Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada,
Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, Toronto, Ontario, Canada,
Neuropsychobiology. 2023;82(3):168-178. doi: 10.1159/000529637. Epub 2023 Apr 4.
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.
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.
There were no genome-wide significant associations with either remission or relapse. However, at a suggestive threshold, SNP rs1026501 (31 kb 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 treatments 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.
Our analyses provide preliminary insights into the genetic architecture of remission and relapse in a well-characterized group of patients with psychotic depression.
对于与精神病性抑郁症治疗结果相关的遗传因素知之甚少。我们探讨了经药物治疗的精神病性抑郁症缓解和复发的基因组相关性。
对 171 名年龄在 18-85 岁之间、有精神病性抑郁发作的男性和女性进行了基因组分析，他们参加了精神病性抑郁症药物治疗研究 II（STOP-PD II）。参与者接受了为期 12 周的开放性舍曲林加奥氮平治疗；那些在 8 周稳定期后达到缓解或接近缓解并保持缓解的患者有资格参加一项为期 36 周的随机对照试验，该试验比较了舍曲林加奥氮平与舍曲林加安慰剂在预防复发方面的效果。
没有与缓解或复发有全基因组显著关联的 SNP。然而，在一个提示性的阈值下，整个样本中的 SNP rs1026501（距 SYNPO2 31 kb）和欧洲血统亚样本中的 rs6844137（SYNPO2 内含子区域内）与缓解的可能性降低有关。在多基因风险分析中，接受抗抑郁治疗后有更大改善的参与者达到缓解的可能性更高。那些达到缓解且具有更高的阿尔茨海默病多基因风险的患者，复发的可能性显著降低。
我们的分析为具有明确特征的精神病性抑郁症患者缓解和复发的遗传结构提供了初步的见解。
