2012:
- Family-Based Intervention with Traumatized Service Members and Their Young Children
- Deployment-Related Mild Traumatic Brain Injury (mTBI): Incidence, Natural History, and Predictors of Recovery in Soldiers Returning from OIF/OEF
2011:
- Small Molecule Activators of the TRK Receptors for Neuroprotection
- Virtual Reality Exposure Therapy to Battle PTSD
- Spouse Telephone BATTLEMIND: A Telephone Support Program for Spouses to Help Soldiers Transition Home
2010:
- Conditioned Fear Extinction and Generalization in Post-Traumatic Stress Disorder
- Treatment of Active Duty Military with PTSD in Primary Care: PTSD-PC Program Early Findings
- High-Throughput Screening of Therapeutic Neural Stimulation Targets: Toward Principles of Preventing and Treating Post-Traumatic Stress Disorder
2012
Family-Based Intervention with Traumatized Service Members and Their Young Children
Posted June 19, 2012
Ellen R. DeVoe, Ph.D., Boston University, Boston, MassachusettsThe ongoing wars in Iraq and Afghanistan (OEF/OIF) have been especially challenging for military families with very young children (birth-5 years) due to more frequent and lengthier deployments and a higher exposure to combat amongst deployed personnel. Young children and parents in OEF/OIF families are faced with prolonged deployment-related separation, and the child-parent relationship may be compromised when a Service Member parent returns from war with combat stress or other deployment-related difficulties. Thus, with funding from a Fiscal Year 2007 Intramural PTSD Investigator-Initiated Research Award, Dr. Ellen DeVoe is investigating the impact of PTSD and deployment separation on very young children in OEF/OIF families.
The primary aim of this project is to develop and test the effectiveness of a home-based reintegration program, entitled Strong Families Strong Forces, to mitigate the impact of deployment separation and the legacy of combat in Service Members returning from war on young children and on the child-parent relationship. Dr. DeVoe and her team have conducted over 80 interviews with Service Members, their spouses and partners, and with key informants to explore the effects of war zone-related trauma on reintegration, parenting, and child-parent relationships. Findings from these interviews have informed the development of the Strong Families Strong Forces Program and a pilot test of the program has been completed. A randomized clinical trial is underway in which 128 OEF/OIF families with young children are assigned either to the treatment group or to a wait-list comparison group. Assessments, including a videotaped structured play observation of the Service Member parent and his or her young child, are conducted pre-, post-, and 3 months following treatment to evaluate the quality of child-parent relationships, parental mental health, parenting, and child developmental status. The outcomes of this research will assist in elucidating the impact of war-related trauma and deployment separation on very young children and their relationships with their military parent(s), and will result in a military relevant intervention which may benefit parents with PTSD and their young children.Links:
Deployment-Related Mild Traumatic Brain Injury (mTBI): Incidence, Natural History, and Predictors of Recovery in Soldiers Returning from OIF/OEF
Posted May 10, 2012Data collected from OIF/OEF veterans indicate that approximately 14%-23% of Soldiers sustain a TBI during deployment. The majority of these injuries are classified as mTBI. While most individuals with mTBI recover within days to a couple of months following the injury, some report injury-related sequelae persisting beyond 3 to 6 months. The high prevalence of mTBI among OIF/OEF veterans highlights the need to better understand the effect of pre-existing and comorbid conditions on the natural history and prognosis of mTBI. Dr. Karen Schwab at the Defense and Veterans Brain Injury Center and collaborators from multiple Military Treatment Facilities, is conducting a prospective longitudinal study of deployment-related mTBI.
The study proposes to collect data from a total of 750 OIF/OEF veterans with mTBI and 750 uninjured Soldiers from Fort Bragg and Fort Carson. All individuals returning from deploy- ment are routinely screened for TBI, and the results of these questionnaires will be used to identify potential cases for the study. Participation in this study will not interfere with routine medical care, and Soldiers with mTBI will receive the usual standard of care treatment. Once enrolled in this study, subjects will participate in a clinical interview, and additional information will be collected related to TBI, neuropsychological status, and pre-existing or comorbid conditions. Telephone inter- views will be conducted at 3, 6, and 12 months after baseline assessment to collect follow-up data on the status of TBI sequelae, issues with employment or functional status, depression, anxiety, and PTSD. Study accrual is ongoing. The data collected in this study will provide important epidemiologic information about the long-term functional effects of deployment-related mTBI.
