Linked Exposures Across Databases: an exposure common data elements aggregation framework to facilitate clinical exposure review.

Understanding the health outcomes of military exposures is of critical importance for Veterans, their health care team, and national leaders. Approximately 43% of Veterans report military exposure concerns to their VA providers. Understanding the causal influences of environmental exposures on health is a complex exposure science task and often requires interpreting multiple data sources; particularly when exposure pathways and multi-exposure interactions are ill-defined, as is the case for complex and emerging military service exposures. Thus, there is a need to standardize clinically meaningful exposure metrics from different data sources to guide clinicians and researchers with a consistent model for investigating and communicating exposure risk profiles. The Linked Exposures Across Databases (LEAD) framework provides a unifying model for characterizing exposures from different exposure databases with a focus on providing clinically relevant exposure metrics. Application of LEAD is demonstrated through comparison of different military exposure data sources: Veteran Military Occupational and Environmental Exposure Assessment Tool (VMOAT), Individual Longitudinal Exposure Record (ILER) database, and a military incident report database, the Explosive Ordnance Disposal Information Management System (EODIMS). This cohesive method for evaluating military exposures leverages established information with new sources of data and has the potential to influence how military exposure data is integrated into exposure health care and investigational models.

Mental Health and Cognition in Women Veterans Enrolled in the Health of Vietnam Era Veteran Women's Study (HealthViEWS).

Objective: This analysis explored relationships between mental health symptoms and conditions and cognitive function in a cohort of Vietnam-era women veterans from the Health of Vietnam Era Veteran Women's Study (HealthViEWS). Methods: Vietnam-era women veterans completed a mail survey assessing self-reported symptom severity of posttraumatic stress disorder (PTSD) and depression. A telephone-based structured interview assessed mental health conditions and cognitive function (telephone interview for cognitive status [TICS]). Participants were categorized using a TICS threshold of ≤29 to designate possible cognitive impairment versus nonimpaired. Separate logistic regression models were used to determine associations between possible cognitive impairment and each self-reported and interviewer-rated assessment of PTSD and depression while adjusting for age, education, race, marital status, and wartime service location. Results: The sample consisted of 4,077 women veterans who were ≥60 years old and completed the TICS. Of these women, 7.20% were categorized with possible cognitive impairment. Logistic regression models indicated that self-reported PTSD and depression symptom severity were each significantly associated with higher odds of possible cognitive impairment (adjusted odds ratios [aOR]: 1.03 [95% confidence interval [CI]: 1.02-1.04] and 1.07 [95% CI: 1.04-1.09], respectively). Women veterans with a probable diagnosis of depression had higher odds of possible cognitive impairment compared to those without depression (aOR: 1.61 [95% CI: 1.07-2.42]). No association was found for probable diagnosis of PTSD. Conclusions: Although further examination remains necessary, results suggest that Vietnam-era women veterans with self-reported PTSD and depression symptom severity or a probable diagnosis of depression may benefit from screening of cognitive function to inform clinical care.

Investigating a clinically informed sleep disturbance threshold for physical and mental health among Gulf War Illness veterans.

Study Objectives: This study (1) assessed sleep quality and health in Gulf War veterans (GWV) meeting the Gulf War Illness (GWI) criteria and (2) compared health associations for both those meeting a "clinically disturbed sleep" threshold, and those below, as determined by the Pittsburgh Sleep Quality Index (PSQI) cutoff for military populations (≥10) on measures of physical, mental, and cognitive health. Methods: Participant data consisted of questionnaires and assessments completed prior to group assignment in a clinical trial. The sample consisted of 147 GWV, where 81.0% were males, and the median age was 53.4 years. Results: The mean (SD) PSQI global score was 12.34 (4.00) with 61% of the sample qualifying as clinically disturbed sleepers according to the cutoff (global PSQI ≥ 10). GWI veterans with PSQI scores ≥10 did not differ from others in age (p = 0.20), sex (p = 0.19), or years of education (p = 0.87), but showed worse GW-related symptomology on the Gulf War Kansas questionnaire (p < 0.01), and poorer mental health on the Veterans Rand-36 (p < 0.01). Conclusions: Disturbed sleep was associated with measures of pain, fatigue, and cognitive health. Our results suggest that a previously determined clinical threshold for clinically disturbed sleep is useful when examining the health status of the study population. Given that GWI is associated with elevated PSQI scores and a high frequency of disturbed sleep, cutoffs determining sleep health should be sensitive to population exposures and health history to improve interpretability.

