Integrating basic and clinical research to support personalized medicine (Genetics, Biomarkers, & Treatment for PTSD)

Recent interest in biomarkers—genetic, metabolic, physiologic, and imaging phenomena—is growing at a rapid pace in the effort to personalize medicine, that is, to find indicators that allow for more specifically targeted prevention and treatment in an individual’s illness. Dr. Risbrough has employed translational research (across animals and humans) to identify genetic markers predictive of vulnerability and treatment response. Using this methodology, Dr. Risbrough and colleagues are examining the role of a gene involved in regulating catecholamine neurotransmission (COMTval158met) in mice (Risbrough, VA Merit). Information gleaned from these animal studies paired with the knowledge of how Veterans with PTSD respond to fear-extinction learning will be used to develop effective treatments (Norman, VA Merit). In addition, CESAMH investigators, in collaboration with other VA and academic centers and the Worldwide Genetic Consortium for PTSD studies are investigating the genetics, genomics and molecular biology of PTSD and trauma to further identify targets for drug development and treatment (Baker, Nievergelt, Hauger, and Neuroscience unit members).

Likewise, brain imaging studies, using various modalities (fMRI, MEG), are being developed to identify diagnostic markers of PTSD and mTBI [Simmons (VA), Spadoni (VA, CDA), Baker (DoD, VA, Jackson Foundation, Navy SEAL Family Fund), Delano-Wood (VA)]. Currently, CESAMH faculty are working to refine imaging modalities to better diagnose individuals in need of mTBI treatment, to investigate changes in brain function that may occur during treatment, and to predict whether co-occurring mTBI predicts PTSD treatment response with psychosocial l treatments (Simmons, Baker, Thorp, Jak, Delano-Wood).


Clinical and Bio – Repository (Genetics, Biomarkers, and Risk of or Resilience to PTSD)

CESAMH has compiled a database of phenotypic information (e.g., measurements of psychiatric symptom, functioning, quality of life) on over 3000 Veterans (Afari and Pittman, eScreening), which, to date, has provided data for 17 manuscripts and 8 pilot studies. A CESAMH human specimen bank to leverage past, current, and future studies to collect, store, and distribute specimens (e.g., blood, saliva, urine, DNA/RNA) is also under development (Nievergelt, Risbrough, Baker). This biological information will be integrated with the existing phenotypic database. This large sample of clinical and biological information allows researchers from CESAMH and nationally to investigate risk factors for and resilience to PTSD and to develop prevention and intervention strategies.


PTSD, Inflammation and Aging (Biomarkers, Integration of Psychiatric and Medical Issues)

There is active investigation into PTSD and co-occurring medical disorders, as well as the underlying genetics and neurobiology associated with the increased morbidity and mortality seen in PTSD. Recently CESAMH investigators found evidence of increased age-related medical comorbidity (including cardiovascular disease, type 2 diabetes, gastrointestinal ulcers, and dementia) and earlier mortality associated with PTSD (Lohr, Palmer, Baker, Kremen). Also, CESAMH researchers have shown that there is accumulating evidence for increased levels of pro-inflammatory markers among people with PTSD. These findings may have implications for the treatment of persons with PTSD suggesting that medical issues should be addressed.


Mind/Body Connection (PTSD Treatment, Rehabilitation, Integration of Psychiatric and Medical Issues)

In light of strong interest in complementary and alternative treatment approaches, CESAMH investigators have been studying these interventions for Veterans with PTSD. Current projects include: Compassion Meditation, a type of meditation that focuses on one’s ability to feel compassion for others (Lang, NCCIH), and Mantram Repetition, a meditative technique that reduces stress (Bormann) and which is being disseminated nationally within the VA Healthcare System (Lindamer, Rodgers). The group hopes to understand changes created by such intervention in both the mind (e.g., symptoms, executive functioning) and body (e.g., psychophysiology, immune response).


CogSMART (Rehabilitation, Biomarkers, Community Partnerships)

Dr. Twamley has developed CogSMART, an evidence-based rehabilitation strategy to remediate cognitive problems due to TBI. To understand and quantify the neurobiological mechanisms of these changes and to explore potential indicators of treatment response, Dr. Simmons (CESAMH pilot funds) collaborated with Dr. Twamley (VA Merit) to examine brain functioning before and after treatment. They found that CogSMART training may have facilitated neural efficiency. Larger studies are needed to replicate these findings. The ultimate goal of CogSMART is to increase rates of successful, competitive employment. A critical next step in the development of this rehabilitation tool is to determine whether these VA studies extend to broader work settings. While some private sector companies have programs to hire Veterans, Veterans with TBI may need additional support to optimize job performance. CESAMH has developed strategic partnerships with PsychArmor and the U.S. Chamber of Commerce to aid in the dissemination of this program (Lindamer, Rodgers). Future research about the real world effects of CogSMART has the potential to improve the productivity of Veterans with TBI, thereby benefitting the Veteran, their families, and their communities.


Technology

CESAMH investigators have embraced technology across a number of modalities. Niloo Afari, PhD and James Pittman, LCSW have developed and tested a web-based, mental health screening for Veterans. Using tablet-based screening, eScreening automatically evaluates and integrates mental health screening results into a Veteran’s medical record. It also provides clinical reminders and documentation and immediately generates customized, patient-centered reports and education materials for Veterans. It also increases access to screening and timely referral to appropriate services without requiring more staff. eScreening is currently available only in the VA San Diego Healthcare Systems, but CESAMH and VA Center of Innovation are developing an enhanced version, expected to be available at multiple VA sites.

Other technologies that are being established and validated via CESAMH support are consumer “wearable” sensors for non-invasive physiological monitoring of stress and physical health disruption in traumatized Veterans (Risbrough, Simmons, Minassian). CESAMH has also supported advancement of imaging technology and analytics for fMRI and MEG assessment of TBI pathology (Simmons, Delano-Wood, Baker in collaboration with Huang). Additionally, CESAMH has provided support for development of technology (spinal cord stimulation and vagal nerve stimulation) for treatment, currently under investigation in collaboration with UCSD engineering (Cal-IT2) (Lerman).