An inverse relationship between cortisol and BDNF levels in schizophrenia: Data from human postmortem and animal studies
An inverse relationship between cortisol and BDNF levels in schizophrenia: Data from human postmortem and animal studies
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DOI：
10.1016/j.nbd.2010.04.017
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发表时间：
2010-09-01
影响因子：
6.1
通讯作者：
Pillai, Anilkumar
中科院分区：
文献类型：
--
作者：
Issa, George;Wilson, Christina;Pillai, Anilkumar
应激和应激诱导的糖皮质激素与包括精神分裂症在内的许多神经精神疾病有关。此外，神经营养因子，脑源性神经营养因子（BDNF）已被证明在应激介导的神经可塑性变化中发挥重要作用，然而，精神分裂症患者糖皮质激素和BDNF水平之间的确切关系尚不清楚。在这里，我们测量了皮质醇（一种主要的糖皮质激素在人类）和BDNF的水平，在前额皮质和脑脊液样本的精神分裂症患者死后。我们还评估了动物模型（产前应激大鼠的后代）额叶皮质和血浆中皮质醇和BDNF的水平，该模型显示出与精神分裂症相似的几种行为和神经内分泌异常。在精神分裂症患者的前额皮质和脑脊液样本中发现皮质醇水平显着增加。精神分裂症患者的前额叶皮层和脑脊液样本中的BDNF水平显著低于年龄匹配的对照组。来自动物研究的数据表明，产前压力的后代有显着较高的血浆和前额叶皮质醇，而BDNF水平显着较低时相比，控制，非压力的后代。此外，从出生后第60天开始的45天奥氮平治疗显著减弱了产前应激诱导的前额叶皮质醇水平升高，但奥氮平治疗后未观察到BDNF水平的变化。在人类和动物研究中都观察到BDNF和皮质醇之间存在显着的负相关性。上述来自人类和动物研究的数据表明，应激激素、皮质醇和神经保护分子BDNF之间的负相关在精神分裂症的病理生理学中起着重要作用。
Stress and stress-induced glucocorticoids have been implicated in many neuropsychiatric disorders including schizophrenia. In addition, the neurotrophin, brain derived neurotrophic factor (BDNF) has been shown to play an important role in stress-mediated changes in neuroplasticity, however, the exact relationship between glucocorticoid and BDNF levels in schizophrenia is unclear. Here, we measured the levels of cortisol (a major glucocorticoid hormone in humans) and BDNF in prefrontal cortex and CSF samples of postmortem schizophrenia subjects. We also assessed the levels of cortisol and BDNF in the frontal cortex and plasma from an animal model (the offspring of prenatally stressed rats), which demonstrates several behavioral and neuroendocrine abnormalities similar to schizophrenia. A significant increase in cortisol levels was found in prefrontal cortex and CSF samples from subjects with schizophrenia. The BDNF levels were significantly lower in prefrontal cortex and CSF samples of subjects with schizophrenia (compared to age-matched controls). Data from animal studies indicated that prenatally stressed offspring have significantly higher plasma and prefrontal cortex cortisol, whereas BDNF levels were significantly lower when compared to control, non-stressed offspring. Moreover, olanzapine treatment for 45days starting at postnatal day 60 significantly attenuated prenatal stress-induced increase in cortisol levels in prefrontal cortex, but no change in BDNF levels was observed after olanzapine treatment. A significant negative correlation between BDNF and cortisol was observed in both human and animal studies. The above data from human and animal studies suggest that a negative association between stress hormone, cortisol and neuroprotective molecule, BDNF plays an important role in the pathophysiology of schizophrenia.