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.


CONCLUSIONS
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.
Department of Neropsychiatry, Osaka Medical College, Takatsuki, Osaka, Japan.
Masaki
M
Nishiguchi
Department of Neropsychiatry, Osaka Medical College, Takatsuki, Osaka, Japan.
Hiroki
H
Kikuyama
Department of Neropsychiatry, Osaka Medical College, Takatsuki, Osaka, Japan.
Tetsufumi
T
Kanazawa
Department of Neropsychiatry, Osaka Medical College, Takatsuki, Osaka, Japan.
Atsushi
A
Tsutsumi
Department of Neropsychiatry, Osaka Medical College, Takatsuki, Osaka, Japan.
Takao
T
Kaneko
Psychological Service and Counseling Center, Kansai University, Suita, Osaka, Japan.
Hiroyuki
H
Uenishi
Department of Neropsychiatry, Osaka Medical College, Takatsuki, Osaka, Japan.
Yasuo
Y
Kawabata
Department of Neropsychiatry, Osaka Medical College, Takatsuki, Osaka, Japan.
Seiya
S
Kawashige
Department of Neropsychiatry, Osaka Medical College, Takatsuki, Osaka, Japan.
Jun
J
Koh
Department of Neropsychiatry, Osaka Medical College, Takatsuki, Osaka, Japan.
Hiroshi
H
Yoneda
Depression; Electroconvulsive therapy; Oct4; Schizophrenia; Sox2; iPS cells