Characterizing Deficit Accumulation Among Gulf War Era Veterans.

BACKGROUND: Veterans of the first Gulf War (1990-1991) are reaching middle and older adulthood in differing degrees of health and biological age. Many Gulf War veterans report myriad negative symptoms classified as Gulf War illness (GWI), a chronic multi-symptom illness. OBJECTIVES: To describe and analyze deficit accumulation, among veterans with Severe GWI (SGWI+) and those without Severe GWI (SGWI-), to assess the association between a medically unexplained illness and aging. DESIGN: This study uses a retrospective cohort design with quasi-longitudinal data. SETTING: The recruitment sample included 10,042 Gulf War era veterans across all four US Census regions. PARTICIPANTS: The analytic sample included 1,054 participants of the GWECB for whom SGWI case status could be determined and who had valid responses for at least 90% of the deficits included in the deficit accumulation index. MEASUREMENTS: Chronic health conditions were retroactively reported, including year of diagnosis, enabling us to create a longitudinal measure of deficit accumulation. This deficit accumulation index (DAI) ranged from 0-1 for each respondent in each year between 1991-2013. We compare veterans with SGWI+ to those with SGWI- using the CDC case definition. RESULTS: Most veterans in our sample could expect to spend more years with moderate or substantial deficits than without deficits. SGWI+ was associated with spending more years with substantial deficits than those with SGWI-. Veterans in middle age (age 35-65) experienced more years with substantial deficits than younger veterans. Individuals with SGWI+ had 13 times the hazard of accumulating substantial deficits than those without. CONCLUSIONS: This study demonstrated that veterans with SGWI+, even those in midlife, experienced aging as measured by accumulating deficits. Practitioners should consider patients with multi-symptom illnesses as at risk of accelerated aging, tailoring treatments to address patients' holistic needs.

Self-reported gastrointestinal disorders among veterans with gulf war illness with and without posttraumatic stress disorder.

BACKGROUND: Gulf War Illness (GWI) is a chronic, multi-symptom disorder affecting 25%-32% of Gulf War veterans. Veterans with GWI disproportionately suffer from gastrointestinal (GI) disorders. Given the increasing evidence supporting a gut-brain axis, we explore the relationship between post-traumatic stress disorder (PTSD), GWI, and self-reported GI disorders among GW veterans. METHODS: Veterans from the Gulf War Era Cohort and Biorepository responded to a mail-based survey (N = 1058). They were stratified by GWI (Centers for Disease Control definition) and PTSD status. This yielded three groups: GWI-, GWI+/PTSD-, and GWI+/PTSD+. Multivariable logistic regression adjusting for demographic and military characteristics examined associations between GWI/PTSD groups and GI disorders. Results were expressed as adjusted odds ratios (aOR) with 95% confidence intervals (95% CI). KEY RESULTS: The most frequently reported GI disorders were irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), and colon polyps (CP). The GWI+/PTSD+ group had a higher odds of these disorders than the GWI+/PTSD- group (aORIBS  = 3.12, 95% CI: 1.93-5.05; aORGERD  = 2.04, 95% CI: 1.44-2.90; aORCP  = 1.85, 95% CI: 1.23-2.80), which had a higher odds of these disorders than the GWI- group (aORIBS  = 4.38, 95% CI: 1.55-12.36; aORGERD  = 2.51 95% CI: 1.63-3.87; aORCP  = 2.57, 95% CI: 1.53-4.32). CONCLUSIONS & INFERENCES: GW veterans with GWI and PTSD have significantly higher odds of specific self-reported GI disorders than the other groups. Given the known bidirectional influences of the gut and brain, these veterans may benefit from a holistic healthcare approach that considers biopsychosocial contributors to the assessment and management of disease.

Critical incident stress debriefing (CISD): a meta-analysis.

Psychological debriefings represent a genre of group crisis interventions. Critical Incident Stress Debriefing (CISD) represents the oldest standardized variation of this genre. Recent reviews have called into question the effectiveness of CISD. In this study 5 previously published investigations were meta-analyzed revealing a large effect size (Cohen's d = .86) supporting the notion that the CISD model of psychological debriefing is an effective crisis intervention.

Pharmacometabolomic mapping of early biochemical changes induced by sertraline and placebo.

In this study, we characterized early biochemical changes associated with sertraline and placebo administration and changes associated with a reduction in depressive symptoms in patients with major depressive disorder (MDD). MDD patients received sertraline or placebo in a double-blind 4-week trial; baseline, 1 week, and 4 weeks serum samples were profiled using a gas chromatography time of flight mass spectrometry metabolomics platform. Intermediates of TCA and urea cycles, fatty acids and intermediates of lipid biosynthesis, amino acids, sugars and gut-derived metabolites were changed after 1 and 4 weeks of treatment. Some of the changes were common to the sertraline- and placebo-treated groups. Changes after 4 weeks of treatment in both groups were more extensive. Pathway analysis in the sertraline group suggested an effect of drug on ABC and solute transporters, fatty acid receptors and transporters, G signaling molecules and regulation of lipid metabolism. Correlation between biochemical changes and treatment outcomes in the sertraline group suggested a strong association with changes in levels of branched chain amino acids (BCAAs), lower BCAAs levels correlated with better treatment outcomes; pathway analysis in this group revealed that methionine and tyrosine correlated with BCAAs. Lower levels of lactic acid, higher levels of TCA/urea cycle intermediates, and 3-hydroxybutanoic acid correlated with better treatment outcomes in placebo group. Results of this study indicate that biochemical changes induced by drug continue to evolve over 4 weeks of treatment and that might explain partially delayed response. Response to drug and response to placebo share common pathways but some pathways are more affected by drug treatment. BCAAs seem to be implicated in mechanisms of recovery from a depressed state following sertraline treatment.

