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.

An ERP measure of non-conscious memory reveals dissociable implicit processes in human recognition using an open-source automated analytic pipeline.

Non-conscious processing of human memory has traditionally been difficult to objectively measure and thus understand. A prior study on a group of hippocampal amnesia (N = 3) patients and healthy controls (N = 6) used a novel procedure for capturing neural correlates of implicit memory using event-related potentials (ERPs): old and new items were equated for varying levels of memory awareness, with ERP differences observed from 400 to 800 ms in bilateral parietal regions that were hippocampal-dependent. The current investigation sought to address the limitations of that study by increasing the sample of healthy subjects (N = 54), applying new controls for construct validity, and developing an improved, open-source tool for automated analysis of the procedure used for equating levels of memory awareness. Results faithfully reproduced prior ERP findings of parietal effects that a series of systematic control analyses validated were not contributed to nor contaminated by explicit memory. Implicit memory effects extended from 600 to 1000 ms, localized to right parietal sites. These ERP effects were found to be behaviorally relevant and specific in predicting implicit memory response times, and were topographically dissociable from other traditional ERP measures of implicit memory (miss vs. correct rejections) that instead occurred in left parietal regions. Results suggest first that equating for reported awareness of memory strength is a valid, powerful new method for revealing neural correlates of non-conscious human memory, and second, behavioral correlations suggest that these implicit effects reflect a pure form of priming, whereas misses represent fluency leading to the subjective experience of familiarity.

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.

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.

Characterization of epidermal bladder cells in Chenopodium quinoa.

Chenopodium quinoa (quinoa) is considered a superfood with its favourable nutrient composition and being gluten free. Quinoa has high tolerance to abiotic stresses, such as salinity, water deficit (drought) and cold. The tolerance mechanisms are yet to be elucidated. Quinoa has epidermal bladder cells (EBCs) that densely cover the shoot surface, particularly the younger parts of the plant. Here, we report on the EBC's primary and secondary metabolomes, as well as the lipidome in control conditions and in response to abiotic stresses. EBCs were isolated from plants after cold, heat, high-light, water deficit and salt treatments. We used untargeted gas chromatography-mass spectrometry (GC-MS) to analyse metabolites and untargeted and targeted liquid chromatography-MS (LC-MS) for lipids and secondary metabolite analyses. We identified 64 primary metabolites, including sugars, organic acids and amino acids, 19 secondary metabolites, including phenolic compounds, betanin and saponins and 240 lipids categorized in five groups including glycerolipids and phospholipids. We found only few changes in the metabolic composition of EBCs in response to abiotic stresses; these were metabolites related with heat, cold and high-light treatments but not salt stress. Na+ concentrations were low in EBCs with all treatments and approximately two orders of magnitude lower than K+ concentrations.

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.

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).

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.

Relationship Functioning in Vietnam Veteran Couples: The Roles of PTSD and Anger.

OBJECTIVE: Posttraumatic stress disorder (PTSD) and anger have been implicated separately in relationship dysfunction for veterans; however, no studies have simultaneously examined the roles of each of these constructs. METHOD: This study examined the roles of PTSD and anger in the relationships of Vietnam veterans and their partners (n = 33 couples) with actor-partner interdependence modeling (APIM). Couples in which the veteran was diagnosed with PTSD (PTSD-positive; n = 20) were compared to couples in which the veteran did not have PTSD (PTSD-negative; n = 13) on measures of frequency of anger and relationship functioning. RESULTS: PTSD-positive and PTSD-negative couples reported similar levels of relationship functioning, yet PTSD-positive veterans reported experiencing anger significantly more often than PTSD-negative veterans. Across groups, anger was predictive of relationship functioning, but PTSD severity was not. CONCLUSIONS: Trait anger may have a more deleterious effect on relationship functioning than PTSD symptoms. Theoretical and clinical implications are discussed.

Acupuncture and meditation for military veterans: first steps of quality management and future program development.

Veterans of all war eras have a high rate of chronic disease, mental health disorders, and chronic multi-symptom illnesses (CMI).(1-3) Many veterans report symptoms that affect multiple biological systems as opposed to isolated disease states. Standard medical treatments often target isolated disease states such as headaches, insomnia, or back pain and at times may miss the more complex, multisystem dysfunction that has been documented in the veteran population. Research has shown that veterans have complex symptomatology involving physical, cognitive, psychological, and behavioral disturbances, such as difficult to diagnose pain patterns, irritable bowel syndrome, chronic fatigue, anxiety, depression, sleep disturbance, or neurocognitive dysfunction.(2-4) Meditation and acupuncture are each broad-spectrum treatments designed to target multiple biological systems simultaneously, and thus, may be well suited for these complex chronic illnesses. The emerging literature indicates that complementary and integrative medicine (CIM) approaches augment standard medical treatments to enhance positive outcomes for those with chronic disease, mental health disorders, and CMI.(5-12.)

Cullin 5 regulates Dab1 protein levels and neuron positioning during cortical development.

Many laminated regions of the mammalian brain develop by the migration of neuronal precursor cells, whose final positions are coordinated by signals from the secreted molecule Reelin. Early events in Reelin signaling have been identified, but the mechanism of signal down-regulation has been unclear. A possible source of negative feedback is the Reelin-induced degradation of the critical intracellular signaling component, Disabled-1 (Dab1). Here we show that degradation of Dab1 depends on Dab1 phosphorylation at specific tyrosine residues and on the E3 ubiquitin ligase component Cullin 5 (Cul5). Cul5 forms complexes with SOCS (suppressors of cytokine signaling) proteins, which bind to phosphorylated Dab1 and target it for degradation in tissue culture cells. Ablation of Cul5 in migrating neurons causes an accumulation of active Dab1 protein and a unique cortical layering defect, characterized by excess migration and buildup of neurons at the top of the cortical plate. The results implicate Cul5 and SOCS proteins in down-regulation of Dab1 in vivo and show that Cul5 plays an essential role in regulating neuron migrations during cortical development, possibly by opposing a promigratory effect of Dab1.