Effects of estrogen on brain development and neuroprotection-implications for negative symptoms in schizophrenia
Effects of estrogen on brain development and neuroprotection-implications for negative symptoms in schizophrenia
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DOI：
10.1016/s0306-4530(02)00126-9
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发表时间：
2003-04-01
影响因子：
3.7
通讯作者：
Kölsch, H
中科院分区：
文献类型：
--
作者：
Rao, ML;Kölsch, H
在过去几年中，越来越多的证据表明，精神分裂症存在性别差异，影响发病年龄、治疗结果和阴性症状的流行。对于后者，在尸检大脑和脑脊液中的精神分裂症患者的阴性症状的多巴胺能活性的减少变得明显。去甲肾上腺素能活性、多巴胺β-羟化酶和代谢产物MHPG的测量值似乎随着阴性症状患者的脑萎缩而降低。在认知功能受损的患者中，5-羟色胺能活性往往较低，如在阴性精神分裂症中所见。在这些患者中，心室扩大与阴性症状的严重程度、低单胺活性和低脑葡萄糖代谢有关。另一方面，非典型抗精神病药物也可调节谷氨酸受体活性，这表明除了胺能神经递质外，还有另一种抗精神病作用机制。这些药物改善多巴胺能传递并减少阴性症状;这表明多巴胺能缺乏是多巴胺模型的延伸。谷氨酸-多巴胺相互作用说明了向皮质、纹状体和下脑干的投射之间的串扰对于表达阴性多巴胺的重要性。另一方面，雌二醇-17 β是最有效的女性性激素，它不仅影响初级和第二性征，而且影响胚胎和胎儿的生长以及大脑胺能网络的发育，这与精神分裂症有关。雌二醇-17 β具有神经保护特性，这与精神分裂症的病程有关，这可能解释了精神分裂症进展和治疗反应方面的显著性别差异。本文综述了精神分裂症阴性症状中激素对神经通路的影响。这表明雌二醇-17 β影响转运蛋白和受体以及神经元系统的形态学外观，并且它可能是改善精神分裂症的神经保护系统的组成部分。(C)2003爱思唯尔科技有限公司版权所有。
Increasing evidence during the last few years suggests that there are gender-specific differences in schizophrenia, influencing the age of onset, treatment outcome and the prevalence of negative symptoms. With respect to the latter in postmortem brain and cerebrospinal fluid of schizophrenic patients with negative symptoms a reduction of dopaminergic activity became evident. Measures of noradrenergic activity, dopamine beta-hydroxylase and the metabolite MHPG, appear to decrease with brain atrophy seen in patients with negative symptoms. Serotonergic activity tends to be low in patients with impaired cognitive function as is seen in negative schizophrenia. In these patients ventricular enlargement is associated with the severity of negative symptoms, low monoamine activity and low cerebral glucose metabolism.On the other hand atypical antipsychotic drugs that modulate also glutamate receptor activity, suggest an additional alternative mechanism of antipsychotic action beyond aminergic neurotransmitters. These drugs improve glutamatergic transmission and decrease negative symptoms; this suggests a glutamatergic deficiency as an extension of the dopamine model.The glutamate-dopamine interaction illustrates the importance of cross-talk between projections to the cortex, striatum, and lower brainstem for the expression of negative symptomatology. On the other hand, estradiol-17beta the most potent female sex hormone influences not only primary and secondary sexual characteristics but also embryonal and fetal growth as well as development of the brain aminergic networks, which are involved in schizophrenia. Estradiol-17beta possesses neuroprotective properties, which are relevant for the course of schizophrenia and this may explain the pronounced gender differences with respect to progression and therapeutic response of schizophrenia. The present review attempts an update and synthesis of the information about the hormonal influence on neuronal pathways in negative symptoms of schizophrenia. It shows that estradiol-17beta influences transporters and receptors as well as the morphological appearance of neuronal systems and that it may be an integral part of the neuroprotective system ameliorating schizophrenia. (C) 2003 Elsevier Science Ltd. All rights reserved.