MRC London Institute of Medical Sciences and Imperial College London Institute of Clinical Sciences, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.
Department of Psychiatry, University of Cambridge, Cambridge, UK.
Transl Psychiatry. 2021 Dec 6;11(1):614. doi: 10.1038/s41398-021-01741-9.
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.
心血管疾病是精神分裂症患者的主要死因。精神分裂症患者表现出同心性心脏重构（CCR）的证据，定义为左心室质量相对于舒张末期容积的增加。CCR 是心脏病的预测因子，但导致精神分裂症中这种情况的分子途径尚不清楚。我们旨在探讨高血压和非高血压途径与 CCR 的相关性及其在精神分裂症中的潜在分子基础。在这项多模态病例对照研究中，我们从精神分裂症患者和健康对照者（HCs）中收集了心脏和全身脂肪磁共振成像（MRI）、临床测量值以及几种已知可能导致 CCR 的心脏代谢生物标志物的血液水平，这些 HCs 是根据年龄、性别、种族和体表面积匹配的。在 50 名参与者中，有 34 名（68%）为男性。与 HCs 相比，精神分裂症患者的心脏同心性增加（d=0.71，95%CI：0.12，1.30；p=0.01），表明 CCR，但心脏总体含量或脂肪组织区域分布无差异。尽管心脏发生了变化，但精神分裂症患者并未表现出高血压 CCR 途径的激活；然而，他们表现出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），下游途径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的激活。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 的存在和代谢异常表型可能导致精神分裂症患者心血管风险增加。如果我们的结果得到证实，针对该途径的治疗可能会降低精神分裂症患者的心血管风险并减少由此导致的预期寿命损失。
