Faculty Bibliography

Major depressive disorder (MDD) in the elderly is a risk factor for dementia, but the precise biological basis remains unknown, hampering the search for novel biomarkers and treatments. In this study, we performed metabolomics analysis of cerebrospinal fluid (CSF) from cognitively intact elderly patients (N = 28) with MDD and age- and gender-matched healthy controls (N = 18). The CSF levels of 177 substances were measured, while 288 substances were below the detection limit. Only ascorbic acid was significantly different, with higher levels in the MDD group at baseline. There were no correlations between CSF ascorbic acid levels and clinical variables in MDD patients at baseline. At the 3-year follow-up, there was no difference of CSF ascorbic acid levels between the two groups. There was a negative correlation between CSF ascorbic acid and CSF amyloid-beta42 levels in all subjects. However, there were no correlations between ascorbic acid and other biomarkers (e.g., amyloid-beta40, total and phosphorylated tau protein). This preliminary study suggests that abnormalities in the transport and/or release of ascorbic acid might play a role in the pathogenesis of late-life depression.

Introduction AL patients may experience severe physical and psychological distress. To address this, we developed a novel intervention called EASE, which includes: 1) tailored psychotherapy; and 2) physical symptom screening, with distressing symptoms triggering early involvement of palliative care. Objectives To assess the feasibility and preliminary efficacy of EASE. Methods Patients were recruited within 2 weeks of admission to a comprehensive cancer center and randomized to receive either EASE or usual care (UC). Physical and psychological symptoms were assessed at baseline, 4, 8 (primary endpoint), and 12 weeks. Intervention patients received 6-10 psychotherapy sessions over 8 weeks, weekly assessment of physical symptoms, and referral to palliative care, triggered by symptoms. Oneway ANOVA was performed to assess mean change scores over time between groups. Results Forty-two patients were randomized to EASE (n=22) or UC (n=20). Predefined feasibility outcomes were met: 86% (19/22) of EASE partic-ipants (goal >64%) completed >50% of psychotherapy sessions; 64% (14/22) completed symptom screenings (goal >50%); and 100% of those with distressing symptoms had >1 meeting with palliative care (goal 100%). There were statistically significant findings favoring EASE for satisfaction with care at 8 (DELTA: 7.39 vs-3.12, p<0.04) and 12 (DELTA: 0.01 vs-6.19, p<0.03) weeks and trends favoring EASE for traumatic stress, depression, quality of life, attachment security, and number, severity, and distress related to physical symptoms at 4, 8, and 12 weeks. Conclusions This randomized pilot trial of EASE showed promising reductions in psychological and physical distress and supports feasibility and need for a larger randomized controlled trial

Posttraumatic stress disorder (PTSD) is associated with increased risk for Type 2 diabetes and cardiovascular disease (cardiometabolic disease), warranting research into targeted prevention strategies. In the present case-control study of 160 young (mean age 32.7 years) male military veterans, we aimed to assess whether PTSD status predicted increased markers of cardiometabolic risk in otherwise healthy individuals, and further, to explore biological pathways between PTSD and these increased markers of cardiometabolic risk. Toward these aims, we compared measures of cardiometabolic risk, namely insulin resistance (IR) (HOMA-IR), metabolic syndrome (MetS) and prediabetes, between 80 PTSD cases and 80 controls without PTSD. We then determined whether PTSD-associated increases in HOMA-IR were correlated with select biological variables from pathways previously hypothesized to link PTSD with cardiometabolic risk, including systemic inflammation (increased C-reactive protein, interleukin-6, and tumor necrosis factor alpha), sympathetic over-activity (increased resting heart rate), and neuroendocrine dysregulation (increased plasma cortisol or serum brain-derived neurotrophic factor (BDNF)). We found PTSD diagnosis was associated with substantially higher HOMA-IR (cases 4.3+/-4.3 vs controls 2.4+/-2.0; p<0.001), and a higher frequency of MetS (cases 21.3% vs controls 2.5%; p<0.001), but not prediabetes (cases 20.0% vs controls 18.8%; p>0.05). Cases also had increased pro-inflammatory cytokines (p<0.01), heart rate (p<0.001), and BDNF (p<0.001), which together predicted increased HOMA-IR (adjusted R2=0.68, p<0.001). Results show PTSD diagnosis in young male military veterans without cardiometabolic disease is associated with increased IR, predicted by biological alterations previously hypothesized to link PTSD to increased cardiometabolic risk. Findings support further research into early, targeted prevention of cardiometabolic disease in individuals with PTSD.

