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Relationships of Cerebrospinal Fluid Monoamine Metabolite Levels With Clinical Variables in Major Depressive Disorder

 Hyung Shin Yoon  ;  Kotaro Hattori  ;  Shintaro Ogawa  ;  Daimei Sasayama  ;  Miho Ota  ;  Toshiya Teraishi  ;  Hiroshi Kunugi 
 JOURNAL OF CLINICAL PSYCHIATRY, Vol.78(8) : e947-e956, 2017 
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Adult ; Age Factors ; Biomarkers/cerebrospinal fluid ; Cerebrospinal Fluid/drug effects ; Cerebrospinal Fluid/metabolism ; Chromatography, Liquid/methods ; Depressive Disorder, Major*/cerebrospinal fluid ; Depressive Disorder, Major*/diagnosis ; Depressive Disorder, Major*/drug therapy ; Depressive Disorder, Major*/psychology ; Diagnostic and Statistical Manual of Mental Disorders ; Female ; Homovanillic Acid/cerebrospinal fluid* ; Humans ; Indoles/cerebrospinal fluid* ; Japan Male ; Methoxyhydroxyphenylglycol/cerebrospinal fluid* ; Middle Aged ; Psychiatric Status Rating Scales ; Psychotropic Drugs/therapeutic use* ; Statistics as Topic
OBJECTIVE: Many studies have investigated cerebrospinal fluid (CSF) monoamine metabolite levels in depressive disorders. However, their clinical significance is still unclear. We tried to determine whether CSF monoamine metabolite levels could be a state-dependent marker for major depressive disorder (MDD) based on analyses stratified by clinical variables in a relatively large sample. METHODS: Subjects were 75 patients with MDD according to DSM-IV criteria and 87 healthy controls, matched for age, sex, and ethnicity (Japanese). They were recruited between May 2010 and November 2013. We measured homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) in CSF samples by high-performance liquid chromatography. We analyzed the relationships of the metabolite levels with age, sex, diagnosis, psychotropic medication use, and depression severity. RESULTS: There was a weak positive correlation between age and 5-HIAA levels in controls (ρ = 0.26, P < .016) and a similar trend in patients, while sex was unrelated to any metabolite. All monoamine metabolites in moderately to severely depressed patients (17-item Hamilton Depression Rating Scale score > 12) were significantly lower than those in controls (P < .0005 for all 3 metabolites). We found that antidepressants decreased the levels of 5-HIAA (ρ = -0.39, P < .001) and MHPG (ρ = -0.49, P < .0001) and that antipsychotics increased levels of HVA (ρ = 0.24, P < .05). There was a strong correlation between HVA and 5-HIAA levels (controls: ρ = 0.79, P = .000001; MDD: ρ = 0.66, P = .000001). HVA levels (ρ = -0.43, P < .001) and 5-HIAA levels (ρ = -0.23, P < .05), but not MHPG levels (ρ = -0.18, P > .1), were related to depression severity. CONCLUSIONS: CSF 5-HIAA and HVA levels could be state-dependent markers in MDD patients. Since 5-HIAA levels greatly decrease with the use of antidepressants, HVA levels might be more useful in the clinical setting.
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1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
Yonsei Authors
Yoon, Hyung Shin(윤형신) ORCID logo https://orcid.org/0000-0003-4389-7578
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