Floatation-REST (restricted environmental stimulation therapy) has shown promising potential as a therapeutic intervention in psychiatric conditions such as anxiety and anorexia nervosa. We speculate that the sensory deprivation might act as a kind of interoceptive training. Within our lab, interoceptive trait prediction error has been used to predict states of anxiety in autistic adults. There is also emerging research conceptualising interoceptive mismatches potentially playing a role in fatigue. Our aim was to run a feasibility study assessing the tolerability of Floatation-REST for participants with disabling fatigue. We also aimed to establish the feasibility of gathering data on mechanistic measures, such as heart rate variability (HRV) and interoception, during floatation.

Participants were recruited via online advertisements and were screened to check they scored at least 36 on the Fatigue Severity Scale (FSS). Pertinent medication changes and previous float experience within the last 6 weeks were amongst the exclusion criteria. Baseline measures included: Modified Fatigue Impact Scale (MFIS); Body Perception Questionaire; hypermobility questionnaire and Tellegen Absorption Scale. Participants completed four 90 minute sessions of floatation-REST across a 2–6 week period with 1 week of ecological momentary sampling (EMS) before and after. Immediate pre and post float measures included testing interoceptive sensibility, accuracy and awareness. HRV was measured during floatation. Change in energy was measured by retrospective subjective assessment, changes in validated fatigue scales and EMS.

Baseline MFIS scores (median = 67.5; range = 55–77) indicated a high degree of severity of participant fatigue. 15 participants were recruited to the study. 13 participants started the float intervention and 11 completed all four sessions. No drop out was due to poor tolerability. Most adverse events were mild, expected and related to the pre/post float testing. HRV data was successfully captured throughout all sessions. Participant surveys described improvements in energy levels, sleep and relaxation and 73% “strongly agreed” to an overall positive effect. Furthermore, both statistically and clinically significant reductions were noted in the mean FSS scores (56.9 to 52.6; p = 0.044) and the MFIS scores (67.0 to 56.4; p = 0.003). Detailed energy assessment was obtained by EMS with 37 to 86 data points per participant.

Floatation-REST appears to be a feasible intervention for people with severe fatigue. EMS, HRV data, interoceptive data and other measures were reliably recorded. Reported subjective benefits were supported by an improvement in objective fatigue scores, though the lack of a control group makes these improvements speculative at present.

Overgeneralised self-blame and worthlessness are key symptoms of major depressive disorder (MDD) and have previously been associated with self-blame-selective changes in connectivity between right superior anterior temporal lobe (rSATL) and subgenual frontal cortices. Another study showed that remitted MDD patients were able to modulate this neural signature using functional magnetic resonance imaging (fMRI) neurofeedback training, thereby increasing their self-esteem. The feasibility and potential of using this approach in symptomatic MDD were unknown.

This single-blind pre-registered randomised controlled pilot trial probed a novel self-guided psychological intervention with and without additional rSATL-posterior subgenual cortex (BA25) fMRI neurofeedback, targeting self-blaming emotions in people with insufficiently recovered MDD and early treatment-resistance (n = 43, n = 35 completers). Participants completed three weekly self-guided sessions to rebalance self-blaming biases.

As predicted, neurofeedback led to a training-induced reduction in rSATL-BA25 connectivity for self-blame v. other-blame. Both interventions were safe and resulted in a 46% reduction on the Beck Depression Inventory-II, our primary outcome, with no group differences. Secondary analyses, however, revealed that patients without DSM-5-defined anxious distress showed a superior response to neurofeedback compared with the psychological intervention, and the opposite pattern in anxious MDD. As predicted, symptom remission was associated with increases in self-esteem and this correlated with the frequency with which participants employed the psychological strategies in daily life.

These findings suggest that self-blame-rebalance neurofeedback may be superior over a solely psychological intervention in non-anxious MDD, although further confirmatory studies are needed. Simple self-guided strategies tackling self-blame were beneficial, but need to be compared against treatment-as-usual in further trials. https://doi.org/10.1186/ISRCTN10526888

To summarise the tolerability profile following an infusion of methylene blue (MB), including subjective effects on mood and energy levels and haemodynamic changes, in patients with Bipolar Affective Disorder (BPAD).

BPAD is associated with mitochondrial dysfunction and impaired cellular energy production. MB is proposed to enhance mitochondria function via rerouting electrons and intracellular reduction of oxidative stress, and is therefore a candidate compound for use as a probe to reveal alterations in brain oxygen metabolism in vivo in patients with BPAD. Although there are reports of MB used as treatment for BPAD, the tolerability and subjective effects of a single IV dose in this population has not yet been defined.

Using a single-blind, randomised, within-subject design, 7 patients with BPAD on stable pharmacological treatment and 6 healthy controls (HCs) received an infusion of 0.5mg/kg MB and a placebo glucose solution one week apart. Visual Analogue Scales (VAS) assessing ‘Mood’ and ‘Energy’ levels were completed by 11 participants, and blood pressure (BP), heart rate (HR) and any subsequent side effects were recorded before and after infusions.

A significant, albeit very small, effect of MB on ‘Mood’ levels relative to placebo was demonstrated, independent of groups (change relative to baseline: 5.5% ± 11 increase (placebo) vs -1.6 % ± 9.5 reduction (MB); p = 0.027). Although there was no effect of MB on energy levels in either group, there appeared to be a trend for a general group difference in ‘Energy’ levels across all trials, with lower ratings in BPAD patients (p = 0.058).

There was a trend for significantly lower post-infusion HR relative to pre-infusion (-6.4 ± 8.8 bpm, p = 0.07. Diastolic BP was higher (3.0 ± 7.8mmHg, p = 0.039). These effects were independent of groups and drug. The most common side effect with MB was mild/moderate pain at infusion site (n = 10/13), resolving within median 32.5 minutes (IQR 6-102), and discoloured urine in 7/13 subjects lasting median 44.5 hours (IQR 36-59). No difference in frequency of side effects reported between groups.

Although limited by small sample size, this tolerability analysis demonstrates a acceptable profile of effects of MB on subjective ratings and blood pressure, in both BPAD and HCs. Common side effects of discoloured urine and pain at infusion site are in line with previous reports in the literature. We observed a small effect of MB on mood ratings which could be related to the discomfort experienced during infusion.