Increases in iPS Transcription Factor (Oct4, Sox2, c-Myc, and Klf4) Gene Expression after Modified Electroconvulsive Therapy

OBJECTIVE: Electroconvulsive therapy (ECT) is a reasonable option for intractable depression or schizophrenia, but a mechanism of action has not been established. One credible hypothesis is related to neural plasticity. Three genes (Oct4, Sox2, c-Myc) involved in the induction of induced pluripotent stem (iPS) cells are Wnt-target genes, which constitute a key gene group involved in neural plasticity through the TCF family. Klf4 is the other gene among Yamanaka's four transcription factors, and increases in its expression are induced by stimulation of the canonical Wnt pathway. METHODS: We compared the peripheral blood gene expression of the four iPS genes (Oct4, Sox2, c-Myc, and Klf4) before and after modified ECT (specifically ECT with general anesthesia) of patients with intractable depression (n=6) or schizophrenia (n=6). Using Thymatron ten times the total bilateral electrical stimulation was evoked. RESULTS: Both assessments of the symptoms demonstrated significant improvement after mECT stimulation. Expression of all four genes was confirmed to increase after initial stimulation. The gene expression levels after treatment were significantly different from the initial gene expression in all twelve cases at the following treatment stages: at the 3rd mECT for Oct4; at the 6th and 10th mECT for Sox2; and at the 3rd, 6th and 10th mECT for c-Myc. CONCLUSION: These significant differences were not present after correction for multiple testing; however, our data have the potential to explain the molecular mechanisms of mECT from a unique perspective. Further studie should be conducted to clarify the pathophysiological involvement of iPS-inducing genes in ECT.

An Association Study of the Signal Transducer and Activator of Transcription 6 Gene With Periodic Psychosis

OBJECTIVE: Recent molecular and genetic investigations have suggested that the current nosology for major psychiatric disorders, based on the "two-entities-principal" is not accurate with respect to clinical observations; patient groups that do not fit to the current operative diagnostic boundaries are readily identified. We aimed to perform an investigation of the signal transducer and activator of transcription 6 (STAT6) gene (located on 12q13), which has an important role in the apoptotic cascade, with patients suffering from periodic psychosis. METHODS: Genetic association study has been employed for the current work. Investigated six tag-SNPs were chosen from Hapmap database. RESULTS: Among six tag-SNPs, one marker (rs10783813), located in the STAT6 gene, showed modest association (p<0.05), although no marker or haplotype block showed association after Bonferroni's correction. CONCLUSION: Future studies will reveal the etiological role of STAT6, and of other genes of the apoptotic cascade, in major psychiatric disorders.