季节性情感障碍的生物钟机制

Biological clock disorder is one of the reasons that trigger depresssion. As a seasonal character and specifier of major depression, seasonal depression becomes to be a good model to investigate the realtionship between biological clock and depression. Clinically, although light therapy and some antidepressant can relieve this disease, but both of them need a long time. In addition, mechanim underlying this disease is not clear due to the lack of ideal animal model. In our preliminary study, C3H mice displayed depresson-like behavior after proper seasonal acclimation. Based on this result, we plan to focus on the role of clock in pituitary and explore how biological clock(pituitary)-TSHβ (pituitary)- deiodinase(hypothalamus) pathway encode melatonin and verify it's effect on secreations of serotonin in the brain. We aim to assure the role of pituitary clock in seasonal depression by these approaches. This study can not only be helpful for the comprehansion of the relationship between clock and depression, but also it can enlighten the clock mechanism underpin other major depression.

生物钟紊乱是诱发抑郁的重要原因之一。作为具有季节特征的重度抑郁发作的特殊类型，季节性抑郁症是研究生物钟与抑郁关系的好模型。临床上，虽然光疗法和抗抑郁药物能够缓解病症，但治疗时间相对较长。此外，由于缺少理想的动物模型，该病的发病机理至今尚不清楚。近期研究提示，垂体可能是调控哺乳动物季节性反应的关键组织，从垂体到下丘脑的TSHβ（垂体）-脱碘酶（下丘脑）逆向调控通路可能在哺乳动物的季节性反应中起关键调控作用。我们在初步研究中发现，C3H小鼠经过适当的季节驯化能够表现出抑郁样行为。本项目将在此基础上，以垂体生物钟为切入点，重点研究垂体生物钟对褪黑素的解码规律及其对中枢神经递质分泌的影响。本研究不仅对理解生物钟在季节性抑郁症发病中的作用有重要价值，而且对于其它重度抑郁症的机理研究亦具有启发意义。

随着工业化和城市化进程的加快，精神类疾病在我国呈现高发态势。在临床上，生物钟紊乱和精神疾病的发生存在很高的关联度。然而，关于两者之间的因果关系，学术界一直存在争论。本项目采用遗传学和神经生物学手段此问题进行了研究，主要发现有：1）在抑郁症发生过程中，生物节律出现组织特异性的改变，可作为该疾病发生的生物标记；2）腹侧被盖区和去甲肾上腺能神经元中的生物钟基因直接参与焦虑和抑郁症的发生；3）生物钟在抑郁症的诱发过程中起到门控作用。本项目的研究成果有助于从生物钟方面来理解精神疾病的发生机制，具有基础和应用两方面的价值。