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.

'She thought the same way I that I thought:' a qualitative study of patient-provider concordance among Gulf War Veterans with Gulf War Illness.

Objective: Medically unexplained symptoms (MUS), such as chronic fatigue syndrome, irritable bowel syndrome, and Gulf War Illness (GWI), are difficult to treat. Concordance-shared understanding between patient and provider about illness causes, course, and treatment-is an essential component of high-quality care for people with MUS. This qualitative paper focuses on the experiences of United States military Veterans living with GWI who have endured unique healthcare challenges. Methods & Measures: Qualitative interviews were conducted with 31 Veterans with GWI to explore factors that contribute to and detract from concordance with their Veteran Affairs (VA) healthcare providers. In addition to being seen by VA primary care, over half of participants also sought care at a War Related Illness and Injury Study Center, which specializes in post-deployment health. Deductive and inductive codes were used to organize the data, and themes were identified through iterative review of coded data. Results: Major themes associated with patient-provider concordance included validation of illness experiences, perceived provider expertise in GWI/MUS, and trust in providers. Invalidation, low provider expertise, and distrust detracted from concordance. Conclusion: These findings suggest providers can foster concordance with MUS patients by legitimizing patients' experiences, communicating knowledge about MUS, and establishing trust.

Gulf War Illness: A Randomized Controlled Trial Combining Mindfulness Meditation and Auricular Acupuncture.

Background: Many Gulf War (GW) Veterans report chronic symptoms including pain, fatigue, and cognitive impairment, commonly defined as Gulf War Illness (GWI). Complementary and integrative health (CIH) therapies may potentially improve multiple symptoms of GWI. Objective: To examine the effectiveness of combining 2 commonly available CIH therapies, mindfulness meditation and auricular acupuncture, in improving health-related functioning and multiple symptom domains of GWI (e.g., pain, fatigue). Methods: This study was a randomized controlled trial in which Veterans with GWI were randomly assigned to either the intervention group (n = 75), wherein they received 2 distinct CIH therapies - mindfulness meditation and auricular acupuncture, or the active control group, wherein they received a GW Health Education (GWHE) program (n = 74), each lasting 8 weeks. Self-report health measures were assessed at baseline, endpoint, and 3 month follow-up. Results: In the intention-to-treat analyses, there were significant between-group differences for mental-health related functioning, fatigue, depression symptoms, and Kansas total severity scores for symptoms in which the CIH group had improved scores for these outcomes at endpoint compared to the GWHE group (all P ≤ .05). The CIH group also had significant reductions in pain interference at endpoint and follow-up compared to baseline (estimated marginal mean difference: -2.52 and -2.22, respectively; all P = .01), whereas no significant changes were observed in the GWHE group. For pain characteristics, the GWHE group had a worsening of pain at endpoint compared to baseline (estimated marginal mean difference: +2.83; P = .01), while no change was observed in the CIH group. Conclusion: Findings suggest a possible beneficial effect of combining 2 CIH therapies, mindfulness meditation and auricular acupuncture, in reducing overall symptom severity and individual symptom domains of fatigue, musculoskeletal, and mood/cognition in Veterans with GWI. Trial Registration: Clinical Trials identifier NCT02180243.

A Cross-sectional Cohort Study to Assess Long-term Neurocognitive and Psychiatric Symptoms of Mefloquine Use in Veterans.

