Leukocyte Gene Expression in Patients with Medication Refractory Depression before and after Treatment with ECT or Isoflurane Anesthesia: A Pilot Study

Abstract

Objective. To evaluate leukocyte gene expression for 9 selected genes (mRNAs) as biological markers in patients with medication refractory depression before and after treatment with ECT or isoflurane anesthesia (ISO). Methods. In a substudy of a nonrandomized open-label trial comparing effects of ECT to ISO therapy, blood samples were obtained before and after 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 significantly higher IL10 and DBI and lower ADRA2A and ASIC3 mRNA (P < 0.025). Both ECT and ISO induced significant decreases after treatment in 4 genes: IL10, NR3C1, DRD4, and Sult1A1. After treatment, patients' DBI, ASIC3, and ADRA2A mRNA remained dysregulated. Conclusion. Significant differences from controls and/or significant changes after ECT or ISO treatment were observed for 7 of the 9 mRNAs studied. Decreased expression of 4 genes after effective treatment with either ECT or ISO suggests possible overlap of underlying mechanisms. Three genes showing dysregulation before and after 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 effects.

Microarray Analysis of Human Blood During Electroconvulsive Therapy

“…Nine target genes, such as ADRA2A , ASIC1 , AISC3 , DBI , DRD4 , IL-10 , NR3C1 , SULT1A1 , and VEGFA , were examined by quantitative real-time-PCR at 22 patients with refractory depression. 29 The design was similar to the current work in terms of the analysis of the peripheral blood sample, although microarray was initially used on our work. As for the array analysis on rat brain, a custom microarray chip (645 genes related to neurotrophic growth factor signaling, neurotransmitter signaling, angiogenesis, vasodilation, and transcription factors) revealed their involvement in acute or chronic electroconvulsive seizure.…”

Rhythms and blues: modulation of oscillatory synchrony and the mechanism of action of antidepressant treatments

“…Therapeutic interventions that act at either basic or more elaborate levels of complexity have been reported to yield similar changes in plasticity and gene expression in humans and/or in animal models, in peripheral blood or brain. These interventions include antidepressant medication and exercise, cognitive behavioral therapy for posttraumatic stress disorder, ECT, altering emotional and physical stress exposure, and cues that entrain circadian rhythms . The effects of these interventions may be transduced through similar mechanisms that subserve signal transduction in learning and memory processes, although this has not been established.…”

Protein biomarkers of mood disorders

“…The role of inflammation in mood disorders is supported by increased mRNA expression of pro-inflammatory cytokines cytokines IL-1α, IL-1β, IL-6, IL-8, IL-10, IFNγ, MIF, and TNFα in these patients compared to controls. 11 …”

“…The role of inflammation in mood disorders is supported by increased mRNA expression of pro-inflammatory cytokines cytokines IL-1α, IL-1β, IL-6, IL-8, IL-10, IFNγ, MIF, and TNFα in these patients compared to controls. 11 Inflammation is also associated with increased oxidative stress. It has been mRNA expression of genes encoding proteins associated with oxidative stress, including cyclooxygenase-2 (COX -2), myeloperoxidase(MPO), phospholipase A2 (PLA2G2A), purine-rich Box-1 (PU.1), and inducible nitric oxide synthase (iNOS) was increased in peripheral blood of patients with recurrent depressive disorder.…”