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1.  A case of frontal neuropsychological and neuroimaging signs following multiple primary-blast exposure 
Neurocase  2011;18(3):258-269.
Blast-related traumatic brain injury (TBI) from the Afghanistan and Iraq wars represents a significant medical concern for troops and veterans. To better understand the consequences of primary-blast injury in humans, we present a case of a Marine exposed to multiple primary blasts during his 14-year military career. The neuropsychological profile of this formerly high-functioning veteran suggested primarily executive dysfunction. Diffusion-tensor imaging revealed white-matter pathology in long fiber tracks compared with a composite fractional-anisotropy template derived from a veteran reference control group without TBI. This study supports the existence of primary blast-induced neurotrauma in humans and introduces a neuroimaging technique with potential to discriminate multiple-blast TBI.
PMCID: PMC3718065  PMID: 21879996
Blast-induced neurotrauma; Closed-head injury; Diffusion-tensor imaging; Executive control; Explosive Ordnance Disposal Service; Fractional anisotropy; Primary blast; Traumatic brain injury; White matter
2.  Neurosteroids and Self-Reported Pain in Veterans Who Served in the U.S. Military After September 11, 2001 
Pain medicine (Malden, Mass.)  2010;11(10):1469-1476.
Nearly half of Operation Enduring Freedom / Operation Iraqi Freedom (OEF/OIF) veterans experience continued pain post-deployment. Several investigations report analgesic effects of allopregnanolone and other neurosteroids in animal models, but few data are currently available focusing on neurosteroids in clinical populations. Allopregnanolone positively modulates GABAA receptors and demonstrates pronounced analgesic and anxiolytic effects in rodents, yet studies examining the relationship between pain and allopregnanolone in humans are limited. We thus hypothesized that endogenous allopregnanolone and other neurosteroid levels may be negatively correlated with self-reported pain symptoms in humans.
We determined serum neurosteroid levels by gas chromatography / mass spectrometry (allopregnanolone, pregnenolone) or radioimmunoassay (dehydroepiandrosterone [DHEA], progesterone, DHEA sulfate [DHEAS]) in 90 male veterans who served in the U.S. military after September 11, 2001. Self-reported pain symptoms were assessed in four areas (low back pain, chest pain, muscle soreness, headache). Stepwise linear regression analyses were conducted to investigate the relationship between pain assessments and neurosteroids, with the inclusion of smoking, alcohol use, age, and history of traumatic brain injury as covariates.
Durham VA Medical Center.
Allopregnanolone levels were inversely associated with low back pain (p=0.044) and chest pain (p=0.013), and DHEA levels were inversely associated with muscle soreness (p=0.024). DHEAS levels were positively associated with chest pain (p=0.001). Additionally, there was a positive association between traumatic brain injury and muscle soreness (p=0.002).
Neurosteroids may be relevant to the pathophysiology of self-reported pain symptoms in this veteran cohort, and could represent future pharmacological targets for pain disorders.
PMCID: PMC2994993  PMID: 20735755
neuroactive steroid; allopregnanolone; pregnenolone; DHEA; nociception; pain; neurosteroid
3.  H.M.’s Personal Crossword Puzzles: Understanding Memory and Language 
Memory (Hove, England)  2008;16(2):89-96.
The amnesic patient H.M. has been solving crossword puzzles nearly all of his life. Here, we analyzed the linguistic content of 277 of H.M.’s crossword-puzzle solutions. H.M. did not have any unusual difficulties with the orthographic and grammatical components inherent to the puzzles. He exhibited few spelling errors, responded with appropriate parts of speech, and provided answers that were, at times, more convincing to observers than those supplied by the answer keys. These results suggest that H.M.’s lexical word-retrieval skills remain fluid despite his profound anterograde amnesia. Once acquired, the maintenance of written language comprehension and production does not seem to require intact medial temporal lobe structures.
