TY - JOUR
T1 - Kynurenine pathway in depression
T2 - A systematic review and meta-analysis
AU - Ogyu, Kamiyu
AU - Kubo, Kaoruhiko
AU - Noda, Yoshihiro
AU - Iwata, Yusuke
AU - Tsugawa, Sakiko
AU - Omura, Yuki
AU - Wada, Masataka
AU - Tarumi, Ryosuke
AU - Plitman, Eric
AU - Moriguchi, Sho
AU - Miyazaki, Takahiro
AU - Uchida, Hiroyuki
AU - Graff-Guerrero, Ariel
AU - Mimura, Masaru
AU - Nakajima, Shinichiro
N1 - Funding Information:
Dr. Noda has received research grants from Japan Health Foundation, Meiji Yasuda Mental Health Foundation, Mitsui Life Social Welfare Foundation, Takeda Science Foundation, SENSHIN Medical Research Foundation, Health Science Center Foundation, and Daiichi Sankyo Scholarship Donation Program. Dr. Noda has received equipment-in-kind support for an investigator-initiated study from Magventure Inc. Dr. Iwata has received fellowship grants from Canadian Institute of Health Research (CIHR), Keio University Medical Science Foundation, Mitsukoshi Foundation, and manuscript fees from Dainippon Sumitomo Pharma.
Funding Information:
Mr. Plitman has received funding from the Vanier Canada Graduate Scholarship, the Ontario Graduate Scholarship, and the Canada Graduate Scholarship—Master’s. Dr. Graff-Guerrero has received support from the United States National Institute of Health, CIHR, OMHF, Consejo Nacional de Ciencia y Tecnología, the Instituto de Ciencia y Tecnología del DF, the Brain & Behavior Research Foundation (Formerly NARSAD), the Ontario Ministry of Health and Long-Term Care, the Ontario Ministry of Research and Innovation Early Research Award, and Janssen. Dr. Uchida has received grants from Eisai, Otsuka Pharmaceutical, Dainippon-Sumitomo Pharma, Mochida Pharmaceutical, Meiji-Seika Pharmaceutical, and Novartis; speaker’s honoraria from Otsuka Pharmaceutical, Eli Lilly, Shionogi, Pfizer, Yoshitomi Yakuhin, Dainippon-Sumitomo Pharma, Meiji-Seika Pharma, MSD, and Janssen Pharmaceutical; and advisory panel payments from Dainippon-Sumitomo Pharma within the past three years. Dr. Mimura has received grants or speaker’s honoraria from Asahi Kasei Pharma, Astellas Pharmaceutical, Daiichi Sankyo, Dainippon-Sumitomo Pharma, Eisai, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutical, Meiji-Seika Pharma, Mochida Pharmaceutical, MSD, Novartis Pharma, Otsuka Pharmaceutical, Pfizer, Shionogi, Takeda, Tanabe Mitsubishi Pharma, and Yoshitomi-Yakuhin within 3 years. Dr. Nakajima has received fellowship grants from CIHR, research support from Japan Society for the Promotion of Science, Japan Research Foundation for Clinical Pharmacology, Naito Foundation, Uehara Memorial Foundation, Takeda Science Foundation, Daiichi Sankyo, and MSD, manuscript fees or speaker’s honoraria from Dainippon Sumitomo Pharma and Yoshitomi Yakuhin within the past three years. Other authors have no financial or other relationship relevant to the subject of this manuscript.
PY - 2018/7
Y1 - 2018/7
N2 - Abnormalities of the kynurenine (KYN) pathway may be implicated in the pathophysiology of depression. However, the relationships between depression and each metabolite of the KYN pathway remain uncertain. Therefore, we conducted a meta-analysis about the levels of the metabolites of KYN pathway between patients with depression and controls. Out of 899 initial records, we identified 22 articles to form the empirical basis. Seventeen, 10, and 18 studies examined levels of kynurenic acid (KYNA), quinolinic acid (QUIN), and KYN, respectively. KYNA and KYN levels were lower in patients with depression in comparison to controls, while QUIN levels did not differ between the two groups. Antidepressant-free patients showed decreased KYNA levels and increased QUIN levels compared with controls. Male ratios of the samples were negatively associated with study SMDs for KYNA. In conclusion, this meta-analysis revealed that patients with depression had decreased level of KYNA and KYN, whereas antidepressant-free patients showed increased level of QUIN. Nevertheless, given the heterogeneity among their sample characteristics, further research is clearly needed.
AB - Abnormalities of the kynurenine (KYN) pathway may be implicated in the pathophysiology of depression. However, the relationships between depression and each metabolite of the KYN pathway remain uncertain. Therefore, we conducted a meta-analysis about the levels of the metabolites of KYN pathway between patients with depression and controls. Out of 899 initial records, we identified 22 articles to form the empirical basis. Seventeen, 10, and 18 studies examined levels of kynurenic acid (KYNA), quinolinic acid (QUIN), and KYN, respectively. KYNA and KYN levels were lower in patients with depression in comparison to controls, while QUIN levels did not differ between the two groups. Antidepressant-free patients showed decreased KYNA levels and increased QUIN levels compared with controls. Male ratios of the samples were negatively associated with study SMDs for KYNA. In conclusion, this meta-analysis revealed that patients with depression had decreased level of KYNA and KYN, whereas antidepressant-free patients showed increased level of QUIN. Nevertheless, given the heterogeneity among their sample characteristics, further research is clearly needed.
KW - Depression
KW - Glutamate
KW - Kynurenic acid
KW - N-methyl-D-aspartate receptor
KW - Neuroinflammation
KW - Quinolinic acid
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U2 - 10.1016/j.neubiorev.2018.03.023
DO - 10.1016/j.neubiorev.2018.03.023
M3 - Review article
C2 - 29608993
AN - SCOPUS:85044973217
VL - 90
SP - 16
EP - 25
JO - Neuroscience and Biobehavioral Reviews
JF - Neuroscience and Biobehavioral Reviews
SN - 0149-7634
ER -