SNSF | P3 Research Database

memory; stress; glucocorticoids; behavioral genetics; neuroimaging; dementia; PTSD; phobia

English title	Memory in Health and Disease - From basic mechanisms to clinical implications
Applicant	De Quervain Dominique
Number	106708
Funding scheme	SNSF Professorships
Research institution	Abteilung für Psychiatrische Forschung Psychiatrische Universitätsklinik Zürich
Institution of higher education	University of Zurich - ZH
Main discipline	Neurology, Psychiatry
Start/End	01.03.2005 - 28.02.2009
Approved amount	1'303'144.00

Lead

Lay summary
Memory processes in health are tightly regulated and any deviation mayresult in a pathological state. In the present project, I propose studiesto investigate the memory modulatory effects of glucocorticoids and toidentify genes related to human memory. Glucocorticoids and memory: We have previously reported thatglucocorticoids can inhibit memory retrieval in animals and humans. Whileelevated glucocorticoid levels are detrimental when information should beretrieved (e.g. during exams), they may actually have beneficial effectsin conditions when memory retrieval is distressing. Post-traumatic stressdisorder (PTSD) represents such a condition because excessive retrieval oftraumatic memories is one of the cardinal symptoms of this disorder.Indeed, we found first evidence that the administration of low-dosecortisol reduces retrieval of traumatic memories in patients with PTSD.These findings may have important clinical implications for the treatmentof anxiety disorders (PTSD, phobias). Anxiety disorders are the mostcommon psychiatric disorders and currently available treatment options arenot satisfactory. In the present project, we will explore the mechanismsunderlying glucocorticoid effects on fear extinction and will explore thetherapeutic efficacy of low-dose glucocorticoids for the treatment of PTSDand phobias. Genes and memory: Studies in twins revealed a roughly 50% heritablecomponent for human memory capacity, indicating that naturally occurringgenetic variations have an important impact on this cognitive ability. Wehave previously reported that a functional genetic variation of theserotonin-2a-receptor affects short-term memory in healthy young humans.In the present project, we will continue to investigate genes related tohuman memory by studying the relation of phenotypic and genetic variationacross individuals. Specifically, we will investigate the impact ofvariations in genes known to be involved in memory-relevant cellularpathways in animals (e.g. CREB) and in genes related to memory-modulatoryneurotransmitter systems. Furthermore, we will study the functionalrelevance and mechanisms of such newly identified memory-related genes inhumans by using in vitro experiments, fMRI, neuropharmacological studiesand transgenic mouse models. The findings may help to understand how genesare involved in regulating human memory functions and how variations inthese genes contribute to differences in memory capacity betweenindividuals. Furthermore, the identification of memory-related genes maypave the way for the development of new drugs to treat memory disorders.