A regulatory pathway model of neuropsychological disruption in Havana syndrome.

Introduction: In 2016 diplomatic personnel serving in Havana, Cuba, began reporting audible sensory phenomena paired with onset of complex and persistent neurological symptoms consistent with brain injury. The etiology of these Anomalous Health Incidents (AHI) and subsequent symptoms remains unknown. This report investigates putative exposure-symptom pathology by assembling a network model of published bio-behavioral pathways and assessing how dysregulation of such pathways might explain loss of function in these subjects using data available in the published literature. Given similarities in presentation with mild traumatic brain injury (mTBI), we used the latter as a clinically relevant means of evaluating if the neuropsychological profiles observed in Havana Syndrome Havana Syndrome might be explained at least in part by a dysregulation of neurotransmission, neuro-inflammation, or both. Method: Automated text-mining of >9,000 publications produced a network consisting of 273 documented regulatory interactions linking 29 neuro-chemical markers with 9 neuropsychological constructs from the Brief Mood Survey, PTSD Checklist, and the Frontal Systems Behavior Scale. Analysis of information flow through this network produced a set of regulatory rules reconciling to within a 6% departure known mechanistic pathways with neuropsychological profiles in N = 6 subjects. Results: Predicted expression of neuro-chemical markers that jointly satisfy documented pathways and observed symptom profiles display characteristically elevated IL-1B, IL-10, NGF, and norepinephrine levels in the context of depressed BDNF, GDNF, IGF1, and glutamate expression (FDR < 5%). Elevations in CRH and IL-6 were also predicted unanimously across all subjects. Furthermore, simulations of neurological regulatory dynamics reveal subjects do not appear to be "locked in" persistent illness but rather appear to be engaged in a slow recovery trajectory. Discussion: This computational analysis of measured neuropsychological symptoms in Havana-based diplomats proposes that these AHI symptoms may be supported in part by disruption of known neuroimmune and neurotransmission regulatory mechanisms also associated with mTBI.

Genetic predictor of current suicidal ideation in US service members deployed to Iraq and Afghanistan.

OBJECTIVE: Suicide is one of the ten leading causes of death in United States and the suicide rate in the military population has increased since the start of the Iraq and Afghanistan wars. However, few biomarkers for current suicidal ideation (CSI) have been identified. The current study examined the association of four candidate genes with CSI in active duty US Army Special Operations Command and National Guard units (n = 3,889) who served in Iraq and Afghanistan between November 2009 and July 2014. METHODS: Current PTSD symptoms and CSI were assessed using the PTSD Checklist (PCL) and PHQ-9, respectively. Traumatic events were assessed using items from the Life Events Checklist (LEC) that met the DSM-IV PTSD criteria of a traumatic stressor. All genotypes of saliva DNA were discriminated using the TaqMan 5'-exonuclease assay. RESULTS: The associations between CSI and brain-derived neurotrophic factor (BDNF), FK506 binding protein (FKBP5), catechol-O-methyltransferase (COMT), or S100A10 (p11) were examined. We found CSI was associated with BDNF (OR = 1.5, 95% CI = 1.5-1.8, P = 0.0002), but not FKBP5, COMT and p11. Female soldiers reported CSI more often than males (χ2 = 7.403, p = 0.0065), although gender did not affect CSI severity. In addition, associations were found between CSI and depression, PTSD, and BDNF, but not traumatic events. The BDNF Val66Met contributed to the severity of CSI even after adjusting to PTSD, depression and LEC. CONCLUSIONS: The associations of BDNF with CSI and its severity suggest that BDNF may be a predictor of suicidal risk and present an opportunity to develop laboratory tools with clinical implications in suicide prevention and treatment.

PTSD symptom severity and sensitivity to blood, injury, and mutilation in U.S. army special operations soldiers.

Sensitivity to blood, injury, and mutilation (SBIM) may increase risk for posttraumatic stress disorder (PTSD), given that traumatic events often involve actual or perceived threat of bodily harm to oneself and/or others, including exposure to blood and other mutilation-related stimuli. A self-report questionnaire was administered to male, active duty, U.S. Army Special Operations Command soldiers who had deployed to Iraq and Afghanistan (n =694 males). We first used exploratory factor analysis to examine whether the 30-item Mutilation Questionnaire (Klorman et al., 1974) comprised a unitary measure of SBIM, finding that 10 of the items form a cohesive SBIM factor. Summed, those 10 SBIM items had a significant bivariate correlation with PTSD symptom severity. In a multiple regression analysis that included demographic characteristics and lifetime trauma exposure, SBIM was positively associated with PTSD symptom severity. Other significant multivariate predictors were high lifetime trauma exposure and junior enlisted rank. When trait neuroticism was added to the model to test the robustness of these findings, the association of SBIM with PTSD symptom severity remained significant. The results suggest that SBIM may be a risk factor for PTSD in male soldiers. Further research is warranted to improve measurement and understanding of SBIM.

Role of Pre-Morbid Factors and Exposure to Blast Mild Traumatic Brain Injury on Post-Traumatic Stress in United States Military Personnel.

