Transcriptome alterations in the prefrontal cortex of subjects with schizophrenia who committed suicide.
To better understand the pathophysiological events associate with suicide in subjects with schizophrenia, we performed a DNA microarray expression profiling of the frontal cortex of subjects with schizophrenia who committed suicide, subjects with schizophrenia who died of non-suicidal causes and matched control subjects. Simultaneous expression profiling for >40,000 genes was performed using HU133A and HU133B Affymetrix oligonucleotide arrays. We conclude that suicide in schizophrenia is associated with a number of gene expression changes in the prefrontal cortex that are distinct from both of that observed in controls and subjects with schizophrenia who did not commit suicide. Furthermore, the observed gene expression signature contains a prefrontal cortical downregulation of the HTR2A serotonin receptor transcript, strengthening previously reported genetic susceptibility reports. As the observed transcript changes are likely developing over days or weeks, these data argue that the molecular predisposition to suicide develops significantly earlier than the act of suicide occurs. Finally, the presented data also strengthens previous reports of neuroimmune transcriptome disturbances in subjects with schizophrenia.
Garbett
Krassimira
K
Department of Psychiatry, Vanderbilt University, Nashville, TN 37232, USA.
Gal-Chis
Rodica
R
Gaszner
Gabor
G
Lewis
David A
DA
Mirnics
Károly
K
D001923:Brain Chemistry; D015536:Down-Regulation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D017397:Prefrontal Cortex / Q000378:metabolism*; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics / Q000378:metabolism*; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism*; D013405:Suicide
D044402:Receptor, Serotonin, 5-HT2A