Hydrocortisone Affects Fatigue and Physical Functioning Through Metabolism of Tryptophan: A Randomized Controlled Trial.

Context: Hydrocortisone (HC) treatment influences health-related quality of life (HRQOL) in secondary adrenal insufficiency (AI). Glucocorticoids regulate tryptophan metabolism through the kynurenine pathway, which modulates mood and energy homeostasis. Objective: This study investigated whether tryptophan metabolism mediated the effect of HC dose on HRQOL in patients with secondary AI. Design, Setting, and Patients: Forty-seven patients with secondary AI participated in this double-blind randomized controlled cross-over trial in the University Medical Center Groningen. Intervention: Patients were treated for two 10-week periods with a daily HC dose of 0.2 to 0.3 mg/kg and 0.4 to 0.6 mg/kg body weight, respectively. Main Outcome Measures: Diary data and questionnaires were used to assess HRQOL. Tryptophan, kynurenine and 3-hydroxykynurenine were measured in serum and dialyzed plasma and the kynurenine-to-tryptophan ratio (Kyn/Trp ratio) ratio was calculated. Results: A higher dose HC was associated with increased levels of tryptophan (95% CI for mean difference 0.37 to 12.5, P = 0.038), reduced levels of kynurenine (95% CI, -0.49 to -0.10, P = 0.004) and 3-hydroxykynurenine (95% CI, -10.6 to -2.35, P = 0.003), and a reduced Kyn/Trp ratio (95% CI, -0.84 to -0.50, P < 0.001). The Kyn/Trp ratio mediated the effect of a higher dose HC on fatigue (P = 0.041) and physical functioning (P = 0.005). Conclusion: Metabolism of tryptophan through the kynurenine pathway is reduced after a 10-week treatment with a higher dose HC and plays a role in the effect of HC on fatigue and physical functioning in patients with secondary AI.

Heart Rate Variability Biofeedback Stress Relief Program for Depression*. A Replicated Single-Subject Design

BACKGROUND: Depressive disorders often have a chronic course and the efficacy of evidence-based treatments may be overestimated. OBJECTIVE: To examine the effectiveness of the Heart Rate Variability Stress Reduction Program (SRP) as a supplement to standard treatment in patients with depressive disorders. METHODS: The SRP was individually administered in eight weekly sessions. Seven participants completed the full protocol and were enrolled in a single-subject ABA multiple baseline experimental design. To perform interrupted time-series analyses, daily measures were completed in a diary (depression, resilience, happiness, heart coherence and a personalized outcome measure). RESULTS: Five out of seven patients improved in depressed mood and/or a personalized outcome measure. The effect of treatment was reversed in four patients during the withdrawal phase. One patient reliably improved on depression, whereas two patients recovered on autonomy and one on social optimism. No consistent relationship was found between the heart rate variability-related level of coherence and self-reported mood levels. CONCLUSIONS: The SRP is beneficial in some domains and for some patients. A prolonged treatment or continued home practice may be required for enduring effects. The intervention had more clinical impact on resilience-related outcome measures than on symptoms. The small sample size does not permit generalization of the results. We recommend future investigation of the underlying mechanisms of the SRP.

Low-intensity blue-enriched white light (750 lux) and standard bright light (10,000 lux) are equally effective in treating SAD. A randomized controlled study.

BACKGROUND: Photoreceptor cells containing melanopsin play a role in the phase-shifting effects of short-wavelength light. In a previous study, we compared the standard light treatment (SLT) of SAD with treatment using short-wavelength blue-enriched white light (BLT). Both treatments used the same illuminance (10,000 lux) and were equally highly effective. It is still possible, however, that neither the newly-discovered photoreceptor cells, nor the biological clock play a major role in the therapeutic effects of light on SAD. Alternatively, these effects may at least be partly mediated by these receptor cells, which may have become saturated as a result of the high illuminances used in the therapy. This randomized controlled study compares the effects of low-intensity BLT to those of high-intensity SLT. METHOD: In a 22-day design, 22 patients suffering from a major depression with a seasonal pattern (SAD) were given light treatment (10,000 lux) for two weeks on workdays. Subjects were randomly assigned to either of the two conditions, with gender and age evenly distributed over the groups. Light treatment either consisted of 30 minutes SLT (5000 °K) with the EnergyLight® (Philips, Consumer Lifestyle) with a vertical illuminance of 10,000 lux at eye position or BLT (17,000 °K) with a vertical illuminance of 750 lux using a prototype of the EnergyLight® which emitted a higher proportion of short-wavelengths. All participants completed questionnaires concerning mood, activation and sleep quality on a daily basis. Mood and energy levels were also assessed on a weekly basis by means of the SIGH-SAD and other assessment tools. RESULTS: On day 22, SIGH-SAD ratings were significantly lower than on day 1 (SLT 65.2% and BLT 76.4%). On the basis of all assessments no statistically significant differences were found between the two conditions. CONCLUSION: With sample size being small, conclusions can only be preliminary. Both treatment conditions were found to be highly effective. The therapeutic effects of low-intensity blue-enriched light were comparable to those of the standard light treatment. Saturation effects may play a role, even with a light intensity of 750 lux. The therapeutic effects of blue-enriched white light in the treatment of SAD at illuminances as low as 750 lux help bring light treatment for SAD within reach of standard workplace and educational lighting systems.