title: CHRNA7 and CHRFAM7A mRNAs: co-localized and their expression levels altered in the postmortem dorsolateral prefrontal cortex in major psychiatric disorders.
abstract: OBJECTIVE
  CHRNA7, coding α-7 nicotinic acetylcholine receptor (α7 nAChR), is involved in cognition through interneuron modulation of dopamine and glutamate signaling. CHRNA7 and its partially duplicated chimeric gene CHRFAM7A have been implicated in schizophrenia through linkage and association studies.
  
  
  METHODS
  Expression of CHRNA7 and CHRFAM7A mRNA was measured in the postmortem prefrontal cortex in more than 700 subjects, including patients with schizophrenia, bipolar disorder, major depression, and normal comparison subjects. The effects of antipsychotics and nicotine, as well as associations of CHRNA7 SNPs with gene expression, were explored. Fluorescent in-situ hybridization was used to examine coexpression of both transcripts in the human cortex.
  
  
  RESULTS
  CHRFAM7A expression and CHRFAM7A/CHRNA7 ratios were higher in fetal compared with postnatal life, whereas CHRNA7 expression was relatively stable. CHRFAM7A expression was significantly elevated in all diagnostic groups, while CHRNA7 expression was reduced in the schizophrenia group and increased in the major depression group compared with the comparison group. CHRFAM7A/CHRNA7 ratios were significantly increased in the schizophrenia and bipolar disorder groups compared with the comparison group. There was no effect of nicotine or antipsychotics and no association of SNPs in CHRNA7 with expression. CHRNA7 and CHRFAM7A mRNAs were expressed in the same neuronal nuclei of the human neocortex.
  
