The Preliminary Research On The Relationship Between Estradiol And Neurotransmitter Metabolites In Depression

BackgroundThe Major Depressive Disorder(MDD) is considered to be one of the most common incapacitating mental disorders,with an estimated lifetime prevalence ranges from 5% to 13% in all adults. In particular, sex differences are prominent in mood and anxiety disorders, a number of studies quantifying a female preponderance ranging from 1.5 to 3 times higher rates of depression. However,the complex diagnostic – phenotypic –genetic–etiologic heterogeneity continues to provide significant obstacles for understanding the pathological mechanisms of gender differences associated with MDD. There is no doubt that hormones making greater contribution to the gender difference of MDD, which may provide a window into mechanisms of affective disturbances in both men and women.Estradiol is the main bioactive constituents of estrogen,2-3% in free state, 40-60% combined with albumin, which are bioavailable. But 40-60% combined with SHBG, which can’t play biological functions. Accumulating evidence have reported estrogen plays a critical role in controlling affect, mood, and anxiety. So it is necessary to detect the changes of estrogen in female MDD patients, and further realize its influence on neurotransmitter metabolites.ObjectiveThe aims of the present study were to explore the differences in serum levels of estrogen and SHBG between female MDD patients and controls to assess the correlation between estrogen and clinical symptoms of MDD. Further the neurotransmitter changes in hippocampus and prefrontal lobe region associated with depression were detected.MethodOur research is divided into three parts:1. To detect the differences in serum levels of Estrogen and SHBG between female MDD patients and Controls, using the ARCHITECT Estradiol and SHBG assay, a Chemiluminescent Microparticle Immunoassay.2. Building and evaluating the mice model of ovariectomy, including the serum level of Estrogen in mice by ovariectomy, Sucrose preference test, body weight, open-field test and forced-swimming test.3. The detection of neurotransmitter changes in hippocampus and prefrontal lobe. Neurotransmitter metabolites of three pathways were detected: the Tryptophan pathway, the GABA pathway and the Catecholamine pathway. Results1. Comparing with health control group, the serum levels of Estrogen is lower in fist-episode drug-na?ve female MDD patients, and statistically significant. While the serum levels of SHBG are paralleled between health control group and fist-episode drug-na?ve female MDD patients.2. Comparing with health control group, the serum level of Estrogen and Sucrose preference are statistically significant lower in mice by ovariectomy; body weight is significant higher. The open-field test shows no significant changes between ovariectomy group and health control group, but the forced-swimming test shows a significant increase in immobility.3. The neurotransmitter metabolites in the hippocampus and the prefrontal lobe were detected. Comparing with health control group, in Tryptophan pathway, the 5-HT is significant lower both in the hippocampus and the prefrontal lobe, N-acetyl serotonin is significant lower in the prefrontal lobe; while the kynurenine and kynurenic acid in the hippocampus are significant higher. In GABA pathway, the succinic acid is significant lower both in the hippocampus and the prefrontal lobe; and Glutathione is significant lower in prefrontal lobe. In Catecholamine pathway, there is no significant changes between ovariectomy group and health control group.Conclusion1. The serum levels of estrogen is lower in fist-episode drug-na?ve female MDD patients, while the levels of SHBG remains same. It is obvious that the biological function of estrogen has changed in MDD female patients.2. By ovariectomy, the levels of estrogen decreased, and the mice showed depression-like behavior: Sucrose preference is significant lower; body weight is significant higher and a significant increase in immobility in the forced-swimming test.3. In the condition of estrogen decreased, the neurotransmitter metabolites in hippocampus and prefrontal lobe changed significantly, then influence the development of depression. Especially the 5- HT and N-acetyl serotonin were significantly decreased; the kynurenine and kynurenic acid were significantly increased and the succinic acid is significantly decreased.