Scantamburlo G, Ansseau M, Legros J J
Service de Psychiatrie et de Psychologie Médicale, CHU, Sart Tilman, Liège, Beigique.
Encephale. 2001 May-Jun;27(3):245-59.
Effects of different psychological stimuli on oxytocin (OT) and vasopressin (AVP) secretion are reviewed in animals and in humans. The secretion of neuropituitary hormones is also discussed in various psychiatric diseases such an anorexia nervosa, bipolar disorder, schizophrenia and obsessive-compulsive disorder. AVP and OT are secreted into the hypophyseal portal circulation by neurons which project from the paraventricular nucleus to the external zone of the median eminence. AVP and OT-containing neurons in the suprachiasmatic and paraventricular nuclei project to limbic areas, including the hippocampus, the subiculum, the ventral nucleus of the amygdala and the nucleus of the diagonal band. Specific AVP receptors which are pharmacologically different from the pressor and antidiuretic AVP receptors have been found in the anterior pituitary. OT receptors have been identified in a variety of forebrain sites. The neurohypophyseal secretion is regulated by the cholinergic muscarinic, histaminergic and beta-adrenergic systems. Stress alters the secretion of one or more of the hypothalamic factors which interact at the pituitary to increase the secretion of ACTH. AVP and OT have been shown to modulate the effect of Corticotropin-Releasing Factor (CRF) on ACTH secretion and appear to play a key role in mediating the ACTH response to stress. Although AVP is a relatively weak secretagogue for ACTH, it markedly potentiates the activity of CRF both in vitro and in vivo. The role of OT is more complex. In vitro, OT stimulates ACTH release at high doses whereas in human it inhibits ACTH secretion at low doses. The type of stressor appear to determine the relative importance of these secretatogues in ACTH response. Several recent studies indicate that psychological stressors display a similar degree of variety of secretagogue release patterns as was found earlier for physical stressors. A bewildering array of technique produces a bewildering array of conclusions. In rats, OT may be an important secretagogue during a novel stimulus, whereas the role for AVP is less clear. Indeed two studies out of ten suggest a stimulating role for AVP. In response to frustration and submission, OT and AVP are secreted. Regarding social isolation, results are difficult to interpret and the role of AVP could be species-dependent. In contrast plasma OT levels do not change. After restraint, ACTH release is primarily mediated by the active increase of OT and AVP does not appear to play a role. When restraint is associated with moderate levels of physical components and during immobilisation, all two secretagogs are involved in the ACTH response. With fear, ACTH response appears to be driven by OT. In humans, one study indicates that high emotionality women increase plasma OT in response to uncontrollable noise. Various neuroendocrine dysregulations have been observed in psychiatric disease. Either an increase or a decrease of the hypothalamic-pituitary-adrenal (HPA) function have been described in several illnesses. Effects of OT appear to be reciprocal to the effects of AVP. OT has been called the "amnestic" neuropeptide due to its capacity to attenuate memory consolidation and retrieval. AVP exhibits a central activating action on mood, memory and selective attention. Underweight patients with anorexia nervosa have abnormally high levels of centrally directed AVP and reduced OT levels. These modifications could enhance the retention of cognitive distortions of aversive consequences of eating. Patients with bipolar disorder show a biphasic secretion of AVP. Depressive episodes are associated with decreased vasopressinergic activity whereas manic episodes involve an increased release. AVP might be responsible for an increased catecholamine activity. In addition, lithium could act as an antagonist to AVP. In schizophrenic patients, studies using the apomorphine stimulation suggest increased oxytoninergic and decreased vasopressinergic functions. These findings are consistent with the beneficial role of AVP on schizophrenic symptoms noted in several trials. The increased OT could be responsible for "positive" symptomatology such as delusions and hallucinations. Obsessive compulsive disorder (OCD) includes a range of cognitive and behavioral disturbances that could be influenced by OT. In animals, several studies have emphasized the role of AVP in promoting repetitive grooming behaviors and maintaining conditioned response to aversive stimuli. In OCD patients, one study have reported that AVP/OT ratio was negatively correlated with symptom severity. However, an independent report found similar AVP concentrations in OC patients without a personal or family history of tic disorder and in normal subjects. Whether these modifications are only a consequence of the central disturbances or whether those peptides could participate in the pathogenesis of these affections remains to be elucidated.
