Refisch Alexander, Papiol Sergi, Schumann Andy, Malchow Berend, Bär Karl-Jürgen
Department of Psychiatry and Psychotherapy, Jena University Hospital, Philosophenweg 3, 07743, Jena, Germany.
Department of Psychiatry and Psychotherapy, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.
Eur Arch Psychiatry Clin Neurosci. 2025 Apr;275(3):863-871. doi: 10.1007/s00406-024-01933-6. Epub 2024 Nov 6.
Cardiac autonomic dysfunction (CADF), mainly characterized by increased heart rate, decreased heart rate variability, and loss of vagal modulation, has been extensively described in patients with schizophrenia (SCZ) and their healthy first-degree relatives. As such, it represents an apparent physiological link that contributes to the increased cardiovascular mortality in these patients. Common genetic variation is a putative underlying mechanism, along with lifestyle factors and antipsychotic medications. However, the extent to which CADF is associated with genetic factors for SCZ is unknown. A sample of 83 drug-naive SCZ patients and 96 healthy controls, all of European origin, underwent a 30-minute autonomic assessment under resting conditions. We incorporated parameters from several domains into our model, including time and frequency domains (mean heart rate, low/high frequency ratio) and compression entropy, each of which provides different insights into the dynamics of cardiac autonomic function. These parameters were used as outcome variables in linear regression models with polygenic risk scores (PRS) for SCZ as predictors and age, sex, BMI, smoking status, principal components of ancestry and diagnosis as covariates. Of the three CADF parameters, SCZ PRS was significantly associated with mean heart rate in the combined case/control sample. However, this association was was no longer significant after including diagnosis as a covariate (p = 0.29). In contrast, diagnostic status is statistically significant for all three CADF parameters, accounting for a significantly greater proportion of the variance in mean heart rate compared to SCZ PRS (approximately 16% vs. 4%). Despite evidence for a common genetic basis of CADF and SCZ, we were unable to provide further support for an association between the polygenic burden of SCZ and cardiac autonomic function beyond the diagnostic state. This suggests that there are other important characteristics associated with SCZ that lead to CADF that are not captured by SCZ PRS.
心脏自主神经功能障碍（CADF）主要表现为心率加快、心率变异性降低以及迷走神经调节功能丧失，在精神分裂症（SCZ）患者及其健康的一级亲属中已有广泛描述。因此，它代表了一种明显的生理联系，导致这些患者心血管死亡率增加。常见的基因变异是一种潜在的潜在机制，同时还有生活方式因素和抗精神病药物。然而，CADF与SCZ遗传因素的关联程度尚不清楚。对83名未使用过药物的SCZ患者和96名健康对照者（均为欧洲血统）进行了静息状态下30分钟的自主神经评估。我们将来自多个领域的参数纳入模型，包括时域和频域（平均心率、低频/高频比值）以及压缩熵，每个参数都能为心脏自主神经功能的动态变化提供不同的见解。这些参数被用作线性回归模型的结果变量，以SCZ的多基因风险评分（PRS）作为预测因子，年龄、性别、体重指数、吸烟状况、祖先主成分和诊断作为协变量。在三个CADF参数中，SCZ PRS与合并病例/对照样本中的平均心率显著相关。然而，将诊断作为协变量纳入后，这种关联不再显著（p = 0.29）。相比之下，诊断状态对所有三个CADF参数均具有统计学意义，与SCZ PRS相比，诊断状态在平均心率方差中所占比例显著更大（约16%对4%）。尽管有证据表明CADF和SCZ存在共同的遗传基础，但除了诊断状态外，我们无法为SCZ的多基因负担与心脏自主神经功能之间的关联提供进一步支持。这表明，与SCZ相关的还有其他重要特征导致CADF，而这些特征未被SCZ PRS所捕捉。
