FGF21 and LEPR polymorphisms predict valproate treatment outcome in patients with bipolar II disorder

Abstract

Background: Valproate (VPA) is a mood stabilizer for treating patients with bipolar disorder (BD) and it is known to be one of risk factors associated with metabolic disturbances in BD patients Recent studies had pointed out the metabolic regulation and mood symptoms might be mediated by the common underlying mechanisms However previous studies have found that hepatokine FGF21 exerts beneficial effects on lipid and glucose regulation Nevertheless current studies indicated that VPA upregulated fibroblast growth factor-21 (FGF21) expression although the role of FGF21 between mood regulation and valproate treatment outcome in bipolar patients is still unknown Therefore we hypothesized that FGF21 is a common mediator in metabolic system and mood disorder In addition the role of leptin-leptin receptor system in mood symptom and metabolic regulation is well studied and our previous studies found that bipolar patient received valproate would increase the peripheral leptin level Besides the leptin receptor gene (LEPR) has been associated with metabolic disturbances yet the association between LEPR polymorphism and valproate-induced metabolic disturbance is still unknown Materials and Methods: we enrolled patients (aged 18–65 years) who met the Diagnostic and Statistical Manual of Mental Disorders 4th version (DSM-IV) and the Chinese Version of the Modified Schedule of Affective Disorder and Schizophrenia-Life Time (SADS-L) diagnostic criteria for BD II consecutively We recruited healthy controls without mental illness from the community All subjects signed the informed consent and the BD II patients started to receive VPA 500-100mg for 12 weeks Concomitant fluoxetine for depressive symptoms or lorazepam for nighttime sedation and insomnia were permitted during the study All BD patients were in major depressive status at the time of study entry with a 17-item Hamilton Depression Rating Scale (HAMD) score >15 The disease severity and metabolic indexes including plasma FGF21 level were measured The same measurements conducted at 2 weeks 8 weeks and 12 weeks in BD II patients after the initiation of valproate treatment The LEPR rs113101 rs1137100 rs1327121 rs8179183 rs12145690 rs4655555 rs6588147 rs10889557 rs9436747 polymorphisms were detected by TaqMan SNP Genotyping Assays Results: We recruited 137 BD II patients and 78 community-dwelling controls The mean age of BD II patients and healthy controls were 32 1±11 6 and 31 0±10 7 years old respectively There were 51 1% female in BD II patients and 56 4% female in healthy controls At baseline the HAMD and YMRS score were higher in BD II patients whereas FGF21 level and metabolic indices did not differ significantly between the controls and BD II patients After 12 weeks of VPA treatment the disease severity significantly improved in BD II patients The FGF21 level (167 7±122 and 207 1±162 3 pg/ml p=0 001) body weight and waist circumference had increased significantly (p

Date of Award	2018 Apr 30
Original language	English
Supervisor	Hui-Hua Chang (Supervisor)