Ramasubbu Rajamannar, Burgess Ashley, Gaxiola-Valdez Ismael, Cortese Filomeno, Clark Darren, Kemp Anne, Goodyear Bradley, Macqueen Glenda, Bech-Hansen N Torben, Foster Jane, Diwadkar Vaibhav A
Department of Psychiatry, University of Calgary, Calgary, AB, Canada.
Department of Clinical Neuroscience, University of Calgary, Calgary, AB, Canada.
Hum Psychopharmacol. 2016 Mar;31(2):144-55. doi: 10.1002/hup.2521. Epub 2016 Feb 16.
Genotype and drug pharmacology may contribute to variations in brain response to antidepressants. We examined the impact of two antidepressants with differential actions on serotonin transporter and the 5-HHTLPR-S/Lg polymorphisms on amygdala responses in major depressive disorder (MDD).
Caucasians with MDD were given either citalopram or quetiapine extended release for 8 weeks. Patients were genotyped for 5-HTTLPR. Clinical efficacy was assessed using the Hamilton Depression Rating Scale. fMRI responses to negative emotional faces were acquired at baseline, week 1 and week 8. The outcome measure was change in amygdala responses at week 8.
Citalopram had no effect on amygdala responses in MDD patients with S/Lg alleles at weeks 1 and 8 compared with baseline, whereas it induced changes in amygdala responses in LL homozygotes. By contrast, quetiapine decreased amygdala responses at both time points in S/Lg carriers, and changes in amygdala responses at week 8 correlated with a reduction in depression scores. The small number of LL homozygotes in quetiapine group was a limitation. Efficacy of both treatments was comparable.
These preliminary data suggest that pharmacological mechanisms and genetics need to be considered in the development of neuroimaging markers for the evaluation of antidepressant treatments.
基因类型和药物药理学可能导致大脑对抗抑郁药反应的差异。我们研究了两种对5-羟色胺转运体作用不同的抗抑郁药以及5-羟色胺转运体基因连锁多态性区域（5-HHTLPR-S/Lg）多态性对重度抑郁症（MDD）患者杏仁核反应的影响。
患有MDD的白种人患者接受西酞普兰或喹硫平缓释剂治疗8周。对患者进行5-HTTLPR基因分型。使用汉密尔顿抑郁量表评估临床疗效。在基线、第1周和第8周采集对负面情绪面孔的功能磁共振成像（fMRI）反应。结果指标是第8周时杏仁核反应的变化。
与基线相比，在第1周和第8周时，西酞普兰对携带S/Lg等位基因的MDD患者的杏仁核反应没有影响，而在LL纯合子中它诱导了杏仁核反应的变化。相比之下，喹硫平在S/Lg携带者的两个时间点均降低了杏仁核反应，并且第8周时杏仁核反应的变化与抑郁评分的降低相关。喹硫平组中LL纯合子数量较少是一个局限性。两种治疗的疗效相当。
这些初步数据表明，在开发用于评估抗抑郁治疗的神经影像标记物时，需要考虑药理机制和遗传学因素。
