Dysregulation of leukocyte gene expression in women with medication-refractory depression versus healthy non-depressed controls

Abstract

BackgroundDepressive Disorders (DD) are a great financial and social burden. Females display 70% higher rate of depression than males and more than 30% of these patients do not respond to conventional medications. Thus medication-refractory female patients are a large, under-served, group where new biological targets for intervention are greatly needed.MethodsWe used real-time quantitative polymerase chain reaction (qPCR) to evaluate mRNA gene expression from peripheral blood leukocytes for 27 genes, including immune, HPA-axis, ion channels, and growth and transcription factors. Our sample included 23 females with medication refractory DD: 13 with major depressive disorder (MDD), 10 with bipolar disorder (BPD). Our comparison group was 19 healthy, non-depressed female controls. We examined differences in mRNA expression in DD vs. controls, in MDD vs. BPD, and in patients with greater vs. lesser depression severity.ResultsDD patients showed increased expression for IL-10, IL-6, OXTR, P2RX7, P2RY1, and TRPV1. BPD patients showed increased APP, CREB1, NFKB1, NR3C1, and SPARC and decreased TNF expression. Depression severity was related to increased IL-10, P2RY1, P2RX1, and TRPV4 expression.ConclusionsThese results support prior findings of dysregulation in immune genes, and provide preliminary evidence of dysregulation in purinergic and other ion channels in females with medication-refractory depression, and in transcription and growth factors in those with BPD. If replicated in future research examining protein levels as well as mRNA, these pathways could potentially be used to explore biological mechanisms of depression and to develop new drug targets.

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

“…On the other hand, no difference in mRNA levels between patients and controls was demonstrated by other studies in small samples of MDD patients (Lai et al 2003;Belzeaux et al 2010;Iacob et al 2013). Another study focussed on mRNA levels in leukocytes demonstrated an opposite finding, i.e., higher CREB mRNA levels in MDD patients compared to controls (Iga et al 2007).…”

Glucocorticoid Receptor-Related Genes: Genotype and Brain Gene Expression Relationships to Suicide and Major Depressive Disorder

“…These isoforms may contribute to the risk of suicide through reduced expression and poorer GR feedback leading to excessive HPA response under stress. Lower NR3C1 (GR) gene expression is reported in the amygdala of suicides compared with controls 48 , and lower NR3C1 expression in suicides with a history of childhood adversity 24 , while no expression differences in NR3C1 were reported between MDD and controls 49 .…”

Replication of genome‐wide association study (GWAS) susceptibility loci in a Latino bipolar disorder cohort

“…It has been implicated in treatment refractory schizophrenia within the Han Chinese population where it was associated with lower NFKB1 gene expression . Elevated NFKB1 gene expression in peripheral blood leukocytes has been proposed as a biological marker for treatment‐refractory bipolar disorder . NFKB1 plays a broad role in central nervous system (CNS) function where it is involved in synaptic plasticity, neurogenesis, differentiation, and neuronal survival (reviewed in ).…”