| BackgroundAccording to the research of WHO in 2000, the whole word incidence of the depression is 11%. Respectly, in domestic situation, the number is 3% to 5% every year. Pros and cons, in our country, only 21% non psychiatric physician in the third Grade first-class hospital can recognize depressive patients. The first reason for the contradiction is that the diagnosis of depression predominantly contingent on a subjective judgement of the doctor, the other is lack of sensitive and reliable laboratory indices to diagnose. Therefore, we make a profound investigation on the pathogenesis of depression, for the best part, within figuring out the instrumental hope to find and pronounced some biomarkers to it.ObjectOur research combines clinical and experimental study and act up the idea of translational research which has become a hot method lately. In the first place, we evaluate the effects of rapid tryptophan depletion (TD) on mood and sleep electroencephalogram in subjects with remitted depression on selective serotonin reuptake inhibitors (SSRIs) by means of systematic review as well as Meta-analysis. And then we focus on the 5-HT systems which was closely related to mental disorder and sleep electroencephalogram change, whilst establish the animal model. At last,we analysis the differentiated protein expression of hippocampus by proteomics research, Picking the physical foundation of pathogenesis in depressive patients.MethodsThe research concludes three parts. Part one is a systematic review and Meta-analysis assessing the effects of rapid tryptophan depletion on mood and sleep electroencephalogram in subjects with remitted depression on selective serotonin reuptake inhibitors. With subsequent part we shape into acute tryptophan depletion animal model in rat. For the last part, we do a proteomics analyses of hippocampus in rat with acute tryptophan depletion.The Technology and Methods :We searched database both at home and abroad to identify clinical randomized controlled trials evaluating the effects of rapid tryptophan depletion on SSRIs treated remitted depression. The quality of the included studies was critically assessed and the data analyses were performed by the Cochrane Collaboration's RevMan 4.2.30 adult male Sprague–Dawley rats, were randomly assigned to one of three groups: acute tryptophan depletion group, amino acid mixture with tryptophan group and saline group. These animals were tested in sugar water consumption test and open field test five-seven hours after TD.As for the results of the systematic review and meta-analysis, hippocampuses were obtained from the TD rats. TCA method were used in proteins extraction, the concentration of hippocampus protein was measured by Bradford method, and two-dimensional gel electrophoresis was applied to separate the proteins before coomassie brilliant blue staining and silver staining. After PDQuest8.2 for gel image analysis, the mass analyses of the individual samples were carried out by using Liquid Chromatography and Mass Spectroscopy. Data was searched in NCBI nonredundant databases. RT-PCR and Western blotting were performed to examine the differentially expressed proteins.ResultsAfter literature retrieval , two high-quality studies(impact factor: 12.257and 6.993) with Jadad score 3 points and 4 points were included.The systematic review results showed that the total and free plasma tryptophan concentrations of TD group decreased significantly comparing with controlled group. Valley value was performed at the eighth hour after TD and came to normal 16 hours later. Meta-analysis showed that HRSD-19 score (WMD 1.37, 95%CI [0.76, 1.99], P<0.001), confusion mood of POMS subscale (WMD 1.17, 95%CI [0.44, 1.91], P=0.002), TST (WMD 127, 95%CI [1.5, 23.9], P=0.03), SL (WMD -8.11, 95%CI [-12.24, -3.98], P=0.01), RD (WMD 0.17, 95%CI [0.04, 0.31], P=0.01), S1 (WMD 2.52, 95%CI [-0.02, 5.07], P=0.05) were significantly different between the TD group and controlled group.Five hours after TD, rats show significant decrease in SWCT and OFT compared with control groups (P<0.05).The numbers of spots of the hippocampus found in the gels were average 1000±20. The matching rate between the groups was 69%. There were 67 spots show significant difference, ranging from pH4.0 to pH 9.0, 20 KD to 75KD.ConclusionTD can reduce the plasma tryptophan concentrations and temporary reverse the depression and confusion moods in depression patients treated with SSRIs.TD can reduce RL and increase REM percentage and REM density in depression patients treated with SSRIs.TD has access to lead to some fleeting depressive symptoms like diminishing interest,deduce activity and anhedonia,are similar to the nucleus symptoms of human major depression. Thus the TD test is suitable for the research of depression pathogenesis.
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