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Memory in Health and Disease - From basic mechanisms to clinical implications

English title Memory in Health and Disease - From basic mechanisms to clinical implications
Applicant De Quervain Dominique
Number 123391
Funding scheme SNSF Professorships
Research institution Abteilung für Psychiatrische Forschung Psychiatrische Universitätsklinik Zürich Universität Zürich
Institution of higher education University of Zurich - ZH
Main discipline Neurology, Psychiatry
Start/End 01.03.2009 - 28.02.2011
Approved amount 532'281.00
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Keywords (12)

memory; stress; glucocorticoids; behavioral genetics; neuroimaging; PTSD; phobia; retrieval; extinction; genes; polymorphism; fMRI

Lay Summary (English)

Lead
Lay summary
In the present project, I will further investigate the memory modulatory effects of glucocorticoids in health and disease and aim to identify and characterize novel memory-related genes in humans. Glucocorticoids and memory: We have previously reported that glucocorticoids can inhibit memory retrieval in animals and healthy humans. While elevated glucocorticoid levels are detrimental when information should be retrieved (e.g. during exams), they may actually have beneficial effects in conditions when memory retrieval is distressing or maladaptive. Indeed, our recent studies provide first evidence that the administration of glucocorticoids reduces retrieval of traumatic memories in post-traumatic stress disorder (PTSD) and fear memory in phobias. Moreover, our data suggest that glucocorticoids promote the extinction of such aversive memories. In the present project I aim tooinvestigate the role of glucocorticoids in memory extinction oexplore the therapeutic efficacy of glucocorticoids in the treatment of PTSD and phobias PTSD and phobias are common mental disorders and current treatment options are not satisfactory. This underscores the importance of developing novel efficacious treatments for these disorders.Genes and memory: Studies in twins revealed a roughly 50% heritable component for human memory capacity, indicating that naturally occurring genetic variations have an important impact on this cognitive ability. Both in candidate gene studies and in an unbiased, pooling-based genome-wide screen, we have identified several genes related to human memory. Furthermore, we were able to characterize the identified genes with functional imaging techniques (fMRI). Currently, we are running an individual genome-wide screen with 1.8 million genetic markers in our population of 350 healthy human subjects and we expect a large number of highly significant signals. Consequently, I aim tooidentify and validate novel memory-related genes in humansocharacterize the newly identified genes (e.g. gene expression, fMRI)The identification and characterization of novel memory-related genes in humans will help to better understand the genetic basis and molecular mechanisms of human memory and will ultimately promote the targeted treatment of memory disorders.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Associated projects

Number Title Start Funding scheme
106708 Memory in Health and Disease - From basic mechanisms to clinical implications 01.03.2005 SNSF Professorships

Abstract

In the present project, I propose to further investigate the memory modulatory effects of glucocorticoids in health and disease and to identify and characterize novel memory-related genes in humans. Glucocorticoids and memory: We have previously reported that glucocorticoids can inhibit memory retrieval in animals and healthy humans. While elevated glucocorticoid levels are detrimental when information should be retrieved (e.g. during exams), they may actually have beneficial effects in conditions when memory retrieval is distressing or maladaptive. Indeed, our recent studies provide first evidence that the administration of glucocorticoids reduces retrieval of traumatic memories in post-traumatic stress disorder (PTSD) and fear memory in phobias. Moreover, our data suggest that glucocorticoids promote the extinction of such aversive memories. I now propose to• investigate the role of glucocorticoids in memory extinction • explore the therapeutic efficacy of glucocorticoids in the treatment of PTSD and phobias PTSD and phobias are common and current treatment options are not satisfactory. This underscores the importance of developing novel efficacious treatments for these disorders.Genes and memory: Studies in twins reveal a roughly 50% heritable component for human memory capacity, indicating that naturally occurring genetic variations have an important impact on this cognitive ability. Both in candidate gene studies and in an unbiased, pooling-based genome-wide screen, we have identified several genes related to human memory. Furthermore, we were able to characterize the identified genes with functional imaging techniques (fMRI). Currently, we are running an individual genome-wide screen with 1.8 million genetic markers in our population of 350 healthy human subjects and we expect a large number of highly significant signals. Consequently, I propose to• identify and validate novel memory-related genes in humans• characterize the newly identified genes (e.g. gene expression, fMRI)Importantly, DNA and fMRI data are already available for the planned analyses and experiments. The identification and characterization of novel memory-related genes in humans will help to better understand the genetic basis and molecular mechanisms of human memory and will ultimately promote the targeted treatment of memory disorders.
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