Department of Old Age Psychiatry, Institute of Psychiatry, King's College London, UK.
J Affect Disord. 2013 Aug 15;150(1):96-103. doi: 10.1016/j.jad.2013.02.028. Epub 2013 May 2.
Polymorphisms in the serotonin transporter gene (5-HTTLPR) modulate amygdala activity in healthy individuals. Increased responses to negative stimuli in carriers of low transcription alleles have been proposed to contribute to the pathogenesis of depression. We sought to investigate the effects of genotype as well as diagnosis in patients with depression.
Subjects with recurrent depression (n=67) and matched healthy controls (n=49) participated in a fMRI task of implicit processing of sad facial stimuli. Effects of biallelic (short (S) and long (L) alleles) and triallelic (including rs25531 A/G single nucleotide variation) models of 5-HTTLPR polymorphisms on amygdala activity and connectivity were investigated.
Significant effects were observed of both genotype and diagnosis on amygdala activity. Increased amygdala activity was associated with 5-HTTLPR genotype in low transcription allele carriers as well as with a diagnosis of depression. The connectivity analysis revealed a main effect of genotype with reduced connectivity to the subgenual region of the anterior cingulate in carriers of the low transcription alleles. There was also a main effect of diagnosis with reduced connectivity to the dorsal region of the anterior cingulate and to the dorsolateral prefrontal cortex in depression. There were no interaction effects between genotype and diagnosis in amygdala activity or connectivity.
Significant independent effects of genotype and diagnosis on amygdala responsivity were revealed. The effects of genotype and diagnosis on amygdala connectivity showed a regional segregation, suggesting that 5-HTTLPR polymorphisms bias frontal-limbic connectivity while the development of depression involves more extensive neural disturbances. These findings point to the potential of connectivity maps as a diagnostic biomarker for depression.
5-羟色胺转运体基因（5-HTTLPR）的多态性调节健康个体的杏仁核活动。携带低转录等位基因的个体对负性刺激的反应增加，被认为有助于抑郁症的发病机制。我们试图研究基因型以及抑郁症患者的诊断对其的影响。
有复发性抑郁症的患者（n=67）和匹配的健康对照组（n=49）参与了一项关于悲伤面孔刺激内隐处理的 fMRI 任务。研究了 5-HTTLPR 多态性的双等位基因（短（S）和长（L）等位基因）和三等位基因（包括 rs25531 A/G 单核苷酸变异）模型对杏仁核活动和连接的影响。
观察到基因型和诊断对杏仁核活动都有显著影响。在低转录等位基因携带者中，5-HTTLPR 基因型与杏仁核活动增加相关，与抑郁症诊断也相关。连接分析显示，基因型的主要效应是降低与前扣带回亚区的连接，而在低转录等位基因携带者中则降低了与前扣带回背侧和背外侧前额叶皮层的连接。在杏仁核活动或连接方面，基因型和诊断之间没有交互作用。
揭示了基因型和诊断对杏仁核反应性的显著独立影响。基因型和诊断对杏仁核连接的影响表现出区域分离，表明 5-HTTLPR 多态性偏向于额-边缘连接，而抑郁症的发展涉及更广泛的神经紊乱。这些发现表明连接图作为抑郁症的诊断生物标志物具有潜力。
