title: Utility of Scalp Hair Follicles as a Novel Source of Biomarker Genes for Psychiatric Illnesses.
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.
authors.affiliation: Laboratory of Molecular Psychiatry, RIKEN Brain Science Institute, Saitama.
authors.forename: Motoko
authors.initials: M
authors.lastname: Maekawa
authors.affiliation: Laboratory of Molecular Psychiatry, RIKEN Brain Science Institute, Saitama.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Laboratory of Molecular Psychiatry, RIKEN Brain Science Institute, Saitama.
authors.forename: Manabu
authors.initials: M
authors.lastname: Toyoshima
authors.affiliation: Laboratory of Molecular Psychiatry, RIKEN Brain Science Institute, Saitama.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohnishi
authors.affiliation: Laboratory of Molecular Psychiatry, RIKEN Brain Science Institute, Saitama.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Iwayama
authors.affiliation: Laboratory of Molecular Psychiatry, RIKEN Brain Science Institute, Saitama; Graduate School of Humanities and Sciences, Department of Life Science, Ochanomizu University, Tokyo.
authors.forename: Chie
authors.initials: C
authors.lastname: Shimamoto
authors.affiliation: Laboratory of Molecular Psychiatry, RIKEN Brain Science Institute, Saitama.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toyota
authors.affiliation: Laboratory of Molecular Psychiatry, RIKEN Brain Science Institute, Saitama.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Nozaki
authors.affiliation: Laboratory of Molecular Psychiatry, RIKEN Brain Science Institute, Saitama.
authors.forename: Shabeesh
authors.initials: S
authors.lastname: Balan
authors.affiliation: Research Center for Child Mental Development, University of Fukui, Fukui.
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsuzaki
authors.affiliation: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Iwata
authors.affiliation: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka.
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Miyashita
authors.affiliation: Department of Psychiatry and Neurobiology, Kanazawa University Graduate School of Medicine, Kanazawa.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kikuchi
authors.affiliation: Departments of Neuropsychiatry, Keio University School of Medicine, Tokyo.
authors.forename: Motoichiro
authors.initials: M
authors.lastname: Kato
authors.affiliation: Physiology, Keio University School of Medicine, Tokyo; Department of Neurology, School of Medicine, Aichi Medical University, Aichi.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Physiology, Keio University School of Medicine, Tokyo; Center for Genomic and Regenerative Medicine, Juntendo University School of Medicine, Tokyo.
authors.forename: Wado
authors.initials: W
authors.lastname: Akamatsu
authors.affiliation: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka.
authors.forename: Norio
authors.initials: N
authors.lastname: Mori
authors.affiliation: Department of Organ Anatomy, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Owada
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo.
authors.forename: Masanari
authors.initials: M
authors.lastname: Itokawa
authors.affiliation: Physiology, Keio University School of Medicine, Tokyo.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
authors.affiliation: Laboratory of Molecular Psychiatry, RIKEN Brain Science Institute, Saitama. Electronic address: takeo@brain.riken.jp.
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000328:Adult; D001321:Autistic Disorder / Q000175:diagnosis / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000097:blood / Q000235:genetics; D005260:Female; D015870:Gene Expression; D018859:Hair Follicle; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D058953:Neural Stem Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012535:Scalp; D012559:Schizophrenia / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D015415:Biomarkers; C403049:CNTNAP2 protein, human; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D008565:Membrane Proteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger
keywords: Autism; CNTNAP2; FABP4; MicroRNA; Schizophrenia; hsa-miR-4449