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Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
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Related Experiment Video

Updated: Jun 18, 2026

Eye Tracking, Cortisol, and a Sleep vs. Wake Consolidation Delay: Combining Methods to Uncover an Interactive Effect of Sleep and Cortisol on Memory
08:08

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Published on: June 18, 2014

Working memory performance is associated with common glucocorticoid receptor gene polymorphisms.

R Kumsta1, S Entringer, J W Koper

  • 1Department of Theoretical and Clinical Psychobiology, University of Trier, Trier, Germany.

Neuropsychobiology
|November 27, 2009
PubMed
Summary
This summary is machine-generated.

Genetic variations in the glucocorticoid receptor (GR) gene influence working memory. Specific GR gene variants interact with sex, affecting cognitive performance and potentially modulating vulnerability to stress-related memory impairments.

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Area of Science:

  • Neuroendocrinology
  • Cognitive Neuroscience
  • Behavioral Genetics

Background:

  • Cortisol modulates human cognitive functions, with known effects on declarative and working memory.
  • The prefrontal cortex, crucial for working memory, has a high density of glucocorticoid (GC) receptors.
  • Genetic factors significantly contribute to memory heritability, suggesting a role for gene polymorphisms.

Purpose of the Study:

  • To investigate if common glucocorticoid receptor (GR) gene polymorphisms modulate cortisol's influence on working memory.
  • To examine the effects of cortisol administration on working memory performance in relation to GR gene variants.

Main Methods:

  • 169 subjects participated in a double-blind, placebo-controlled study.
  • Working memory was assessed using an item recognition task after administration of 10 mg hydrocortisone (cortisol) or placebo.
  • Genotyping was performed for common GR gene polymorphisms (ER22/23EK, N363S, BclI, 9 beta A3669G).

Main Results:

  • No general impairing effect of hydrocortisone on working memory was observed.
  • A significant sex x genotype interaction was found for working memory performance (p = 0.02).
  • Female heterozygous carriers of the 9 beta G allele showed faster reaction times, while heterozygous men with the 9 beta G allele were slower.

Conclusions:

  • Variants of the GR gene may explain genetic variance in cognitive performance.
  • GR gene polymorphisms might modulate individual vulnerability to memory impairments associated with stress and psychiatric disorders.
  • The findings highlight the complex interplay between genetics, hormones, and cognitive function, particularly working memory.