摘要
目的：1、探讨抑郁症临床特征与神经内分泌改变的相关性；
2．明确难治性抑郁症与非难治性抑郁症神经内分泌改变的差异；
3．探讨抑郁症与躯体疾病共病的影响因素及相关分析；
方法：
抑郁症患者神经内分泌与临床特征的研究和难治性抑郁症神经内分泌研究：采用多中心、前瞻性、分层、随机对照研究和队列研究设计相结合的临床研究方法。根据纳入、排除标准，到目前为止共收集416例。对纳入对象进行HPA轴和HPT轴相关生化指标检验，同时对入组对象进行临床指标评定。数据的录入、管理和锁定由四川大学公共卫生学院医学统计学教研室指定数据管理员负责。
抑郁症患者与躯体疾病共病的研究：本研究为横断面回顾性研究，对2005年3月1日至2006年8月31日在四川大学华西医院心理卫生中心住院治疗的抑郁症患者，按信息检索法，根据各个病房出院记录对所有抑郁症患者的住院号进行登记，抽样后到病案室进行资料检索，对资料信息进行登记录入。共收集241名抑郁症患者，其中并发躯体疾病者114名，完成神经内分泌检测的117名。
结果：
1．抑郁症临床特征与神经内分泌的相关分析结果
根据神经内分泌指标把患者分为正常组(HPA轴和HPT轴均正常)、HPA轴异常组、HPT轴异常组、异常组(HPA轴和HPT轴均异常)四组。
四组抑郁症患者神经内分泌改变与临床特征比较结果显示：
正常组抑郁症患者性别差异无显著性，年龄低于HPT轴异常组和异常组；对体重的影响高于HPT轴异常组，低于异常组；Hamilton焦虑量表总分、入睡困难项评分、激越症状项评分、肌肉系统症状评分、呼吸系统症状评分、植物神经系统评分明显低于HPT轴异常；快感缺失项评分明显高于HPA轴异常组；生殖泌尿系统评分明显高于其它三组。
HPA轴异常组抑郁症患者在性别上差异无显著性；对体重、睡眠的影响明显低于HPT轴异常组；激越症状明显高于正常组和HPT轴异常组；肌肉系统项评分明显高于正常组；呼吸系统项评分明显低于HPT轴异常组；抑郁心境项评分低于正常组；植物神经系统项评分明天高于其它三组。
HPT轴异常组女性发病率明显高于男性；对体重的影响明显低于其它三组；年龄、HAMA焦虑量表总分明显高于正常组：HAMD睡眠因子分明显高于异常组；入睡困难项评分明显高于正常组和异常组；睡眠深度项评分明显高于异常组，激越项、紧张项评分明显低于HPA轴异常组，呼吸系统项评分高于正常组和HPA轴异常组。
异常组抑郁症患者性别上差异无显著性；对体重影响高于正常组和HPA轴异常组；对睡眠的影响特别是入睡困难和睡眠深度影响低于HPT轴异常组；迟滞项评分高于其它三组；生殖系统项评分低于正常组；植物神经系统评分低于HPA轴异常组。
不同药物对四组抑郁症患者疗效的比较
四组抑郁症患者治疗后有效率差异无显著性；治疗前后减分率组间比较差异无显著性，两两比较显示：HPA轴异常组抑郁症患者HAMD体重因子减分率与异常组比较差异具有显著性，明显高于异常组患者，其余比较差异无显著性。
各个组抑郁症患者随机使用三类药物疗效比较显示：
正常组、HPT轴异常组和异常组抑郁症患者随机使用三类药物治疗减分率组间比较及两两比较疗效差异无显著性。
HPA轴异常组接受三类药物治疗的患者组间比较显示HAMD精神焦虑项减分率、HAMA精神焦虑因子减分率差异具有显著性。两两比较显示：使用三环类药物治疗的抑郁症患者的HAMD总分减分率、HAMA精神焦虑因子减分率明显高于使用其它两类药物的患者，使用三环类药物的抑郁症患者的HAMD躯体焦虑因子减分率、HAMD精神焦虑项减分率明显高于接受SNRI类药物治疗的患者。其余比较差异无显著性。对不同药物治疗后四组抑郁症患者减分率比较显示：
四组抑郁症患者使用三环类药物治疗前后组间差异无显著性。两两比较显示：HPA轴异常组患者与HPT轴异常组患者HAMD总分减分率、HAMA躯体焦虑因子减分率和HAMD精神焦虑项减分率的差异具有显著性，HPA轴异常组减分率明显高于HPT轴异常组；HPA轴异常组与HPT轴异常组和异常组HAMD躯体焦虑因子减分率的差异具有显著性，HPA轴异常组患者减分率明显高于HPT轴异常组和异常组患者减分率；异常组患者HAMD睡眠因子减分率与HPT轴异常组患者的差异具有显著性，异常组患者减分率高于HPT轴异常组患者；HPA轴异常组患者与正常组和HPT轴异常组患者HAMA精神焦虑减分率的比较具有显著性差异，HPA轴异常组患者减分率明显高于正常组和HPT轴异常组患者。
四组抑郁症患者使用SSRIs药物治疗前后各因子减分率组间比较差异无显著性：两两比较显示：异常组HAMA躯体焦虑因子减分率与HPT轴异常组的差异具有显著性，异常组均高于HPT轴异常组患者；异常组与正常组和HPA轴异常组HAMD体重因子减分率的差异具有显著性，异常组低于正常组和HPA轴异常组。
2．难治性抑郁症神经内分泌分析结果
难治性抑郁症患者、非难治组抑郁症患者两者在性别、教育年限、发病年龄、总病程、发作次数和家族史方面具有显著性差异。
两组患者入组时各量表评定分析结果显示：难治组Hamilton抑郁量表行为阻滞因子分、病态人格因子分高于非难治组；非难治组Hamilton抑郁量表体重因子分、MMPI抑郁因子分和MMPI癔症因子分高于难治组；两组减分率比较显示：非难治组Hamilton抑郁(总减分率、躯体焦虑因子减分率、行为阻滞因子减分率、白罪因子减分率)、Hamilton焦虑(总减分率、焦虑躯体化因子减分率及精神焦虑因子减分率)减分率高于难治组。
难治性抑郁症与非难治性抑郁症患者神经内分泌指标与常模比较显示：难治性和非难治性抑郁症患者肾上腺皮质激素、ACTH、总T4在治疗前与常模差异有显著性，均高于正常值，治疗后接近正常值；TSH、游离T3、游离T4、总T3治疗前与常模差异有显著性，均低于常模，治疗后接近常模。
两组抑郁症患者治疗前后整体神经内分泌指标比较显示：皮质醇、ACTH治疗前后差异具有显著性，治疗后呈现下降趋势；TSH、游离T3、游离T4、总T3和总T4差异无显著性，但TSH、游离T3、游离T4和总T3治疗后呈现上升趋势，总T4治疗后呈现下降趋势。