本文综述了不同心理刺激对动物和人类催产素（OT）和血管加压素（AVP）分泌的影响。还讨论了这些神经垂体激素在各种精神疾病（如神经性厌食症、双相情感障碍、精神分裂症和强迫症）中的分泌情况。AVP和OT由从室旁核投射到正中隆起外侧区的神经元分泌到垂体门脉循环中。视交叉上核和室旁核中含AVP和OT的神经元投射到边缘区域，包括海马体、下托、杏仁核腹侧核和斜角带核。在前垂体中发现了与升压和抗利尿AVP受体药理学不同的特定AVP受体。OT受体已在多种前脑部位被鉴定出来。神经垂体的分泌受胆碱能毒蕈碱、组胺能和β-肾上腺素能系统调节。应激会改变一种或多种下丘脑因子的分泌，这些因子在垂体相互作用以增加促肾上腺皮质激素（ACTH）的分泌。AVP和OT已被证明可调节促肾上腺皮质激素释放因子（CRF）对ACTH分泌的作用，并且似乎在介导ACTH对应激的反应中起关键作用。虽然AVP对ACTH来说是一种相对较弱的促分泌素，但它在体外和体内均能显著增强CRF的活性。OT的作用更为复杂。在体外，高剂量的OT刺激ACTH释放，而在人体内，低剂量的OT抑制ACTH分泌。应激源的类型似乎决定了这些促分泌素在ACTH反应中的相对重要性。最近的几项研究表明，心理应激源与早期发现的物理应激源一样，呈现出多种促分泌素释放模式。一系列令人困惑的技术得出了一系列令人困惑的结论。在大鼠中，在新异刺激期间OT可能是一种重要的促分泌素，而AVP的作用尚不清楚。实际上，十项研究中有两项表明AVP具有刺激作用。在应对挫折和屈服时，OT和AVP会分泌。关于社会隔离，结果难以解释，AVP的作用可能因物种而异。相比之下，血浆OT水平没有变化。束缚后，ACTH的释放主要由OT的活性增加介导，AVP似乎不起作用。当束缚与适度的身体因素相关以及在固定期间，两种促分泌素都参与ACTH反应。在恐惧状态下，ACTH反应似乎由OT驱动。在人类中，一项研究表明，情绪易激动的女性在面对无法控制的噪音时血浆OT会增加。在精神疾病中观察到了各种神经内分泌失调。在几种疾病中都描述了下丘脑 - 垂体 - 肾上腺（HPA）功能的增加或减少。OT的作用似乎与AVP的作用相反。由于OT能够减弱记忆巩固和提取，它被称为“遗忘性”神经肽。AVP对情绪、记忆和选择性注意力具有中枢激活作用。神经性厌食症的体重过轻患者中枢导向的AVP水平异常高，OT水平降低。这些改变可能会增强对进食厌恶后果的认知扭曲的保留。双相情感障碍患者表现出AVP的双相分泌。抑郁发作与血管加压素能活性降低有关，而躁狂发作则涉及释放增加。AVP可能导致儿茶酚胺活性增加。此外，锂可能作为AVP的拮抗剂。在精神分裂症患者中，使用阿扑吗啡刺激的研究表明催产素能功能增加，血管加压素能功能降低。这些发现与几项试验中观察到的AVP对精神分裂症症状的有益作用一致。OT增加可能导致“阳性”症状，如妄想和幻觉。强迫症（OCD）包括一系列认知和行为障碍，可能受OT影响。在动物中，多项研究强调了AVP在促进重复梳理行为和维持对厌恶刺激的条件反应中的作用。在OCD患者中，一项研究报告称AVP/OT比值与症状严重程度呈负相关。然而，一份独立报告发现，没有抽动障碍个人或家族史的OC患者与正常受试者的AVP浓度相似。这些改变仅仅是中枢紊乱的结果，还是这些肽可能参与这些疾病的发病机制，仍有待阐明。
