Hormonal and genetic modulation of memory processes in healthy humans: focus on cortisol and "HDAC5"

Individual differences in memory performance can be due to the influence of various hormones as well as genetic variations and epigenetic modifications. These complex molecular and genetic mechanisms can impact learning, memory consolidation and retrieval differentially. This thesis deals with the modulation of memory processes in healthy human subjects focusing on two viewpoints. Firstly, by addressing the influence of the stress hormone cortisol, as evidence from animal and human studies shows that cortisol can enhance memory consolidation and impair retrieval. Secondly, by analyzing genetic and epigenetic data to find a target associated with synaptic plasticity and memory formation.
To investigate if stress, induced by the cold pressor test, affects memory processes, a fear-conditioning paradigm was used. The stress group showed an increase in the cortisol level and reduced retrieval of the conditioned fear memory. In a further study, we investigated if inter-individual changes in basal cortisol levels affect episodic memory. Results showed an association between stronger decreases in cortisol levels during retrieval and a better recall performance.
In a large genetic study we focused on genetic polymorphisms tagging histone deacetylase 5 (HDAC5), a gene associated with synaptic plasticity and memory formation in animal models. We detected significant associations between these polymorphisms and episodic memory performance, especially for emotional information. Surprisingly, these polymorphisms were strongly associated with expression levels of a transcript in the vicinity of HDAC5.
These results may have implications for the understanding of the mechanisms underlying memory formation in healthy subjects and the interpretation of genetic data. Additionally, our results may have clinical implications for different neuropsychiatric disorders, such as depression, anxiety disorders or posttraumatic stress disorder, for which learning and memory play an important role.