  
  CONCLUSIONS
  These data show preferential fetal CHRFAM7A expression in the human prefrontal cortex and suggest abnormalities in the CHRFAM7A/CHRNA7 ratios in schizophrenia and bipolar disorder, due mainly to overexpression of CHRFAM7A. Given that these transcripts are coexpressed in a subset of human cortical neurons and can interact to alter function of nAChRs, these results support the concept of aberrant function of nAChRs in mental illness.
authors.affiliation: From the Human Brain Collection Core, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Md.; the Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Hikarigaoka, Fukushima City, Fukushima, Japan; the Unit on Neural Circuits and Adaptive Behaviors, National Institute of Mental Health, National Institutes of Health, Bethesda, Md.; the Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore; the Department of Psychiatry and Behavioral Sciences, John Hopkins University School of Medicine, Baltimore; and the Department of Neurology, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Kunii
authors.affiliation: From the Human Brain Collection Core, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Md.; the Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Hikarigaoka, Fukushima City, Fukushima, Japan; the Unit on Neural Circuits and Adaptive Behaviors, National Institute of Mental Health, National Institutes of Health, Bethesda, Md.; the Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore; the Department of Psychiatry and Behavioral Sciences, John Hopkins University School of Medicine, Baltimore; and the Department of Neurology, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Zhang
authors.affiliation: From the Human Brain Collection Core, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Md.; the Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Hikarigaoka, Fukushima City, Fukushima, Japan; the Unit on Neural Circuits and Adaptive Behaviors, National Institute of Mental Health, National Institutes of Health, Bethesda, Md.; the Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore; the Department of Psychiatry and Behavioral Sciences, John Hopkins University School of Medicine, Baltimore; and the Department of Neurology, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
authors.affiliation: From the Human Brain Collection Core, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Md.; the Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Hikarigaoka, Fukushima City, Fukushima, Japan; the Unit on Neural Circuits and Adaptive Behaviors, National Institute of Mental Health, National Institutes of Health, Bethesda, Md.; the Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore; the Department of Psychiatry and Behavioral Sciences, John Hopkins University School of Medicine, Baltimore; and the Department of Neurology, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Hyde
authors.affiliation: From the Human Brain Collection Core, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Md.; the Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Hikarigaoka, Fukushima City, Fukushima, Japan; the Unit on Neural Circuits and Adaptive Behaviors, National Institute of Mental Health, National Institutes of Health, Bethesda, Md.; the Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore; the Department of Psychiatry and Behavioral Sciences, John Hopkins University School of Medicine, Baltimore; and the Department of Neurology, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Whitney
authors.initials: W
authors.lastname: McFadden
authors.affiliation: From the Human Brain Collection Core, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Md.; the Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Hikarigaoka, Fukushima City, Fukushima, Japan; the Unit on Neural Circuits and Adaptive Behaviors, National Institute of Mental Health, National Institutes of Health, Bethesda, Md.; the Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore; the Department of Psychiatry and Behavioral Sciences, John Hopkins University School of Medicine, Baltimore; and the Department of Neurology, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Joo Heon
authors.initials: JH
authors.lastname: Shin
authors.affiliation: From the Human Brain Collection Core, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Md.; the Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Hikarigaoka, Fukushima City, Fukushima, Japan; the Unit on Neural Circuits and Adaptive Behaviors, National Institute of Mental Health, National Institutes of Health, Bethesda, Md.; the Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore; the Department of Psychiatry and Behavioral Sciences, John Hopkins University School of Medicine, Baltimore; and the Department of Neurology, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Amy
authors.initials: A
authors.lastname: Deep-Soboslay
authors.affiliation: From the Human Brain Collection Core, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Md.; the Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Hikarigaoka, Fukushima City, Fukushima, Japan; the Unit on Neural Circuits and Adaptive Behaviors, National Institute of Mental Health, National Institutes of Health, Bethesda, Md.; the Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore; the Department of Psychiatry and Behavioral Sciences, John Hopkins University School of Medicine, Baltimore; and the Department of Neurology, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Tianzhang
authors.initials: T
authors.lastname: Ye
authors.affiliation: From the Human Brain Collection Core, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Md.; the Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Hikarigaoka, Fukushima City, Fukushima, Japan; the Unit on Neural Circuits and Adaptive Behaviors, National Institute of Mental Health, National Institutes of Health, Bethesda, Md.; the Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore; the Department of Psychiatry and Behavioral Sciences, John Hopkins University School of Medicine, Baltimore; and the Department of Neurology, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: From the Human Brain Collection Core, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Md.; the Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Hikarigaoka, Fukushima City, Fukushima, Japan; the Unit on Neural Circuits and Adaptive Behaviors, National Institute of Mental Health, National Institutes of Health, Bethesda, Md.; the Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore; the Department of Psychiatry and Behavioral Sciences, John Hopkins University School of Medicine, Baltimore; and the Department of Neurology, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Joel E
authors.initials: JE
authors.lastname: Kleinman
authors.affiliation: From the Human Brain Collection Core, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Md.; the Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Hikarigaoka, Fukushima City, Fukushima, Japan; the Unit on Neural Circuits and Adaptive Behaviors, National Institute of Mental Health, National Institutes of Health, Bethesda, Md.; the Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore; the Department of Psychiatry and Behavioral Sciences, John Hopkins University School of Medicine, Baltimore; and the Department of Neurology, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Kuan Hong
authors.initials: KH
authors.lastname: Wang
authors.affiliation: From the Human Brain Collection Core, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Md.; the Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Hikarigaoka, Fukushima City, Fukushima, Japan; the Unit on Neural Circuits and Adaptive Behaviors, National Institute of Mental Health, National Institutes of Health, Bethesda, Md.; the Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore; the Department of Psychiatry and Behavioral Sciences, John Hopkins University School of Medicine, Baltimore; and the Department of Neurology, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Lipska
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001714:Bipolar Disorder / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000235:genetics*
chemical_list: C579167:Chrna7 protein, human; D012333:RNA, Messenger; D064569:alpha7 Nicotinic Acetylcholine Receptor