2011
Small Molecule Activators of the TRK Receptors for Neuroprotection
Posted August 24, 2011
Nicholas J. Webster, Ph.D., Veterans Medical Research Foundation of San DiegoTraumatic Brain Injury (TBI) is one of the major causes of mortality and morbidity in children and young adult civilians as well as among active duty military personnel. TBI usually results in the loss of neurons within the region of the brain known as the hippocampus, an effect that can occur over a period of many days following the insult. Despite improvements in surgical treatment of the primary insult, there are currently no therapies that provide neuroprotection to mitigate this secondary or delayed damage subsequently leading to poor prognosis and chronic cognitive impairment. It is well-known that the neurotrophins acting through the nerve growth factor Trk receptors promote survival of multiple neuronal cell types and stimulate in vitro neuronal regeneration. Although preclinical and clinical findings suggest that neurotrophins are a promising therapy for TBI, they are not good drug candidates due to their poor pharmacokinetic behavior and bioavailability at the desired targets. So a lot of effort has been devoted to the search for novel small-molecule activators that will mimic the desired neuroregenerative responses of neurotrophins.
Dr. Webster, a recipient of an Intramural TBI Investigator-Initiated Research Award, is focusing on the development of neuroprotective drugs that will activate the Trk receptors to prevent the neuronal cell death following TBI and improve cognitive function. To date, Dr. Webster and his colleagues, Dr. Stan Krajewski at the Burnham Institute for Medical Research and Dr. Michael Pirrung at the University of California, Riverside, have (1) identified the lead drug, 5E5, and 38 other promising compounds based on their ability to activate the TrkB receptor, (2) completed an in vivo evaluation of the neuroprotective effects of 5E5 utilizing two mouse models of neurodegeneration, and (3) tested their lead drug 5E5 in a controlled cortical impact model for brain injury. The in vivo results indicated that treatment with 5E5 delayed the onset of cognitive impairments and improved the ability of the mice to learn spatial information when given before or after the onset of symptoms in both models of neurodegeneration. The drug also exerted a neuroprotective effect, reduced the magnitude of the brain injury as measured by a smaller contusion area, and improved motor skills in the cortical impact model of TBI. With funding from an FY09 Investigator-Initiated Research Award, Dr. Webster, Dr. Krajewski, and Dr. Pirrung will continue preclinical development studies of neuroprotective agents activating Trk receptors in the hope of identifying novel therapeutic modalities for TBI.
Link:
Technical Abstract: Small Molecule Activators of the TRK Receptors for Neuroprotection
Virtual Reality Exposure Therapy to Battle PTSD
Posted August 16, 2011
Gregory Gahm, Ph.D., and Greg Reger, Ph.D., The Geneva Foundation
Prolonged Exposure Therapy (PE) is one of the most effective treatments for post-traumatic stress disorder (PTSD). However, PE requires the patient to revisit their traumatic memory in an emotionally engaging way. Soldiers face unique barriers to care compared to civilian populations. Following combat deployments, many Soldiers suffering from PTSD are emotionally detached and avoid the painful memories associated with the traumatic event, which can limit their ability to engage in the PE treatment process. In addition, some Soldiers report concerns about stigma associated with seeking help through traditional "talk therapies." Virtual Reality Exposure Therapy (VRET) holds the potential to provide effective therapy for PTSD and to improve access to care for Soldiers who might otherwise avoid treatment due to stigma. VR works by immersing a participant in a realistic computer-generated world that simulates the sources of combat stress. By revisiting the traumatic event in a sensory-rich environment, the investigators hypothesize that participants may experience heightened physiological arousal, and clinical outcomes may be significantly improved compared to those from traditional PE. Dr. Gregory Gahm and Dr. Greg Reger are conducting a randomized clinical trial comparing VRET to traditional PE in the treatment of combat-related PTSD in OIF/OEF Soldiers. Returning Soldiers diagnosed with PTSD will be randomized to receive 10 sessions of either VRET or PE or a waitlist control group (that will wait several weeks to be placed in a treatment group). The study will compare the efficacy of the two treatments and will also compare psychophysiological arousal during VRET and PE treatment sessions. This data will help demonstrate whether the multi-sensory nature of VRET increases arousal and whether increased arousal contributes to better treatment outcomes. Perceptions of stigma, patient satisfaction, and treatment adherence will be evaluated for the two treatments. The investigators hope that Soldiers will find the gaming aspect of VRET appealing and lessen the stigma associated with seeking help. The study is in collaboration with the Department of Psychology at Madigan Army Medical Center and is currently recruiting Soldiers from that facility. In addition, the investigators are planning to extend the study to Soldiers at Womack Army Medical Center at Fort Bragg, North Carolina.