INTRODUCTION: To evaluate the associations between neurocognitive and psychiatric health outcomes with mefloquine or any antimalarial exposure. MATERIALS AND METHODS: Medical records were systematically reviewed to identify veterans that indicated antimalarial medication use. Linear regression was performed to examine associations between mefloquine/antimalarial exposure and health outcomes. The mefloquine-exposed group was further compared with normative populations for the same health outcomes. RESULTS: In the adjusted models, no significant differences were noted between the two exposure groups and the unexposed group for any of the health measures (P-value > 0.05). When compared to normative population samples, the mefloquine-exposed group had poorer health and greater neurobehavioral symptom severity or cognitive complaints. CONCLUSION: This study suggests that mefloquine use by veterans referred for intensive evaluation of their military deployment exposures and health was not associated with increased, long-term, neurocognitive/psychiatric symptoms compared to unexposed veterans.

Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Clinical Normative Data for Gulf War Veterans.

OBJECTIVE: Heterogenous test batteries and methods applied in neurocognitive research on Gulf War Veterans (GWVs) limit the translation of findings to clinical practice. A clinical data set is necessary. METHODS: Neurocognitive screening data from treatment-seeking GWVs were collected from multiple sites and compiled, informed by consideration of performance validity. RESULTS: Repeatable Battery for the Assessment of Neuropsychological Status scores revealed the cognitive profile for GWVs (n = 189) as poorer across multiple domains when compared with similarly educated, nonveteran peers. However, mean scores generally remained within normal clinical limits. Data tables are presented to establish a comparison group for use in clinical care. CONCLUSIONS: When assessing cognitive symptoms in GWVs, attention to education level and interpretation of subtle deficits is warranted. Current results highlight the importance of nuanced translation of neurocognitive research findings into clinical practice with GWVs.

Mapping the network biology of metabolic response to stress in posttraumatic stress disorder and obesity.

The co-occurrence of stress-induced posttraumatic stress disorder (PTSD) and obesity is common, particularly among military personnel but the link between these conditions is unclear. Individuals with comorbid PTSD and obesity manifest other physical and psychological problems, which significantly diminish their quality of life. Current understanding of the pathways connecting stress to PTSD and obesity is focused largely on behavioral mediators alone with little consideration of the biological regulatory mechanisms that underlie their co-occurrence. In this work, we leverage prior knowledge to systematically highlight such bio-behavioral mechanisms and inform on the design of confirmatory pilot studies. We use natural language processing (NLP) to extract documented regulatory interactions involved in the metabolic response to stress and its impact on obesity and PTSD from over 8 million peer-reviewed papers. The resulting network describes the propagation of stress to PTSD and obesity through 34 metabolic mediators using 302 documented regulatory interactions supported by over 10,000 citations. Stress jointly affected both conditions through 21 distinct pathways involving only two intermediate metabolic mediators out of a total of 76 available paths through this network. Moreover, oxytocin (OXT), Neuropeptide-Y (NPY), and cortisol supported an almost direct propagation of stress to PTSD and obesity with different net effects. Although stress upregulated both NPY and cortisol, the downstream effects of both markers are reported to relieve PTSD severity but exacerbate obesity. The stress-mediated release of oxytocin, however, was found to concurrently downregulate the severity of both conditions. These findings highlight how a network-informed approach that leverages prior knowledge might be used effectively in identifying key mediators like OXT though experimental verification of signal transmission dynamics through each path will be needed to determine the actual likelihood and extent of each marker's participation.

A common language for Gulf War Illness (GWI) research studies: GWI common data elements.

