Study On The Relationship Between Thyroxine And Norepinephrine In The Clinical Treatment Of Major Depressive Disorder

BackgroundMajor Depressive Disorder(MDD)is a common clinical syndrome with a high incidence and recurrence rate,which brings a heavy burden to the society and the families of depressive patients.Its etiology has not been studied clearly.The relationship between the treatment of clinical depression and thyroxine and norepinephrine has been rarely reported in related literature.In this study,we studied the changes of thyroid hormone and norepinephrine levels during the treatment of MDD patients with antidepressants,and explored the possible relationship between THX and NE levels.By comparing the expression differences of norepinephrine transporter-regulated Notch signaling pathway of SLC6A2 in MDD patients and healthy people,we explored the regulation of norepinephrine transporter-regulated Notch signaling pathway.The expression of related factors in depression can provide useful clues for the etiology,clinical characteristics and therapeutic effect of anti-MDD drugs.Objective1.To explore the effects of paroxetine(SSRIs)and venlafaxine(SNRIs)which are commonly used on thyroid hormone and norepinephrine levels in the treatment of depression and explore the relationship between thyroxine and norepinephrine in the treatment of depression furthermore.2.To investigate the expression of norepinephrine transporter-regulated Notch signaling pathway in depression by comparing the expression differences of related factors between MDD patients and healthy people.Method1.Research object:180 inpatients with depression in the Second Affiliated Hospital of Xinxiang Medical Collegewho were selected from Sep.2015 to Sep.2017.The all met the national classification scheme and diagnostic criteria for mental disorders(3rd edition)(CCMD-3)for depression diagnosis.180 health examinees in our hospital during the same period were selected as the control group.2.Grouping:The patients with depression were randomly divided into three groups,60 in each group.Group 1 was treated with paroxetine at a dose of 20-40 mg/d.Group 2 was treated with venlafaxine tablets for antidepressant at a dose of 70-220 mg/d,Group 3 was treated with venlafaxine combined with paroxetine at a dose of half of the two doses.3.Blood samples were collected from abdominal and elbow veins at 6:00 a.m.before treatment and 2,4,6,8 weeks after treatment.The serum levels of total triiodothyronine(TT3),total thyroxine(TT4),free triiodothyronine(FT3),free thyroxine(FT4),thyroid stimulating hormone(TSH)and norepinephrine(NE)were measured by ELISA.At the same time,the chief physician of the three mental health departments evaluated the Hamilton Depression Scale and the Hamilton Anxiety Scale for patients with depression.DNA and RNA were extracted from peripheral blood of 180 patients with depression and 180 normal controls.Real-time PCR was used to detect the expression of Notch1,RBP-jk,Numb,Hes1 and Norepinephrine transporter(NET)mRNA in Notch signaling pathway.NET genotyping was detected by PCR and mass spectrometry.4.Statistical analysis:The data obtained in this paper were processed by SPSS 20.0 software,and the data were processed by one-way analysis of variance(ANOVA).It was used to compare the two pairs in the group by Least significant difference(LSD).Result1.The scores of HAMD17 and HAMA17 in the experimental group before treatment were not statistically significant.The scores of HAMD17 and HAMA17 in the venlafaxine group and venlafaxine combined with paroxetine group were higher than those in paroxetine at the 2nd,4th,6th and 8th week of treatment.Group,the difference had statistically significant(P <0.005).2.Compared with the normal group,the levels of thyroxine and norepinephrine were lower in patients with depression.The level of hormones treated by drugs were increased,especially in the combination of venlafaxine + paroxetine group.3.NET gene expression was not found in the peripheral blood of the two groups;the expression of Notch1 in the peripheral blood Notch signaling pathway was lower in the depressed patients than in the control group(P =0.001),while the RBP-jk(P =0.005)and Numb(P)inhibiting the activity of the Notch pathway were observed.=0.002)The expression was higher than the control group.There was a statistically significant difference in the expression of RBP-jk(P =0.005)and Numb(P =0.003)between the three genotypes of NET gene rs2242446 in patients with depression,RBP-jk(P =0.008)and Numb(type BC).P =0.006)expression was higher than TT type;after genotype combination,it was found that patients with rs2242446 C allele(CC+TC type)RBP-jk(P =0.001)and Numb(P =0.001)were expressed.Higher than the TT type.Hes1 expression was lower in patients with rs28386840 T allele(AT+TT)than in AA(P =0.028).Conclusion1.Paroxetine can improve NE level in MDD patients,especially in the combination group of venlafaxine and paroxetine.Antidepressant drugs can positively affect NE and thyroxine levels,thus exerting antidepressant effects.2 The abnormal expression of RBP-jk,Numb and T allele at rs2242446 and rs28386840 of NET gene in patients with depression,affects Notch signaling pathway and leads to depression,and its mechanism needs further study.