非难治性抑郁症患者治疗前后比较显示：皮质醇、ACTH治疗前后差异具有显著性，治疗后呈现下降趋势；其余差异无显著性，TSH、游离T3、游离T4和总T3治疗后呈现上升趋势，总T4治疗后呈现下降趋势。
难治性抑郁症患者治疗前后比较显示：ACTH治疗前后差异具有显著性，治疗后呈现下降趋势；其余差异无显著性，TSH、游离T3、游离T4和总T3治疗后呈现上升趋势，皮质醇、总T4治疗后呈现下降趋势。
治疗前和治疗后难治性和非难治性抑郁症患者神经内分泌比较显示：TSH差异具有显著性，其余差异无显著；治疗前非难治组肾上腺皮质激素、ACTH、TSH、游离T4高于难治组，非难治组游离T3、总T低于难治组；治疗后非难治组肾上腺皮质激素、TSH、游离T3、游离T4和总T3高于难治组，非难治组ACTH、游离T3和总T4低于难治组。四组抑郁症患者使用SNRIs药物治疗前后HAMD迟滞项减分率差异具有显著性；两两比较显示：HPA轴异常组患者与其它三组差异均有显著性，HPA轴异常组患者减分率明显低其它三组患者。
3．抑郁症躯体疾病共病分析结果
抑郁症患者躯体疾病共病率为47．10％；抑郁症患者高发躯体疾病分别为：肠激惹综合症(7％)、高血压(6．6％)、冠心病(5．8％)、糖尿病(5．0％)、脑卒中(4．5％)和更年期综合症(3．3％)；性别、年龄、婚姻状况、病程、抑郁症发作次数及发病年龄为抑郁症与躯体疾病共病的易患因素；神经内分泌改变也是抑郁症患者与躯体疾病共病的高发的危险因素。
结论：
1．抑郁症患者临床特征与不同神经内分泌轴具有相关性：HPA轴异常组抑郁症患者在多伴有激越症状；HPT轴异常组抑郁症患者多发于年龄偏大的女性，体重改变不明显；多伴睡眠障碍和焦虑症状，常出现自杀观念，其至严重的自杀行为：异常组抑郁症患者多伴体重减轻和明显自责及迟滞症状；正常组抑郁症患者在多伴有：泌尿生殖系统症状及快感缺失等症状。
2．四组抑郁症患者Hamilton抑郁量表总分减分率差异无显著性，四组抑郁症患者治疗均比较好。不同神经内分泌轴改变的抑郁症对三类抗抑郁药物的反应存在差异。三环类药物对HPA轴异常伴有明显焦虑症状抑郁症患者疗效优于SNRIs类药物。SSRIs类药物治疗对伴有HAMA躯体焦虑的异常组抑郁症患者疗效优于HPT轴异常组抑郁症患者；而对伴体重改变的正常组和HPA轴均异常组抑郁症患者治疗疗效优于异常组抑郁症患者。SNRIs类药物对伴有迟滞症状的HPA轴异常组抑郁症患者疗效明显低其它三组患者。
3．难治性与非难治性抑郁症患者在性别、教育年限、发病年龄、总病程、发作次数和家庭史方面差异有显著性。难治性组抑郁症患者临床特征与非难治抑郁症患者有一定的差异；非难治性抑郁症患者治疗疗效高于难治性抑郁症患者。难治性和非难治性抑郁症患者神经内分泌与常模有一定的差异。
4．难治性和非难治性抑郁症患者治疗前后神经内分泌指标发生改变，两者改变有一定差异。
5．抑郁症患者躯体共病率47．10％；肠激惹综合症、高血压、冠心病、糖尿病、脑卒中和更年期综合症为抑郁症患者躯体疾病的高发疾病。性别、年龄、婚姻状况、病程、抑郁症发作次数及发病年龄为抑郁症与躯体疾病的易患因素；神经内分泌改变也是抑郁症与躯体疾病共病的高发的危险因素。
Purpose:
1. Correlation analysis of clinical features and neuroendocrine diversity of depression patients.
2. To investigate the neuroendocrine difference between TRD and non-TRD;
3. To acquire the influence factors of co morbidity of physical disease and depression, and implement correlation analysis.
Method:
The study of neuroendocrine and clinic features of depression patients and the neuroendocrine character of the patients with TRD: This study was a prospective hierarchies random control study, executed in several centers. 416 patients entered the study. All the patients were divided into 2 groups-depression patients that had never been treated and TRD. HPA axle and HPT axle biochemistry detection were implemented, so as clinic index evaluation. Data management was performed by the department of medical statistics of Public Health school, Sichuan University.
The study of comobidity of depression and physical disease was a cross section retrospective study. The medical histories of all the patients (241) with depression in Psychological Health Center of Huaxi Hospital since 1st March, 2005 to 31th August, 2006 entered the study. 114 patients were complicated by physical disease. Neuroendocrine detections were implemented in 117 patients.
