. 2021 Aug 12;7(1):37.

doi: 10.1038/s41537-021-00167-y.

Fingertip advanced glycation end products and psychotic symptoms among adolescents

Mitsuhiro Miyashita^#^{1

2

3

4}, Syudo Yamasaki^#⁵, Shuntaro Ando⁶, Kazuhiro Suzuki^{1

3

4

7}, Kazuya Toriumi¹, Yasue Horiuchi¹, Akane Yoshikawa^{1

3}, Atsushi Imai², Yukihiro Nagase^{3

4}, Yasuhiro Miyano^{1

2

8}, Tomoko Inoue¹, Kaori Endo⁵, Yuko Morimoto⁵, Masaya Morita⁶, Tomoki Kiyono⁶, Satoshi Usami⁹, Yuji Okazaki², Toshiaki A Furukawa¹⁰, Mariko Hiraiwa-Hasegawa¹¹, Masanari Itokawa^{1

2}, Kiyoto Kasai^{6

12}, Atsushi Nishida¹³, Makoto Arai¹⁴

Affiliations

¹ Schizophrenia Research Project, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
² Department of Psychiatry, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan.
³ Department of Psychiatry, Takatsuki Clinic, Akishima, Japan.
⁴ Department of Psychiatry, Takatsuki Hospital, Hachioji, Japan.
⁵ Research Center for Social Science & Medicine, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
⁶ Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
⁷ Department of Psychiatry, Shinshu University School of Medicine, Matsumoto, Japan.
⁸ Niigata University Graduate School of Medical and Dental Science, Niigata, Japan.
⁹ Center for Research and Development on Transition from Secondary to Higher Education, The University of Tokyo, Tokyo, Japan.
¹⁰ Health Promotion & Human Behavior, Kyoto University School of Public Health, Kyoto, Japan.
¹¹ Department of Evolutionary Studies of Biosystems, The Graduate University for the Advanced Studies, SOKENDAI, Hayama, Japan.
¹² The International Research Center for Neurointelligence (WPI-IRCN) at The University of Tokyo Institutes for Advanced Study (UTIAS), University of Tokyo, Tokyo, Japan.
¹³ Research Center for Social Science & Medicine, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. nsihida-at@igakuken.or.jp.
¹⁴ Schizophrenia Research Project, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. arai-mk@igakuken.or.jp.

^# Contributed equally.

PMID: 34385440
PMCID: PMC8361014
DOI: 10.1038/s41537-021-00167-y

Fingertip advanced glycation end products and psychotic symptoms among adolescents

Mitsuhiro Miyashita et al. NPJ Schizophr. 2021.

. 2021 Aug 12;7(1):37.

doi: 10.1038/s41537-021-00167-y.

Authors

Affiliations

¹ Schizophrenia Research Project, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
² Department of Psychiatry, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan.
³ Department of Psychiatry, Takatsuki Clinic, Akishima, Japan.
⁴ Department of Psychiatry, Takatsuki Hospital, Hachioji, Japan.
⁵ Research Center for Social Science & Medicine, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
⁶ Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
⁷ Department of Psychiatry, Shinshu University School of Medicine, Matsumoto, Japan.
⁸ Niigata University Graduate School of Medical and Dental Science, Niigata, Japan.
⁹ Center for Research and Development on Transition from Secondary to Higher Education, The University of Tokyo, Tokyo, Japan.
¹⁰ Health Promotion & Human Behavior, Kyoto University School of Public Health, Kyoto, Japan.
¹¹ Department of Evolutionary Studies of Biosystems, The Graduate University for the Advanced Studies, SOKENDAI, Hayama, Japan.
¹² The International Research Center for Neurointelligence (WPI-IRCN) at The University of Tokyo Institutes for Advanced Study (UTIAS), University of Tokyo, Tokyo, Japan.
¹³ Research Center for Social Science & Medicine, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. nsihida-at@igakuken.or.jp.
¹⁴ Schizophrenia Research Project, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. arai-mk@igakuken.or.jp.

^# Contributed equally.

