Effect of escitalopram versus placebo on GRa messenger RNA expression in peripheral blood
cells of healthy individuals with a family history of depression - a secondary outcome analysis from
the randomized AGENDA trial
Sammanfattning
Background Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed as first-line
drugs for
the treatment of depression. However, the mechanisms of action for SSRIs are unclear and besides
neurotransmitter modulation may depend on modulation of the hypothalamic-pituitary-adrenal (HPA)
system. The glucocorticoid receptor (GR) isoform a plays an important role in the negative feedback
regulation of the HPA axis and reduced GRa messenger RNA (mRNA) expression has been shown in
mood disorder patients and first-degree relatives compared to healthy individuals with no family
history
of psychiatric disorders. Aim Based on the AGENDA trial dataset, we analysed whether an
intervention
with SSRI versus placebo decreases the GRa mRNA expression in peripheral blood cells in healthy
firstdegree
relatives of patients with major depression. Methods The participants (N ¼ 80) were randomly
allocated to receive daily tablets of escitalopram 10 mg versus placebo for 4 weeks. GRa mRNA
expression levels in peripheral blood were measured using reverse transcription polymerase chain
reaction. Results Four weeks of intervention with escitalopram decreased the relative change from
baseline in the expression of GRa mRNA compared with placebo (p ¼ 0.002). Conclusion These
findings
from a randomized trial suggest that a 4-week escitalopram administration to healthy participants
results
in a decrease in GRa mRNA expression levels in peripheral blood compared with inert placebo. The
decrease in GRa mRNA expression levels may reflect a decrease in the HPA axis activity.