Results:
All the depression patients were divided into 4 groups through neuroendocrine indexes - normal group, HPA axle abnormal group, HPT axle abnormal group.
The results of comparison of neuroendocrine indexes diversity and clinic features: There was no difference in sex, but the age of normal group is lower than HPT axle abnormal group and abnormal group. And weight of the normal group is higher than HPT axle abnormal group and lower than abnormal group. Total Hamilton anxiety scale score, DFA score, agitate symptom score, muscular system symptom score, respiratory system symptom score, ANS symptom score of normal group is significantly lower than HPT axle abnormal group. Pleasant sensation absence of normal group is higher than HPA axle abnormal group. GUS score of normal group is higher than the other groups.
In HPT axle abnormal group, mobidity of female was higher than male,influence to weight is lower than the other groups. Age, total HAMA anxiety scale score was higher than normal groups. HAMD sleep factor score was higher than abnormal group. DFA score is higher than normal group and abnormal group. Sleep depth factor score was higher than abnormal group, agitate, tense score was lower than HPA axle abnormal group. Respiration system score was higher than normal group and HPA axle abnormal group.
HPA axle abnormal group: influence to weight, sleep was lower than HPT axle abnormal group; Agitate score was higher than normal group and HPT axle abnormal group; Musculation score was higher than normal group; Respiratory system score was lower than HPT axle abnormal group; Depression mental state score was lower than normal group; ANS score was higher than the other groups.
Abnormal group: Influence to weight was higher than normal group and HPA axle abnormal group; influence to sleep was lower than HPT axle abnormal group; Delay score was higher than the other groups; Genital system score was lower than normal group; ANS score was lower than HPA axle abnormal group.
Curative effect of medicines to the patients: Among the 4 groups, the effect of the medicines had no difference, and the score decreasing rate had no difference between before and after treatment; The HAMD weight decreasing factor decreasing rate of HPA axle abnormal group is higher than abnormal group.
3 medicines was used randomly in each group: In normal group, HPT axle abnormal group and abnormal group, the score decreasing rate had no significant difference.
