Personalised relaxation practice to improve sleep and functioning in patients with chronic fatigue syndrome and depression: study protocol for a randomised controlled trial.

BACKGROUND: Chronic fatigue syndrome (CFS) and major depressive disorder (MDD) are both debilitating but heterogeneous conditions sharing core features of fatigue, unrefreshing sleep, and impaired functioning. The aetiology of these conditions is not fully understood, and 'best-practice' treatments are only moderately effective in relieving symptoms. Unrecognised individual differences in the response to such treatments are likely to underlie poor treatment outcomes. METHODS/DESIGN: We are undertaking a two-group, parallel, randomised controlled trial (RCT) comparing the effects of a personalised relaxation intervention on sleep quality, daytime symptoms, and functioning in patients with CFS (n = 64) and MDD (n = 64). Following identification of the method that best enhances autonomic responding (such as heart rate variability), participants randomised to the active intervention will practise their recommended method nightly for 4 weeks. All participants will keep a sleep diary and monitor symptoms during the trial period, and they will complete two face-to-face assessments, one at baseline and one at 4 weeks, and a further online assessment to evaluate lasting effects of the intervention at 2 months. Assessments include self-report measures of sleep, wellbeing, and function and monitoring of autonomic responses at rest, in response to the relaxation method and during nocturnal sleep. Treatment outcomes will be analysed using linear mixed modelling. DISCUSSION: This is the first RCT examining the effects of a personalised relaxation intervention, pre-tested to maximise the autonomic relaxation response, in patients with unrefreshing sleep and fatigue attributed to CFS or MDD. Detailed monitoring of sleep quality and symptoms will enable sensitive detection of improvements in the core symptoms of these debilitating conditions. In addition, repeated monitoring of autonomic functioning can elucidate mechanisms underlying potential benefits. The findings have translational potential, informing novel, personalised symptom management techniques for these conditions, with the potential for better clinical outcomes. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ANZCTR), ACTRN12616001671459 . Registered on 5 December 2016.

The joy of heartfelt music: An examination of emotional and physiological responses.

Music-listening can be a powerful therapeutic tool for mood rehabilitation, yet quality evidence for its validity as a singular treatment is scarce. Specifically, the relationship between music-induced mood improvement and meaningful physiological change, as well as the influence of music- and person-related covariates on these outcomes are yet to be comprehensively explored. Ninety-four healthy participants completed questionnaires probing demographics, personal information, and musical background. Participants listened to two prescribed musical pieces (one classical, one jazz), an "uplifting" piece of their own choice, and an acoustic control stimulus (white noise) in randomised order. Physiological responses (heart rate, respiration, galvanic skin response) were recorded throughout. After each piece, participants rated their subjective responses on a series of Likert scales. Subjectively, the self-selected pieces induced the most joy, and the classical piece was perceived as most relaxing, consistent with the arousal ratings proposed by a music selection panel. These two stimuli led to the greatest overall improvement in composite emotional state from baseline. Psycho-physiologically, self-selected pieces often elicited a "eustress" response ("positive arousal"), whereas classical music was associated with the highest heart rate variability. Very few person-related covariates appeared to affect responses, and music-related covariates (besides self-selection) appeared arbitrary. These data provide strong evidence that optimal music for therapy varies between individuals. Our findings additionally suggest that the self-selected music was most effective for inducing a joyous state; while low arousal classical music was most likely to shift the participant into a state of relaxation. Therapy should attempt to find the most effective and "heartfelt" music for each listener, according to therapeutic goals.

Does genotype mask the relationship between psychological factors and immune function?

This paper examined the interaction between genetic influences of the polymorphic human leukocyte antigens (DRB1 and DQB1) and psychological distress on the development of cellular immunity to the novel antigen, keyhole limpet hemocyanin (KLH). Participants (n = 227) were immunized with KLH and the development of cutaneous delayed-type hypersensitivity (DTH) against KLH was examined 3 weeks later. Distress was assessed using the Profile of Mood States. DNA was typed for the serologically defined DRB1 and DQB1 antigens. There was a significant correlation between distress at immunization and the development of DTH skin test responses to KLH (n = 214, r = .24, p = .003). HLA DQ2 was weakly associated with a decreased likelihood of developing a cutaneous delayed-type hypersensitivity response against KLH (odds ratio [OR] = 1.6; confidence interval [CI] 0.9-2.7). HLA DQ5 was weakly associated with an increased likelihood of responding to the antigen (OR=0.6; CI=0.3-1.0). The correlation between distress and immune function in HLA DQ2 negative individuals was .34 (n = 136, p = .00) and in HLA DQ2 positive individuals it was .06 (n = 74, p =. 64). For HLA DQ5 negative individuals the correlation was .26 (n = 140, p = .00) and for HLA DQ5 positive individuals it was .22 (n = 70, p = .07). These results suggest that the distress/immune relationship in genetically susceptible or protected individuals may be underestimated in psychoneuroimmunology research.

Influences of distress and alcohol consumption on the development of a delayed-type hypersensitivity skin test response.

OBJECTIVE: This paper reports the effects of naturally occurring levels of distress on the development of delayed-type hypersensitivity (DTH) skin test responses. These in vivo measures provide a biologically relevant assessment of cellular immune competence. METHODS: Subjects (N = 166) were immunized (baseline) with the novel antigen, keyhole limpet hemocyanin (KLH), and DTH skin test responses against KLH were assessed 3 weeks later (follow-up). The CMI Multitest (Merieux, France), which evaluates DTH responses to a panel of seven antigens, was also administered at follow-up. Emotional distress was assessed at baseline and follow-up by the Profile of Mood States. RESULTS: Distress levels at baseline were associated with a reduced likelihood of developing DTH responses against KLH at follow-up (r = -0.22, p =.01). There was no relationship between distress at follow-up and cutaneous DTH in response to KLH (r = 0.09, p =.24) or in the Multitest (r = -0.03, p =.70). In addition, higher levels of alcohol consumption at baseline (r = -0.19, p =.02) and at follow-up (r = -0.20, p =.01) were associated with a decreased likelihood of developing cutaneous DTH against KLH. CONCLUSIONS: Everyday levels of distress predicted the capacity of the cellular arm of the immune system to exhibit recall responses to an antigen, when the experimental paradigm allowed the assessment of distress at the time of antigen sensitization. Moderate alcohol consumption independently affected cutaneous DTH.