James Gregory M, Baldinger-Melich Pia, Philippe Cecile, Kranz Georg S, Vanicek Thomas, Hahn Andreas, Gryglewski Gregor, Hienert Marius, Spies Marie, Traub-Weidinger Tatjana, Mitterhauser Markus, Wadsak Wolfgang, Hacker Marcus, Kasper Siegfried, Lanzenberger Rupert
Department of Psychiatry and Psychotherapy, Medical University of Vienna Vienna, Austria.
Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna Vienna, Austria.
Front Hum Neurosci. 2017 Feb 6;11:48. doi: 10.3389/fnhum.2017.00048. eCollection 2017.
Selective serotonin reuptake inhibitors (SSRIs) modulate serotonergic neurotransmission by blocking reuptake of serotonin from the extracellular space. Up to now, it remains unclear how SSRIs achieve their antidepressant effect. However, task-based and resting state functional magnetic resonance imaging studies, have demonstrated connectivity changes between brain regions. Here, we use positron emission tomography (PET) to quantify SSRI's main target, the serotonin transporter (SERT), and assess treatment-induced molecular changes in the interregional relation of SERT binding potential (BP). Nineteen out-patients with major depressive disorder (MDD) and 19 healthy controls (HC) were included in this study. Patients underwent three PET measurements with the radioligand [C]DASB: (1) at baseline, (2) after a first SSRI dose; and (3) following at least 3 weeks of daily intake. Controls were measured once with PET. Correlation analyses were restricted to brain regions repeatedly implicated in MDD pathophysiology. After 3 weeks of daily SSRI administration a significant increase in SERT BP correlations of anterior cingulate cortex and insula with the amygdala, midbrain, hippocampus, pallidum and putamen ( < 0.05; false discovery rate, FDR corrected) was revealed. No significant differences were found when comparing MDD patients and HC at baseline. These findings are in line with the clinical observation that treatment response to SSRIs is often achieved only after a latency of several weeks. The elevated associations in interregional SERT associations may be more closely connected to clinical outcomes than regional SERT occupancy measures and could reflect a change in the regional interaction of serotonergic neurotransmission during antidepressant treatment.
选择性5-羟色胺再摄取抑制剂（SSRIs）通过阻断细胞外空间中5-羟色胺的再摄取来调节5-羟色胺能神经传递。到目前为止，尚不清楚SSRIs如何实现其抗抑郁作用。然而，基于任务和静息状态的功能磁共振成像研究已证明脑区之间的连接性发生了变化。在此，我们使用正电子发射断层扫描（PET）来量化SSRIs的主要靶点——5-羟色胺转运体（SERT），并评估治疗引起的SERT结合潜能（BP）区域间关系的分子变化。本研究纳入了19名重度抑郁症（MDD）门诊患者和19名健康对照者（HC）。患者使用放射性配体[C]DASB进行了三次PET测量：（1）基线时；（2）首次服用SSRI剂量后；以及（3）每日服用至少3周后。对照者进行了一次PET测量。相关性分析仅限于反复与MDD病理生理学相关的脑区。每日服用SSRI 3周后，前扣带回皮质和岛叶与杏仁核、中脑、海马体、苍白球和壳核之间的SERT BP相关性显著增加（<0.05；错误发现率，FDR校正）。在基线时比较MDD患者和HC时未发现显著差异。这些发现与临床观察结果一致，即对SSRIs的治疗反应通常仅在几周的潜伏期后才能实现获得。区域间SERT关联的升高可能比区域SERT占有率测量更紧密地与临床结果相关，并且可能反映了抗抑郁治疗期间5-羟色胺能神经传递的区域相互作用的变化。
