Does diminished oxytocin modulate stress vulnerability in Schizophrenia

描述（由申请人提供）：我们的工作表明，水失衡的精神分裂症患者对心理应激的反应是下丘脑-垂体-肾上腺（HPA）轴和抗利尿激素（精氨酸加压素：AVP）的活性增强。此外，这些发现似乎可归因于海马功能障碍，这反过来又可能与潜在的精神疾病直接相关。AVP异常可能导致危及生命的水中毒和HPA轴异常可能是一个更普遍的大脑介导的脆弱性心理压力的一部分。我们的初步研究结果表明，也有一个赤字密切相关的神经激素，催产素，在这些患者中，可能有助于增强AVP和HPA轴的反应，心理压力，以及一个特别致命的形式的精神分裂症（即赤字综合征）的特点是极端的社会赤字。本研究的目的是证实催产素调节的假定缺陷，并开始确定催产素治疗可以恢复神经内分泌和行为功能的程度。目的我将证实或反驳水失衡患者的催产素水平较低。目的II将评估血浆催产素与社会缺陷和缺陷综合征之间的关联。目的III将评估鼻内催产素是否使水平衡患者对应激的增强的AVP和HPA轴反应正常化。目的IV将确定鼻内催产素是否改善低血浆催产素患者的社会缺陷。这些探索性研究具有创新性，可能直接导致针对严重精神疾病的顽固性和致命性特征的新治疗方式。公共卫生相关性：精神分裂症是人类所知的最具破坏性的疾病之一。我们对这种疾病的理解和治疗是基于最近对大脑调节的激素如何决定我们对压力和社会情况的反应的见解。我们研究了一组精神分裂症患者，他们在这些激素的调节方面表现出异常，我们的数据表明，这与他们的压力耐受力差和情绪判断受损有关。我们想看看我们是否可以通过鼻腔喷雾剂给予其中一种激素（催产素）来逆转这些缺陷。这项工作有可能增加我们对精神分裂症病因的理解，并确定新的治疗方法。

DESCRIPTION (provided by applicant): Our work indicates that schizophrenic patients with water imbalance have enhanced activity of the hypothalamic-pituitary-adrenal (HPA) axis and the antidiuretic hormone (arginine vasopressin: AVP) in response to psychological stress. Furthermore, these findings appear attributable to hippocampal dysfunction, which may in turn be directly related to the underlying psychiatric disorder. The AVP abnormality likely contributes to life threatening water intoxication and the HPA axis abnormality may be part of a more general hippocampal-mediated vulnerability to psychological stress. Our pilot findings indicate that there is also a deficit in the closely related neurohormone, oxytocin, in these patients that may contribute to enhanced AVP and HPA axis responses to psychological stress, as well as to a particularly virulent form of schizophrenia (i.e. deficit syndrome) characterized by extreme social deficits. The goal of this study is to confirm the putative deficits in oxytocin regulation, and begin to determine the extent that neuroendocrine and behavioral functions can be restored with oxytocin treatment. Aim I will confirm or disprove that oxytocin levels are lower in patients with water imbalance. Aim II will assess the association between plasma oxytocin versus social deficits and the deficit syndrome. Aim III will assess if intranasal oxytocin normalizes the enhanced AVP and HPA axis responses to stress in patients with water balance. Aim IV will determine if intranasal oxytocin ameliorates social deficits in patients with low plasma oxytocin. These exploratory studies are innovative and could directly lead to new therapeutic modalities for intractable and virulent features of severe mental illness. PUBLIC HEALTH RELEVANCE: Schizophrenia is one of the most devastating illnesses known to man. Our efforts to understand and treat this disease are based on recent insights into how hormones regulated by the brain determine our responses to stress and to social situations. We study a group of people with schizophrenia who exhibit abnormalities in the regulation of these hormones, which our data suggest, are related to their poor stress tolerance and impaired emotional judgment. We want to see if we can reverse these deficits by giving one of the hormones (oxytocin) by a nasal spray. This work has the potential to increase our understanding of what causes schizophrenia, as well as to identify novel therapies.