Brain Inj：SLC6A4基因变体与创伤后抑郁发病有关

　　导致创伤后抑郁（PTD）的因素包括，继发性损伤的化学级联及外伤性脑损伤（TBI）后的精神社会因素等。当前，对5-羟色胺在病理学中的作用及原发性抑郁症的治疗还存在一定的争议，且5-羟色胺在TBI继发PTD中可能发挥的作用尚不明确。

　　近期发表在Brain Inj上一项研究对羟色胺的功能及TBI后一年内发生PTD的遗传性风险进行了评估。研究发现TBI与抑郁症的风险基因之间存在一种独特的具有损伤和时间特异性相互作用。 

　　共109名有中重度外伤的受试者参与研究，研究者对羟色胺转运基因变体[SLC6A4(5-HTTLPR, rs25331)，内含子2的一个可变数的串联重复变体]进行研究。使用患者健康问卷（PHQ-9）对受试者外伤后6个月及/或12月时的抑郁状况进行评估。

　　研究发现，外伤后6个月，有情绪障碍历史及携带5-HTTLPR,L-纯合子的受试者PTD发病风险相对较高。与重度抑郁症相反，无情绪障碍历史的受试者（n=80）、S-纯合子携带者与L-纯合子携带者相比，前两者的抑郁症发病率比后者低2.803倍。外伤后12个月，LG-携带者发生PTD的概率相对较小。时域分析法的结果也显示，外伤恢复过程中5-HTTLPR与PTD的发展之间存在联系。

Variants of SLC6A4 in depression risk following severe TBI

Background: Post-traumatic depression (PTD) may be a result of several factors like secondary injury chemical cascades as well as psycho-social factors following traumatic brain injury (TBI). While the role of serotonin in the pathology and treatment of idiopathic major depression may be somewhat controversial, it is unclear what role serotonin may play in PTD following a TBI.

Objective: To assess serotonergic function and genetic risk for PTD development over 1 year following TBI.

Research design: Examination of variation in the serotonin transporter gene [SLC6A4 (5-HTTLPR, rs25331, and a variable number of tandem repeats variant in Intron 2)] in 109 subjects with moderate–severe injury. Depression was assessed using the Patient Health Questionnaire (PHQ-9) at 6 and/or 12 months post-injury.

Main outcomes and results: At 6 months post-injury, subjects with a history of pre-morbid mood disorders and 5-HTTLPR L-homozygotes were at greater risk for PTD. Contrary to major depression, subjects without pre-morbid mood disorders (n = 80) and S-carriers were 2.803-times less likely to be depressed compared to L-homozygotes. At 12 months post-injury, LG-carriers were also less likely to experience PTD. Temporal analysis also showed 5-HTTLPR associations in PTD development across recovery.

Conclusions: This study suggests a unique injury- and temporally-specific interaction between TBI and genetic risk for depression.