Abstract
The tryptophan hydroxylase isoform-2 gene (Tph2) is located on chromosome 12 and is expressed primarily in brain tissue. Although the tryptophan hydroxylase isoform-1 gene (Tph1) has been reported to have a genetic association with bipolar disorder and schizophrenia, the Tph1 isoform is expressed at much lower levels than Tph2 (150-fold less in the mouse brain). We hypothesized that bipolar disorder and schizophrenia are associated with abnormal levels of TPH2 mRNA in the brain. TPH2 and β-actin mRNA levels in postmortem brain were quantified using real-time PCR. mRNA samples provided by the Stanley Foundation Array Collection were derived from the dorsolateral prefrontal cortex (Brodmann Area 46) of 35 bipolar, 35 schizophrenic, and 35 control subjects. There were significant differences in the mRNA levels among bipolar, schizophrenic, and normal subjects [F(2,102)=3.58; p=0.031]. A greater amount of TPH2 mRNA was found in the bipolar group in comparison with control subjects (Tukey's test: p=0.024). Further investigations of Tph2 are needed to clarify the potential role of this gene in the pathophysiology of bipolar disorder.
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Acknowledgements
This work was made possible through the support of the Canadian Institutes for Health Research (CIHR) and the National Alliance for Research in Schizophrenia and Depression (NARSAD). AHCW is a CIHR Clinician-Scientist Fellow and NARSAD Young Investigator, and HHMVT holds a Canada Research Chair in Neurobiology. VDL is supported by a Postdoctoral Research Fellowship and a Pilot Grant from the American Foundation for Suicide Prevention. Postmortem brain tissue mRNA and DNA were donated by The Stanley Medical Research Institute Array Collection courtesy of Drs. Michael B. Knable, E. Fuller Torrey, Maree J. Webster, Serge Weis, and Robert H. Yolken. The authors would also like to thank Mahawib Semralul for her technical assistance. All experiments were carried out in accordance with Canadian legal and ethical requirements.
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De Luca, V., Likhodi, O., Van Tol, H.H.M. et al. Tryptophan hydroxylase 2 gene expression and promoter polymorphisms in bipolar disorder and schizophrenia. Psychopharmacology 183, 378–382 (2005). https://doi.org/10.1007/s00213-005-0191-4
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DOI: https://doi.org/10.1007/s00213-005-0191-4