A Study And Application Of Hair Dehydroepiandrosterone And Cortisol Assessing The Long-term HPA Activity For Dissertation Of Doctor

Hypothalamic-Pituitary-Adrenal axis(HPA axis)is the main organ in human beings which responses to stress.The dysfunction of HPA axis causes serious of physiological and psychological diseases.Therefore,it is critical to develop a comprehensive and accurate assessment to the chronic activity of HPA axis.Previous studies mainly focused on salivary or serum cortisol as a biomarker of HPA activity.However,cortisol is the product of HPA axis while regulates HPA negative feedback.It can hardly precisely assess the HPA activity.What was worse,cortisol in saliva or serum can only present short-term cortisol level in vivo and assess short-term HPA activity.It is essential that multiple and continuous sampling is applied for long-term assessment to HPA axis.In order to overcome these shortcomings,more biomarkers are involved including hair cortisol,hair dehydroepiandrosterone(DHEA)and the ratio of hair cortisol to hair DHEA.DHEA can inhibit the negative feedback to HPA axis on multiple levels while the ratio is the biomarker of immunity function of HPA axis.Meanwhile,hair matrix has long-term stability.Thus,the aim is to develop a novel assessment to long-term HPA activity with multiple biomarkers including hair cortisol,DHEA and the ratio.For this purpose,it was firstly developed an assay of simultaneous determination of hair cortisol and hair DHEA by high performance liquid chromatography tandem mass spectrometry.Afterwards,the consistency was confirmed by the correlation between hair biomarkers and salivary biomarkers.The long-term stability of hair biomarkers was examined by three hair samples across one year.The sensitivity of hair biomarkers was verified in three model populations.Finally,the novel assessment was applied in healthy population with different levels of stress and depression.The results are followed: 1.1-cm-length hair samples were collected from 138 college students coupled with corresponding salivary samples.There were significant correlations between hair biomarkers and salivary biomarkers(ps < 0.01)which meant there was moderate consistency.The coefficients of correlations were 0.452 for cortisol,0.380 for DHEA and 0.336 for the ratio,respectively.2.Three times hair samples across one year from 85 college students was used for stability confirmation.The results showed weak to moderate long-term relative stability of hair biomarkers(ps < 0.05).Specially,the intra-class correlation coefficients were 0.501 for cortisol,0.689 for DHEA and 0.580 for the ratio,respectively.Moreover,hair DHEA showed long-term reproducibility.3.The sensitivity of hair biomarkers was verified in heroin addiction population,cannabis addiction population and methamphetamine addiction population.The heroin addiction patients with methadone maintained treatment showed no significant hair cortisol(p = 0.051),but increased ratio(p < 0.01)and decreased hair DHEA(p < 0.001).The cannabis addiction but withdrawal participants showed lower hair DHEA(p < 0.001),higher ratio(p < 0.01)but normal hair cortisol(p > 0.05).The methamphetamine addiction patients showed different hair cortisol(p < 0.001),hair DHEA(p < 0.001)and hair ratio(p < 0.05)levels in different withdrawal stages.These results indicated that the novel assessment to HPA activity is more comprehensive and accurate compared to the traditional assessment with single biomarker.4.The application was done in college students and adults with different perceived stress levels and depression levels.The students with higher stress levels showed lower ratio(p < 0.05),but hair cortisol and DHEA were not significant different to control’s.There were not any significant differences among hair biomarkers in adults with different stress levels.The hair DHEA and ratio of college students were higher in those with higher depression levels while hair DHEA of adults showed significant differences between depression group and controls.Compared to the assessment with single biomarker,the novel assessment with multiple biomarkers to HPA axis was more comprehensive and sensitive.Above all,the novel assessment with multiple biomarkers including hair cortisol,hair DHEA and hair ratio could better evaluate the long-term HPA activity.