Replication of an empirical approach to delineate the heterogeneity of chronic unexplained fatigue

<p>Abstract</p> <p>Background</p> <p>Chronic fatigue syndrome (CFS) is defined by self-reported symptoms. There are no diagnostic signs or laboratory markers, and the pathophysiology remains inchoate. In part, difficulties identifying and replicating biomarkers and elucidating the pathophysiology reflect the heterogeneous nature of the syndromic illness CFS. We conducted this analysis of people from defined metropolitan, urban, and rural populations to replicate our earlier empirical delineation of medically unexplained chronic fatigue and CFS into discrete endophenotypes. Both the earlier and current analyses utilized quantitative measures of functional impairment and symptoms as well as laboratory data. This study and the earlier one enrolled participants from defined populations and measured the internal milieu, which differentiates them from studies of clinic referrals that examine only clinical phenotypes.</p> <p>Methods</p> <p>This analysis evaluated 386 women identified in a population-based survey of chronic fatigue and unwellness in metropolitan, urban, and rural populations of the state of Georgia, USA. We used variables previously demonstrated to effectively delineate endophenotypes in an attempt to replicate identification of these endophenotypes. Latent class analyses were used to derive the classes, and these were compared and contrasted to those described in the previous study based in Wichita, Kansas.</p> <p>Results</p> <p>We identified five classes in the best fit analysis. Participants in Class 1 (25%) were polysymptomatic, with sleep problems and depressed mood. Class 2 (24%) was also polysymptomatic, with insomnia and depression, but participants were also obese with associated metabolic strain. Class 3 (20%) had more selective symptoms but was equally obese with metabolic strain. Class 4 (20%) and Class 5 (11%) consisted of nonfatigued, less symptomatic individuals, Class 4 being older and Class 5 younger. The classes were generally validated by independent variables. People with CFS fell equally into Classes 1 and 2. Similarities to the Wichita findings included the same four main defining variables of obesity, sleep problems, depression, and the multiplicity of symptoms. Four out of five classes were similar across both studies.</p> <p>Conclusion</p> <p>These data support the hypothesis that chronic medically unexplained fatigue is heterogeneous and can be delineated into discrete endophenotypes that can be replicated. The data do not support the current perception that CFS represents a unique homogeneous disease and suggests broader criteria may be more explanatory. This replication suggests that delineation of endophenotypes of CFS and associated ill health may be necessary in order to better understand etiology and provide more patient-focused treatments.</p

The impact of childhood trauma on psychosocial functioning and physical health in a non-clinical community sample of young adults

Objective: Given the fundamental emotional, social and physical development that occurs during the early years of life, childhood experiences are formative in shaping a person’s life trajectory. Childhood trauma is a prevalent, multifaceted issue with well-documented long-term adverse health effects in clinical populations however; the impact of childhood trauma in the community is less clear. To address this, this study investigated how childhood trauma may impact physical and psychological health, sleep quality and autonomic function in a non-clinical community sample of adults. Method: Participants completed questionnaires, an in-laboratory autonomic assessment (including stress reactivity to mental and physical stressors) and overnight autonomic and sleep monitoring. Overall childhood trauma and its subtypes (e.g. physical abuse, emotional neglect) were defined using the Childhood Trauma Questionnaire. Results: We identified 22 childhood trauma cases (total score > 36) and, of the 89 non-childhood trauma cases, some individuals also experienced significant levels of trauma in one or more of the childhood trauma subtypes. Childhood trauma and some trauma subtypes were significantly correlated with a myriad of negative physiological and physical health outcomes including elevated psychological distress, increased sleep disturbances, reduced emotional wellbeing and lower perceived social support. Autonomic dysregulation was found in those with high levels of childhood trauma, which was reflected in an increased stress response to laboratory tasks. Notably, the experience of physical abuse in childhood was significantly associated with alterations in nocturnal heart rate and heart rate variability. Conclusion: Together, these results highlight that childhood trauma can have lasting detrimental consequences on an individual’s emotional and physical health, sleep quality and stress reactivity. © The Royal Australian and New Zealand College of Psychiatrists 2019

The average change in HRV (as rMSSD) from resting baseline in response to cognitive task performance in patients with CFS and healthy control participants.

<p>Error bars represent the standard error of the mean (SEM). HRV  =  heat rate variability; rMSSD  =  root mean square of successive differences of R-R intervals; CFS  =  chronic fatigue syndrome.</p

Correlations between baseline rMSSD (ms) values and cognitive performance outcomes.

<p>The correlations coefficients (<i>r</i>) are from Pearson correlations; rMSSD  =  root mean square of successive differences of R-R intervals; RT  =  reaction time.</p

Clinical characteristics patients with CFS and of healthy participants.

<p>Values are group means and (standard deviations). CFS  =  chronic fatigue syndrome; SOMA  =  somatic subscale of the SPHERE (somatic and psychological health report); K10 =  Kessler 10; BDQ  =  brief disability questionnaire; PSQI  =  Pittsburgh Sleep Quality Index; McGill  =  Short form McGill Pain Questionnaire.</p

A hypothetical model of altered neurovisceral communication underlying the documented impairments in autonomic activation and behavioural self-regulation in CFS.

<p>PFC  =  prefrontal cortex; HRV  =  heat rate variability; CFS  =  chronic fatigue syndrome.</p