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A workshop titled Beyond the Symptom: The Biology of Fatigue was held virtually September 27-28, 2021. It was jointly organized by the Sleep Research Society and the Neurobiology of Fatigue Working Group of the NIH Blueprint Neuroscience Research Program. For access to the presentations and video recordings, see: https://neuroscienceblueprint.nih.gov/about/event/beyond-symptom-biology-fatigue. The goals of this workshop were to bring together clinicians and scientists who use a variety of research approaches to understand fatigue in multiple conditions and to identify key gaps in our understanding of the biology of fatigue. This workshop summary distills key issues discussed in this workshop and provides a list of promising directions for future research on this topic. We do not attempt to provide a comprehensive review of the state of our understanding of fatigue, nor to provide a comprehensive reprise of the many excellent presentations. Rather, our goal is to highlight key advances and to focus on questions and future approaches to answering them.

Positive social experiences may induce oxytocin release. However, previous studies of moral elevation have generally utilized cross-sectional and simple modeling approaches to establish the relationship between oxytocin and emotional stimuli. Utilizing a cohort of 30 non-lactating women (aged 23.6 ± 5.7 years), we tested whether exposure to a video identified as capable of eliciting moral elevation could change plasma oxytocin levels. Uniquely, we utilized a high-frequency longitudinal sampling approach and multilevel growth curve modeling with landmark registration to test physiological responses. The moral elevation stimulus, versus a control video, elicited significantly greater reports of being "touched/inspired" and "happy/joyful". However, the measured plasma oxytocin response was found to be markedly heterogeneous. While the moral elevation stimulus elicited increased plasma oxytocin as expected, this increase was only modestly larger than that seen following the control video. This increase was also only present in some individuals. We found no relationship between plasma oxytocin and self-report responses to the stimulus. From these data, we argue that future studies of the relationship between oxytocin and emotion need to anticipate heterogeneous responses and thus incorporate comprehensive individual psychological data; these should include evidence-based variables known to be associated with oxytocin such as a history of trauma, and the individual's psychological and emotional state at the time of testing. Given the complexity of physiological oxytocin release, such studies also need to incorporate frequent biological sampling to properly examine the dynamics of hormonal release and response.

Sensory hypersensitivity is one manifestation of the central sensitization that may underlie conditions such as fibromyalgia and chronic fatigue syndrome. We conducted five studies designed to develop and validate the Sensory Hypersensitive Scale (SHS); a 25-item self-report measure of sensory hypersensitivity. The SHS assesses both general sensitivity and modality-specific sensitivity (e.g. touch, taste, and hearing). 1202 participants (157 individuals with chronic pain) completed the SHS, which demonstrated an adequate overall internal reliability (Cronbach's alpha) of 0.81, suggesting the tool can be used as a cross-modality assessment of sensitivity. SHS scores demonstrated only modest correlations (Pearson's r) with depressive symptoms (0.19) and anxiety (0.28), suggesting a low level of overlap with psychiatric complaints. Overall SHS scores showed significant but relatively modest correlations (Pearson's r) with three measures of sensory testing: cold pain tolerance (-0.34); heat pain tolerance (-0.285); heat pain threshold (-0.271). Women reported significantly higher scores on the SHS than did men, although gender-based differences were small. In a chronic pain sample, individuals with fibromyalgia syndrome demonstrated significantly higher SHS scores than did individuals with osteoarthritis or back pain. The SHS appears suitable as a screening measure for sensory hypersensitivity, though additional research is warranted to determine its suitability as a proxy for central sensitization., Author(s): Eric A. Dixon[sup.1] , Grant Benham[sup.2] , John A. Sturgeon[sup.1] , Sean Mackey[sup.1] , Kevin A. Johnson[sup.1] , Jarred Younger[sup.1] [sup.3] Author Affiliations: (1) Department of Anesthesia, Division of [...]

The role of attachment style in relation to forgiveness was investigated in 2 betrayal interviews. Blood pressure and heart rate were assessed, along with attachment style, forgiveness, empathy, and emotional expressiveness. Securely attached individuals were more forgiving of the specific offense, had higher levels of trait forgiveness, and expressed more positive emotion. Securely attached adults had lower interview systolic blood pressure and exhibited greater blood pressure recovery. Attachment style may be an independent antecedent of forgiveness.