Peripheral PDLIM5 expression in bipolar disorder and the effect of olanzapine administration

Mohd Aizat Zain,Sharmilla Kanagasundram,Zahurin Mohamed,Gavin P Reynolds,Suffee Nusrat Jahan,Nor Zuraida Zainal

doi:10.1186/1471-2350-13-91

Mohd Aizat Zain, Sharmilla Kanagasundram + Show 4 more

Open Access

https://doi.org/10.1186/1471-2350-13-91

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Abstract

BackgroundOne of the genes suggested to play an important role in the pathophysiology of bipolar disorder (BPD) is PDLIM5, which encodes LIM domain protein. Our main objective was to examine the effect of olanzapine treatment on PDLIM5 mRNA expression in the peripheral blood leukocytes of BPD patients.MethodsWe measured the expression of PDLIM5 mRNA from 16 patients with BPD Type I after 0, 4, and 8 weeks of treatment with olanzapine using quantitative real-time PCR. The Young Mania Rating Scale was used to evaluate the severity of manic symptoms in BPD patients. We also compared PDLIM5 mRNA expression in treatment-naïve BPD patients with that in healthy control subjects.ResultsNo significant difference was found in PDLIM5 mRNA expression between patients before olanzapine treatment and following 4 and 8 weeks of treatment (p>0.05). Although we observed a significant reduction in the severity of manic symptoms in all BPD patients (p<0.05), the effectiveness of the medication did not significantly correlate with the expression of PDLIM5 mRNA (p>0.05). Interestingly, PDLIM5 mRNA expression differed significantly between treatment-naïve BPD patients and healthy control subjects (p=0.002).ConclusionPDLIM5 mRNA expression did not appear to be a reflection of the efficacy of olanzapine in reducing the manic symptoms of BPD. The significant difference in expression of PDLIM5 mRNA in the peripheral blood leukocytes of treatment-naïve BPD patients versus that of healthy control subjects, however, suggests that it may be a good biological marker for BPD.

Highlights

One of the genes suggested to play an important role in the pathophysiology of bipolar disorder (BPD) is PDLIM5, which encodes LIM domain protein
We showed that there was no significant difference between PDLIM5 mRNA expression before and after 4 and 8 weeks of medication (Figure 2)
The results indicated that there was a significant association between PDLIM5 mRNA expression and the occurrence of BPD in the Indian patients (p=0.028), with a trend towards a positive association in the Chinese BPD patients (p=0.064)

Summary

Introduction

One of the genes suggested to play an important role in the pathophysiology of bipolar disorder (BPD) is PDLIM5, which encodes LIM domain protein. Strong evidence from twin, adoption, family, and linkage studies has shown that BPD is associated with genetic factors, with an estimated heredity of 63%[1]. On the basis of evidence reported in genetic association and expression studies, PDLIM5 is a promising candidate gene for BPD [2]. LIM domains are cysteine-rich double zinc fingers composed of 50 to 60 amino acids that are involved in protein-protein interactions such as cytoskeleton organization, cell lineage specification, organ development, and oncogenesis. LIM domains are members of the Enigma class of proteins, including the Enigma homologue (ENH), a family of proteins that possess a 100-amino acid PDZ domain in the N terminus and one to three LIM domains in the C terminus. The formation of the PKCε-ENH-N-type Ca2+ channel complex has been hypothesized to have an important role in the molecular basis and efficiency of cellular signalling [4,5]

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