Oliva Vincenzo, Martone Alfonso, Fanelli Giuseppe, Domschke Katharina, Minelli Alessandra, Gennarelli Massimo, Martini Paolo, Bortolomasi Marco, Maron Eduard, Squassina Alessio, Pisanu Claudia, Kasper Siegfried, Zohar Joseph, Souery Daniel, Montgomery Stuart, Albani Diego, Forloni Gianluigi, Ferentinos Panagiotis, Rujescu Dan, Mendlewicz Julien, De Ronchi Diana, Baune Bernhard T, Serretti Alessandro, Fabbri Chiara
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Departament de Medicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), c. Casanova, 143, 08036, Barcelona, Spain.
Neurosci Appl. 2024 Jan 22;3:103937. doi: 10.1016/j.nsa.2024.103937. eCollection 2024.
A significant proportion of patients with major depressive disorder (MDD) do not experience remission after one or more pharmacological treatments. Research has explored brain structural measures, particularly hippocampal volume, as potential predictors of treatment response, as well as genetic factors. This study investigated the association of polygenic scores (PGSs) for seven subcortical brain volumes (including the hippocampus, nucleus accumbens, amygdala, and caudate nucleus) with treatment non-response and non-remission in MDD. Patients with MDD were recruited in the context of five clinical studies, including a total of 3637 individuals. PGSs were estimated using a Bayesian framework and continuous shrinkage priors (PRS-CS-auto) after standard genotype quality control and imputation. Logistic regressions were performed between PGSs and non-response or non-remission in each sample, adjusting for age, sex, baseline symptom severity, recruitment sites, and population stratification. Results were meta-analysed across samples, using a random-effect model. No association was significant in the meta-analysis after Bonferroni correction. The top finding was found for the caudate volume PGS and non-remission (OR = 1.09, 95% CI = 1.01-1.19, p = 0.036), with no evidence of heterogeneity. Leave-one-out sensitivity analyses showed that this result was influenced by the two largest samples in the meta-analysis. This result should be considered as preliminary as it did not reach the Bonferroni-adjusted significance threshold. Future studies with greater statistical power may enhance the predictive performance of PGSs and contribute to the identification of polygenic predictors of treatment outcomes in MDD, contributing to precision psychiatry.
相当一部分重度抑郁症（MDD）患者在接受一种或多种药物治疗后并未实现症状缓解。研究探索了脑结构测量指标，特别是海马体体积，以及基因因素，将其作为治疗反应的潜在预测指标。本研究调查了七种皮质下脑区体积（包括海马体、伏隔核、杏仁核和尾状核）的多基因分数（PGS）与MDD治疗无反应和未缓解之间的关联。MDD患者是在五项临床研究中招募的，共纳入3637名个体。在进行标准基因型质量控制和插补后，使用贝叶斯框架和连续收缩先验（PRS-CS-auto）估计PGS。在每个样本中，对PGS与无反应或未缓解情况进行逻辑回归分析，并对年龄、性别、基线症状严重程度、招募地点和群体分层进行校正。使用随机效应模型对各样本结果进行荟萃分析。经Bonferroni校正后，荟萃分析中无显著关联。尾状核体积PGS与未缓解情况的关联最为显著（OR = 1.09，95% CI = 1.01 - 1.19，p = 0.036），且无异质性证据。留一法敏感性分析表明，该结果受荟萃分析中两个最大样本的影响。由于未达到Bonferroni校正后的显著性阈值，该结果应视为初步结果。未来具有更大统计效力 的研究可能会提高PGS的预测性能，并有助于识别MDD治疗结果的多基因预测指标，从而推动精准精神病学的发展。