AIMS: The Gulf War Illness programs (GWI) of the United States Department of Veteran Affairs and the Department of Defense Congressionally Directed Medical Research Program collaborated with experts to develop Common Data Elements (CDEs) to standardize and systematically collect, analyze, and share data across the (GWI) research community. MAIN METHODS: A collective working group of GWI advocates, Veterans, clinicians, and researchers convened to provide consensus on instruments, case report forms, and guidelines for GWI research. A similar initiative, supported by the National Institute of Neurologic Disorders and Stroke (NINDS) was completed for a comparative illness, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and provided the foundation for this undertaking. The GWI working group divided into two sub-groups (symptoms and systems assessment). Both groups reviewed the applicability of instruments and forms recommended by the NINDS ME/CFS CDE to GWI research within specific domains and selected assessments of deployment exposures. The GWI CDE recommendations were finalized in March 2018 after soliciting public comments. KEY FINDINGS: GWI CDE recommendations are organized in 12 domains that include instruments, case report forms, and guidelines. Recommendations were categorized as core (essential), supplemental-highly recommended (essential for specified conditions, study types, or designs), supplemental (commonly collected, but not required), and exploratory (reasonable to use, but require further validation). Recommendations will continually be updated as GWI research progresses. SIGNIFICANCE: The GWI CDEs reflect the consensus recommendations of GWI research community stakeholders and will allow studies to standardize data collection, enhance data quality, and facilitate data sharing.

The relationship between Gulf War Illness symptom severity and heart rate variability: A pilot study.

INTRODUCTION: Gulf War Illness (GWI) is a chronic multisymptom illness affecting 250,000+ veterans of the '90-'91 Gulf War which remains under-explored in terms of its physiological characteristics. We investigated whether subjective GWI symptom severity scores were related to objective measures of autonomic nervous system activity. METHODS: We estimated activity in the two major branches of the autonomic nervous system (the parasympathetic nervous system [PNS] and the sympathetic nervous system [SNS]) via metrics of heart rate variability in a sample of Veterans who met established criteria for GWI with varying degrees of self-reported symptom severity. We hypothesized that subjective symptom severity scores would be inversely related to PNS activity and positively related to SNS activity. RESULTS: Significant negative relationships were observed between the root mean square of successive differences of beat-to-beat intervals (a measure of PNS activity) and symptom severity, both overall and across specific GWI symptom categories (sp. fatigue [r = -0.574], gastrointestinal [r = -0.544]). Furthermore, significant positive relationships were observed between the cardiac sympathetic index and symptom severity, both overall and across specific symptom categories (sp. cognitive [r = 0.721], fatigue [r = 0.560], gastrointestinal [r = 0.694], skin [r = 0.686]). CONCLUSIONS: Metrics of PNS activation revealed a negative relationship with self-reported symptom severity, while metrics of SNS activation revealed a positive relationship. The present results improve our understanding of the physiology of GWI and provide a new window from which to consider this medically unexplained illness.

Acoustic and language analysis of speech for suicidal ideation among US veterans.

BACKGROUND: Screening for suicidal ideation in high-risk groups such as U.S. veterans is crucial for early detection and suicide prevention. Currently, screening is based on clinical interviews or self-report measures. Both approaches rely on subjects to disclose their suicidal thoughts. Innovative approaches are necessary to develop objective and clinically applicable assessments. Speech has been investigated as an objective marker to understand various mental states including suicidal ideation. In this work, we developed a machine learning and natural language processing classifier based on speech markers to screen for suicidal ideation in US veterans. METHODOLOGY: Veterans submitted 588 narrative audio recordings via a mobile app in a real-life setting. In addition, participants completed self-report psychiatric scales and questionnaires. Recordings were analyzed to extract voice characteristics including prosodic, phonation, and glottal. The audios were also transcribed to extract textual features for linguistic analysis. We evaluated the acoustic and linguistic features using both statistical significance and ensemble feature selection. We also examined the performance of different machine learning algorithms on multiple combinations of features to classify suicidal and non-suicidal audios. RESULTS: A combined set of 15 acoustic and linguistic features of speech were identified by the ensemble feature selection. Random Forest classifier, using the selected set of features, correctly identified suicidal ideation in veterans with 86% sensitivity, 70% specificity, and an area under the receiver operating characteristic curve (AUC) of 80%. CONCLUSIONS: Speech analysis of audios collected from veterans in everyday life settings using smartphones offers a promising approach for suicidal ideation detection. A machine learning classifier may eventually help clinicians identify and monitor high-risk veterans.

Impact of Wartime Stress Exposures and Mental Health on Later-Life Functioning and Disability in Vietnam-Era Women Veterans: Findings From the Health of Vietnam-Era Women's Study.

