Does diminished oxytocin modulate stress vulnerability in Schizophrenia

催产素减少是否会调节精神分裂症的应激脆弱性

基本信息

批准号：
7905947
负责人：
MORRIS Benjamin GOLDMAN
金额：
$ 24.12万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-04 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7905947
关键词：
Acute Adrenal Glands Affect Anterior Argipressin Behavioral Brain Cognitive deficits Corticotropin Data Diagnosis Discrimination Disease Emotional Emotions Equilibrium Exhibits Face Functional disorder Goals Hippocampus (Brain)Hormones Human Hyponatremia Hypothalamic structure Judgment Lead Life Mammals Measures Mediating Mental disorders Modality Neurohormones Neuropeptides Neurosecretory Systems Nose Oral Oxytocin Pathology Patients Phase Pilot Projects Pituitary Gland Plasma Polydipsia Psychological Stress Psychotic Disorders Public Health Randomized Regulation Research Schizophrenia Social Behavior Social Functioning Stress Structure Testing Therapeutic Agents Vasopressin Antagonist Vasopressins Virulent Water Water Intoxication Work base biological adaptation to stress deficit syndrome disability hormone regulation hypothalamic-pituitary-adrenal axis improved indexing innovation insight man novel novel therapeutics public health relevance research study response severe mental illness social stress tolerance

项目摘要

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.

描述（由申请人提供）：我们的工作表明，水不平衡的精神分裂症患者的下丘脑 - 垂体 - 肾上腺（HPA）轴的活性增强了，响应心理压力的抗利尿剂激素（精氨酸加压素：AVP）的活性增强。此外，这些发现似乎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异常可能有助于威胁生命的水中毒，而HPA轴异常可能是海马介导的更为普遍的海马介导的脆弱性的一部分。我们的试点调查结果表明，这些患者的密切相关的神经激素（催产素）也存在缺陷，这些患者可能有助于增强AVP和HPA轴对心理压力的反应，以及对以极端社会缺陷为特征的精神分裂症（即赤字综合征）的特别有毒形式。这项研究的目的是确认催产素调节中的假定缺陷，并开始确定可以通过催产素治疗来恢复神经内分泌和行为功能的程度。目的，我将确认或反驳水不平衡患者的催产素水平较低。 AIM II将评估血浆催产素与社会缺陷与赤字综合征之间的关联。 AIM III将评估鼻内催产素是否使水平患者的AVP和HPA轴对压力的反应增强。 AIM IV将确定鼻内催产素是否可以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，可以直接导致新的治疗方式，以实现严重精神疾病的顽固性和有毒特征。公共卫生相关性：精神分裂症是人类已知的最破坏性疾病之一。我们理解和治疗这种疾病的努力是基于对大脑调节激素如何决定压力和社会情况的反应的最新见解。我们研究一群精神分裂症患者，他们在调节这些激素中表现出异常，我们的数据表明，这与他们的压力耐受性差和情绪判断受损有关。我们想看看是否可以通过鼻喷雾剂给出一种激素（催产素）来逆转这些缺陷。这项工作有可能提高我们对导致精神分裂症的原因以及鉴定新疗法的理解。