Supplementary Material for: Genomic Investigation of Remission and Relapse of Psychotic Depression Treated with Sertraline Plus Olanzapine: the STOP-PD II Study

Introduction: Little is known regarding genetic factors associated with treatment outcome of psychotic depression. We explored genomic associations of remission and relapse of psychotic depression treated with pharmacotherapy. Methods: Genomic analyses were performed in 171 men and women aged 18-85 years with an episode of psychotic depression who participated in the Study of the Pharmacotherapy of Psychotic Depression II (STOP-PD II). Participants were treated with open-label sertraline plus olanzapine for up to 12 weeks; those who achieved remission or near-remission and maintained it following 8 weeks of stabilization were eligible to participate in a 36-week randomized controlled trial that compared sertraline plus olanzapine with sertraline plus placebo in preventing relapse. Results: There were no genome-wide significant associations with either remission or relapse. However, at a suggestive threshold, SNP rs1026501 (31kb from SYNPO2) in the whole sample and rs6844137 (within the intronic region of SYNPO2) in the European-ancestry subsample were associated with a decreased likelihood of remission. In polygenic risk analyses, participants who had greater improvement after antidepressant treatment showed a higher likelihood of reaching remission. Those who achieved remission and had a higher polygenic risk for Alzheimer’s disease had a significantly decreased likelihood of relapse. Conclusion: Our analyses provide preliminary insights into the genetic architecture of remission and relapse in a well-characterized group of patients with psychotic depression.

引言：目前学界对与精神病性抑郁症治疗结局相关的遗传因素所知甚少。本研究针对接受药物治疗的精神病性抑郁症患者的缓解与复发情况，探究其基因组关联特征。
方法：本研究纳入参与《精神病性抑郁症药物治疗研究II（Study of the Pharmacotherapy of Psychotic Depression II, STOP-PD II）》的171名年龄介于18~85岁的精神病性抑郁症发作患者，开展基因组分析。受试者接受开放标签舍曲林（sertraline）联合奥氮平（olanzapine）治疗，疗程最长为12周；在经过8周稳定期后达到缓解或近似缓解并维持该状态的受试者，可进入为期36周的随机对照试验，该试验比较舍曲林联合奥氮平与舍曲林联合安慰剂预防复发的疗效。
结果：未发现与缓解或复发存在全基因组显著关联的遗传位点。不过在提示性关联阈值下，全样本中的单核苷酸多态性（Single Nucleotide Polymorphism, SNP）rs1026501（位于SYNPO2基因下游31kb处），以及欧洲血统亚样本中的rs6844137（位于SYNPO2基因内含子区域内），均与缓解概率降低相关。在多基因风险分析中，抗抑郁治疗后改善程度更显著的受试者，达到缓解的概率更高。达到缓解且阿尔茨海默病多基因风险更高的受试者，其复发概率显著降低。
结论：本研究针对一组特征明确的精神病性抑郁症患者群体开展分析，为阐明精神病性抑郁症缓解与复发的遗传结构提供了初步见解。