Mild traumatic brain injury (mTBI), the signature injury of the recent wars in Afghanistan and Iraq, is a prevalent and potentially debilitating condition that is associated with symptoms of post-traumatic stress/post-traumatic stress disorder (PTS/PTSD). Prior mTBI, severity and type of injury (blast vs. non-blast), and baseline psychiatric illness are thought to impact mTBI outcomes. It is unclear if the severity of pre-morbid PTS/PTSD is a risk factor of post-injury levels of PTS and mTBI symptoms. The objective of the study was to examine predictors of post-injury PTS/PTSD, including pre-morbid PTS symptoms, and physical and cognitive symptoms in the sub-acute phase (1 week-3 months) following an acute mTBI. A retrospective review of medical records was performed of 276 servicemen assigned to the United States Army Special Operations Command referred for mTBI evaluation between December 2009 and March 2011. Post-Concussion Symptom Scale and PTSD Checklist scores were captured pre- and post-injury. A total of 276 records were reviewed. Pre-morbid and post-injury data were available for 91% (251/276). Of the 54% (136/251) of personnel with mTBI, 29% (39/136) had positive radiology findings and 11% (15/136) met criteria for clinical PTS symptoms at baseline. Logistic regression analysis found baseline PTS symptoms predicted personnel who met clinical levels of PTSD. Receiver operating characteristic curve analysis revealed that baseline PTS (p = 0.001), baseline mTBI symptoms (p = 0.001), and positive radiology (magnetic resonance imaging or computed tomography) findings for complicated mTBI (p = 0.02) accurately identified personnel with clinical levels of PTSD following mTBI. Years of military service, combat deployment status, age, and injury mechanism (blast vs. non-blast) were not associated with increased risk of PTS following mTBI. Pre-morbid PTS symptoms are associated with an increased risk for clinical levels of PTS following a subsequent mTBI. Symptom severity and positive radiologic findings may amplify this risk. At-risk personnel may benefit from early identification and intervention.

The effects of combat-related mild traumatic brain injury (mTBI): Does blast mTBI history matter?

BACKGROUND: The effects of mild traumatic brain injury (mTBI) have received significant attention since the beginning of the conflicts in Afghanistan and Iraq. Surprisingly, little is known about the temporal nature of neurocognitive impairment, mTBI, and posttraumatic stress (PTS) symptoms following combat-related mTBI. It is also unclear as to the role that blast exposure history has on mTBI and PTS impairments and symptoms. The purposes of this study were to examine prospectively the effects of mTBI on neurocognitive performance as well as mTBI and PTS symptoms among US Army Special Operations Command personnel and to study the influence of history of blast mTBI on these effects. METHODS: Eighty US Army Special Operations Command personnel with (n = 19) and without (n = 61) a history of blast-related mTBI completed the military version of the Immediate Post-concussion Assessment Cognitive Test (ImPACT), Post Concussion Symptom Scale (PCSS), and the PTSD Checklist (PCL) at baseline as well as 1 day to 7 days and 8 days to 20 days following a combat-related mTBI. RESULTS: Results indicated that verbal memory (p = 0.002) and processing speed (p = 0.003) scores were significantly lower and mTBI symptoms (p = 0.001) were significantly higher at 1 day to 7 days after injury compared with both baseline and 8 days to 20 days after injury. PTS remained stable across the three periods. Participants with a history of blast mTBI demonstrated lower verbal memory at 1 day to 7 days after mTBI compared with participants without a history of blast mTBI (p = 0.02). CONCLUSION: Decreases in neurocognitive performance and increased mTBI symptoms are evident in the first 1 day to 7 days following combat-related mTBI, and a history of blast-related mTBI may influence these effects. LEVEL OF EVIDENCE: Epidemiologic/prognostic study, level II.

Relationship of combat experiences and alcohol misuse among U.S. Special Operations Soldiers.

This study examined the association between specific combat experiences and postdeployment hazardous drinking patterns on selected military populations that are considered high risk, such as personnel belonging to U.S. Army Special Operations Forces. Data collection were conducted in a 5-year span in which 1,323 Special Operations Forces Soldiers were surveyed anonymously from 3 to 6 months after returning from deployment to Iraq/Afghanistan regarding their combat experiences and mental health. Combat items were independently analyzed and placed into the following categories: (1) Fighting, (2) Killing, (3) Threat to oneself, (4) Death/Injury of others, and (5) Atrocities. Alcohol misuse was measured using the Alcohol Use Disorders Identification Test-Consumption. Of the Soldiers sampled, 15% (N = 201) screened positive for alcohol misuse 3 to 6 months postdeployment. Combat experiences relating to fighting, threat to oneself, and atrocities were significantly related to alcohol misuse when analyzed individually. However, when factors were analyzed simultaneously, combat experiences in the fighting category were significantly associated with a positive screen for alcohol misuse. In conclusion, Soldiers belonging to certain elite combat units are significantly more likely to screen positive for alcohol misuse if they are exposed to specific types of fighting combat experiences versus any other type of combat exposure.

