Motoko Maekawa1, Kazuo Yamada1, Manabu Toyoshima1, Tetsuo Ohnishi1, Yoshimi Iwayama1, Chie Shimamoto2, Tomoko Toyota1, Yayoi Nozaki1, Shabeesh Balan1, Hideo Matsuzaki3, Yasuhide Iwata4, Katsuaki Suzuki4, Mitsuhiro Miyashita5, Mitsuru Kikuchi6, Motoichiro Kato7, Yohei Okada8, Wado Akamatsu9, Norio Mori4, Yuji Owada10, Masanari Itokawa5, Hideyuki Okano11, Takeo Yoshikawa12. 1. Laboratory of Molecular Psychiatry, RIKEN Brain Science Institute, Saitama. 2. Laboratory of Molecular Psychiatry, RIKEN Brain Science Institute, Saitama; Graduate School of Humanities and Sciences, Department of Life Science, Ochanomizu University, Tokyo. 3. Research Center for Child Mental Development, University of Fukui, Fukui. 4. Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka. 5. Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo. 6. Department of Psychiatry and Neurobiology, Kanazawa University Graduate School of Medicine, Kanazawa. 7. Departments of Neuropsychiatry, Keio University School of Medicine, Tokyo. 8. Physiology, Keio University School of Medicine, Tokyo; Department of Neurology, School of Medicine, Aichi Medical University, Aichi. 9. Physiology, Keio University School of Medicine, Tokyo; Center for Genomic and Regenerative Medicine, Juntendo University School of Medicine, Tokyo. 10. Department of Organ Anatomy, Yamaguchi University Graduate School of Medicine, Ube, Japan. 11. Physiology, Keio University School of Medicine, Tokyo. 12. Laboratory of Molecular Psychiatry, RIKEN Brain Science Institute, Saitama. Electronic address: takeo@brain.riken.jp.
Abstract
BACKGROUND: Identifying beneficial surrogate genetic markers in psychiatric disorders is crucial but challenging. METHODS: Given that scalp hair follicles are easily accessible and, like the brain, are derived from the ectoderm, expressions of messenger RNA (mRNA) and microRNA in the organ were examined between schizophrenia (n for first/second = 52/42) and control subjects (n = 62/55) in two sets of cohort. Genes of significance were also analyzed using postmortem brains (n for case/control = 35/35 in Brodmann area 46, 20/20 in cornu ammonis 1) and induced pluripotent stem cells (n = 4/4) and pluripotent stem cell-derived neurospheres (n = 12/12) to see their role in the central nervous system. Expression levels of mRNA for autism (n for case/control = 18/24) were also examined using scalp hair follicles. RESULTS: Among mRNA examined, FABP4 was downregulated in schizophrenia subjects by two independent sample sets. Receiver operating characteristic curve analysis determined that the sensitivity and specificity were 71.8% and 66.7%, respectively. FABP4 was expressed from the stage of neurosphere. Additionally, microarray-based microRNA analysis showed a trend of increased expression of hsa-miR-4449 (p = .0634) in hair follicles from schizophrenia. hsa-miR-4449 expression was increased in Brodmann area 46 from schizophrenia (p = .0007). Finally, we tested the expression of nine putative autism candidate genes in hair follicles and found decreased CNTNAP2 expression in the autism cohort. CONCLUSIONS: Scalp hair follicles could be a beneficial genetic biomarker resource for brain diseases, and further studies of FABP4 are merited in schizophrenia pathogenesis.
BACKGROUND: Identifying beneficial surrogate genetic markers in psychiatric disorders is crucial but challenging. METHODS: Given that scalp hair follicles are easily accessible and, like the brain, are derived from the ectoderm, expressions of messenger RNA (mRNA) and microRNA in the organ were examined between schizophrenia (n for first/second = 52/42) and control subjects (n = 62/55) in two sets of cohort. Genes of significance were also analyzed using postmortem brains (n for case/control = 35/35 in Brodmann area 46, 20/20 in cornu ammonis 1) and induced pluripotent stem cells (n = 4/4) and pluripotent stem cell-derived neurospheres (n = 12/12) to see their role in the central nervous system. Expression levels of mRNA for autism (n for case/control = 18/24) were also examined using scalp hair follicles. RESULTS: Among mRNA examined, FABP4 was downregulated in schizophrenia subjects by two independent sample sets. Receiver operating characteristic curve analysis determined that the sensitivity and specificity were 71.8% and 66.7%, respectively. FABP4 was expressed from the stage of neurosphere. Additionally, microarray-based microRNA analysis showed a trend of increased expression of hsa-miR-4449 (p = .0634) in hair follicles from schizophrenia. hsa-miR-4449 expression was increased in Brodmann area 46 from schizophrenia (p = .0007). Finally, we tested the expression of nine putative autism candidate genes in hair follicles and found decreased CNTNAP2 expression in the autism cohort. CONCLUSIONS:Scalp hair follicles could be a beneficial genetic biomarker resource for brain diseases, and further studies of FABP4 are merited in schizophrenia pathogenesis.
Authors: Ashley Ansel; Joshua P Rosenzweig; Philip D Zisman; Michal Melamed; Benjamin Gesundheit Journal: Front Neurosci Date: 2017-01-05 Impact factor: 4.677
Authors: M Toyoshima; W Akamatsu; Y Okada; T Ohnishi; S Balan; Y Hisano; Y Iwayama; T Toyota; T Matsumoto; N Itasaka; S Sugiyama; M Tanaka; M Yano; B Dean; H Okano; T Yoshikawa Journal: Transl Psychiatry Date: 2016-11-01 Impact factor: 6.222
Authors: A Uezato; N Yamamoto; Y Iwayama; S Hiraoka; E Hiraaki; A Umino; E Haramo; M Umino; T Yoshikawa; T Nishikawa Journal: Transl Psychiatry Date: 2015-10-06 Impact factor: 6.222