OBJECTIVE: The effect of stress exposures and mental health sequelae on health-related outcomes is understudied among older women veterans. We examined a) the impact of wartime stress exposures on later-life functioning and disability in Vietnam-era women veterans and b) the extent to which mental health conditions known to be associated with stress-posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and generalized anxiety disorder (GAD)-are associated with additional later-life functioning and disability. METHODS: Data were collected in 2011 to 2012 using a mail survey and telephone interview of 4219 women veterans who were active duty during the Vietnam Era. Health functioning was assessed using the Veterans RAND 36-Item Health Survey, and disability was assessed using the World Health Organization Disability Assessment Schedule 2.0. Wartime exposures were assessed using the Women's War-Zone Stressor Scale-Revised; the Composite International Diagnostic Interview, version 3.0 was used to assess PTSD, MDD, and GAD. RESULTS: Several wartime stress exposures-including job-related pressures, dealing with death, and sexual discrimination and harassment-were associated with worse later-life health (ß ranges, -0.04 to -0.26 for functioning, 0.05 to 0.30 for disability). Current PTSD was linked with lower health functioning (physical, ß = -0.06; mental, ß = -0.15) and greater disability (ß = 0.14). Current MDD and GAD were also associated with lower mental health functioning (MDD, ß = -0.29; GAD, ß = -0.10) and greater disability (MDD, ß = 0.16; GAD, ß = 0.06). CONCLUSIONS: Results underscore the importance of detection and treatment of the potential long-term effects of wartime stressors and mental health conditions among women veterans.

Synthesis and Pharmacological Characterization of 2-(2,6-Dichlorophenyl)-1-((1S,3R)-5-(3-hydroxy-3-methylbutyl)-3-(hydroxymethyl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-one (LY3154207), a Potent, Subtype Selective, and Orally Available Positive Allosteric Modulator of the Human Dopamine D1 Receptor.

Clinical development of catechol-based orthosteric agonists of the dopamine D1 receptor has thus far been unsuccessful due to multiple challenges. To address these issues, we identified LY3154207 (3) as a novel, potent, and subtype selective human D1 positive allosteric modulator (PAM) with minimal allosteric agonist activity. Conformational studies showed LY3154207 adopts an unusual boat conformation, and a binding pose with the human D1 receptor was proposed based on this observation. In contrast to orthosteric agonists, LY3154207 showed a distinct pharmacological profile without a bell-shaped dose-response relationship or tachyphylaxis in preclinical models. Identification of a crystalline form of free LY3154207 from the discovery lots was not successful. Instead, a novel cocrystal form with superior solubility was discovered and determined to be suitable for development. This cocrystal form was advanced to clinical development as a potential first-in-class D1 PAM and is now in phase 2 studies for Lewy body dementia.

Social rehabilitation for military veterans with traumatic brain injury, psychological trauma, and chronic neuropsychiatric symptoms: Intervention development and initial outcomes.

OBJECTIVE: A subset of military veterans who have experienced both traumatic brain injury and psychological trauma present with chronic neuropsychiatric symptoms and experience persistent obstacles to social reintegration. This project aimed to develop a novel treatment targeting the unmet social rehabilitation needs of these veterans. Initial intervention development, feasibility, and outcome data are explored. METHOD: Four treatment groups were conducted (n = 20). A treatment workbook was developed during Groups 1 and 2 (n = 10) and research data were collected from Groups 3 and 4 (n = 10). RESULTS: There was a 0% attrition rate across all groups with unanimous requests for additional sessions. T test effect sizes were analyzed with bias-corrected Hedges' g. Improvements were observed on measures of depression (p = .026, g = 0.73), empathic perspective taking (p = .007, g = 0.94), social cognition (p = .002-.678, g = 0.27-1.30 across multiple measures), social relationships (p = .007, g = 1.50), traumatic brain injury-related quality of life (social: p = .014, g = 0.68, emotional: p = .009, g = 1.28) and nonsocial executive functioning (p = .006, g = 0.54). CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Preliminary evidence from this exploratory study suggests that targeting multiple layers of social competence using a combined psychotherapy and cognitive rehabilitation approach holds promise. Larger, controlled studies are needed to further evaluate the feasibility and efficacy of this intervention. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Veteran participation in the integrative health and wellness program: Impact on self-reported mental and physical health outcomes.

