PTSD: National Center for PTSD
Clinical Neurosciences Division Laboratories
Clinical Neurosciences Division Laboratories
Clinical Neurosciences Division laboratories focus on research involving the neurobiological basis of traumatic stress. A description of each laboratory at this division follows.
Molecular Genetics
This laboratory is focused on understanding the genetic and epigenetic basis of psychiatric illness, including PTSD, substance dependence, and anxiety disorders. Investigators use genome-wide association studies (GWAS), to screen DNA for genetic variations across large numbers of research participants. In these linkage and association studies, investigators look for differences in genes between people affected with the disorder compared to those not affected. By identifying genotypes (i.e. the set of genes in our DNA responsible for a particular trait) and phenotypes (i.e. the physical expression, or characteristics of that trait) researchers can build a gene variant profile related to disease risk.
Molecular Genetics
This laboratory is focused on understanding the genetic and epigenetic basis of psychiatric illness, including PTSD, substance dependence, and anxiety disorders. Investigators use genome-wide association studies (GWAS), to screen DNA for genetic variations across large numbers of research participants. In these linkage and association studies, investigators look for differences in genes between people affected with the disorder compared to those not affected. By identifying genotypes (i.e. the set of genes in our DNA responsible for a particular trait) and phenotypes (i.e. the physical expression, or characteristics of that trait) researchers can build a gene variant profile related to disease risk.
Molecular Neuroscience
This laboratory studies the molecular and cellular basis of complex behaviors, particularly those related to stress, depression, PTSD and suicidality, as well as responses and mechanisms underlying the actions of psychotropic drugs in both human and animal models. The Clinical Neurosciences Division serves as the primary research laboratory for the VA National PTSD Brain Bank in collaboration with the Boston VA Healthcare System. The VA National PTSD Brain Bank is a biorepository that studies postmortem brain tissue of PTSD and major depressive disorder (MDD) donors, to characterize gene expression associated with stress and suicide. Results from this research may lead to blood-based biomarkers that could be used to diagnose disease and monitor treatment response. This multidisciplinary program of research includes: identification of gene expression profiles using custom and whole genome microarray platforms; secondary validation at the mRNA and protein levels; modulation of targeted genes by pharmacological, recombinant, viral vector, and mutant mouse approaches; analysis of neuronal and glial cell proliferation, maturation and survival; and behavioral analysis using established models of stress, anxiety, and depression/antidepressant responses. This integrated approach has resulted in the discovery of novel gene targets underlying the actions of stress and antidepressant agents.
Neuroimaging
This laboratory conducts research dedicated to the neural evaluation of PTSD, mood, anxiety and suicidality with an emphasis on the roles of synaptic connectivity and neuroenergetics. The program aims to generate models or biomarkers, which consider biological and psychosocial factors in the pathogenesis of PTSD and the mechanisms underlying treatment response. Investigators within this lab use multimodal neuroimaging, such as positron emission tomography (PET), magnetic resonance imaging (MRI and fMRI) and spectroscopy, to investigate functional activation patterns, concentrations of neurotransmitters, the structure and shape of brain regions, and energy demands throughout the brain. This work also includes large-scale mapping of the PTSD brain connectome (i.e. a brain circuitry map), machine learning and artificial intelligence methods. Investigators also use electroencephalogram (EEG) to evaluate changes in electrical activity in the brain pre/post pharmacotherapy treatment. The laboratory will be deploying the first Magnetoencephalography (MEG) unit within the VA Healthcare System. MEG is a cutting-edge, highly sensitive technology with greater sensitivity than EEG, capable of high temporal resolution of electrical activity in deep brain structures. MEG is an important investigative tool for next-generation PTSD research. By using these state-of-the-art brain imaging techniques to study the neurobiological underpinnings of PTSD and its associated comorbidities, this laboratory aims to identify novel targets for treatment development.
Cognitive Neuroscience
Hallmark symptoms of PTSD involve alterations in memory, attention, learning and problem solving, underscoring the detrimental impact that stress and trauma has on cognitive functioning. This laboratory investigates the psychophysiological impact of stress and trauma on the brain and how it affects autonomic, sensory, and cognitive processes between individuals with and without PTSD, to better predict phenotypes of risk and resilience. Investigators in this laboratory use a variety of tools, including brain imaging (fMRI) and physical reactivity (skin conductance, vagal tone) to conduct psychophysiological research on heightened responsiveness to trauma reminders. Cognitive processing abnormalities are observed by neuroimaging and electrophysiologic evidence of reduced ability to attend to task-relevant information and increased attention to trauma-related information in individuals with PTSD, suggesting more difficulty in unlearning fear for service members exposed to trauma upon return to civilian life.
Translational Psychiatric Epidemiology
The translational psychiatric epidemiology laboratory focuses on the epidemiology of trauma-related disorders across the lifespan, linking advances in genetics, molecular neuroscience and neuroimaging, into new approaches for diagnosis, prevention and treatment of disease. This laboratory employs the use of surveys, DNA collection, family history, biomarkers and computational modeling to develop phenotypes and generate hypotheses about co-occurring environmental risk. Recent work has examined a broad range of topics related to civilian and military trauma, including health and psychosocial correlates of partial and full PTSD; dimensional structure and neurobiological correlates of trauma-related psychopathology; protective effects of psychological resilience and social support; posttraumatic growth; a nationally representative profile of veterans who use the VA as their primary source of healthcare; and genetic and psychosocial correlates of risk and resilience to suicidality.
Experimental Therapeutics
The overarching goal of the experimental therapeutics laboratory is to validate biomarkers and therapeutic targets and to subsequently test treatment strategies for PTSD and its associated comorbidities most notably substance use disorders and suicidality but also depression, insomnia, and anger. This group builds upon the research of other Clinical Neurosciences Division laboratories in order to design new, more effective and specific treatment agents. These can be augmented using imaging procedures and tissue biomarkers to assign and follow treatment response, in order to develop phenotypes for individuals who are more likely to respond to a treatment, allowing researchers to identify subtypes of responders and match drugs to individualize a patient's care. Research involves experimental psychopharmacologic paradigms for PTSD and related conditions as well as pharmacological enhancement of traditional behavioral therapies such as prolonged exposure therapy (PE), cognitive processing therapy (CPT) and written exposure therapy (WET); transcranial direct current stimulation on learning, memory, and brain circuitry; augmentation therapies to study the effect on neuroinflammation and treatment remission; mindfulness based stress reduction, as well as other novel therapies still in development.
