Department of Psychology, Uppsala University, Uppsala, Sweden.
The Beijer Laboratory, Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden.
Transl Psychiatry. 2021 Nov 3;11(1):559. doi: 10.1038/s41398-021-01682-3.
It has been extensively debated whether selective serotonin reuptake inhibitors (SSRIs) are more efficacious than placebo in affective disorders, and it is not fully understood how SSRIs exert their beneficial effects. Along with serotonin transporter blockade, altered dopamine signaling and psychological factors may contribute. In this randomized clinical trial of participants with social anxiety disorder (SAD) we investigated how manipulation of verbally-induced expectancies, vital for placebo response, affect brain monoamine transporters and symptom improvement during SSRI treatment. Twenty-seven participants with SAD (17 men, 10 women), were randomized, to 9 weeks of overt or covert treatment with escitalopram 20 mg. The overt group received correct treatment information whereas the covert group was treated deceptively with escitalopram, described as an active placebo in a cover story. Before and after treatment, patients underwent positron emission tomography (PET) assessments with the [C]DASB and [C]PE2I radiotracers, probing brain serotonin (SERT) and dopamine (DAT) transporters. SAD symptoms were measured by the Liebowitz Social Anxiety Scale. Overt was superior to covert SSRI treatment, resulting in almost a fourfold higher rate of responders. PET results showed that SERT occupancy after treatment was unrelated to anxiety reduction and equally high in both groups. In contrast, DAT binding decreased in the right putamen, pallidum, and the left thalamus with overt SSRI treatment, and increased with covert treatment, resulting in significant group differences. DAT binding potential changes in these regions correlated negatively with symptom improvement. Findings support that the anxiolytic effects of SSRIs involve psychological factors contingent on dopaminergic neurotransmission while serotonin transporter blockade alone is insufficient for clinical response.
选择性 5-羟色胺再摄取抑制剂（SSRIs）在情感障碍中的疗效是否优于安慰剂一直存在广泛争议，而 SSRI 如何发挥其有益作用尚不完全清楚。除了阻断 5-羟色胺转运体，改变多巴胺信号和心理因素也可能起作用。在这项针对社交焦虑障碍（SAD）患者的随机临床试验中，我们研究了言语诱导的预期如何影响大脑单胺转运体，并在 SSRI 治疗期间影响症状改善。27 名 SAD 患者（17 名男性，10 名女性）被随机分为 9 周的艾司西酞普兰 20mg 公开治疗或隐蔽治疗。公开组接受正确的治疗信息，而隐蔽组则以隐蔽的方式用艾司西酞普兰治疗，在一个掩盖故事中被描述为一种活性安慰剂。在治疗前后，患者接受了 [C]DASB 和 [C]PE2I 放射性示踪剂的正电子发射断层扫描（PET）评估，探测大脑中的 5-羟色胺（SERT）和多巴胺（DAT）转运体。SAD 症状通过 Liebowitz 社交焦虑量表进行测量。公开组 SSRI 治疗明显优于隐蔽组，导致应答者的比例几乎高出四倍。PET 结果表明，治疗后 SERT 占有率与焦虑减轻无关，两组均较高。相比之下，在公开的 SSRI 治疗中，右侧壳核、苍白球和左侧丘脑的 DAT 结合减少，而在隐蔽的治疗中则增加，导致两组之间存在显著差异。这些区域的 DAT 结合潜能变化与症状改善呈负相关。研究结果支持 SSRI 的抗焦虑作用涉及依赖于多巴胺能神经传递的心理因素，而单胺转运体阻断本身不足以产生临床反应。