PMID: 34385440
PMCID: PMC8361014
DOI: 10.1038/s41537-021-00167-y

Abstract

Case control studies have suggested that advanced glycation end products play a key role in the pathophysiology of chronic schizophrenia. However, the longitudinal association between advanced glycation end products and psychotic symptoms among drug-naïve adolescents remains unclear. This study examined whether advanced glycation end products could predict the trajectory of psychotic symptoms in drug-naive adolescents using data from prospective population-based biomarker subsample study of the Tokyo Teen Cohort. A total of 277 community-dwelling adolescents aged 13 years without antipsychotic medication were analyzed. Fingertip advanced glycation end products were measured in adolescents using noninvasive technology that can be used quickly. The trajectory of psychotic symptoms in a 12-month follow-up was assessed by experienced psychiatrists using a semi-structured interview. Of the 277 participants, 13 (4.7%) experienced persistent psychotic symptoms (psychotic symptoms at baseline and follow-up), 65 (23.5%) experienced transient psychotic symptoms (psychotic symptoms at baseline or follow-up), and 199 (71.8%) did not have psychotic symptoms. Multinomial logistic regression analysis adjusted for age and sex revealed that baseline fingertip advanced glycation end products might predict the risk of persistent psychotic symptoms (odds ratio = 1.68; 95% confidence interval, 1.05-2.69; P = 0.03). Altogether, fingertip advanced glycation end products potentially predicted the trajectory of psychotic symptoms among drug-naive adolescents, which indicated its involvement in the pathophysiology of early psychosis. Further studies are required to identify strategies to reduce adolescent advanced glycation end products, which may contribute to preventing the onset of psychosis.

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Conflict of interest statement

M.M. reports grants from the Japan Society for the Promotion of Science (JSPS) during the conduct of the study and others from Kowa Co. Ltd., outside the submitted work. Additionally, M.M. has a patent PCT/JP2008/063803 with royalties paid to Kowa Co. Ltd. S.Y. reports grants from JSPS during the conduct of the study. S.A. reports grants from JSPS during the conduct of the study. A.I. reports personal fees from Otsuka, and Meiji, outside the submitted work. Y.N. reports personal fees from Otsuka, Takeda, MSD, Eisai, Lily, Sumitomo Dainippon Pharma, Pfizer, Meiji, Yoshitomi, Novartis, Janssen, and Lundbeck, outside the submitted work. T.A.F. reports personal fees from Mitsubishi Tanabe Pharma, MSD, and Shionogi and a grant from Mitsubishi Tanabe Pharma, outside the submitted work. Additionally, T.A.F. has a pending patent (2018-177688). M.I. reports other from Mitsubishi Tanabe Pharma, Sumitomo Dainippon Pharma, Pfizer, and CHUGAI, outside the submitted work. Additionally, M.I. has a patent PCT/JP2008/063803 with royalties paid to Kowa Co. Ltd. K.K. reports grants from JSPS from null, during the conduct of the study, personal fees from Daiichi Sankyo, personal fees from Otsuka, personal fees from Meiji Seika Pharma, grants and personal fees from MSD, personal fees from Yoshitomi, grants and personal fees from Astellas, personal fees from Mochida, grants and personal fees from Sumitomo Dainippon Pharma, grants and personal fees from Eisai, personal fees from Fuji-Film RI Pharma, grants from Lily, grants from Takeda, and grants from Mitsubishi Tanabe Pharma, outside the submitted work. A.N. reports grants from JSPS during the conduct of the study. M.A. reports grants from JSPS, grants from the Uehara Memorial Foundation, grants from the Sumitomo Foundation during the conduct of the study, and others from Kowa Co. Ltd., outside the submitted work. Additionally, M.A. has a patent PCT/JP2008/063803 with royalties paid to Kowa Co. Ltd. The other authors declare no competing interests.

Figures

**Fig. 1. The association between fingertip advanced glycation end products and the trajectory of psychotic symptoms.**
Odds ratios (OR) for standardized scores of fingertip AGEs from multinomial logistic regression analysis potentially predicting persistence of psychotic symptoms for 1 year among adolescents (reference: no psychotic symptoms at baseline and follow-up) adjusting for age at baseline and sex. Error bars indicate the 95% confidence interval.

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Fingertip advanced glycation end products and psychotic symptoms among adolescents

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Fingertip advanced glycation end products and psychotic symptoms among adolescents

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