PMCID: PMC3045671  PMID: 18286414
hippocampus; language; memory; amnesia; crosswords
4.  Comparison of SNOMED CT versus Medcin Terminology Concept Coverage for Mild Traumatic Brain Injury 
Traumatic Brain Injury (TBI) is a “signature” injury of the current wars in Iraq and Afghanistan. Structured electronic data regarding TBI findings is important for research, population health and other secondary uses but requires appropriate underlying standard terminologies to ensure interoperability and reuse. Currently the U.S. Department of Veterans Affairs (VA) uses the terminology SNOMED CT and the Department of Defense (DOD) uses Medcin.
We developed a comprehensive case definition of mild TBI composed of 68 clinical terms. Using automated and manual techniques, we evaluated how well the mild TBI case definition terms could be represented by SNOMED CT and Medcin, and compared the results. We performed additional analysis stratified by whether the concepts were rated by a TBI expert panel as having High, Medium, or Low importance to the definition of mild TBI.
SNOMED CT sensitivity (recall) was 90% overall for coverage of mild TBI concepts, and Medcin sensitivity was 49%, p < 0.001 (using McNemar’s chi square). Positive predictive value (precision) for each was 100%. SNOMED CT outperformed Medcin for concept coverage independent of import rating by our TBI experts.
SNOMED CT was significantly better able to represent mild TBI concepts than Medcin. This finding may inform data gathering, management and sharing, and data exchange strategies between the VA and DOD for active duty soldiers and veterans with mild TBI. Since mild TBI is an important condition in the civilian population as well, the current study results may be useful also for the general medical setting.
PMCID: PMC3243122  PMID: 22195156
5.  Association of trauma exposure with psychiatric morbidity in military veterans who have served since September 11, 2001 
Journal of psychiatric research  2009;43(9):830-836.
This study examined the association of lifetime traumatic stress with psychiatric diagnostic status and symptom severity in veterans serving in the US military after 9/11/01.
Data from 356 US military veterans were analyzed. Measures included a standardized clinical interview measure of psychiatric disorders, and paper-and-pencil assessments of trauma history, demo-graphic variables, intellectual functioning, posttraumatic stress disorder (PTSD) symptoms, depression, alcohol misuse, and global distress.
Ninety-four percent of respondents reported at least one traumatic stressor meeting DSM-IV criterion A for PTSD (i.e., life threatening event to which the person responded with fear, helplessness or horror), with a mean of four criterion A traumas. Seventy-one percent reported serving in a war-zone, with 50% reporting occurrence of an event meeting criterion A. The rate of current psychiatric disorder in this sample was: 30% PTSD, 20% major depressive disorder, 6% substance abuse or dependence and 10% for the presence of other Axis I psychiatric disorders. After accounting for demographic covariates and combat exposure, childhood physical assault and accident/disasters were most consistently associated with increased likelihood of PTSD. However, PTSD with no comorbid major depressive disorder or substance use disorder was predicted only by combat exposure and adult physical assault. Medical/unexpected-death trauma and adult physical assault were most consistently associated with more severe symptomatology.
Particular categories of trauma were differentially associated with the risk of psychiatric diagnosis and current symptom severity. These findings underscore the importance of conducting thorough assessment of multiple trauma exposures when evaluating recently post-deployed veterans.
PMCID: PMC2754834  PMID: 19232639
Traumatic stress; Posttraumatic stress disorder; Combat
6.  Factorial Invariance of Posttraumatic Stress Disorder Symptoms Across Three Veteran Samples 
Journal of traumatic stress  2008;21(3):309-317.
Research generally supports a 4-factor structure of posttraumatic stress disorder (PTSD) symptoms. However, few studies have established factor invariance by comparing multiple groups. This study examined PTSD symptom structure using the Davidson Trauma Scale (DTS) across three veteran samples: treatment-seeking Vietnam-era veterans, treatment-seeking post-Vietnam-era veterans, and Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veteran research participants. Confirmatory factor analyses of DTS items demonstrated that a 4-factor structural model of the DTS (reexperiencing, avoidance, numbing, and hyperarousal) was superior to five alternate models, including the conventional 3-factor model proposed by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV; American Psychiatric Association, 1994). Results supported factor invariance across the three veteran cohorts, suggesting that cross-group comparisons are interpretable. Implications and applications for DSM-IV nosology and the validity of symptom measures are discussed.
PMCID: PMC2745604  PMID: 18553409

Results 1-6 (6)