Fingertip advanced glycation end products and psychotic symptoms among adolescents

Miyashita, Mitsuhiro; Yamasaki, Syudo; Ando, Shuntaro; Suzuki, Kazuhiro; Toriumi, Kazuya; Horiuchi, Yasue; Yoshikawa, Akane; Nagase, Yukihiro; Miyano, Yasuhiro; Inoue, Tomoko; Endo, Kaori; Morimoto, Yuko; Morita, Masaya; Kiyono, Tomoki; Usami, Satoshi; Okazaki, Yuji; Furukawa, Toshi A; Hiraiwa‐Hasegawa, Mariko; Itokawa, Masanari; Kasai, Kazuhiko; Nishida, Atsushi; Arai, Makoto

doi:10.1038/s41537-021-00167-y

Cited by 8 publications

(11 citation statements)

References 44 publications

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“…Previous studies have reported AGE accumulation in patients with schizophrenia 16 – 18 , and higher AGE accumulation rate 19 . Furthermore, we recently reported that increased AGE levels predict persistent psychotic symptoms in drug-naïve adolescents 20 . The role of AGEs in the development of psychosis may involve brain inflammation.…”

Section: Discussionmentioning

confidence: 95%

“…Furthermore, studies have reported that patients with schizophrenia have higher AGE levels 16 – 18 , and possibly higher AGE accumulation rate 19 than controls. A recent longitudinal cohort study showed that AGEs can predict psychotic symptom trajectories among drug-naïve adolescents 20 . Thus, there is a need to understand the role of AGEs in the association between muscle strength and psychosis to elucidate the biological mechanisms and early modifiable factors of psychosis.…”

Section: Introductionmentioning

confidence: 99%

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Role of advanced glycation end products in the longitudinal association between muscular strength and psychotic symptoms among adolescents

et al. 2022

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Muscular strength, assessed by handgrip, is a risk indicator for psychiatric disorders, including psychosis. However, the biological mechanisms underlying this association remain unclear. Since advanced glycation end products (AGEs) play a key role in skeletal muscle underdevelopment and psychosis, we examined the role of AGEs in the longitudinal association between muscular strength and psychotic symptoms among adolescents. We first evaluated the direction of the relationship between handgrip strength and urine levels of pentosidine, a representative AGEs in a population-based birth cohort of 1,542 adolescents at ages 12 and 14. Then, we examined the role of AGEs in the longitudinal association between handgrip strength and thought problems (TP), as a psychotic symptom indicator, in a subsample of 256 adolescents at ages 13 and 14. An autoregressive cross-lagged model revealed that handgrip strength at age 12 negatively predicted pentosidine levels at age 14 (β = −0.20, p < 0.001), whereas pentosidine levels at age 12 did not predict handgrip strength at age 14 (β = 0.04, p = 0.062). Moreover, pentosidine levels had a significant indirect effect on the relationship between handgrip strength and TP (standard indirect effect = −0.051, p = 0.012), which remained significant after adjusting for gender and preceded TP and pentosidine levels. Thus, adolescents with low muscular strength are at a high risk of developing psychotic symptoms, which could be mediated by AGEs. Future studies need to investigate whether interventions focused on muscular strength prevent the accumulation of AGEs and thereby prevent the development of psychosis.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Role of advanced glycation end products in the longitudinal association between muscular strength and psychotic symptoms among adolescents

et al. 2022

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“…Plasma pentosidine AGEs were shown to be connected to SCZ in earlier investigations ( 50 – 52 ) and serve as a helpful biomarker for the treatment-resistant-like phenotype ( 53 ). Elevated levels of AGEs may result in psychotic symptoms by inducing brain inflammation ( 54 ). In fact, AGEs cause elevation of proinflammatory cytokines through binding to a membrane-bound receptor, RAGE, that is present on membrane of astrocytes, microglia, and neurons ( 55 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of key long non-coding RNA-associated competing endogenous RNA axes in Brodmann Area 10 brain region of schizophrenia patients

