Utility of Scalp Hair Follicles as a Novel Source of Biomarker Genes for Psychiatric Illnesses

Motoko Maekawa, Kazuo Yamada, Manabu Toyoshima, Tetsuo Ohnishi, Yoshimi Iwayama, Chie Shimamoto, Tomoko Toyota, Yayoi Nozaki, Shabeesh Balan, Hideo Matsuzaki, Yasuhide Iwata, Katsuaki Suzuki, Mitsuhiro Miyashita, Mitsuru Kikuchi, Motoichiro Kato, Yohei Okada, Wado Akamatsu, Norio Mori, Yuji Owada, Masanari ItokawaHideyuki Okano, Takeo Yoshikawa

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26 Citations (Scopus)

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.

Original languageEnglish
Article number12288
Pages (from-to)116-125
Number of pages10
JournalBiological Psychiatry
Volume78
Issue number2
DOIs
Publication statusPublished - 2015 Jul 15

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Keywords

  • Autism
  • CNTNAP2
  • FABP4
  • MicroRNA
  • Schizophrenia
  • hsa-miR-4449

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Maekawa, M., Yamada, K., Toyoshima, M., Ohnishi, T., Iwayama, Y., Shimamoto, C., Toyota, T., Nozaki, Y., Balan, S., Matsuzaki, H., Iwata, Y., Suzuki, K., Miyashita, M., Kikuchi, M., Kato, M., Okada, Y., Akamatsu, W., Mori, N., Owada, Y., ... Yoshikawa, T. (2015). Utility of Scalp Hair Follicles as a Novel Source of Biomarker Genes for Psychiatric Illnesses. Biological Psychiatry, 78(2), 116-125. [12288]. https://doi.org/10.1016/j.biopsych.2014.07.025