BACKGROUND: Few studies have longitudinally examined predictors of posttraumatic stress disorder (PTSD) in a nationally representative sample of US veterans. We examined predictors of warzone-related PTSD over a 25-year span using data from the National Vietnam Veterans Longitudinal Study (NVVLS). METHODS: The NVVLS is a follow-up study of Vietnam theater veterans (N = 699) previously assessed in the National Vietnam Veterans Readjustment Study (NVVRS), a large national-probability study conducted in the late 1980s. We examined the ability of 22 premilitary, warzone, and postmilitary variables to predict current warzone-related PTSD symptom severity and PTSD symptom change in male theater veterans participating in the NVVLS. Data included a self-report Health Questionnaire survey and a computer-assisted telephone Health Interview Survey. Primary outcomes were self-reported PTSD symptoms assessed by the PTSD Checklist for DSM-5 (PCL 5) and Mississippi PTSD Scale (M-PTSD). RESULTS: Predictors of current PTSD symptoms most robust in hierarchical multivariable models were African-American race, lower education level, negative homecoming reception, lower current social support, and greater past-year stress. PTSD symptoms remained largely stable over time, and symptom exacerbation was predicted by African-American race, lower education level, younger age at entry into Vietnam, greater combat exposure, lower current social support, and greater past-year stressors. CONCLUSIONS: Findings confirm the robustness of a select set of risk factors for warzone-related PTSD, establishing that these factors can predict PTSD symptom severity and symptom change up to 40 years postdeployment.

Posttraumatic stress disorder (PTSD) has been regarded as a signature injury of war and elevated to one of the major behavioral health problems faced by military service members and veterans deployed to warzones. In PTSD diagnosis, self-report measures have often been used with a cutoff score to identify those with an elevated likelihood of having PTSD prior to conducting a second-tier diagnostic interview. With an attempt to guide the selection of cutoffs in self-report PTSD measures for various purposes, this study examined how five common criteria for establishing an optimal cutoff influenced the performance of self-report measures for warzone PTSD in relation to the Clinician Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and whether the influence differed for the PTSD Checklist for DSM-5 and the Mississippi Scale for Combat-Related PTSD. Using a probability sample of Vietnam theater veterans in the National Vietnam Veterans Longitudinal Study, results showed that in both self-report measures, the Youden Index criterion yielded the optimal cutoff that led to better test performance. (PsycINFO Database Record

INTRODUCTION: Several lines of evidence indicate that increased inflammation is associated with Post-Traumatic Stress Disorder (PTSD). We have previously reported that peripheral inflammatory markers are significantly higher in combat-exposed veterans with than without PTSD. This study was designed to replicate these findings in a new study cohort using the same population and recruitment strategies. METHODS: Sixty-one male war veterans (31 PTSD and 30 control subjects) were included in this replication study. Levels of Interleukin-6, Tumor Necrosis Factor-alpha, Gamma interferon, and high-sensitivity C-reactive protein were quantified in blood samples. A standardized "total pro-inflammatory score" was calculated to limit the number of statistical comparisons. The Clinician Administered PTSD Scale (CAPS) rating scale was used to assess PTSD symptom severity. RESULTS: PTSD subjects had significantly higher total pro-inflammatory scores compared to non-PTSD subjects in unadjusted analysis (Cohen's d=0.75, p=0.005) as well as after adjusting for potentially confounding effects of age, BMI, smoking, and potentially interfering medications and somatic co-morbidities (p=0.023). There were no significant correlations between inflammatory markers and severity of symptoms within the PTSD group. CONCLUSIONS: We replicated, in a new sample, our previous finding of increased inflammatory markers in combat-exposed PTSD subjects compared to combat-exposed non-PTSD controls. These findings strongly add to the growing literature suggesting that immune activation may be an important aspect of PTSD pathophysiology, although not directly correlated with current PTSD symptom levels in the PTSD group.