Complementary and integrative health (CIH) services are being used more widely across the nation, including in both military and veteran hospital settings. Literature suggests that a variety of CIH services show promise in treating a wide range of physical and mental health disorders. Notably, the Department of Veterans Affairs is implementing CIH services within the context of a health care transformation, changing from disease based health care to a personalized, proactive, patient-centered approach where the veteran, not the disease, is at the center of care. This study examines self-reported physical and mental health outcomes associated with participation in the Integrative Health and Wellness Program, a comprehensive CIH program at the Washington DC VA Medical Center and one of the first wellbeing programs of its kind within the VA system. Using a prospective cohort design, veterans enrolled in the Integrative Health and Wellness Program filled out self-report measures of physical and mental health throughout program participation, including at enrollment, 12 weeks, and 6 months. Analyses revealed that veterans reported significant improvements in their most salient symptoms of concern (primarily pain or mental health symptoms), physical quality of life, wellbeing, and ability to participate in valued activities at follow-up assessments. These results illustrate the potential of CIH services, provided within a comprehensive clinic focused on wellbeing not disease, to improve self-reported health, wellbeing, and quality of life in a veteran population. Additionally, data support recent VA initiatives to increase the range of CIH services available and the continued growth of wellbeing programs within VA settings. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Assessment of a Revised Wartime Experiences Scale for Vietnam-Era Women: The Health of Vietnam-Era Women's Study (HealthViEWS).

PURPOSE: Few wartime experiences scales capture unique issues related to women's service, address their military roles, or have been validated with women. The Women's Wartime Stressor Scale was developed for use with women who served during the Vietnam era, primarily as nurses in Vietnam. We revised this measure by modifying existing items, adding new items, and revising response formats to create a scale less nursing specific and nondeployment specific, and conducted a preliminary assessment of the revised scale. METHODS: The Women's Wartime Exposure Scale-Revised (WWES-R) was included in a mail survey as part of the U.S. Department of Veterans Affairs Health of Vietnam-Era Women's Study (HealthViEWS) study. Construct and criterion validity, and internal consistency, were assessed with a sample of 4,839 women veterans using exploratory factor analysis, analysis of variance, and multiple linear regression. RESULTS: Six wartime experience factors consistent with previous research were identified and scales were created based on salient item loadings. Compared with women serving in the United States, women serving in Vietnam had higher mean scores on all scales, and nurses had significantly higher scores on three scales than non-nurses. CONCLUSIONS: Evaluation of the WWES-R suggests service and/or deployment location and service in a military health care versus a non-health care role may predict women veterans' reports of certain wartime experiences. Further psychometric evaluation of the WWES-R is recommended with later era veterans and through comparisons to other wartime exposure measures.

Neuropsychological measurement of inhibitory control in posttraumatic stress disorder: An exploratory antisaccade paradigm.

OBJECTIVE: The aim of the study was to uncover inhibitory control dynamics and assess antisaccade eye-tracking tasks for relevance in a veteran posttraumatic stress disorder (PTSD) population. METHOD: Participants were 36 veterans enrolled at the Washington DC Veterans Affairs Medical Center. The groups (PTSD diagnosed vs. controls) did not vary between age and sex. Participants completed a testing battery of clinical neuropsychological measures and two different eye-tracking conditions, one that utilized face stimuli and one with standard shape stimuli, which test pro- (PS) and antisaccade (AS) eye movements. RESULTS: Veterans with PTSD, t(33) = 2.2, p = .04, took longer to respond than controls in the standard condition AS. In the face condition, a group by task interaction was seen with increased latency for PTSD veterans in the AS versus PS task, F(3, 33) = 3.99, p = .05, with a large overall effect (Hedges' g = 1.18, p < .001) compared to controls. After controlling for depression, analyses suggested that only the face condition AS task significantly predicted dimensions of PTSD symptomology measured by the Clinician Administered PTSD Scale (CAPS) for veterans with PTSD. CONCLUSIONS: This is the first study to extend AS findings to PTSD and suggests a specific capability to measure inhibitory control using eye-tracking technology. We discuss the notion that reduced capacity to regulate facial-related processing affects cognitive and attentional control networks of PTSD patients, potentially representing a core cognitive deficit.

