Self-Reported Autonomic Dysregulation in Gulf War Illness

ABSTRACT Introduction Autonomic nervous system dysregulation is commonly observed in Gulf War illness (GWI). Using a new sample, we sought to replicate and extend findings from a previous study that found autonomic symptoms predicted physical functioning in Veterans with GWI. Materials and Methods A linear regression model was used to predict physical functioning (36-item Short Form Health Survey (SF-36); n = 73, 75% male). First, we examined the predictive value of independent variables individually in the model including: the 31-item Composite Autonomic Symptom Score (COMPASS-31) total score, body mass index (BMI), mental health burden (i.e., post-traumatic stress disorder [PTSD] and/or depression), and COMPASS-31 subscales: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor. Next, we estimated linear regression models containing the three variables (autonomic symptoms, BMI, and mental health burden) identified as predictors of physical functioning from the prior study. Results These linear regression models significantly predicted physical functioning and accounted for 15% of the variance with COMPASS-31, 36.6% of variance with COMPASS-31 and BMI, and 38.2% of variance with COMPASS-31, BMI, and mental health burden. Then, forward step-wise linear regressions were applied to explore new models including COMPASS-31 subscales. Two new models accounted for more of the variance in physical functioning: 39.3% with added gastrointestinal symptoms (β = −2.206, P = .001) and 43.4% of variance with both gastrointestinal (β = −1.592, P = .008) and secretomotor subscales (β = −1.533, P = .049). Unlike the previous study we intended to replicate, mental health burden was not a significant predictor in any of our models. Conclusions Treatments that address autonomic dysregulation should be prioritized for research and clinical recommendations for Veterans with GWI who experience chronic pain.

Weight management in youth with rapid-onset obesity with hypothalamic dysregulation, hypoventilation, autonomic dysregulation, and neural crest tumor (ROHHAD-NET): literature search and case report

Objectives Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, autonomic dysregulation, and neural endocrine tumor (ROHHAD-NET) syndrome is a youth-onset constellation of symptoms including rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation. Despite growing understanding of the clinical classification of this syndrome there is limited investigation into treatment of the rapid-onset obesity which can be progressive and life-limiting. The purpose of this case report is to describe the clinical timeline and treatment of severe obesity in a patient with of ROHHAD-NET and propose recommendations for the treatment of associated obesity. Case presentation We present the case of a 10-year-old female with a clinical presentation consistent with ROHHAD-NET who achieved clinically meaningful weight loss with a combination of lifestyle modification and anti-obesity pharmacotherapies. We report on the use of three separate pharmacological agents and ultimately the referral for bariatric surgery. Conclusions Given that early-onset obesity and hypoventilation are life-limiting components of this condition, early recognition and treatment are essential to improve health outcomes.

Autonomic Nervous System Function in Anorexia Nervosa: A Systematic Review

Background: Autonomic nervous system (ANS) dysfunction has been suggested to contribute to the high prevalence of cardiovascular complications in individuals with anorexia nervosa (AN), yet has not been thoroughly investigated. The current review aimed to synthesize the evidence of basal ANS function in individuals with a current diagnosis of AN and those with a previous diagnosis who had achieved weight restoration, as compared to controls.Methods: A systematic review of nine databases was conducted and studies that were published in a peer-review journal, in English, that included at least one assessment of ANS function in individuals with a current or previous diagnosis of AN were selected. Forty-six studies were included with a total of 811 participants with a current diagnosis of AN and 123 participants with a previous diagnosis of AN.Results: ANS function was assessed through heart rate variability (n = 27), orthostatic challenge, blood pressure variability or baroreflex sensitivity (n = 11), adrenergic activity (n = 14), skin conductance level (n = 4), and pupillometry (n = 1). Individuals with AN demonstrated increased parasympathetic activity and decreased sympathetic activity, suggestive of autonomic dysregulation. Following weight restoration, autonomic function trended toward, or was equivalent to, control levels.Discussion: Autonomic dysregulation is indicated through a range of assessments in individuals with AN. Future investigations should utilize a variety of assessments together in order to conclusively establish the nature of autonomic dysfunction in AN, and following extended weight restoration. Moreover, investigation into the co-occurrence of ANS function and cardiovascular risk is required.

Patients who complain of autonomic dysregulation: A cross-sectional study of patients with somatic symptom disorder

Background: Somatic symptom disorder (SSD) is common in medical settings but has been underdiagnosed. Stigma related to psychiatric illness was one of the barriers to making the diagnosis. More and more SSD patients who visited psychiatric clinics with physical complaints identify themselves as having ‘autonomic dysregulation’ in Taiwan. Aims: This study aimed to investigate the characteristics of patients with a subjective diagnosis of ‘autonomic dysregulation’. Method: We assessed the sociodemographic profile, medical/psychiatric diagnoses, subjective psychiatric diagnoses, perceived psychiatric stigma, help-seeking attitude, and healthcare utilization of 122 participants with SSD. Participants who identified themselves as having ‘autonomic dysregulation’ ( n = 84) were compared to those who did not (n=38). Results: Participants with a subjective diagnosis of ‘autonomic dysregulation’ were younger and had a higher education level than those who did not have such a subjective diagnosis. They also had higher scores on the Patient Health Questionnaire-15 (PHQ-15) and Health Anxiety Questionnaire (HAQ), whereas comorbid psychiatric diagnoses were similar in the two groups. Participants with and without a subjective diagnosis of ‘autonomic dysregulation’ did not have a significant difference in perceived psychiatric stigma and help-seeking attitude/behaviors. In a multiple logistic regression model, only age was associated with having a subjective diagnosis of ‘autonomic dysregulation’. Conclusion: Among SSD patients, those who identify themselves as having ‘autonomic dysregulation’ tend to have higher somatic distress and health anxiety than those who do not. ‘Autonomic dysregulation’ is not associated with perceived psychiatric stigma.

Autoimmune profiling suggests paraneoplastic etiology in pediatric ROHHAD

ROHHAD (Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation and Autonomic Dysregulation) is a rare, yet severe pediatric disorder resulting in hypothalamic dysfunction and frequent sudden death. Genetic and other investigations have failed to identify an etiology or diagnostic test. Frequent co-occurrence of neuroblastic tumors (NTs) and cerebrospinal fluid inflammation point to an autoimmune paraneoplastic neurological syndrome (PNS); however, specific anti-neural autoantibodies, a hallmark of PNS, have not been identified. Here, we screened antibodies from a curated cohort of ROHHAD patients (n=9) and controls (n=150) using a programmable phage display of the human peptidome (PhIP-Seq). Our ROHHAD cohort exhibited frequent association with NTs (8/9) and features consistent with autoimmune etiology. Autoantibodies to Zinc finger and SCAN domain-containing protein 1 (ZSCAN1) were discovered and orthogonally validated in 7 of 9 ROHHAD patients, all of whom had NTs, and shown to be absent in non-ROHHAD pediatric patients with NTs. Notably, human ZSCAN1 expression was confirmed in ROHHAD tumor and healthy human hypothalamus. Our results support the notion that tumor-associated ROHHAD is a pediatric PNS, potentially initiated by an immune response to peripheral NT. ZSCAN1 autoantibodies may aid in an accurate diagnosis of ROHHAD, thus providing a means toward early detection and treatment. Lastly, given the absence of the ZSCAN1 gene in rodents, our study highlights the value of human-based approaches in addition to the classical rodent-based approaches for detecting novel PNS subtypes.