Abstract：
Cardiovascular diseases are the leading cause of death in schizophrenia. Patients with schizophrenia show evidence of concentric cardiac remodelling (CCR), defined as an increase in left-ventricular mass over end-diastolic volumes. CCR is a predictor of cardiac disease, but the molecular pathways leading to this in schizophrenia are unknown. We aimed to explore the relevance of hypertensive and non-hypertensive pathways to CCR and their potential molecular underpinnings in schizophrenia. In this multimodal case-control study, we collected cardiac and whole-body fat magnetic resonance imaging (MRI), clinical measures, and blood levels of several cardiometabolic biomarkers known to potentially cause CCR from individuals with schizophrenia, alongside healthy controls (HCs) matched for age, sex, ethnicity, and body surface area. Of the 50 participants, 34 (68%) were male. Participants with schizophrenia showed increases in cardiac concentricity (d = 0.71, 95% CI: 0.12, 1.30; p = 0.01), indicative of CCR, but showed no differences in overall content or regional distribution of adipose tissue compared to HCs. Despite the cardiac changes, participants with schizophrenia did not demonstrate activation of the hypertensive CCR pathway; however, they showed evidence of adipose dysfunction: adiponectin was reduced (d = -0.69, 95% CI: -1.28, -0.10; p = 0.02), with evidence of activation of downstream pathways, including hypertriglyceridemia, elevated C-reactive protein, fasting glucose, and alkaline phosphatase. In conclusion, people with schizophrenia showed adipose tissue dysfunction compared to body mass-matched HCs. The presence of non-hypertensive CCR and a dysmetabolic phenotype may contribute to excess cardiovascular risk in schizophrenia. If our results are confirmed, acting on this pathway could reduce cardiovascular risk and resultant life-years lost in people with schizophrenia.
摘要：
心血管疾病是精神分裂症患者死亡的主要原因。精神分裂症患者表现出同心心脏重塑（CCR）的证据，定义为左心室质量超过舒张末期容积的增加。CCR是心脏病的预测因子,但是导致精神分裂症的分子途径是未知的。我们旨在探讨精神分裂症中高血压和非高血压通路与CCR及其潜在分子基础的相关性。在这项多模态案例控制研究中，我们收集了心脏和全身脂肪磁共振成像（MRI），临床措施,以及已知可能导致精神分裂症患者CCR的几种心脏代谢生物标志物的血液水平，除了年龄匹配的健康对照（HCs），性别,种族,和体表面积。在50名参与者中，34(68%)为男性。精神分裂症患者的心脏同心度增加(d=0.71,95%CI:0.12,1.30;p=0.01),指示CCR，但与HC相比，脂肪组织的总体含量或区域分布没有差异。尽管心脏有变化,精神分裂症患者未发现高血压CCR通路激活;他们显示了脂肪功能障碍的证据：脂联素降低（d=-0.69，95％CI：-1.28，-0.10；p=0.02），有下游途径激活的证据，包括高甘油三酯血症,C反应蛋白升高，空腹血糖,和碱性磷酸酶。总之,与体重匹配的HCs相比,精神分裂症患者表现出脂肪组织功能障碍.非高血压CCR和代谢异常表型的存在可能导致精神分裂症患者心血管风险过高。如果我们的结果得到证实,作用于这一途径可以降低精神分裂症患者的心血管风险和由此导致的寿命损失。
