Goldman Morris B
Northwestern University, Department of Psychiatry, 446 East Ontario, Suite 7-100, Chicago, IL 60611, USA.
Schizophr Res. 2014 Aug;157(1-3):204-13. doi: 10.1016/j.schres.2014.06.001. Epub 2014 Jul 1.
To identify the mechanism of unexplained hyponatremia and primary polydipsia in schizophrenia and its relationship to the underlying psychiatric illness.
Briefly review previous studies that led to the conclusion the hyponatremia reflects altered hippocampal inhibition of peripheral neuroendocrine secretion. In greater detail, present the evidence supporting the hypothesis that circuit dysfunction associated with the hyponatremia and the polydipsia contributes to the underlying mental disorder.
Polydipsic patients with and without hyponatremia exhibit enhanced neuroendocrine responses to psychological stress in proportion to structural deformations on their anterior hippocampus, amygdala and anterior hypothalamus. Nonpolydipsic patients exhibit blunted responses and deformations on other hippocampal and amygdala surfaces. The deformations in polydipsic patients are also proportional to diminished peripheral oxytocin levels and impaired facial affect recognition that is reversed by intranasal oxytocin. The anterior hippocampus is at the hub of a circuit that modulates neuroendocrine and other responses to psychological stress and is implicated in schizophrenia. Preliminary data indicate that other measures of stress reactivity are also enhanced in polydipsics and that the functional connectivity of the hippocampus with the other structures in this circuitry differs in schizophrenia patients with and without polydipsia.
Polydipsia may identify a subset of schizophrenia patients whose enhanced stress reactivity contributes to their mental illness. Stress reactivity may be a symptom dimension of chronic psychosis that arises from circuit dysfunction that can be modeled in animals. Hence polydipsia could be a biomarker that helps to clarify the pathophysiology and heterogeneity of psychosis as well as identify novel therapies. Clinical investigators should consider obtaining indices of water balance, as these may help them unravel and more concisely interpret their findings. Basic researchers should assess if the polydipsic subset is a patient group particularly suitable to test hypotheses arising from their translational studies.
确定精神分裂症患者不明原因低钠血症和原发性烦渴的机制及其与潜在精神疾病的关系。
简要回顾先前得出低钠血症反映海马体对周围神经内分泌分泌抑制改变这一结论的研究。更详细地介绍支持以下假设的证据：与低钠血症和烦渴相关的回路功能障碍导致潜在精神障碍。
有和无低钠血症的烦渴患者，其神经内分泌对心理应激的反应增强，且与前海马体、杏仁核和下丘脑前部的结构变形程度成正比。非烦渴患者的反应迟钝，海马体和杏仁核其他表面存在变形。烦渴患者的变形也与外周催产素水平降低和面部情感识别受损成正比，而鼻内给予催产素可逆转这种情况。前海马体位于调节神经内分泌及其他心理应激反应的回路中心，且与精神分裂症有关。初步数据表明，烦渴患者的其他应激反应指标也增强，且在有和无烦渴的精神分裂症患者中，海马体与该回路中其他结构的功能连接不同。
烦渴可能识别出一部分精神分裂症患者，其增强的应激反应导致了他们的精神疾病。应激反应可能是慢性精神病的一个症状维度，源于可在动物模型中模拟的回路功能障碍。因此，烦渴可能是一种生物标志物，有助于阐明精神病的病理生理学和异质性，以及识别新的治疗方法。临床研究人员应考虑获取水平衡指标，因为这些指标可能有助于他们理清并更简洁地解释研究结果。基础研究人员应评估烦渴亚组是否是一个特别适合检验其转化研究中产生的假设的患者群体。
