PMID- 24971450
OWN - NLM
STAT- MEDLINE
DCOM- 20151002
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 6
DP  - 2014
TI  - The noradrenaline metabolite MHPG is a candidate biomarker from the manic to the 
      remission state in bipolar disorder I: a clinical naturalistic study.
PG  - e100634
LID - 10.1371/journal.pone.0100634 [doi]
LID - e100634
AB  - 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 (rho = 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.
FAU - Kurita, Masatake
AU  - Kurita M
AD  - Sato Hospital, Koutokukai, 948-1 Kunugizuka, Nanyo, Yamagata, Japan; Department 
      of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku 
      University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, Japan; Department of Psychiatry 
      and Behavioral Science, Graduate School of Medicine, Nippon Medical School, 
      Bunkyo-ku, Tokyo, Japan.
FAU - Nishino, Satoshi
AU  - Nishino S
AD  - Sato Hospital, Koutokukai, 948-1 Kunugizuka, Nanyo, Yamagata, Japan; Department 
      of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku 
      University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, Japan.
FAU - Numata, Yukio
AU  - Numata Y
AD  - Sato Hospital, Koutokukai, 948-1 Kunugizuka, Nanyo, Yamagata, Japan.
FAU - Okubo, Yoshiro
AU  - Okubo Y
AD  - Department of Psychiatry and Behavioral Science, Graduate School of Medicine, 
      Nippon Medical School, Bunkyo-ku, Tokyo, Japan.
FAU - Sato, Tadahiro
AU  - Sato T
AD  - Sato Hospital, Koutokukai, 948-1 Kunugizuka, Nanyo, Yamagata, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140627
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 534-82-7 (Methoxyhydroxyphenylglycol)
RN  - X4W3ENH1CV (Norepinephrine)
RN  - X77S6GMS36 (Homovanillic Acid)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antipsychotic Agents/therapeutic use
MH  - Biomarkers/blood
MH  - Bipolar Disorder/*blood/*diagnosis/drug therapy/pathology
MH  - Brain-Derived Neurotrophic Factor/blood
MH  - Chromatography, High Pressure Liquid
MH  - Electrochemical Techniques
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Homovanillic Acid/blood
MH  - Humans
MH  - Male
MH  - Methoxyhydroxyphenylglycol/*blood
MH  - Middle Aged
MH  - Norepinephrine/*metabolism
MH  - Remission Induction
MH  - Severity of Illness Index
PMC - PMC4074114
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/06/28 06:00
MHDA- 2015/10/03 06:00
PMCR- 2014/06/27
CRDT- 2014/06/28 06:00
PHST- 2013/11/27 00:00 [received]
PHST- 2014/05/29 00:00 [accepted]
PHST- 2014/06/28 06:00 [entrez]
PHST- 2014/06/28 06:00 [pubmed]
PHST- 2015/10/03 06:00 [medline]
PHST- 2014/06/27 00:00 [pmc-release]
AID - PONE-D-13-47659 [pii]
AID - 10.1371/journal.pone.0100634 [doi]
PST - epublish
SO  - PLoS One. 2014 Jun 27;9(6):e100634. doi: 10.1371/journal.pone.0100634. 
      eCollection 2014.