Association of plasma cytokines and antidepressant response following mild-intensity whole-body hyperthermia in major depressive disorder.

Whole-body hyperthermia (WBH) shows promise for the treatment of major depressive disorder (MDD). Because MDD is associated with increased inflammation, and anti-inflammatory agents show some promise as antidepressants, the current study sought to identify the acute and longer-term immune effects of WBH in participants with MDD and to explore whether these effects associate with the procedure's antidepressant properties. Thirty participants who met DSM-IV-TR criteria for MDD were randomized to receive a single session of WBH (n = 16) or sham treatment (n = 14). Hamilton Depression Rating Scale (HDRS) scores were assessed at baseline and 1, 2, 4, and 6 weeks post-treatment (WBH vs. sham), and plasma cytokine concentrations were assessed at baseline, immediately post-treatment, and 1 and 4 weeks post-treatment. As previously reported, WBH produced a rapid and sustained antidepressant effect. When compared to sham, WBH increased plasma interleukin (IL)-6 immediately post-treatment (time by treatment: χ2(3, N=108) = 47.33, p < 0.001), while having no effect on other cytokines acutely and no impact on IL-6, or any other cytokine, at 1 or 4 weeks post treatment. In the study sample as a whole, increased IL-6 post-treatment was associated with reduced HDRS depression scores over the 6 weeks of follow-up (F(1, 102.3) = 6.74, p = 0.01). These results suggest a hitherto unrecognized relationship between hyperthermia, the immune system, and depression, and may point to WBH as a novel modality for exploring behavioral effects of IL-6 when the cytokine is activated in isolation from the inflammatory mediators with which it frequently travels.

Neighborhood-level sleep health and childhood opportunities.

Objectives: Regional sleep differences may reflect other important indicators of health and well-being. Examining sleep health at the regional level can help inform policies to improve population health. We examined the relationship between neighborhood-level adult sleep health (modeled in this study via adult sleep duration) and other health metrics and multiple indicators of child-relevant opportunity. Methods: Data were obtained from the "500 Cities" data collected by the CDC, including the proportion of the adult population in each tract that report obtaining at least 7 h of sleep. The Child Opportunity Index (COI) provides indices for "education," "health and environment," and "social and economic" domains, as well as a global score. When data were merged, 27,130 census tracts were included. Linear regression analyses examined COI associated with the proportion of the adult population obtaining 7 h of sleep. Results: Adult sleep duration was associated with global COI, such that for each additional percent of the population that obtains ≥ 7 h of sleep, COI increases by 3.6 points (95%CI[3.57, 3.64]). Each component of COI was separately related to adult sleep duration. All associations were attenuated but significant in adjusted analyses. In stepwise analyses, sleep health via adult sleep duration emerged as the strongest correlate of global COI, accounting for 57.2% of the variance (p < 0.0001). Similarly, when stepwise analyses examined each component of COI as dependent variable, sleep health consistently emerged as the most substantial correlate (all p < 0.0001). Conclusion: Community levels of sufficient sleep are associated with greater childhood opportunities, which itself is robustly associated with a wide range of health and economic outcomes. Future work can examine whether this association can develop into scalable interventions.

Whole-Body Hyperthermia for the Treatment of Major Depressive Disorder: A Randomized Clinical Trial.

IMPORTANCE: Limitations of current antidepressants highlight the need to identify novel treatments for major depressive disorder. A prior open trial found that a single session of whole-body hyperthermia (WBH) reduced depressive symptoms; however, the lack of a placebo control raises the possibility that the observed antidepressant effects resulted not from hyperthermia per se, but from nonspecific aspects of the intervention. OBJECTIVE: To test whether WBH has specific antidepressant effects when compared with a sham condition and to evaluate the persistence of the antidepressant effects of a single treatment. DESIGN, SETTING, AND PARTICIPANTS: A 6-week, randomized, double-blind study conducted between February 2013 and May 2015 at a university-based medical center comparing WBH with a sham condition. All research staff conducting screening and outcome procedures were blinded to randomization status. Of 338 individuals screened, 34 were randomized, 30 received a study intervention, and 29 provided at least 1 postintervention assessment and were included in a modified intent-to-treat efficacy analysis. Participants were medically healthy, aged 18 to 65 years, met criteria for major depressive disorder, were free of psychotropic medication use, and had a baseline 17-item Hamilton Depression Rating Scale score of 16 or greater. INTERVENTIONS: A single session of active WBH vs a sham condition matched for length of WBH that mimicked all aspects of WBH except intense heat. MAIN OUTCOMES AND MEASURES: Between-group differences in postintervention Hamilton Depression Rating Scale scores. RESULTS: The mean (SD) age was 36.7 (15.2) years in the WBH group and 41.47 (12.54) years in the sham group. Immediately following the intervention, 10 participants (71.4%) randomized to sham treatment believed they had received WBH compared with 15 (93.8%) randomized to WBH. When compared with the sham group, the active WBH group showed significantly reduced Hamilton Depression Rating Scale scores across the 6-week postintervention study period (WBH vs sham; week 1: -6.53, 95% CI, -9.90 to -3.16, P < .001; week 2: -6.35, 95% CI, -9.95 to -2.74, P = .001; week 4: -4.50, 95% CI, -8.17 to -0.84, P = .02; and week 6: -4.27, 95% CI, -7.94 to -0.61, P = .02). These outcomes remained significant after evaluating potential moderating effects of between-group differences in baseline expectancy scores. Adverse events in both groups were generally mild. CONCLUSIONS AND RELEVANCE: Whole-body hyperthermia holds promise as a safe, rapid-acting, antidepressant modality with a prolonged therapeutic benefit. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01625546.