No effects of acute tryptophan depletion on anxiety or mood in weight-recovered female patients with anorexia nervosa.

BACKGROUND: Previous studies have suggested that individuals recovered from anorexia nervosa (AN) are characterized by increased serotonergic (5-HT) activity that might be related to elevated levels of anxiety. Assuming these traits to be also present in individuals at risk for AN, it was further hypothesized that restricting food intake might be a means to temporarily alleviate dysphoric affective states by reducing central nervous availability of tryptophan (TRP), the sole precursor of 5-HT. One study that supported this hypothesis found anxiolytic effects in individuals with a history of AN during an experimentally induced short-term depletion of TRP supply to the brain. METHODS: In this placebo-controlled, double-blind cross-over study, 22 patients weight-recovered from AN (recAN) and 25 healthy control participants (HC) completed questionnaires assessing anxiety and momentary mood during acute tryptophan depletion (ATD), a dietary intervention that lowers central 5-HT synthesis. RESULTS: The ATD procedure effectively reduced the ratio of TRP to competing for large neutral amino acids in the peripheral blood, indicating decreased TRP supply to the brain. Effects of ATD on anxiety and mood did not differ between recAN and HC. Bayesian null hypothesis testing confirmed these initial results. DISCUSSION: Our results do not support the hypothesis that short-term depletion of TRP and its impact on the brain 5-HT reduces anxiety or improves mood in AN. As the evidence for the role of 5-HT dysfunction on affective processes in patients with AN is limited, further studies are needed to assess its relevance in the pathophysiology of AN.

Increased self-reported delay of gratification in acutely underweight, but not remitted anorexia nervosa.

OBJECTIVE: Laboratory experiments using delay discounting tasks have delivered some evidence of an increased capacity to delay reward in anorexia nervosa (AN). Overall, however, findings have been inconclusive and no comprehensive studies of self-reported tendency to forgo immediate gratification in favor of long-term rewards exist in AN. METHOD: A total of 71 acutely underweight female inpatients with AN (acAN); 52 women long-term weight-recovered from AN (recAN); and 120 healthy control women completed the Delaying Gratification Inventory (DGI). Fifty-two acAN were reassessed after short-term weight rehabilitation. Separate cross-sectional and longitudinal group comparisons tested for differences in DGI subscales (food, physical pleasure, social interaction, money, and achievement) and total scores. RESULTS: DGI scores were elevated in acAN even after removing food-related items and accounting for comorbid symptoms. DGI scores remained relatively elevated following short-term weight rehabilitation, but no differences were evident between recAN and HC. DISCUSSION: This study delivers self-report evidence supporting the notion of an increased propensity to delay gratification in individuals acutely ill with AN which does not appear to change with partial weight restoration alone. A reduction in the tendency to delay reward may thus be an important cognitive correlate of long-term recovery in AN.

Strengthened Default Mode Network Activation During Delay Discounting in Adolescents with Anorexia Nervosa After Partial Weight Restoration: A Longitudinal fMRI Study.

The capacity of patients with anorexia nervosa (AN) to resist food-based rewards is often assumed to reflect excessive self-control. Previous cross-sectional functional magnetic resonance imaging (fMRI) studies utilizing the delay discounting (DD) paradigm, an index of impulsivity and self-control, suggested altered neural efficiency of decision-making in acutely underweight patients (acAN) and a relative normalization in long-term, weight-recovered individuals with a history of AN (recAN). The current longitudinal study tested for changes in functional magnetic resonance imaging (fMRI) activation during DD associated with intensive weight restoration treatment. A predominately adolescent cohort of 22 female acAN patients (mean age-15.5 years) performed an established DD paradigm during fMRI at the beginning of hospitalization and again after partial weight restoration (≥12% body mass index (BMI) increase). Analyses investigated longitudinal changes in both reward valuation and executive decision-making processes. Additional exploratory analyses included comparisons with data acquired in aged-matched healthy controls (HC) as well as probes of functional connectivity between empirically identified nodes of the "task-positive" frontoparietal control network (FPN) and "task-negative" default-mode network (DMN). While treatment was not associated with changes in behavioral DD parameters or activation, specific to reward processing, deactivation of the DMN during decision-making was significantly less pronounced following partial weight restoration. Strengthened DMN activation during DD might reflect a relative relaxation of cognitive overcontrol or improved self-referential, decision-making. Together, our findings present further evidence that aberrant decision-making in AN might be remediable by treatment and, therefore, might constitute an acute effect rather than a core trait variable of the disorder.

