Psychiatry Li Lab
Li Lab

RESEARCH FOCUS

Veterans with post-traumatic stress disorder (PTSD) may persistently re-experience of a traumatic event and require treatment tailored to the unique nature of combat, military culture. A special challenge to mitigate stress-induced anxiety disorder with pharmacological intervention and promoting resilience of symptoms of PTSD are the main research commitment.

OUR APPROACH

Elevated startle response and hyperarousal are hallmarks of PTSD and are generally considered to evince fear (DSM V). To further examine the long lasting efficacy of corticosterone in treating hyperarousal and elevated fear, our present study utilized a learned helplessness stress model in which rats are restrained and subjected to tail shock for three days. These stressed rats develop a delayed long-lasting exaggeration of the acoustic startle response (ASR) and retarded body weight growth, similar to symptoms of PTSD patients.

FINDINGS

We demonstrate that both pre-stress and post-stress administration of corticosterone mitigates a subsequent exaggeration of the ASR measured 14 days after cessation of the stress protocol. Furthermore, the mitigating efficacy of pre-stress administration of corticosterone (3 mg/kg/day for three days) appeared to last significantly longer, up to 21 days after the cessation of the stress protocol, in comparison to that of post-stress administration of corticosterone. In addition, pre-stress administration of corticosterone mitigates the retardation of body weight growth otherwise resulting from the stress protocol. The relative efficacy of pre versus post administration of corticosterone on stress induced exaggeration of innate fear response and stress-retarded body weight growth indicate that exogenous corticosterone administration within an appropriate time windows are efficacious in diminishing traumatic stress induced pathophysiological processes. The outcomes of informatics of using a neuronal gene array approach in determining the expression profile of mitochondria-focused genes in the amygdala complex of this animal model of PTSD were a further understanding of the metabolic and neuronal signaling mechanisms in response to traumatic stress and corticosterone treatment associated with mitigation of delayed and exaggerated fear. The outcome of current research will shed light for the prophylactic and therapeutic intervention for PTSD.

Read More About the Study

 

In addition, our paper "Corticosterone mitigates the stress response in an animal model of PTSD" (PMID: 25307716), was listed as a highlighted paper by the editor. Based on evidence that glucocorticoid can enhance the memory forgetting process in both healthy humans and animals, we hypothesized that the administration of glucocorticoid agonist prior to or following stress could promote the traumatic memory forgetting process and, potentially, prevent traumatic memory retrieval in PTSD patients. Thus, long lasting efficacy of corticosterone applied 30 minutes prior to or after traumatic stress episode mitigated the innate exaggerated acoustic startle response (ASR) lasting up to 21 days or 14 days respectively in an animal model of PTSD. As a result of recognition by neuroscientists in the field, the research was recognized as a "Milestone of Scientific Discoveries for the Psychological Healthy/Traumatic Brain Injury Program" by the CDMRP, and Dr. Li was invited to present this work at the 14th Annual Congress of International Drug Discovery Science and Technology held in South Korea in 2016.

Read More About the Study

 

More Studies From PSY

Zhang Lab

Wynn Lab

Choi Lab

Glickman Lab