Gene expression in peripheral blood in treatment-free major depression

Abstract

Background:Peripheral gene expression of several molecular pathways has been studied in major depressive disorder (MDD) with promising results. We sought to investigate some of these genes in a treatment-free Latino sample of Mexican descent.Material and Methods:The sample consisted of 50 MDD treatment-free cases and 50 sex and age-matched controls. Gene expression of candidate genes of neuroplasticity (BDNF, p11, and VGF), inflammation (IL1A, IL1B, IL4, IL6, IL7, IL8, IL10, MIF, and TNFA), the canonical Wnt signaling pathway (TCF7L2, APC, and GSK3B), and mTOR, was compared in cases and controls. RNA was obtained from blood samples. We used bivariate analyses to compare subjects versus control mean mRNA quantification of target genes and lineal regression modelling to test for effects of age and body mass index on gene expression.Results:Most subjects were female (66%) with a mean age of 26.7 (SD 7.9) years. Only GSK3B was differentially expressed between cases and controls at a statistically significant level (p = 0.048). TCF7L-2 showed the highest number of correlations with MDD-related traits, yet these were modest in size.Discussion:GSK3B encodes a moderator of the canonical Wnt signaling pathway. It has a role in neuroplasticity, neuroprotection, depression, and other psychiatric phenotypes. We found that adding population diversity has the potential to elicit distinct peripheral gene expression markers in MDD and MDD-related traits. However, our results should only be considered as hypothesis-generating research that merits further replication in larger cohorts of similar ancestry.

Elevated Epidermal Growth Factor (EGF) as Candidate Biomarker of Mood Disorders—Longitudinal Study in Adolescent and Young Adult Patients

“…The treatment prediction model also established a link with interleukin-1 beta mRNA [ 53 ]. No differences in the expression of MIF mRNA in drug-free MDD were found [ 54 ]. A genetic study in the adolescent group revealed the association of MIF polymorphisms with anxiety and attenuated cortisol reactivity [ 55 ].…”

Deletion or inhibition of prolyl oligopeptidase blocks lithium‐induced phosphorylation of GSK3b and Akt by activation of protein phosphatase 2A

“…One main mechanism for lithium is considered to be direct inhibition of glycogen synthase kinase 3β (GSK3b) via phosphorylation that has been comprehensively presented in various models (for reviews, see Freland and Beaulieu and Malhi and Outhred 3,4 ) and in patients with bipolar disorder 5 . Additionally, dysregulated GSK3b has been connected with several mental disorders where lithium has therapeutic effect, but the results are not unambiguous 6–9 . GSK3b is an important kinase in the cell, regulating, for example, glucose response, neuronal plasticity and apoptosis, and GSK3b inhibition by lithium has been shown to reduce apoptosis and to induce neuronal plasticity and growth via brain‐derived neurotrophic factor (BDNF; for review, see Freland and Beaulieu 3 ).…”

“…5 Additionally, dysregulated GSK3b has been connected with several mental disorders where lithium has therapeutic effect, but the results are not unambiguous. [6][7][8][9] GSK3b is an important kinase in the cell, regulating, for example, glucose response, neuronal plasticity and apoptosis, and GSK3b inhibition by lithium has been shown to reduce apoptosis and to induce neuronal plasticity and growth via brain-derived neurotrophic factor (BDNF; for review, see Freland and Beaulieu 3 ). Another important target for biological effects of lithium is protein kinase B (Akt, PKB), 10 and lithium induces the activation of Akt by phosphorylating it.…”