The noradrenaline metabolite MHPG is a candidate biomarker between the depressive, remission, and manic states in bipolar disorder I: two long-term naturalistic case reports

Abstract

Masatake Kurita,1–3 Satoshi Nishino,1,2 Yukio Numata,1 Yoshiro Okubo,3 Tadahiro Sato11Sato Hospital, Koutokukai, Nanyo, Yamagata, Japan; 2Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan; 3Department of Psychiatry and Behavioral Science, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, JapanBackground: Treatment of the depressive and manic states in bipolar disorder I (BDI) is a challenge for psychiatrists. Despite the recognized importance of the switch phenomenon, the precise mechanisms underlying this process are yet to be shown. We conducted a naturalistic study in two BDI patients to determine whether biological markers (monoamine metabolites and brain-derived neurotrophic factor [BDNF]) are associated with the switch between depressive and manic states.Case presentation and methods: Blood sampling and mood assessments were performed at 2-week intervals over a period of 2 (Case 1, n=72) and 6 (Case 2, n=183) years. Plasma concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) were analyzed by high-performance liquid chromatography with electrochemical detection. Plasma BDNF was assayed by sandwich ELISA (enzyme-linked immunosorbent assay).Results: MHPG had the highest standardized coefficient (β) in the multiple regression analysis. We found a significant positive correlation between Young Mania Rating Scale scores and plasma MHPG levels (Case 1: р=0.429; Case 2: р=0.488), and a significant negative correlation between Montgomery–Asberg Depression Rating Scale scores and MHPG levels (Case 1: р=-0.542; Case 2: р=-0.465). Conversely, no significant correlation was found between the level of BDNF and the presence of a manic or depressive state, and although HVA had a slightly stronger correlation than MHPG, the levels of neither of these were found to significantly correlate with the symptoms.Conclusion: These data suggest that peripheral MHPG levels (which is related to noradrenaline levels in the brain) could be used as a biomarker of mood states in BDI. The noradrenaline level in the brain is likely to reflect the clinical characteristics of the switch process in BDI, and has prognostic significance for the treatment of both manic and depressive states.Keywords: brain-derived neurotrophic factor (BDNF), monoamine, dopamine, homovanilic acid (HVA), depression, pathophysiology, mood disorder