et al. 2022

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Schizophrenia (SCZ) is a serious mental condition with an unknown cause. According to the reports, Brodmann Area 10 (BA10) is linked to the pathology and cortical dysfunction of SCZ, which demonstrates a number of replicated findings related to research on SCZ and the dysfunction in tasks requiring cognitive control in particular. Genetics' role in the pathophysiology of SCZ is still unclear. Therefore, it may be helpful to understand the effects of these changes on the onset and progression of SCZ to find novel mechanisms involved in the regulation of gene transcription. In order to determine the molecular regulatory mechanisms affecting the SCZ, the long non-coding RNA (lncRNA)-associated competing endogenous RNAs (ceRNAs) axes in the BA10 area were determined using a bioinformatics approach in the present work. A microarray dataset (GSE17612) consisted of brain post-mortem tissues of the BA10 area from SCZ patients and matched healthy subjects was downloaded from the Gene Expression Omnibus (GEO) database. This dataset included probes for both lncRNAs and mRNAs. Using the R software's limma package, the differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were found. The RNA interactions were also discovered using the DIANA-LncBase and miRTarBase databases. In the ceRNA network, positive correlations between DEmRNAs and DElncRNAs were evaluated using the Pearson correlation coefficient. Finally, lncRNA-associated ceRNA axes were built by using the co-expression and DElncRNA-miRNA-DEmRNA connections. We identified the DElncRNA-miRNA-DEmRNA axes, which included two key lncRNAs (PEG3-AS1, MIR570HG), seven key miRNAs (hsa-miR-124-3p, hsa-miR-17-5p, hsa-miR-181a-5p, hsa-miR-191-5p, hsa-miR-26a-5p, hsa-miR-29a-3p, hsa-miR-29b-3p), and eight key mRNAs (EGR1, ETV1, DUSP6, PLOD2, CD93, SERPINB9, ANGPTL4, TGFB2). Furthermore, DEmRNAs were found to be enriched in the “AGE-RAGE signaling pathway in diabetic complications”, “Amoebiasis”, “Transcriptional misregulation in cancer”, “Human T-cell leukemia virus 1 infection”, and “MAPK signaling pathway”. This study offers research targets for examining significant molecular pathways connected to the pathogenesis of SCZ, even though the function of these ceRNA axes still needs to be investigated.

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“…In healthy controls, a significant association of AGE-accumulation with ethnicity and tobacco exposure was found. Another longitudinal study reported that skin AGE concentrations may predict the risk of persistent psychotic symptoms (odds ratio = 1.68, CI = 1.05-2.69) in drug-naive adolescents over a 12-month follow-up period [128]. These findings were suggestive of the involvement of AGEs in the pathophysiology of early psychosis.…”

Section: Schizophreniamentioning

confidence: 93%

“…A number of studies have indicated that AGEs may be associated with schizophrenia [96,128]. One systematic review revealed that AGE accumulation, in either skin or blood, was elevated in patients with schizophrenia compared to healthy controls [96].…”

Section: Schizophreniamentioning

confidence: 99%

The Effects of Dietary Advanced Glycation End-Products on Neurocognitive and Mental Disorders

et al. 2022

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Advanced glycation end products (AGEs) are glycated proteins or lipids formed endogenously in the human body or consumed through diet. Ultra-processed foods and some culinary techniques, such as dry cooking methods, represent the main sources and drivers of dietary AGEs. Tissue accumulation of AGEs has been associated with cellular aging and implicated in various age-related diseases, including type-2 diabetes and cardiovascular disease. The current review summarizes the literature examining the associations between AGEs and neurocognitive and mental health disorders. Studies indicate that elevated circulating AGEs are cross-sectionally associated with poorer cognitive function and longitudinally increase the risk of developing dementia. Additionally, preliminary studies show that higher skin AGE accumulation may be associated with mental disorders, particularly depression and schizophrenia. Potential mechanisms underpinning the effects of AGEs include elevated oxidative stress and neuroinflammation, which are both key pathogenetic mechanisms underlying neurodegeneration and mental disorders. Decreasing dietary intake of AGEs may improve neurological and mental disorder outcomes. However, more sophisticated prospective studies and analytical approaches are required to verify directionality and the extent to which AGEs represent a mediator linking unhealthy dietary patterns with cognitive and mental disorders.

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Fingertip advanced glycation end products and psychotic symptoms among adolescents

Cited by 8 publications

References 44 publications

Role of advanced glycation end products in the longitudinal association between muscular strength and psychotic symptoms among adolescents

Role of advanced glycation end products in the longitudinal association between muscular strength and psychotic symptoms among adolescents

Identification of key long non-coding RNA-associated competing endogenous RNA axes in Brodmann Area 10 brain region of schizophrenia patients

The Effects of Dietary Advanced Glycation End-Products on Neurocognitive and Mental Disorders

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