Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta, GA 30912, USA.
Neurobiol Dis. 2010 Sep;39(3):327-33. doi: 10.1016/j.nbd.2010.04.017. Epub 2010 May 6.
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 45 days 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.
应激和应激诱导的糖皮质激素被认为与许多神经精神疾病有关，包括精神分裂症。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，精神分裂症中糖皮质激素和 BDNF 水平的确切关系尚不清楚。在这里，我们测量了尸检精神分裂症患者前额叶皮质和脑脊液样本中的皮质醇（人类主要的糖皮质激素）和 BDNF 水平。我们还评估了来自动物模型（产前应激大鼠的后代）的前额叶皮质和血浆中的皮质醇和 BDNF 水平，该模型表现出与精神分裂症相似的几种行为和神经内分泌异常。精神分裂症患者前额叶皮质和脑脊液样本中的皮质醇水平显著升高。精神分裂症患者前额叶皮质和脑脊液样本中的 BDNF 水平明显降低（与年龄匹配的对照组相比）。动物研究数据表明，产前应激的后代血浆和前额叶皮质中的皮质醇水平显著升高，而 BDNF 水平则明显低于对照、未应激的后代。此外，从出生后第 60 天开始，奥氮平治疗 45 天可显著减弱产前应激引起的前额叶皮质皮质醇水平升高，但奥氮平治疗后 BDNF 水平没有变化。在人类和动物研究中都观察到 BDNF 与皮质醇之间存在显著的负相关。来自人类和动物研究的上述数据表明，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。
