title: Molecular signatures associated with cognitive deficits in schizophrenia: a study of biopsied olfactory neural epithelium.
abstract: Cognitive impairment is a key feature of schizophrenia (SZ) and determines functional outcome. Nonetheless, molecular signatures in neuronal tissues that associate with deficits are not well understood. We conducted nasal biopsy to obtain olfactory epithelium from patients with SZ and control subjects. The neural layers from the biopsied epithelium were enriched by laser-captured microdissection. We then performed an unbiased microarray expression study and implemented a systematic neuropsychological assessment on the same participants. The differentially regulated genes in SZ were further filtered based on correlation with neuropsychological traits. This strategy identified the SMAD 5 gene, and real-time quantitative PCR analysis also supports downregulation of the SMAD pathway in SZ. The SMAD pathway has been important in multiple tissues, including the role for neurodevelopment and bone formation. Here the involvement of the pathway in adult brain function is suggested. This exploratory study establishes a strategy to better identify neuronal molecular signatures that are potentially associated with mental illness and cognitive deficits. We propose that the SMAD pathway may be a novel target in addressing cognitive deficit of SZ in future studies.
authors.affiliation: Department of Psychiatry, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Horiuchi
authors.affiliation: Department of Psychiatry, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Kondo
authors.affiliation: Department of Psychiatry, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: K
authors.initials: K
authors.lastname: Okada
authors.affiliation: Department of Mental Health, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Takayanagi
authors.affiliation: Department of Psychiatry, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Psychiatry, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: T
authors.initials: T
authors.lastname: Ho
authors.affiliation: Department of Psychiatry, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Varvaris
authors.affiliation: Department of Psychiatry, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: K
authors.initials: K
authors.lastname: Tajinda
authors.affiliation: Department of Psychiatry, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: H
authors.initials: H
authors.lastname: Hiyama
authors.affiliation: Pharmacology Research Labs, Astellas Pharma Inc., Tsukuba-shi, Ibaraki, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ni
authors.affiliation: Lieber Institute for Brain Development, Baltimore, MD, USA.
authors.forename: C
authors.initials: C
authors.lastname: Colantuoni
authors.affiliation: Department of Psychiatry, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: D
authors.initials: D
authors.lastname: Schretlen
authors.affiliation: Department of Psychiatry, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: N G
authors.initials: NG
authors.lastname: Cascella
authors.affiliation: Department of Psychiatry, Johns Hopkins University, Baltimore, MD, USA.|Hugo W Moser Research Institute at Kennedy Krieger, Baltimore, MD, USA.
authors.forename: J
authors.initials: J
authors.lastname: Pevsner
authors.affiliation: Department of Psychiatry, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: K
authors.initials: K
authors.lastname: Ishizuka
authors.affiliation: Department of Psychiatry, Johns Hopkins University, Baltimore, MD, USA.|Department of Mental Health, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: A
authors.initials: A
authors.lastname: Sawa
mesh_terms: D000328:Adult; D001706:Biopsy; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D009831:Olfactory Mucosa / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D051902:Smad5 Protein / Q000235:genetics*
chemical_list: C497797:SMAD5 protein, human; D051902:Smad5 Protein