Minocycline as adjunctive treatment for major depressive disorder: Pooled data from two randomized controlled trials

Background: Randomized controlled clinical trials that have investigated minocycline as an adjunctive treatment for major depressive disorder have proved promising. Data from two studies were pooled to evaluate more definitively whether the addition of minocycline to standard treatment for major depressive disorder leads to an improvement of depressive symptoms when compared with placebo. Methods: Both studies were multi-site, double-blinded, placebo-controlled trials of minocycline 200 mg/day added to treatment as usual during a 12-week period. The primary outcome measure was change in depressive symptoms (Montgomery–Asberg Depression Rating Scale in Dean et al. and Hamilton Depression Rating Scale in Husain et al.). Secondary outcomes were change in depression severity (Montgomery–Asberg Depression Rating Scale for Dean et al. and 9-item Patient Health Questionnaire in Husain et al.), anxiety severity (Hamilton Anxiety Rating Scale in Dean et al. and Generalized Anxiety Disorder 7-item scale in Husain et al.) and functional status, which were also evaluated as potential mediators on the primary outcome. Results: A total of 112 participants were included in the pooled data (Dean et al., n = 71; Husain et al., n = 41). A significant change from baseline to week 12 was noted in depressive symptoms – differential change (Placebo vs Minocycline): 9.0, 95% confidence interval = [4.2, 13.9], Cohen’s D (95% confidence interval): 0.71 [0.29, 1.14], p < 0.001 – anxiety severity – differential change (Placebo vs Minocycline): 0.38, confidence interval = [0.00, 0.75], Cohen’s D (95% confidence interval): 0.41 [0.00, 0.82], p = 0.050) and functional status – differential change (Placebo vs Minocycline): 1.0, 95% confidence interval = [0.4, 1.5], Cohen’s D (95% confidence interval): 0.76 [0.34, 1.19], p = 0.001). Duration of illness, current use of benzodiazepine and pain medication were identified as moderators, whereas functional status as a mediator/predictor. Conclusion: The improvement of depressive symptoms, anxiety severity and functional status is promising and suggests that minocycline has potential as an adjunctive treatment for major depressive disorder. However, further studies are warranted to confirm therapeutic effects of minocycline in major depressive disorder. Trial registrations: NCT02263872, registered October 2014, and ACTRN12612000283875, registered March 2012.

A-108 Differential Change in Eye Movement Performance Among Male Collegiate Athletes With Variable Exposure to Head Impacts

Objective The primary aim of this study was to evaluate the use of eye movement testing to detect change in cognitive and sensorimotor processing among male club collegiate athletes following a season of participation in collision sports of variable exposure. We predicted that collision sport athletes (COLL) exposed to subconcussive head trauma would demonstrate longer reaction times (latency) on saccadic eye movement tasks with executive demands (antisaccade and memory-guided saccade [MGS] tasks), greater antisaccade inhibitory errors, and poorer MGS accuracy, a measure of spatial working memory, from pre-season to post-season, whereas non-collision sport athletes (NON-COLL) would demonstrate stability overtime. We predicted that longitudinal change in eye movement performance would be greater than change observed on ImPACT (Immediate Post-Concussion Assessment and Cognitive Test). Method Collegiate club athletes with variable exposure to contact sports participation [COLL-High Dose, n = 8; COLL-Low Dose, n = 9; NON-COLL, n = 17] completed eye movement and ImPACT assessments pre-season and post-season. Results NON-COLL demonstrated shorter post-season versus pre-season antisaccade and MGS latencies, whereas COLL groups showed stable, longer, or more attenuated (relative to NON-COLL) shorter latencies (ps ≤ .001). NON-COLL demonstrated improved MGS spatial accuracy over the season, whereas COLL groups showed poorer or stable accuracy (ps &lt; .05). No differential change was observed in pre-season to post-season ImPACT performance among groups. Conclusions This pilot study provides preliminary evidence for the use of eye movement testing as a sensitive marker of subtle changes in attentional control and working memory resulting from participation in collision sports.

Automated volumetric breast density measures: differential change between breasts in women with and without breast cancer

Background Given that breast cancer and normal dense fibroglandular tissue have similar radiographic attenuation, we examine whether automated volumetric density measures identify a differential change between breasts in women with cancer and compare to healthy controls. Methods Eligible cases (n = 1160) had unilateral invasive breast cancer and bilateral full-field digital mammograms (FFDMs) at two time points: within 2 months and 1–5 years before diagnosis. Controls (n = 2360) were matched to cases on age and date of FFDMs. Dense volume (DV) and volumetric percent density (VPD) for each breast were assessed using Volpara™. Differences in DV and VPD between mammograms (median 3 years apart) were calculated per breast separately for cases and controls and their difference evaluated by using the Wilcoxon signed-rank test. To simulate clinical practice where cancer laterality is unknown, we examined whether the absolute difference between breasts can discriminate cases from controls using area under the ROC curve (AUC) analysis, adjusting for age, BMI, and time. Results Among cases, the VPD and DV between mammograms of the cancerous breast decreased to a lesser degree (− 0.26% and − 2.10 cm3) than the normal breast (− 0.39% and − 2.74 cm3) for a difference of 0.13% (p value < 0.001) and 0.63 cm3 (p = 0.002), respectively. Among controls, the differences between breasts were nearly identical for VPD (− 0.02 [p = 0.92]) and DV (0.05 [p = 0.77]). The AUC for discriminating cases from controls using absolute difference between breasts was 0.54 (95% CI 0.52, 0.56) for VPD and 0.56 (95% CI, 0.54, 0.58) for DV. Conclusion There is a small relative increase in volumetric density measures over time in the breast with cancer which is not found in the normal breast. However, the magnitude of this difference is small, and this measure alone does not appear to be a good discriminator between women with and without breast cancer.