The noradrenaline metabolite MHPG is a candidate biomarker from the manic to the remission state in bipolar disorder I: a clinical naturalistic study.

Masatake Kurita,Yoshiro Okubo,Satoshi Nishino,Tadahiro Sato,Yukio Numata,Chunyu Liu

doi:10.1371/journal.pone.0100634

Masatake Kurita, Yoshiro Okubo + Show 4 more

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https://doi.org/10.1371/journal.pone.0100634

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Journal: PloS one	Publication Date: Jun 27, 2014
Citations: 43	License type: CC BY 4.0

Affiliation: Nippon Medical School, Satou Hospital, Tohoku University

Abstract

Remission is the primary goal of treatment for bipolar disorder I (BDI). Metabolites of noradrenaline and dopamine, 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA), respectively, are reduced by treatment with antipsychotics, but whether these phenomena are caused by antipsychotics or by the pathophysiology of BDI is not known. Interactions between brain-derived neurotrophic factor (BDNF) and mood disorders have also been suggested. We conducted a multifaceted study in BDI patients to ascertain if biological markers are associated with the manic state. Patients with Young Mania Rating Scale (YMRS) scores >20 participated in the study. Final analyses involved 24 BDI patients (13 men and 11 women). We used YMRS scores to identify mania stages in individual BDI patients (i.e., manic syndrome, response and remission stages). Statistical analyses were done using one-way repeated-measures analyses of variance (rep-ANOVA) throughout manic syndrome, response and remission stages. Plasma concentrations of MHPG and HVA were analyzed by high-performance liquid chromatography with electrochemical detection. Plasma levels of BDNF were measured by sandwich enzyme-linked immunosorbent assay. BDI patients had significantly reduced plasma levels of MHPG throughout manic syndrome, response and remission stages (rep-ANOVA, p = 0.002). Without a case of response state, there was a significant positive correlation between YMRS scores and plasma levels of MHPG (ρ = 0.33, p = 0.033, n = 48). Plasma levels of HVA and BDNF were not significantly altered throughout manic syndrome, response and remission stages. These data suggest that the peripheral level of MHPG (which is associated with noradrenaline levels in the brain) could be used as a biomarker for the manic state in BDI. The MHPG level is likely to reflect the clinical characteristics of the manic syndrome in BDI, and noradrenaline may reflect the pathophysiology from manic to remission states.

Highlights

Bipolar disorder I (BDI) is an episodic illness characterized by recurrent manic, mixed, and depressive episodes with an estimated global lifetime prevalence of 1–5% [1]
The response stage was defined as a reduction in the Young Mania Rating Scale (YMRS) score of,50% from the manic syndrome stage
The remission stage was defined as a YMRS score #8 [15,16]

Summary

Introduction

Bipolar disorder I (BDI) is an episodic illness characterized by recurrent manic, mixed, and depressive episodes with an estimated global lifetime prevalence of 1–5% [1]. Recent evidence suggests that atypical antipsychotics are effective for the treatment of manic syndrome [5,6]. It is known that levels of the metabolites of noradrenaline and dopamine, 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA), respectively, are higher in bipolar manic patients more than in normal control [7,8], are reduced by treatment with antipsychotic agents [8]. Several reports have suggested that antipsychotics can induce depression or extrapyramidal symptoms (EPS) in bipolar manic patients [9,10,11]. Whether the decreased levels of MHPG and HVA are caused by the carryover effect of antipsychotics or by the pathophysiology of BDI is not known

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