Link:
Spouse Telephone BATTLEMIND: A Telephone Support Program for Spouses to Help Soldiers Transition Home
Posted July 12, 2011
Linda Nichols, Ph.D. and Jennifer Martindale-Adams, Ed., VA Medical Center, Memphis, Tennessee
The BATTLEMIND Training System was originally developed by the Walter Reed Army Institute of Research to help soldiers reintegrate and adapt their combat skills back into civilian life. Although reintegration difficulties and mental health symptoms increase during the first year for returning veterans, face-to-face training for spouses of OEF/OIF service members has typically been offered on a one-time basis, which does not provide ongoing support as new reintegration challenges appear. Dr. Linda Nichols and Dr. Jennifer Martindale-Adams at the VA Medical Center in Memphis are expanding the Spouse BATTLEMIND training program into a year-long, telephone-based support group in order to investigate its effectiveness. The program provides telephone support group sessions to spouses that are designed to educate, build coping skills, improve access to services for veteran and family, and serve as a source of shared support. So far, 60 spouses have been enrolled in the feasibility trial, plus the recent addition of 26 Wounded Warrior Project spouses. Over the period of one year, each group of 6-10 spouses and a trained Group Leader have hour-long structured telephone sessions once a month. The content of the session includes ways the returning service member, spouse, and family may have changed during deployment, with emphasis placed on compromise and negotiation in personal relationships; strategies to reduce or eliminate reunion and reintegration difficulties; strategies to support the returning soldier; and cues to alert spouses when to seek mental health services for the soldier, children, or themselves. The investigators are evaluating participant satisfaction and changes in spouse self-report of depression, anxiety, relationship satisfaction, and family communication. If successful, the investigators hope to disseminate the program for use across the Department of Defense and the Department of Veterans Affairs. The Army's recent change from the BATTLEMIND rubric will provide more flexibility in session topics and in how sessions are scheduled, and in the future will be called Spouse READI (Resilience Education and Deployment Information.)
Link:
Public and Technical Abstracts: Reintegration: The Role of Spouse Telephone Battlemind
2010
Conditioned Fear Extinction and Generalization in Post-Traumatic Stress Disorder
Posted September 16, 2010
Seth Norrholm, Ph.D., Emory University
In fiscal year 2007 (FY07), Dr. Seth Norrholm was awarded a PTSD New Investigator Award to develop a new clinical assessment tool to aid in the treatment of post-traumatic stress disorder (PTSD) in war veterans. A hallmark feature of PTSD is the patient's inability to distinguish between dangerous and safe situations. The ability to inhibit fear can be tested in a simple laboratory experiment that uses the startle response as a way to measure fear. One paradigm Dr. Norrholm has examined is conditioned fear extinction in which fear learned through classical conditioning is subsequently extinguished. Specifically, combat-exposed Operation Enduring Freedom/Operation Iraqi Freedom veterans with PTSD, a psychiatric control group with major depression, and a healthy control group are presented with colored shapes with or without an aversive air blast, responses to concurrently presented acoustic startle are recorded, and extinction training is initiated 10 minutes after acquisition. Interestingly, Dr. Norrholm found that veterans with PTSD displayed greater fear-potentiated startle to the safety cue as well as delayed extinction of fear-potentiated startle compared to the healthy controls. Dr. Norrholm is also in the process of accessing stimulus generalization. This assessment will follow the presentation of the cues used in fear conditioning. In a pilot subject, rather than discriminating between stimuli, the subject showed a generalization gradient of fear-potentiated startle responses to tones within the test range. This suggests that stimulus generalization to acoustic startle responses may be a useful psychophysiological tool that may give insight into the generalization of fear in PTSD patients. Moreover, Dr. Norrholm suggests that use of the fear-potentiated startle paradigm will be an asset in determining extinction of learned fear. These exciting findings have been presented at both local and international conferences.