Pretreatment metabotype as a predictor of response to sertraline or placebo in depressed outpatients: a proof of concept.

The purpose of this study was to determine whether the baseline metabolic profile (that is, metabotype) of a patient with major depressive disorder (MDD) would define how an individual will respond to treatment. Outpatients with MDD were randomly assigned to sertraline (up to 150 mg per day) (N=43) or placebo (N=46) in a double-blind 4-week trial. Baseline serum samples were profiled using the liquid chromatography electrochemical array; the output was digitized to create a 'digital map' of the entire measurable response for a particular sample. Response was defined as ≥50% reduction baseline to week 4 in the 17-item Hamilton Rating Scale for Depression total score. Models were built using the one-out method for cross-validation. Multivariate analyses showed that metabolic profiles partially separated responders and non-responders to sertraline or to placebo. For the sertraline models, the overall correct classification rate was 81% whereas it was 72% for the placebo models. Several pathways were implicated in separation of responders and non-responders on sertraline and on placebo including phenylalanine, tryptophan, purine and tocopherol. Dihydroxyphenylacetic acid, tocopherols and serotonin were common metabolites in separating responders and non-responders to both drug and placebo. Pretreatment metabotypes may predict which depressed patients will respond to acute treatment (4 weeks) with sertraline or placebo. Some pathways were informative for both treatments whereas other pathways were unique in predicting response to either sertraline or placebo. Metabolomics may inform the biochemical basis for the early efficacy of sertraline.

Positive affect is associated with cardiovascular reactivity, norepinephrine level, and morning rise in salivary cortisol.

Positive affect was examined as a predictor of (1) cardiovascular reactivity during a sadness and an anger recall task and recovery following the protocol, (2) epinephrine (EPI) and norepinephrine (NOREPI) reactivity and level during the recall protocol, and (3) the diurnal pattern of salivary cortisol. Sample was 328 individuals. Negative affect, age, race, sex, smoking status, income, and BMI were adjusted. During sadness recall, positive affect was inversely related to systolic blood pressure (p=.007) and diastolic blood pressure (p=.049) reactivity, and unrelated to heart rate (p=.226). Positive affect was unrelated to reactivity during anger recall (ps>.19), and was unrelated to recovery at the end of the recall protocol. Positive affect was inversely related to the mean level of NOREPI (p=.046), and unrelated to EPI (p=.149). Positive affect was inversely related to the increase in cortisol 30 min post awakening (p=.042), and unrelated to the evening decline in cortisol levels (p=.174). Positive emotions may be relevant to good health.

IQ in late adolescence/early adulthood, risk factors in middle age and later all-cause mortality in men: the Vietnam Experience Study.

OBJECTIVE: To examine the role of potential mediating factors in explaining the IQ-mortality relation. DESIGN, SETTING AND PARTICIPANTS: A total of 4316 male former Vietnam-era US army personnel with IQ test results at entry into the service in late adolescence/early adulthood in the 1960/1970s (mean age at entry 20.4 years) participated in a telephone survey and medical examination in middle age (mean age 38.3 years) in 1985-6. They were then followed up for mortality experience for 15 years. MAIN RESULTS: In age-adjusted analyses, higher IQ scores were associated with reduced rates of total mortality (hazard ratio (HR)(per SD increase in IQ) 0.71; 95% CI 0.63 to 0.81). This relation did not appear to be heavily confounded by early socioeconomic position or ethnicity. The impact of adjusting for some potentially mediating risk indices measured in middle age on the IQ-mortality relation (marital status, alcohol consumption, systolic and diastolic blood pressure, pulse rate, blood glucose, body mass index, psychiatric and somatic illness at medical examination) was negligible (<10% attenuation in risk). Controlling for others (cigarette smoking, lung function) had a modest impact (10-17%). Education (0.79; 0.69 to 0.92), occupational prestige (0.77; 0.68 to 0.88) and income (0.86; 0.75 to 0.98) yielded the greatest attenuation in the IQ-mortality gradient (21-52%); after their collective adjustment, the IQ-mortality link was effectively eliminated (0.92; 0.79 to 1.07). CONCLUSIONS: In this cohort, socioeconomic position in middle age might lie on the pathway linking earlier IQ with later mortality risk but might also partly act as a surrogate for cognitive ability.