Rao M L, Kölsch H
Department of Psychiatry and Psychotherapy, Medical Department of the University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany.
Psychoneuroendocrinology. 2003 Apr;28 Suppl 2:83-96. doi: 10.1016/s0306-4530(02)00126-9.
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-l7beta 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-l7beta 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.
过去几年越来越多的证据表明，精神分裂症存在性别特异性差异，这会影响发病年龄、治疗效果以及阴性症状的患病率。就后者而言，在有阴性症状的精神分裂症患者的尸检大脑和脑脊液中，多巴胺能活性降低变得明显。去甲肾上腺素能活性的指标，如多巴胺β-羟化酶和代谢物MHPG，似乎会随着阴性症状患者出现的脑萎缩而降低。血清素能活性在阴性精神分裂症患者中往往较低，这类患者存在认知功能受损。在这些患者中，脑室扩大与阴性症状的严重程度、单胺活性低和脑葡萄糖代谢低有关。另一方面，也调节谷氨酸受体活性的非典型抗精神病药物提示了除胺能神经递质之外的另一种抗精神病作用机制。这些药物改善谷氨酸能传递并减少阴性症状；这表明谷氨酸能缺乏是多巴胺模型的一种延伸。谷氨酸-多巴胺相互作用说明了投射到皮层、纹状体和脑干下部之间的相互作用对于阴性症状表达的重要性。另一方面，最有效的雌性激素雌二醇-17β不仅影响第一性征和第二性征，还影响胚胎和胎儿的生长以及参与精神分裂症的脑胺能网络的发育。雌二醇-17β具有神经保护特性，这与精神分裂症的病程相关，这可能解释了精神分裂症在进展和治疗反应方面存在明显性别差异的原因。本综述试图更新并综合有关激素对精神分裂症阴性症状中神经元通路影响的信息。结果表明，雌二醇-17β会影响转运体和受体以及神经元系统形态外观，并且它可能是改善精神分裂症的神经保护系统的一个组成部分。