Residual effects of combat-related mild traumatic brain injury.

Mild traumatic brain injury (mTBI) has gained considerable notoriety during the past decade of conflict in Afghanistan and Iraq. However, the relationship between combat-related mTBI and residual mTBI symptoms, post-traumatic stress disorder (PTSD) symptoms, and neurocognitive deficits remains unclear. The purpose of the study was to compare residual mTBI and PTSD symptoms, and neurocognitive deficits among U.S. Army Special Operations Command (USASOC) personnel with diagnosed blunt, blast, and blast-blunt combination mTBIs. This study involved a retrospective medical records review of 27,169 USASOC personnel who completed a military version of the Immediate Post-Concussion Assessment Cognitive Test (ImPACT), Post-Concussion Symptom Scale (PCSS), and PTSD Checklist (PCL) between November 2009 and December 2011. Of the 22,203 personnel who met criteria for the study, 2,813 (12.7%) had a diagnosis of at least one mTBI. A total of 28% (n=410) of USASOC personnel with a history of diagnosed mTBI reported clinical levels of PTSD symptoms. Personnel with a history of diagnosed blunt (OR=3.58), blast (OR=4.23) or combination (OR=5.73) mTBI were at significantly (p=0.001) greater risk of reporting clinical levels of PTSD symptoms than those with no history of mTBI. A dose-response gradient for exposure to blast/combination mTBI on clinical levels of PTSD symptoms was also significant (p=0.001). Individuals with blast/combination mTBIs scored higher in residual mTBI (p=0.001) and PTSD symptoms (p=0.001), and performed worse on tests of visual memory (p=0.001), and reaction time (p=0.001) than those with blunt or no mTBI history. Individuals with combination mTBIs scored lower in verbal memory (p=0.02) than those with blunt mTBIs. Residual PTSD and mTBI symptoms appear to be more prevalent in personnel with blast mTBI. A dose-response gradient for blast mTBI and symptoms suggests that repeated exposures to these injuries may have lingering effects.

Special operations forces and incidence of post-traumatic stress disorder symptoms.

To determine the rates of Post-traumatic Stress Disorder (PTSD) positive symptom scores in Special Operations Forces (SOF) personnel, an anonymous survey of SOF was employed, incorporating the PTSD Checklist (PCL-M) with both demographic and deployment data. Results indicate that all SOF units studied scored above the accepted cut-offs for PTSD positive screening.1 When total symptom severity score exceeded established cutoff points and were combined with criteria for Diagnostic and Statistical Manual of Mental Disorders, Edition 4 (DSM-IV) diagnosis of PTSD,2 approximately 16?20% of respondents met scoring threshold for positive screening, almost double those of conventional Army units. Collectively, Special Forces (SF) Soldiers and SOF combat-arms Soldiers had significantly higher PLC-M scores than their non-combat-arms SOF counterparts. SOF Soldiers with three or more deployments to Afghanistan had significantly higher PCL-M scores. Considering the evidence suggesting that SOF Soldiers are hyper-resilient to stress, these results should drive further research schemata and challenge clinical assumptions of PTSD within Special Operations.

Preparing soldiers for the stress of combat.

UNLABELLED: Protracted use of stressors during military training courses does not necessarily enhance a Soldier?s ability to regulate stress on the battlefield. Extensive stress during training can be a contributing factor to suboptimal neurologic and overall long-term health. Prolonged high-stress military training programs, as well as extended duration combat deployments, should be comprehensively scrutinized for opportunities to preserve health and increase combat effectiveness. Contemporary research in neuroscience and psychology can provide insight into training techniques that can be used to control stress and optimize performance in combat. Physical fitness training programs can elevate the stress threshold. Extensive situational training can also inoculate Soldiers to specific combat stressors. Training methods such as these will enable Soldiers to achieve higher levels of performance while under enemy fire and are encouraged for units deploying to combat. KEYWORDS: combat stress, military training, military deployment, physical training, post-traumatic stress disorder, sleep deprivation, stress inoculation training.

Mild traumatic brain injury literature review and proposed changes to classification.

Mild traumatic brain injury (mTBI) reportedly occurs in 8-22% of U.S. servicemembers who conduct combat operations in Afghanistan and Iraq. The current definition for mTBI found in the medical literature, to include the Department of Defense (DoD) and Veterans Administration (VA) clinical practice guidelines is limited by the parameters of loss of consciousness, altered consciousness, or post-traumatic amnesia, and does not account for other constellations of potential symptoms. Although mTBI symptoms typically resolve within seven days, some servicemembers experience symptoms that continue for weeks, months, or years following an injury. Mild TBI is one of few disorders in medicine where a benign and misleading diagnostic classification is bestowed on patients at the time of injury, yet still can be associated with lifelong complications. This article comprehensively reviews the clinical literature over the past 20 years and proposes a new classification for TBI that addresses acute, sub-acute, and chronic phases, and includes neurocognitive, somatic, and psychological symptom presentation.