An Allosteric Potentiator of the Dopamine D1 Receptor Increases Locomotor Activity in Human D1 Knock-In Mice without Causing Stereotypy or Tachyphylaxis.

Allosteric potentiators amplify the sensitivity of physiologic control circuits, a mode of action that could provide therapeutic advantages. This hypothesis was tested with the dopamine D1 receptor potentiator DETQ [2-(2,6-dichlorophenyl)-1-((1S,3R)-3-(hydroxymethyl)-5-(2-hydroxypropan-2-yl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-one]. In human embryonic kidney 293 (HEK293) cells expressing the human D1 receptor, DETQ induced a 21-fold leftward shift in the cAMP response to dopamine, with a Kb of 26 nM. The maximum response to DETQ alone was ∼12% of the maximum response to dopamine, suggesting weak allosteric agonist activity. DETQ was ∼30-fold less potent at rat and mouse D1 receptors and was inactive at the human D5 receptor. To enable studies in rodents, an hD1 knock-in mouse was generated. DETQ (3-20 mg/kg orally) caused a robust (∼10-fold) increase in locomotor activity (LMA) in habituated hD1 mice but was inactive in wild-type mice. The LMA response to DETQ was blocked by the D1 antagonist SCH39166 and was dependent on endogenous dopamine. LMA reached a plateau at higher doses (30-240 mg/kg) even though free brain levels of DETQ continued to increase over the entire dose range. In contrast, the D1 agonists SKF 82958, A-77636, and dihydrexidine showed bell-shaped dose-response curves with a profound reduction in LMA at higher doses; video-tracking confirmed that the reduction in LMA caused by SKF 82958 was due to competing stereotyped behaviors. When dosed daily for 4 days, DETQ continued to elicit an increase in LMA, whereas the D1 agonist A-77636 showed complete tachyphylaxis by day 2. These results confirm that allosteric potentiators may have advantages compared with direct-acting agonists.

A Pilot Study of Interpersonal Psychotherapy for PTSD in Women Veterans.

OBJECTIVE: This pilot study aimed to determine whether interpersonal psychotherapy (IPT) for posttraumatic stress disorder (PTSD) would be effective with a sample of women veterans who experienced military-related PTSD. METHOD: Women veterans presenting for mental health services through the Trauma Services Program at the Washington, DC, Veterans Affairs Medical Center (VAMC) were referred to the study by Veterans Affairs (VA) clinicians if they experienced trauma during their military service and scored > 35 on the PTSD Checklist-Military Version. A total of 20 women completed a baseline assessment and were referred to treatment, the first trial of this treatment method with a veteran sample. Of the 15 women veterans who started treatment, 10 completed a trial of 12 individual sessions. Assessments were conducted posttreatment and at three months posttreatment follow-up. RESULTS: There was a significant decline in PTSD symptom severity from baseline to posttreatment, and these gains were maintained at three-month follow-up. Approximately one-third of the group no longer met full criteria for PTSD diagnosis, results that are comparable to studies of evidence-based treatments for PTSD (prolonged exposure and cognitive processing therapy) in military samples. CONCLUSIONS: IPT, a non-trauma-focused intervention that aims to increase social support and improve interpersonal functioning, shows promise as another means of addressing PTSD in veterans. It should be tested in a larger sample to determine if IPT for PTSD might serve as an alternative for veterans who would prefer a non-trauma-focused intervention to address their difficulties.