TY - JOUR
T1 - CHRNA7 and CHRFAM7A mRNAs
T2 - Co-localized and their expression levels altered in the postmortem dorsolateral prefrontal cortex in major psychiatric disorders
AU - Kunii, Yasuto
AU - Zhang, Wenyu
AU - Xu, Qing
AU - Hyde, Thomas M.
AU - McFadden, Whitney
AU - Shin, Joo Heon
AU - Deep-Soboslay, Amy
AU - Ye, Tianzhang
AU - Li, Chao
AU - Kleinman, Joel E.
AU - Wang, Kuan Hong
AU - Lipska, Barbara K.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - Objective: CHRNA7, coding a-7 nicotinic acetylcholine receptor (a7 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. Method: 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 hybridizationwasused 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. Therewasnoeffect 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.
AB - Objective: CHRNA7, coding a-7 nicotinic acetylcholine receptor (a7 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. Method: 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 hybridizationwasused 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. Therewasnoeffect 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.
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U2 - 10.1176/appi.ajp.2015.14080978
DO - 10.1176/appi.ajp.2015.14080978
M3 - Article
C2 - 26206074
AN - SCOPUS:84946134056
SN - 0002-953X
VL - 172
SP - 1122
EP - 1130
JO - American Journal of Psychiatry
JF - American Journal of Psychiatry
IS - 11
ER -
