Antipsychotic drug use is correlated with CRP40/mortalin mRNA expression in the dorsolateral prefrontal cortex of human postmortem brain specimens

Gabriele, Joseph P.; Pontoriero, Giuseppe F.; Thomas, Nancy; Ferro, Mark A.; Mahadevan, Geetha; MacCrimmon, Duncan J.; Pristupa, Zdenek B.; Mishra, Ram K.

doi:10.1016/j.schres.2009.12.039

« Previous Next »Schizophrenia Research
Volume 119, Issue 1 , Pages 228-231, June 2010

Antipsychotic drug use is correlated with CRP40/mortalin mRNA expression in the dorsolateral prefrontal cortex of human postmortem brain specimens

Joseph P. Gabriele
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada
- Corresponding author. McMaster University, 1200 Main St. West, HSC Rm 4N81, Hamilton, Ontario, Canada L8N 3Z5. Tel.: +1 905 525 9140x22617.
Giuseppe F. Pontoriero
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada
Nancy Thomas
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada
Mark A. Ferro
- Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada
Geetha Mahadevan
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada
Duncan J. MacCrimmon
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada
Zdenek B. Pristupa
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada
Ram K. Mishra
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada

Received 15 July 2009; received in revised form 21 December 2009; accepted 29 December 2009. published online 25 January 2010.

Abstract

Heat shock proteins act as intracellular chaperones by assisting with proper protein folding in response to various cellular stresses. In doing so, these proteins protect the cell from unwanted protein aggregation, which in turn, plays an important role in the pathogenesis of numerous disorders. Previous reports from our laboratory have described a 40kDa catecholamine regulated heat shock-like protein (CRP40), an alternate gene product of the 70kDa mitochondrial heat shock protein, mortalin. CRP40 shares an intimate association with dopaminergic activity, specifically as it pertains to dopamine dysregulation in schizophrenia. This study investigates human CRP40/mortalin mRNA expression within dorsolateral prefrontal cortex postmortem specimens from normal control, schizophrenic and bipolar patients obtained from the Stanley Medical Research Institute. Real-time polymerase chain reaction was carried out for all patient samples (n=105; n=35 per group) in a blinded manner. No significant alterations in CRP40/mortalin mRNA expression levels were observed between control, bipolar and schizophrenic patients. However, multiple regression demonstrated a distinct positive correlation between CRP40/mortalin mRNA expression and lifetime use of antipsychotic drugs within the schizophrenic patient profile, after controlling for important confounding factors. Thus, the data suggest that human CRP40/mortalin is modulated by dopaminergic activity and may act to protect neurons from excess catecholamine activity in regions of the brain associated with psychosis.