BACKGROUND Lithium, one of the few effective treatments for bipolar depression (BPD), has been hypothesized to work by enhancing serotonergic transmission. Despite preclinical evidence, it is unknown whether lithium acts via the serotonergic system. Here we examined the potential of serotonin transporter (5-HTT) or serotonin 1A receptor (5-HT1A) pre-treatment binding to predict lithium treatment response and remission. We hypothesized that lower pre-treatment 5-HTT and higher pre-treatment 5-HT1A binding would predict better clinical response. Additional analyses investigated group differences between BPD and healthy controls and the relationship between change in binding pre- to post-treatment and clinical response. Twenty-seven medication-free patients with BPD currently in a depressive episode received positron emission tomography (PET) scans using 5-HTT tracer [11C]DASB, a subset also received a PET scan using 5-HT1A tracer [11C]-CUMI-101 before and after 8 weeks of lithium monotherapy. Metabolite-corrected arterial input functions were used to estimate binding potential, proportional to receptor availability. Fourteen patients with BPD with both [11C]DASB and [11C]-CUMI-101 pre-treatment scans and 8 weeks of post-treatment clinical scores were included in the prediction analysis examining the potential of either pre-treatment 5-HTT or 5-HT1A or the combination of both to predict post-treatment clinical scores. RESULTS We found lower pre-treatment 5-HTT binding (p = 0.003) and lower 5-HT1A binding (p = 0.035) were both significantly associated with improved clinical response. Pre-treatment 5-HTT predicted remission with 71% accuracy (77% specificity, 60% sensitivity), while 5-HT1A binding was able to predict remission with 85% accuracy (87% sensitivity, 80% specificity). The combined prediction analysis using both 5-HTT and 5-HT1A was able to predict remission with 84.6% accuracy (87.5% specificity, 60% sensitivity). Additional analyses BPD and controls pre- or post-treatment, and the change in binding were not significant and unrelated to treatment response (p > 0.05). CONCLUSIONS Our findings suggest that while lithium may not act directly via 5-HTT or 5-HT1A to ameliorate depressive symptoms, pre-treatment binding may be a potential biomarker for successful treatment of BPD with lithium. CLINICAL TRIAL REGISTRATION PET and MRI Brain Imaging of Bipolar Disorder Identifier: NCT01880957; URL: https://clinicaltrials.gov/ct2/show/NCT01880957.

中文翻译：

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使用 5-HTT 和 5-HT1A PET 预测双相抑郁症的锂治疗反应。

背景锂是为数不多的双相抑郁症 (BPD) 的有效治疗方法之一，已被假设通过增强 5-羟色胺能传递发挥作用。尽管有临床前证据，但尚不清楚锂是否通过血清素系统起作用。在这里，我们检查了 5-羟色胺转运蛋白 (5-HTT) 或 5-羟色胺 1A 受体 (5-HT1A) 预处理结合预测锂治疗反应和缓解的潜力。我们假设较低的治疗前 5-HTT 和较高的治疗前 5-HT1A 结合将预测更好的临床反应。其他分析调查了 BPD 和健康对照之间的组差异以及治疗前后结合变化与临床反应之间的关系。目前处于抑郁发作期的 27 名无药物 BPD 患者接受了使用 5-HTT 示踪剂 [11C] DASB 的正电子发射断层扫描 (PET) 扫描，其中一部分还接受了使用 5-HT1A 示踪剂 [11C]-CUMI- 的 PET 扫描101 在锂单药治疗 8 周前后。代谢物校正的动脉输入函数用于估计结合潜力，与受体可用性成正比。14 名具有 [11C] DASB 和 [11C]-CUMI-101 治疗前扫描和 8 周治疗后临床评分的 BPD 患者被纳入预测分析，检查治疗前 5-HTT 或 5 -HT1A 或两者的组合来预测治疗后的临床评分。结果 我们发现较低的预处理 5-HTT 结合 (p = 0.003) 和较低的 5-HT1A 结合 (p = 0. 035）均与改善临床反应显着相关。治疗前 5-HTT 以 71% 的准确度（77% 的特异性，60% 的敏感性）预测缓解，而 5-HT1A 结合能够以 85% 的准确度（87% 的敏感性，80% 的特异性）预测缓解。使用 5-HTT 和 5-HT1A 的联合预测分析能够以 84.6% 的准确度（87.5% 的特异性，60% 的敏感性）预测缓解。附加分析 BPD 和对照治疗前或治疗后，结合变化不显着且与治疗反应无​​关 (p > 0.05)。结论 我们的研究结果表明，虽然锂可能不会通过 5-HTT 或 5-HT1A 直接作用以改善抑郁症状，但治疗前结合可能是锂成功治疗 BPD 的潜在生物标志物。双相情感障碍的临床试验注册 PET 和 MRI 脑成像标识符：NCT01880957；网址：https://clinicaltrials.gov/ct2/show/NCT01880957。