基于性激素介导神经递质Glu/GABA失衡的青少年PTSD性别差异及机制研究

伤害造成的疾病负担有增加的趋势，约25%严重伤害患者可并发创伤后应激障碍(PTSD)，影响患者的康复与预后，且已证实神经递质失衡是PTSD的重要原因。我们前期研究发现儿童PTSD患病率性别差异明显，女童显著高于男童，且在青少年阶段更明显。但青少年伤害总发生率性别差异并不显著，故女性PTSD高如用伤害发生更多无法解释，应存在影响性别差异的其他因素。研究表明性激素介导了多种疾病的性别差异，其是否能够影响神经递质平衡从而导致青少年PTSD性别差异尚不清楚。.本研究通过短期队列，收集伤害与对照青少年人口学特征、伤害类型与程度等，随访诊断是否发生PTSD，检测血液性激素及神经递质Glu、GABA。并通过PTSD动物模型检测应激期性激素、神经递质含量，行为学测试记忆功能和情绪反应，病理检查神经损伤情况。研究结果可阐明性激素与神经递质失衡影响PTSD性别差异的机制，供分性别差异性治疗及预防PTSD时参考。

The disease burden of injuries has an increased tendency, and it is reported that about 25% of patients after the severe injuries may induce PTSD (posttraumatic stress disorder, PTSD). PTSD affects the recovery and prognosis of injured/traumatic patients. Moreover, it has been proved that the imbalance of neurotransmitters is an important cause of PTSD. In our previous studies, we found that the significant gender difference of PTSD prevalence is existed in children, girls are significantly higher than boys, and more obvious in adolescent stage. However, the total injury rate is little gender difference in adolescents. Therefore, the higher PTSD in female could not be well explained as higher injuries in females than male, and there should be other factors that could affect the differences in gender susceptibility. In other aspect, the gonadal hormone mediate gender differences with a variety of diseases has been reported. However, it is still unclear of whether gonadal hormones can affect neurotransmitter balance and its possible mechanisms on gender differences in adolescent PTSD..In this proposal, we prepare to use a short-period cohort study to collect the demographic characteristics, injury types and degrees in injured group and control group in adolescents. Then they are followed up and diagnosed whether PTSD happened, and determine the contents of gonadal hormone, the neurotransmitter Glu (glutamate, Glu) and GABA (γ-aminobutyrate, GABA). In animal experiment part, the gonadal hormone and neurotransmitter (Glu, GABA in blood and hippocampus) were detected in a PTSD rat model, and the memory function and change of emotional response were assessed by behavioral experiments, then the neurological injuries were also confirmed by pathological sections. The results of this study can clarify the effects of gonadal hormones, neurotransmitter imbalance and its mechansims on gender differences in adolescent PTSD, and provide a reference for the differential treatment and prevention of PTSD in different gender populations.