Plasma oxytocin level and OXTR predict antidepressant treatment outcome in patients with major depressive disorder

Abstract

Background: Major depressive disorder (MDD) patients have depressive mood caused by dysfunction of stress system Patients regulate depressive mood through antidepressants but some of them cause energy metabolic disturbance Recent studies indicated that oxytocin - oxytocin receptors system has effect on reducing stress response as well as regulating energy emotion and social process Genetic factors may involve in individual difference Oxytocin receptor polymorphism (OXTR) was associated with MDD and with stress response However there was no study focusing on oxytocin level and OXTR as predicting factors for antidepressant treatment outcome in MDD patients Aims: In this study we aimed to investigate (1) the correlation between plasma oxytocin and clinical features in healthy controls and in MDD patients (2) the association between OXTR and clinical features in healthy controls and in MDD patients and (3) the prediction of treatment outcome by plasma oxytocin or OXTR after antidepressant treatment in patients with MDD Materials and Methods: Patients (aged 18–65 years) who met the Diagnostic and Statistical Manual of Mental Disorders 4th version (DSM-IV) for major depressive disorder and Hamilton depression rating scale (HAMD) greater than 15 scores were enrolled consecutively by trained psychiatrists MDD patients were randomly treated with fluoxetine or venlafaxine MDD patients were assessed HAMD at baseline and week 2 4 and 6 Cognitive function tests and fasting blood sample detected metabolic indices and oxytocin level were collected at baseline and after 6 weeks of treatment In addition we also collected questionnaire including social support life event scales and WHO quality of life In addition healthy controls were enrolled from community through advertisement Result: We recruited 131 MDD patients and 96 healthy controls in this study The mean age of MDD patients and healthy controls were 39 4±12 6 and 33 3±12 1 years old respectively There were 26 9% male in MDD patients and 42 7% male in healthy controls MDD patients had higher HAMD scores fasting blood glucose oxytocin level and CRP compared to controls Moreover MDD patients had lower weight leptin cognitive function test social support scale and WHO quality of life than controls After treatment the HAMD scores and cognitive function were significant improved in MDD patients However TG and CRP were elevated Result 1: Plasma oxytocin was negatively correlated with insulin and the homeostasis model of assessment for insulin resistance (HOMA-IR) in healthy controls The change of oxytocin was positively correlated with the change of the homeostasis model of assessment for pancreatic β-cell secretory function (HOMA-β) in patients with MDD after treatment Result 2: Controls with GG genotype had higher HAMD and cortisol than those with A allele Moreover patients with GG genotype had higher fasting blood sugar HbA1c and LDL than those with A allele After treatment patients with GG genotype also had higher HbA1c and oxytocin Result 3: Baseline oxytocin was negatively correlated with the change of oxytocin in MDD patients On the other hand patients with GG genotype decreased more cholesterol and LDL after treatment Patients with GG genotype improved more dominant finger with FTT test by antidepressant intervention Patients with GG genotype decreased more HbA1c by higher social support effect after treatment Conclusion: Our findings suggest that higher oxytocin level would have lower insulin resistance in healthy controls but not in patients with MDD In addition patients with the GG genotype whom have lower oxytocin level were more sensitive to metabolic regulation from treatment These findings also indicate that oxytocin level and OXTR are important moderators that shape metabolic features

Date of Award	2016 Aug 18
Original language	English
Supervisor	Hui-Hua Chang (Supervisor)