Tissue Stiffness is Not Related to Pain Experience: An Individually Controlled Study in Patients with Chronic Neck and Back Pain.

BACKGROUND: Massage therapies such as cupping are often applied in patients with chronic neck and back pain with the assumption that they can reduce increased tissue stiffness and, therefore, improve pain. The aim of this study was to clarify whether tissue stiffness is related to pain experience in patients with chronic (>3 months) back and neck pain and whether it can be altered by a cupping massage. METHODS: The tissue stiffness of the point of subjectively felt maximum pain intensity of 40 patients with neck (n = 20) or lower back pain (n = 20) was measured by a myometer. Exact contralateral side served as an individual control. Side of higher stiffness was then treated with a cupping massage. 5, 10, 15, and 20 minutes as well as 24 hours after treatment, tissue stiffness was measured again. Patients rated their pain on a standardized pain questionnaire (neck pain disability score (NDI) or Oswestry disability index (ODI), respectively) before and 24 hours after treatment. RESULTS: Compared to the contralateral control side, the more painful side did not exhibit an increased stiffness of myofascial tissue before treatment (p=0.827). The tissue stiffness and the side difference between treated and nontreated control sides decreased significantly after cupping (p=0.002 and p=0.001, respectively) but returned to baseline after 24 hours. NDI and ODI scores significantly decreased 24 hours after cupping (NDI: p=0.012, ODI: p=0.002). CONCLUSION: Tissue stiffness might not be related to pain experience in patients with chronic neck and lower back pain. Trial registration: German Clinical Trial Register (DRKS00011281).

Effects of hyperthermic baths on depression, sleep and heart rate variability in patients with depressive disorder: a randomized clinical pilot trial.

BACKGROUND: Despite advances in the treatment of depression, one-third of depressed patients fail to respond to conventional antidepressant medication. There is a need for more effective treatments with fewer side effects. The primary aim of this study was to determine whether hyperthermic baths reduce depressive symptoms in adults with depressive disorder. METHODS: Randomized, two-arm placebo-controlled, 8-week pilot trial. Medically stable outpatients with confirmed depressive disorder (ICD-10: F32/F33) who were moderately depressed as determined by the 17-item Hamilton Scale for Depression (HAM-D) score ≥18 were randomly assigned to 2 hyperthermic baths (40 °C) per week for 4 weeks or a sham intervention with green light and follow-up after 4 weeks. Main outcome measure was the change in HAM-Dtotal score from baseline (T0) to the 2-week time point (T1). RESULTS: A total of 36 patients were randomized (hyperthermic baths, n = 17; sham condition, n = 19). The intention-to-treat analysis showed a significant (P = .037) difference in the change in HAM-Dtotal score with 3.14 points after 4 interventions (T1) in favour of the hyperthermic bath group compared to the placebo group. CONCLUSIONS: This pilot study suggests that hyperthermic baths do have generalized efficacy in depressed patients. TRIAL REGISTRATION: DRKS00004803 at drks-neu.uniklinik-freiburg.de, German Clinical Trials Register (registration date 2016-02-02), retrospectively registered.

Pomegranate (Punica granatum) Seed Oil for Treating Menopausal Symptoms: An Individually Controlled Cohort Study.

