Dr. O'Donovan's research focuses on how psychological stress increases risk for mental and physical health problems

Aoife O'Donovan, PhD

Director, THRIVE Laboratory

Assistant Professor at UCSF

 

 

 

Our Research

People who experience traumatic or enduring psychological stress are more likely to develop psychiatric disorders and age-related diseases such as cardiovascular, autoimmune and neurodegenerative disorders. Our research is focused on revealing how psychological stress “gets under the skin” and more precisely “into cells” to affect mental and physical health. We aim to identify the psychological and biological factors that account for the adverse effects of psychological stress, and ultimately to drive the development of targeted interventions to reduce such negative effects of stress. To this end, we are currently focused on examining the effects of specific kinds of psychological stress on indices and mechanisms of biological aging including telomere shortening,  inflammatory activity and oxidative stress.

 

Overview

People who experience enduring or traumatic psychological stress are at increased risk for psychiatric disorders and for the early development of diseases of aging such as cardiovascular, autoimmune and neurodegenerative disorders. Our research is focused on identifying the psychological and biological factors that account for the adverse health effects of chronic and traumatic psychological stress, with a particular focus on immunological factors such as inflammation and leukocyte telomere shortening. 

 

Common Mechanism of Stress Effects on Health - Inflammation

Experimental research indicates that inflammation may be a mechanism of psychiatric symptoms as well as cellular aging and multiple diverse diseases of aging. Could inflammation also play a role in the adverse health outcomes associated with stress exposure?  Our accumulating evidence suggests that it might.  Across studies, we found elevated inflammation in groups with severe traumatic stress exposure and pessimism as well as in those with high levels of anxiety, major depression and suicidal ideation. Moreover, we found higher pro-inflammatory signaling through NF-κB and decreased anti-inflammatory signaling through glucocorticoid receptors (GR) in patients with PTSD compared with individuals without PTSD.  We are now working to extend these findings in new studies and new populations.

 

Common Mechanism of Stress Effects on Health - Cellular Aging

Telomeres are DNA-protein complexes that cap the ends of chromosomes and protect against damage to DNA. Due to the end replication problem, telomeres may not fully replicate when cells divide and thus, telomeres can shorten with each cycle of cell division. In humans, short immune cell telomere length has emerged as a risk factor for chronic diseases of aging and early mortality. Thus, accelerated telomere shortening may play a role in the relationship between psychological stress and diseases of aging. Drs. Elissa Epel, Jue Lin, Elizabeth Blackburn and colleagues reported the first evidence in support of this hypothesis in 2004. Specifically, these investigators reported that mothers with high levels of perceived stress had significantly shorter telomeres and higher levels of oxidative stress.

Subsequently, we have also found that different types of psychological stress are associated with short telomere length. In particular, working with Drs. Epel, Lin, and Blackburn as well as Drs. Thomas Neylan, Owen Wolkowitz and others, we have observed short telomere length in samples with higher levels of dispostional pessimism, PTSD, and childhood trauma.  These support the idea that accelerated telomere shortening may be part of the pathway from psychological stress to disease development. Our goal now is to understand how stressful life experiences could influence the length of our telomeres.

 

Common Psychological Mechanism - Threat Sensitivity 

Across the stress-related psychological variables that our research focuses on (i.e. pessimism, childhood trauma, anxiety, suicidal ideation and PTSD), there is a common tendency towards heightened sensitivity to threatening information.  Such greater sensitivity to threatening information may be caused by elevated inflammation but may also drive biological stress responses and promote biological aging. In support of this model, we found that women who anticipated greater threat in response to a standardized acute  laboratory stressor had shorter telomere length.  Future work will be focused on clarifying the relationship between threat sensitivity and immunological factors in both observational and intervention studies.