Link:
Treatment of Active Duty Military with PTSD in Primary Care: PTSD-PC Program Early Findings
Posted June 14, 2010
Lt Col Jeffrey Cigrang, Ph.D., Wilford Hall Medical Center, San Antonio, Texas; Sheila Rauch, Ph.D., at VA Ann Arbor Healthcare System and University of Michigan Medical School, Ann Arbor Michigan; Laura Avila, Ph.D., at Brooke Army Medical Center, San Antonio, Texas
The South Texas Research Organizational Network Guiding Studies on Trauma and Resilience (STRONG STAR), a multidisciplinary and multi-institutional research consortium focusing on post-traumatic stress disorder (PTSD), received a Department of Defense Fiscal Year 2007 PTSD Multidisciplinary Research Consortium Award. Under this award, Lt Col Jeffrey Cigrang and his partnering investigators, Drs. Sheila Rauch and Laura Avila, have been exploring a psychotherapy treatment for deployment-related PTSD. A substantial number of veterans of the wars in Iraq and Afghanistan are currently affected by PTSD, yet many report having received no professional help or inadequate help in the past year. Concern that one's military peers and leadership may negatively judge mental health help-seeking can be a significant barrier to accessing care in a specialty mental health clinic. The primary care (PC) clinic may be a more favorable environment for treatment of PTSD in terms of reduced stigma and increased reach to military members. PC is also an ideal setting for offering relatively brief, first-line help to service members with PTSD as part of a larger stepped model of care. These investigators are conducting an ongoing pilot study of a cognitive-behavioral treatment (CBT) designed for use by psychologists working in an integrated PC clinic that see active-duty military with deployment-related PTSD. The CBT protocol is comprised of four to six individual 30-minute appointments with a PC psychologist and practice assignments conducted over six to eight weeks. Treatment content is primarily based on an exposure model but includes elements of both prolonged exposure and cognitive processing therapies. Participants were recruited for the pilot study trial from the population of patients referred to the PC psychologist by their PC manager during routine clinical care. Participants are active-duty or activated reserve Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) veterans seeking help for deployment-related PTSD symptoms with a PCL-M (scaled self-report PTSD questionnaire) score >32, and interest in treatment for PTSD in PC. Those with moderate to severe suicide risk, current alcohol dependence, psychotic disorder, or severe traumatic brain injury were not eligible to participate. To date, 10 participants have completed treatment and a one-month post-treatment evaluation. At one month post-treatment five participants (50%) no longer met criteria for PTSD. Psychological assessments given at follow-up indicated that the average PTSD symptom severity was significantly reduced from baseline as measured by both interviewer-administered and self-report inventories, the average depression symptom severity was also significantly reduced, and overall mental health functioning was increased. Six- and twelve-month follow-up evaluations are currently being conducted. These early findings are highly encouraging for the use of PTSD-PC as a viable first-step treatment protocol in the context of PC. Further, this intervention may help overcome barriers to care, such as stigma regarding mental health treatment, and meet the needs of many active-duty OIF/OEF veterans seeking help for PTSD.
Link:
Public and Technical Abstracts: The STRONG STAR Multidisciplinary PTSD Research Consortium
High-Throughput Screening of Therapeutic Neural Stimulation Targets: Toward Principles of Preventing and Treating Post-Traumatic Stress Disorder
Posted June 2, 2010
Edward Boyden, Ph.D., Massachusetts Institute of Technology, Cambridge, MassachusettsPost-traumatic stress disorder (PTSD) is characterized by extreme anxiety and fear, exacerbated by the cues and contexts associated with the initial trauma. Treatments such as psychotherapy are only partially effective, and while a few drugs have shown some efficacy, side effects are common. A treatment for PTSD that could directly correct the aberrant neural activity in the affected neural circuits, without altering the functions of unrelated neural circuits, would be of enormous value to persons suffering from PTSD. Dr. Edward Boyden, a researcher at the Massachusetts Institute of Technology, is currently investigating such an approach. If successful, these studies will identify neural circuit targets whose activation or silencing could be used to treat PTSD by a noninvasive means. By pinpointing these sites, Dr. Boyden believes that brain stimulation could be used to create circuit-specific interventions. Dr. Boyden received a PTSD Concept Award to pursue this innovative research.
In the first year of this study, Dr. Boyden found that the optical activation of infralimbic cortex neurons during exposure therapy in a mouse model of PTSD resulted in rapid and enduring remission of PTSD symptoms. To conduct these experiments, viruses expressing light-activated proteins in neurons were injected throughout the mouse brain. An array of optical fibers was then used to deliver light to specific areas of the brain, making it possible to turn on and off brain regions for precise lengths of time. The results of these studies have revealed a major new target for PTSD neuromodulation therapy and may advance translational efforts to use deep brain stimulation or transcranial magnetic stimulation to modulate neural circuits. Dr. Boyden is currently seeking collaborators to translate this technology into the clinic. These techniques appear to be safe and effective in non-human primates, and Dr. Boyden suggests that optical neural control might someday be suitable for use in human patients.
Publications:
Boyden ES and Chow BY. 2010. "Defining an Algorithm for Inventing from Nature." Column, Technology Review. 1/19/2010.
Chan SY, Bernstein JG, and Boyden ES. 2009. Scalable fluidic injector arrays for viral targeting of intact 3-D brain circuits. Journal of Visualized Experiments 35 http://www.jove.com/index/details.stp?id=1489, doi:10.3791/1489.
Chow BY, Han X, Dobry AS, Qian X, Chuong AS, Li M, Henninger MA, Belfort GM, Lin Y, Monahan PE, Boyden E. 2010. High-performance genetically-targetable optical neural silencing via the class of light-driven proton pumps. Nature 463(7277):98-102.
Han X, Qian X, Bernstein JG, Zhou HH, Franzesi GT, Stern P, Bronson RT, Graybiel AM, Desimone R, Boyden ES. 2009. Millisecond-timescale optical control of neural dynamics in the nonhuman primate brain. Neuron 62(2):191-198.
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