphic,5-HTTLPR）之间的关系。方法 以4 5例P S D及41例U D患者作为研究对象,以149名正常人作对照,应用聚合酶链式反应（polymerase chain reaction,PCR）扩增技术测定所有研究对象的5-HTTLPR的基因型和等位基因,PSD和UD患者组患者使用氟西汀治疗12周,在基线及12周治疗末时使用汉密尔顿抑郁量表（Hamilton depressive scale,HAMD）-17项评定疾病严重程度及疗效。结果 5-HTTLPR的3种基因型（S/S、S/L和L/L）和等位基因（S和L）在PSD组、UD组和正常对照组之间的分布差异无统计学意义;PSD和UD组S/S纯合子与S/L杂合子及L/L纯合子的基线评分相比差异具有统计学意义;12周治疗后两组患者治愈组和未治愈组之间S/S与S/L和L/L基因型、S和L等位基因分布具有统计学差异。结论 5-HTTLPR与PSD及UD均无显著关联,S/S基因型患者可能抑郁症状较重,12周治疗后携带S/S基因型和S等位基因患者的临床痊愈率较低。     

Lack of evidence for association of the serotonin transporter gene SLC6A4 with autism.

BACKGROUND: The serotonin transporter (5-HTT) has long been considered likely to play a role in autism. Hyperserotonemia has been consistently found in a proportion of autistic patients, and the use of selective serotonin reuptake inhibitors (SSRIs) can have a positive effect in treating some symptoms of autism. Specific variants of the 5-HTT gene, SLC6A4, especially the insertion-deletion 5-HTTLPR promoter locus, have been found to modulate its expression and transporter function. METHODS: We examined the transmission of the short or long allele of 5-HTTLPR locus to affected individuals, using a large cohort of 352 families. In addition, we screened five single nucleotide polymorphisms (SNPs) in the 5' region of SLC6A4 previously reported to be positively associated with autism, as well as 4 additional SNPs also in the 5' region. RESULTS: No association of the 5-HTTLPR locus with autism was found. Furthermore, no evidence for association of any of the nine SNPs covering the SLC6A4 gene, or any of their haplotypes, was observed in our study. Using obsessive-compulsive behaviors (OCB), severe OCBs or rigid-compulsive subsets of our cohort gave the same negative results. CONCLUSIONS: SLC6A4 variants do not appear to be significantly involved in the liability to autism.     

No association of serotonin transporter gene (SLC6A4) with schizophrenia and bipolar disorder in Japanese patients: association analysis based on linkage disequilibrium

Summary. Serotonin transporter gene (SLC6A4) is one of the most promising candidate genes for psychiatric disorders such as schizophrenia (SCZ) and bipolar disorder (BP). Two functional polymorphisms, 5HTTLPR and 5HTTVNTR, have been a focus for genetic association analyses; however, no conclusive results have been obtained. We conducted, 1) a mutation search of SLC6A4, 2) LD mapping to select ‘tagging’ markers (10 SNPs and 5HTTVNTR, while 5HTTLPR was treated as an independent marker because of its allelic form), and 3) association analysis of these ‘tagging’ markers and independent markers (5HTTLPR and Asn605Lys) with SCZ and BP in Japanese patients. In this mutation search, a nonsynonymous SNP, Asn605Lys, was detected. No associations of ‘tagging’ markers and independent markers with such conditions were found. These results indicate that SLC6A4 might not play a major role in SCZ and BP in Japanese patients, a finding that agrees with both the common disease-common variant hypothesis and common disease-rare variant hypothesis.     

The effect of mouse spinal cord transection on the antinociceptive response to the γ-aminobutyric acid agonists THIP (4, 5, 6, 7-tetrahydroisoxazolo [5, 4-c]pyridine-3-ol) and baclofen

The antinociceptive responses to the γ-aminobutyric acid receptor agonists THIP (4, 5, 6, 7-tetrahydroisoxazolo[5, 4-c]pyridine-3-ol) and baclofen were examined in spinally transected mice to define the central nervous system site of action for these drugs. Nociception was assessed using a tail-immersion assay. The results indicated that spinal transection (T6–T10) completely abolished the antinociceptive responses to THIP and baclofen, attenuated those to oxotremorine and morphine, but did not reduce the response to clonidine. The results suggest that the antinociceptive responses to THIP and baclofen are mediated by an action at supraspinal sites rostral to T6.