Bäckman Julia, Wallert John, Halvorsen Matthew, Crowley James J, Mataix-Cols David, Rück Christian
Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, USA.
Discov Ment Health. 2025 Jun 2;5(1):82. doi: 10.1007/s44192-025-00213-6.
Depressive and anxiety disorders are leading causes of disability globally. Therapist-guided, Internet-delivered cognitive behaviour therapy (ICBT) is an established treatment for depression and anxiety, but a considerable proportion of treated patients do not achieve sufficient improvement. Predicting symptom changes based solely on clinical variables is challenging, and genetic data could offer additional insights into who might benefit most from ICBT. We conducted a study of 2,668 adults (62% women, average age 35.6) from the Swedish MULTI-PSYCH cohort, to investigate the association between polygenic scores (PGS) for eight psychiatric and cognitive traits and symptom change after ICBT. All participants had been diagnosed with depression, panic disorder or social anxiety disorder. The primary outcome was a harmonised symptom score. Using large discovery data sets, PGSs were computed for ADHD, autism spectrum disorder, bipolar disorder, major depressive disorder and schizophrenia, cross-disorder psychopathology, educational attainment, and intelligence. Linear mixed-effects models identified a significant negative association between PGS for educational attainment (PGS-EDU) and symptom severity in the adjusted model (B = - 0.69, p = 0.034), suggesting that a higher PGS-EDU was associated with lower symptom severity. There was also a significant PGS-EDU*time interaction, indicating that PGS-EDU also influenced the symptom change rate. When excluding outliers, these effects remained statistically significant. No other PGSs were statistically significant. Sensitivity analysis showed that self-reported education level provided a stronger association to the outcome than PGS-EDU, indicating that the potential clinical applications of PGS are currently limited. While these results await replication, they could have important implications for how the ICBT could be adapted to suit a wider portion of the population.
抑郁和焦虑症是全球致残的主要原因。由治疗师指导、通过互联网提供的认知行为疗法（ICBT）是治疗抑郁和焦虑的既定方法，但相当一部分接受治疗的患者没有取得足够的改善。仅根据临床变量预测症状变化具有挑战性，而基因数据可以为谁可能从ICBT中获益最多提供更多见解。我们对来自瑞典多心理队列的2668名成年人（62%为女性，平均年龄35.6岁）进行了一项研究，以调查八种精神和认知特征的多基因评分（PGS）与ICBT后症状变化之间的关联。所有参与者均被诊断患有抑郁症、恐慌症或社交焦虑症。主要结果是一个统一的症状评分。利用大型发现数据集，计算了注意力缺陷多动障碍、自闭症谱系障碍、双相情感障碍、重度抑郁症和精神分裂症、跨障碍精神病理学、教育程度和智力的PGS。线性混合效应模型在调整模型中确定了教育程度PGS（PGS-EDU）与症状严重程度之间存在显著负相关（B = -0.69，p = 0.034），表明较高的PGS-EDU与较低的症状严重程度相关。PGS-EDU*时间交互作用也显著，表明PGS-EDU也影响症状变化率。排除异常值后，这些效应在统计学上仍然显著。没有其他PGS具有统计学意义。敏感性分析表明，自我报告的教育水平与结果的关联比PGS-EDU更强，表明PGS目前的潜在临床应用有限。虽然这些结果有待重复验证，但它们可能对ICBT如何适应更广泛人群具有重要意义。