Context • In the folk medicine of Mediterranean countries and in ancient Ayurveda, Punica granatum seeds (ie, pomegranate seeds) have been used for treatment of various disorders, including those that nowadays are classified as menopausal symptoms (MSs). Pomegranate seed oil (PSO) from those seeds mainly contains unsaturated fatty acids such as γ-linoleic acid and linolenic acid, but it also includes phytoestrogens. It is, therefore, regarded as a promising option for treating MSs today. Objectives • The study intended to investigate the safety and effectiveness of PSO as a defined P granatum seed oil for patients with MSs. Design • The research team designed an individually controlled, investigator-initiated cohort study. Setting • The treatments were performed at 2 institutions: (1) the Center for Complementary Medicine at the University Medical Center Freiburg (Freiburg, Germany); and (2) in the medical practice of H. Fischer (Freiburg, Germany). Participants • Seventy-eight patients, who had a mean duration of MSs of 46 mo, participated in the study. Intervention • After 4 wk without treatment, which functioned as a period providing an individual control, each participant took 1000 mg of PSO daily in 2 capsules for 8 wk. Outcome Measures • The symptom severity was scored on the German version of the menopausal rating scale (MRS) at baseline, after 4 wk without treatment, after 4 wk of treatment, and postintervention, with 0 = absence of symptoms and 4 = very strong symptoms. The efficacy and tolerability were estimated on scales from 0-4. Each participant's 17ß estradiol was determined at baseline and after postintervention using the patient's sera. The content of the ß-sitosterol was determined in the PSO preparations by gas chromatography. Results • The content of ß-sitosterol in the PSO used in the study was 6.3 mg/1000 mg. In the intention to treat analysis, most MRS symptoms were significantly and relevantly reduced (eg, hot flushes changed from 2.32 ± 1.04 to 1.41 ± 1.07, P < .001). Remarkably, urogenital tract symptoms (ie, a dry vagina) also significantly improved, moving from 1.32 ± 1.43 to 0.85 ± 1.19, P < .001. Few patients reported gastrointestinal symptoms. The tolerability was excellent at 3.69 ± 0.71 after 4 wk of treatment and 3.71 ± 0.65 after 8 wk of treatment. The 17ß estradiol was unchanged. Conclusions • Participants showed significant improvements in all domains of the MRS, remarkably including the difficult-to-treat urogenital symptoms. No changes occurred in the 17ß-estradiol in patients' sera after the PSO treatment. The results are promising and encourage the investigation of PSO rich in ß-sitosterol for treatment of MSs in placebo-controlled studies.

Fever Therapy With Intravenously Applied Mistletoe Extracts for Cancer Patients: A Retrospective Study.

PURPOSE: So-called spontaneous remissions in cancer often seem to occur after febrile events. Mistletoe preparations (MPs) are used off-label intravenously to induce fever within concepts of integrative oncology. We wanted to investigate the frequency of febrile reactions and safety related to intravenously applied MPs (IAMPs). METHODS: This was a retrospective analysis of data from consecutive cancer patients who were treated in 2 anthroposophic hospitals with IAMPs. The main outcome parameter was the rate of core temperature increase to ≥38.5°C within 24 hours after IAMPs. Secondary outcome parameters were Common Toxicity Criteria for Adverse Events (CTCAE; version 4.0). RESULTS: 59 patients, with in total 567 IAMPs, were analyzed; 45 patients (76%, 95% CI = 65%-87%) had an increase of core temperature to ≥38.5°C after at least 1 treatment. Mean increase in temperature was 1.5°C ± 0.8°C. Adverse events were mostly fever-related symptoms (headache, joint pain, shivering). Grade 1 allergic reactions were documented in 0.6% of treatments. CTCAEs grade 3 to 5 did not occur; 38/59 patients had advanced and/or metastatic disease. CONCLUSION: IAMPs resulted in febrile reactions to >38.5°C in the majority of patients and can be considered as safe. Adverse events were mostly related to fever and were not severe.