Mehta Urvakhsh Meherwan, Roy Neelabja, Bahuguna Ashutosh, Kotambail Ananthapadmanabha, Arunachal Gautham, Venkatasubramanian Ganesan, Thirthalli Jagadisha
Department of Psychiatry, National Institute of Mental Health and Neuro-Sciences (NIMHANS), Bangalore 560029, India.
Department of Psychiatry, National Institute of Mental Health and Neuro-Sciences (NIMHANS), Bangalore 560029, India.
Psychiatry Res. 2024 Dec;342:116201. doi: 10.1016/j.psychres.2024.116201. Epub 2024 Sep 18.
We aimed to assess the incremental value of schizophrenia polygenic risk score (PgRS) and resting-state functional brain connectivity (rsFC) when added to clinical data in predicting the six-week response to oral risperidone (Risperdal) in schizophrenia. Fifty-seven, 54, and 43 individuals in a group of never-before-treated first-episode schizophrenia had good quality whole-genome sequencing (10x), rsFC, and both genomic and rsFC data, respectively, at baseline. Symptom severity ratings were obtained at baseline and six-weeks of oral risperidone (Risperdal) treatment. The primary outcome was the percentage change in the Positive and Negative Syndrome Scale Total scores after risperidone (Risperdal) treatment. Clinical, PgRS, and rsFC determinants of treatment response were first evaluated independently. Subsequently, three blocks of hierarchical multiple regression analyses with leave-one-out cross-validation (n = 43), were implemented to study clinical, clinical + PgRS and clinical + PgRS + rsFC determinants of treatment response. While the combined clinical variables did not show a statistically significant prediction of treatment response, adding PgRS (9 % R change) and rsFC (26 % R change) in hierarchical steps, significantly improved the overall proportion of variance explained in treatment response. This proof-of-concept investigation underscores the incremental benefits offered by genetic and neuroimaging metrics over clinical measures in determining prospectively-ascertained short-term treatment response in first-episode schizophrenia.
我们旨在评估精神分裂症多基因风险评分（PgRS）和静息态脑功能连接（rsFC）在添加到临床数据中时，对预测精神分裂症患者口服利培酮（维思通）六周反应的增量价值。一组从未接受过治疗的首发精神分裂症患者中，分别有57例、54例和43例在基线时具有高质量的全基因组测序（10x）、rsFC以及基因组和rsFC数据。在基线和口服利培酮（维思通）治疗六周时获得症状严重程度评分。主要结局是利培酮（维思通）治疗后阳性和阴性症状量表总分的百分比变化。首先独立评估治疗反应的临床、PgRS和rsFC决定因素。随后，进行了三个层次的多元回归分析，并采用留一法交叉验证（n = 43），以研究治疗反应的临床、临床+PgRS和临床+PgRS+rsFC决定因素。虽然综合临床变量对治疗反应的预测没有统计学意义，但在分层步骤中添加PgRS（R变化9%）和rsFC（R变化26%），显著提高了治疗反应中可解释的总体方差比例。这项概念验证研究强调了在确定首发精神分裂症前瞻性确定的短期治疗反应方面，遗传和神经影像学指标相对于临床测量的增量益处。
