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额颞叶有效连接性作为对SSRI给药抗抑郁反应的可能预测指标。

Fronto-limbic effective connectivity as possible predictor of antidepressant response to SSRI administration.

作者信息

Vai Benedetta, Bulgarelli Chiara, Godlewska Beata R, Cowen Philip J, Benedetti Francesco, Harmer Catherine J

机构信息

IRCCS Ospedale San Raffaele, Department of Clinical Neurosciences, Milan, Italy; Department of Human Studies, Libera Università Maria Ss. Assunta, Roma, Italy.

IRCCS Ospedale San Raffaele, Department of Clinical Neurosciences, Milan, Italy.

出版信息

Eur Neuropsychopharmacol. 2016 Dec;26(12):2000-2010. doi: 10.1016/j.euroneuro.2016.09.640. Epub 2016 Oct 15.

Abstract

The timely selection of the optimal treatment for depressed patients is critical to improve remission rates. The detection of pre-treatment variables able to predict differential treatment response may provide novel approaches for treatment selection. Selective serotonin reuptake inhibitors (SSRIs) modulate the fronto-limbic functional response and connectivity, an effect preceding the overt clinical antidepressant effects. Here we investigated whether the cortico-limbic connectivity associated with emotional bias measured before SSRI administration predicts the efficacy of antidepressant treatment in MDD patients. fMRI and Dynamic Causal Modeling (DCM) were combined to study if effective connectivity might differentiate healthy controls (HC) and patients affected by major depression who later responded (RMDD, n=21), or failed to respond (nRMDD, n=12), to 6 weeks of escitalopram administration. Sixteen DCMs exploring connectivity between anterior cingulate cortex (ACC), ventrolateral prefrontal cortex (VLPFC), Amygdala (Amy), and fusiform gyrus (FG) were constructed. Analyses revealed that nRMDD had reduced endogenous connectivity from Amy to VLPFC and to ACC, with an increased connectivity and modulation of the ACC to Amy connectivity when processing of fearful emotional stimuli compared to HC. RMDD and HC did not significantly differ among themselves. Pre-treatment effective connectivity in fronto-limbic circuitry could be an important factor affecting antidepressant response, and highlight the mechanisms which may be involved in recovery from depression. These results suggest that fronto-limbic connectivity might provide a neural biomarker to predict the clinical outcome to SSRIs administration in major depression.

摘要

及时为抑郁症患者选择最佳治疗方法对于提高缓解率至关重要。检测能够预测不同治疗反应的治疗前变量可能为治疗选择提供新方法。选择性5-羟色胺再摄取抑制剂(SSRI)可调节额叶-边缘系统的功能反应和连接性,这一效应先于明显的临床抗抑郁作用出现。在此,我们研究了在给予SSRI之前测量的与情绪偏差相关的皮质-边缘连接性是否能预测重度抑郁症(MDD)患者抗抑郁治疗的疗效。将功能磁共振成像(fMRI)和动态因果模型(DCM)相结合,以研究有效连接性是否能区分健康对照者(HC)以及在接受6周艾司西酞普兰治疗后有反应的重度抑郁症患者(RMDD,n = 21)或无反应的患者(nRMDD,n = 12)。构建了16个探索前扣带回皮质(ACC)、腹外侧前额叶皮质(VLPFC)、杏仁核(Amy)和梭状回(FG)之间连接性的DCM。分析显示,与HC相比,nRMDD从Amy到VLPFC和ACC的内源性连接性降低,在处理恐惧情绪刺激时ACC到Amy的连接性增加且有调节作用。RMDD和HC之间无显著差异。额叶-边缘回路的治疗前有效连接性可能是影响抗抑郁反应的一个重要因素,并突出了可能参与抑郁症康复的机制。这些结果表明,额叶-边缘连接性可能提供一种神经生物标志物来预测重度抑郁症患者服用SSRI后的临床结局。

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