Abstract
Bipolar disorder is a severe, lifelong psychiatric disease. The main underlying pathophysiology of the disease is still incomprehensible. Various studies have suggested that many genes of small impact in combination with environmental factors contribute to the expression of the disease. In this study comparative transcriptomic profiling to characterize skin fibroblasts’ gene expression of bipolar disorder patients compared to healthy controls has been performed. Skin fibroblast cells from bipolar disorder patients (n=10) and marched healthy controls (n=5) have been cultured. RNA was extracted and then hybridized onto Illumina Human HT-12 v4 Expression BeadChips. Differentially expressed genes between bipolar disorder samples and healthy controls were identified by performing unequal t-test on log 2 transformed expression values. The resulting gene list was obtained by setting the p-value threshold to 0.05 and by removing genes that presented a fold change ≥ |0.5| (in log 2 scale). We concluded to 457 differentially expressed genes. Among them 127 showed an upregulation and 330 were downregulated. Τhe expression alterations of selected genes were validated by quantitative real-time polymerase chain reaction. In order to derive better insight into the biological mechanisms related to the differentially expressed genes, the lists of significant genes were subjected to pathway analysis and target prioritization indicating various processes such as calcium ion homeostasis, positive regulation of apoptotic process and cellular response to retinoic acid.
Highlights
Bipolar Disorder (BD) known as manic depressive illness is a prevalent and severe psychiatric disorder characterized by mania cycled with depression
RNA samples extracted from the five healthy control subjects were pooled into two samples for the microarray analysis, in order to limit the individual case-tocase variation of gene expression that is unrelated to BD
By applying the statistical criteria and according to GOrevenge results (Supplementary Table 14), PPARG and ENPP1 were among the candidate hub genes and their gene expression alterations between BD and healthy control samples have been confirmed from the quantitative polymerase chain reaction (qPCR) analysis
Summary
Bipolar Disorder (BD) known as manic depressive illness is a prevalent and severe psychiatric disorder characterized by mania cycled with depression. Bipolar disorder has three subtypes: bipolar I (one or more manic or mixed episodes usually followed by major depressive episodes), bipolar II (one or more major depressive episodes followed by one or more hypomanic episodes) and cyclothymic disorder (many hypomanic episodes and depressive symptoms for more than two years) [3]. The disease is treatable mainly with lithium in combination with antidepressants , other mood stabilizers and with psychotherapy [4]. The pharmacological treatment mainly targets imbalanced biogenic monoamine neurotransmitter systems [5]. The disease remains incurable with possible relapse episodes even after maintenance treatment [6]
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