Predictors of PTSD Symptom Change Among Outpatients in the U.S. Department of Veterans Affairs Health Care System.

Although the U.S. Department of Veterans Affairs (VA) has prioritized care for posttraumatic stress disorder (PTSD), many patients with PTSD remain symptomatic. Patterns of PTSD symptom change are not well understood. Thus, the current study was designed to categorize and investigate potential predictors of symptom trajectories in patients with PTSD. The sample comprised 2,237 VA patients who were diagnosed with PTSD in 2013 and completed at least 4 PTSD Checklist (PCL) assessments over 12 weeks. Latent trajectory analysis was used to identify latent classes of patients based on PCL scores. Based on model fit indices, 3 trajectories were identified. Compared to patients in the mild-improving trajectory (21.9%), those in the severe-stable trajectory (34.3%) were more likely to be male, relative risk ratio (RRR) = 1.48, 95% CI [1.08, 2.02]; non-White, RRR = 1.77, 95% CI [1.33, 2.35]; Hispanic, RRR = 2.07, 95% CI [1.40, 3.04]; and have comorbid depression, RRR = 1.58, 95% CI [1.25, 1.99]. Compared to patients in the moderate-improving trajectory (43.8%), those in the severe-stable trajectory were more likely to have sleep disorders, RRR = 1.25, 95% CI [1.01, 1.55]. Our findings suggest that male veterans, minority veterans, and veterans with certain comorbid conditions may be less likely to achieve improved PTSD symptoms. Targeted efforts are needed to improve outcomes for PTSD patients on nonremitting trajectories and to improve the consistency of PTSD assessment across the VA health care system.

Allopregnanolone elevations following pregnenolone administration are associated with enhanced activation of emotion regulation neurocircuits.

BACKGROUND: The neurosteroid allopregnanolone is a potent allosteric modulator of the gamma-aminobutyric acid type A receptor with anxiolytic properties. Exogenous administration of allopregnanolone reduces anxiety, and allopregnanolone blockade impairs social and affective functioning. However, the neural mechanism whereby allopregnanolone improves mood and reduces anxiety is unknown. In particular, brain imaging has not been used to link neurosteroid effects to emotion regulation neurocircuitry. METHODS: To investigate the brain basis of allopregnanolone's impact on emotion regulation, participants were administered 400 mg of pregnenolone (n=16) or placebo (n=15) and underwent 3T functional magnetic resonance imaging while performing the shifted-attention emotion appraisal task, which probes emotional processing and regulation. RESULTS: Compared with placebo, allopregnanolone was associated with reduced activity in the amygdala and insula across all conditions. During the appraisal condition, allopregnanolone increased activity in the dorsal medial prefrontal cortex and enhanced connectivity between the amygdala and dorsal medial prefrontal cortex, an effect that was associated with reduced self-reported anxiety. CONCLUSIONS: These results demonstrate that in response to emotional stimuli, allopregnanolone reduces activity in regions associated with generation of negative emotion. Furthermore, allopregnanolone may enhance activity in regions linked to regulatory processes. Aberrant activity in these regions has been linked to anxiety psychopathology. These results thus provide initial neuroimaging evidence that allopregnanolone may be a target for pharmacologic intervention in the treatment of anxiety disorders and suggest potential future directions for research into neurosteroid effects on emotion regulation neurocircuitry.

Quantification of insulin-like growth factor-1 in dried blood spots for detection of growth hormone abuse in sport.

There is significant evidence that athletes are using recombinant human growth hormone (rhGH) to enhance performance, and its use is banned by the World Anti-Doping Agency and professional sports leagues. Insulin-like growth factor-1 (IGF-1) is the primary mediator of growth hormone action and is used as a biomarker for the detection of rhGH abuse. The current biomarker-based method requires collection and expedited shipment of venous blood which is costly and may decrease the number of tests performed. Measurement of GH biomarkers in dried blood spots (DBS) would considerably simplify sample collection and shipping methods to allow testing of a greater number of samples regardless of location. A method was developed to quantify intact IGF-1 protein in DBS by liquid chromatography-tandem mass spectrometry. A step-wise acid-acetonitrile extraction was optimized to achieve a sensitive assay with a lower limit of quantification of 50 ng/mL. IGF-1 remained stable at room temperature for up to 8 days, which would allow shipment of DBS cards at ambient temperature. In a comparison between plasma concentrations of IGF-1 and concentrations measured from venous and finger prick DBS, there was good correlation and agreement, r(2) of 0.8551 and accuracy of 86-113 % for venous DBS and r(2) of 0.9586 and accuracy of 89-122 % for finger prick DBS. The method is intended for use as a rapid screening method for IGF-1 to be used in the biomarker method of rhGH abuse detection.