In HPA axle abnormal group, score decreasing rate of HAMD and HAMA anxiety had significant difference among the 3 medicines. Comparing between each medicine, total score decreasing rate of HAMD and HAMA anxiety factor in tricyclic group was higher than in the other two groups.
After used different medicines, the score decreasing rate in the 4 groups were compared:
After used tricyclic medicine, the score decreasing rate had no difference among the 4 groups. Compared each group: The score decreasing rate of total HAMD, HAMA physical anxiety factor, HAMD mind anxiety factor of the HPA axle abnormal group was higher than that of HPT axle abnormal group. The score decreasing rate of HAMD physical anxiety factor of the HPA axle abnormal group was higher than that of HPT axle abnormal group. The score decreasing rate of sleep factor of the abnormal group was higher than that of HPT axle abnormal group. The score decreasing rate of total HAMD, HAMA physical anxiety factor, HAMD mind anxiety factor of the HPA axle abnormal group was higher than that of HPT axle abnormal group.
After used SSRIs medicine, the score decreasing rate had no difference among the 4 groups. Comparing each medicine group, score decreasing rate of HAMA physical anxiety factor in HPT axle abnormal group was higher than in the other two groups. Score decreasing rate of HAMD weight factor of normal group was lower than that of the HPA axle abnormal group.
After used SNRIs medicine, the score decreasing rate of HAMD delay factor had significant difference among the 4 groups. Comparing each medicine group.
There was significant difference between TRD and non-TRD in sex, education time, age of outset, total course of disease, frequency of break out and family history.
The result of scale evaluation at the beginning of the study: TRD group is higher than non- TRD group in block factor score and morbid personality factor score through Hamilton depression scales. And the non-TRD group is higher than TRD group in weight factor score, MMPI depression factor score and MMPI hysteria factor score. Score decreasing rate: non-TRD group was higher than TRD group in Hamilton depression and Hamilton anxiety.
Comparison the neuroendocrine index between the patients and normal persons: ACH, lib-T3(before treatment), lib-T4(before treatment), total T3(before treatment), lib-T4(after treatment), total T3(after treatment),ACTH(in TRD group before treatment), TSH( in TRD group before treatment) was significantly different between patients and normal people. ACH, ACTH, total T4 of patients group was higher than normal before treatment, and became normal level after treatment. TSH, lib-T3, lib-T4, total T3 of patients group was lower than normal before treatment, and became normal after treatment.
Comparison of entire between before and after treatment in the two groups: Hydrocortisone, ACTH significantly decreased after treatment. The diversity of TSH, lib-T3, lib-T4, total T3, and total T4 was not obvious. In the non-TRD group, the level of hydrocortisone, ACTH decreased significantly. And in the TRD group, the level of ACTH decreased significantly. The level of TSH in both groups decreased significantly.
The rate of comobidity of depression and physical disease is 47.10%. And the physical disease that could suffer from depression easily includes irritablebowel syndrome(7%), hypertension(6.6%), CAD(5.8%), diabetes(5.0%), stroke (4.5%)and menopause syndrome(3.3%). The liability factor of the comobidity includes sex, age, marriage, course of disease, frequency and age of outset of depression, neuroendocrine alteration.
Conclusion:
1. Correlation of clinical features and neuroendocrine diversity of depression patients. Agitate symptom often existed in HPA axle abnormal group.Elder women suffered HPT axle abnormal depression frequently, but weight diversity was not obvious; Sleep disorder and anxiety often exist in HPT axle abnormal group. Self-reproach and delay symptom often existed in abnormal group. Patients of normal depression group were often combined with hebetude, interest absence, early awaking, frequent micturition, urgency,menopause, frigidity, astyphia, impotence, and anhedonia. There was no difference among 4 groups on Hamilton depression scale score. Tricyclic was better than SNRIs on treating HPA axle abnormal depression. SSRIs was more effective on HPA axle abnormal group than on HPT axle abnormal group. SNRIs showed less effective on HPA axle abnormal group than on the other 3 groups.
2. There was significant difference between TRD group and non-TRD group on sex, education time, age of break out, total course, frequency, and family history. As to delay factor score, weight factor score, TRD group was higher than non-TRD. After treatment, ACH, ACTH, total T4 showed decline trend,as TSH, lib-T3, lib-T4, total T3 increased. Cmparing TRD and non-TRD group, all the neuroendocrine indexes had no difference, except TSH.3.47.10% of the depression patients suffered from physical disease, which included irritable bowel syndrome, hypertension, CAD, diabetes, cerebral apoplexy, menopause syndrome. The liability factors of comobidity of depression and physical disease included sex, age, marriage status, course of disease, frequency of depression and age of break out.
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