Tissue-Specific Oxysterols as Predictors of Antidepressant (Escitalopram) Treatment Response in Patients With Major Depressive Disorder

There is growing evidence that disturbances in cholesterol metabolism may be involved in major depressive disorder (MDD). However, it is not known if cholesterol metabolites present in the brain and periphery can be used to diagnose and predict the MDD patient’s response to antidepressant treatment. A total of 176 subjects (85 MDD patients and 91 healthy controls) were included in this study. The expression of peripheral and brain-specific oxysterols and related gene polymorphisms were investigated in all subjects. The severity of depression was measured using the 17-Item Hamilton Depression Rating Scale (HAMD), 16-item Quick Inventory of Depressive Symptoms–Self-Report (QIDS16), and Patient Health Questionnaire (PHQ) for all MDD patients before and after 12 weeks of antidepressant treatment. MDD patients expressed higher plasma levels of 24(S)-hydroxycholesterol (24OHC, mainly secreted from the brain) compared to healthy controls, and the higher levels of 24OHC is associated with 24OHC synthetase (CYP46A1) gene polymorphisms. In MDD patients, an improved response to the 12-week antidepressant treatment is associated with a reduction of both 24OHC and 27-hydroxycholesterol (27OHC, mainly secreted from the peripheral system) levels relative to baseline levels. Non-responders exhibited increased levels of oxysterols at the end of treatment compared to the baseline. The superior reduction in oxysterol levels correlated with the better outcomes from the antidepressant treatment. These data suggest a potential role for oxysterols as diagnostic and treatment response-related indicators for MDD. The clinical trial of this study is appropriate technology study of MDD diagnosis and treatment based on objective indicators and measurement (Chinese Clinical Trial Registry Identifier: ChiCTR-OOC-17012566) (http://www.chictr.org.cn/showproj.aspx?proj=21377).