Research Article
Leukocyte Gene Expression in Patients with Medication
Refractory Depression before and after Treatment with ECT or
Isoflurane Anesthesia: A Pilot Study
E. Iacob,
1,2
S. C. Tadler,
1
K. C. Light,
1
H. R. Weeks,
1,3
K. W. Smith,
1
A. T. White,
1,4
R. W. Hughen,
1
T. A. VanHaitsma,
4
L. A. Bushnell,
3
and A. R. Light
1,2
1
Department of Anesthesiology, University of Utah Health Sciences Center, Salt Lake City, UT, USA
2
Neuroscience Program, University of Utah Health Sciences Center, Salt Lake City, UT, USA
3
Department of Psychiatry, University of Utah, Salt Lake City, UT, USA
4
Department of Exercise and Sport Science, University of Utah, Salt Lake City, UT, USA
Correspondence should be addressed to E. Iacob; eli.iacob@gmail.com
Received 29 January 2014; Accepted 22 March 2014; Published 13 April 2014
Academic Editor: Michael Berk
Copyright © 2014 E. Iacob et al. his is an open access article distributed under the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Objective. To evaluate leukocyte gene expression for 9 selected genes (mRNAs) as biological markers in patients with medication
refractory depression before and ater treatment with ECT or isolurane anesthesia (ISO). Methods. In a substudy of a
nonrandomized open-label trial comparing efects of ECT to ISO therapy, blood samples were obtained before and ater treatment
from 22 patients with refractory depression, and leukocyte mRNA was assessed by quantitative PCR. Patients’ mRNAs were also
compared to 17 healthy controls. Results. Relative to controls, patients before treatment showed signiicantly higher IL10 and DBI
and lower ADRA2A and ASIC3 mRNA ( < 0.025). Both ECT and ISO induced signiicant decreases ater treatment in 4 genes:
IL10, NR3C1, DRD4, and Sult1A1. Ater treatment, patients’ DBI, ASIC3, and ADRA2A mRNA remained dysregulated. Conclusion.
Signiicant diferences from controls and/or signiicant changes ater ECT or ISO treatment were observed for 7 of the 9 mRNAs
studied. Decreased expression of 4 genes ater efective treatment with either ECT or ISO suggests possible overlap of underlying
mechanisms. hree genes showing dysregulation before and ater treatment may be trait-like biomarkers of medication refractory
depression. Gene expression for these patients has the potential to facilitate diagnosis, clarify pathophysiology, and identify potential
biomarkers for treatment efects.
1. Introduction
Blood-based biomarkers are important to the understanding,
diagnosis, and treatment of medical disorders. hey can be
especially helpful when the disorder is poorly understood,
complex, or where the diferentiation of subgroups may
have important implications for treatment and long-term
outcomes. In the case of depressive disorders (DD), one
subgroup where biomarkers would be especially useful con-
sists of those patients who are refractory to pharmacologic
antidepressant therapies. Previous studies have suggested that
gene expression (mRNA) on white blood cells may provide
useful biomarkers for patients with DD, including those with
refractory depression [1, 2].
Patients with medication refractory depression (typically
deined by failure to achieve remission with two or more
trials of diferent antidepressant regimens) represent almost
one-third of all patients with DD [3]. here are relatively
few treatment options for these patients. Electroconvulsive
therapy (ECT) is widely acknowledged to be the most
efective option, achieving remission in 55–90% of the cases,
even among patients who were previously refractory [4, 5].
Despite its safety and eicacy [6], many millions of patients
with refractory DD elect not to receive ECT due, in large
part, to misperceptions about this treatment being painful
or traumatic or to concerns regarding associated adverse
cognitive efects, most of which are, however, temporary
[7, 8]. his has encouraged eforts to ind alternative therapies
Hindawi Publishing Corporation
Depression Research and Treatment
Volume 2014, Article ID 582380, 12 pages
http://dx.doi.org/10.1155/2014/582380