IMPORTANCE: β-Adrenergic stimulation elicits heart palpitations and dyspnea, key features of acute anxiety and sympathetic arousal, yet no neuroimaging studies have examined how the pharmacologic ...modulation of interoceptive signals is associated with fear-related neurocircuitry in individuals with generalized anxiety disorder (GAD). OBJECTIVE: To examine the neural circuitry underlying autonomic arousal induced via isoproterenol, a rapidly acting, peripheral β-adrenergic agonist akin to adrenaline. DESIGN, SETTING, AND PARTICIPANTS: This crossover randomized clinical trial of 58 women with artifact-free data was conducted from January 1, 2017, to November 31, 2019, at the Laureate Institute for Brain Research in Tulsa, Oklahoma. EXPOSURES: Functional magnetic resonance imaging was used to assess neural responses during randomized intravenous bolus infusions of isoproterenol (0.5 and 2.0 μg) and saline, each administered twice in a double-blind fashion. MAIN OUTCOMES AND MEASURES: Blood oxygen level–dependent responses across the whole brain during isoproterenol administration in patients with GAD vs healthy comparators. Cardiac and respiratory responses, as well as interoceptive awareness and anxiety, were also measured during the infusion protocol. RESULTS: Of the 58 female study participants, 29 had GAD (mean SD age, 26.9 6.8 years) and 29 were matched healthy comparators (mean SD age, 24.4 5.0 years). During the 0.5-μg dose of isoproterenol, the GAD group exhibited higher heart rate responses (b = 5.34; 95% CI, 2.06-8.61; P = .002), higher intensity ratings of cardiorespiratory sensations (b = 8.38; 95% CI, 2.05-14.71; P = .01), higher levels of self-reported anxiety (b = 1.04; 95% CI, 0.33-1.76; P = .005), and significant hypoactivation in the ventromedial prefrontal cortex (vmPFC) that was evident throughout peak response (Cohen d = 1.55; P < .001) and early recovery (Cohen d = 1.52; P < .001) periods. Correlational analysis of physiological and subjective indexes and percentage of signal change extracted during the 0.5-μg dose revealed that vmPFC hypoactivation was inversely correlated with heart rate (r56 = −0.51, adjusted P = .001) and retrospective intensity of both heartbeat (r56 = −0.50, adjusted P = .002) and breathing (r56 = −0.44, adjusted P = .01) sensations. Ventromedial prefrontal cortex hypoactivation correlated inversely with continuous dial ratings at a trend level (r56 = −0.38, adjusted P = .051), whereas anxiety (r56 = −0.28, adjusted P = .27) and chronotropic dose 25 (r56 = −0.14, adjusted P = .72) showed no such association. CONCLUSIONS AND RELEVANCE: In this crossover randomized clinical trial, women with GAD exhibited autonomic hypersensitivity during low levels of adrenergic stimulation characterized by elevated heart rate, heightened interoceptive awareness, increased anxiety, and a blunted neural response localized to the vmPFC. These findings support the notion that autonomic hyperarousal may be associated with regulatory dysfunctions in the vmPFC, which could serve as a treatment target to help patients with GAD more appropriately appraise and regulate signals of sympathetic arousal.
Anorexia nervosa (AN) is characterized by low body weight, disturbed eating, body image disturbance, anxiety, and interoceptive dysfunction. However, the neural processes underlying these ...dysfunctions in AN are unclear. This investigation combined an interoceptive pharmacological probe, the peripheral β-adrenergic agonist isoproterenol, with resting-state functional magnetic resonance imaging to examine whether individuals with AN relative to healthy comparison participants show dysregulated neural coupling in central autonomic network brain regions.
Resting-state functional magnetic resonance imaging was performed in 23 weight-restored female participants with AN and 23 age- and body mass index–matched healthy comparison participants before and after receiving isoproterenol infusions. Whole-brain functional connectivity (FC) changes were examined using central autonomic network seeds in the amygdala, anterior insular cortex, posterior cingulate cortex, and ventromedial prefrontal cortex after performing physiological noise correction procedures.
Relative to healthy comparison participants, adrenergic stimulation caused widespread FC reductions in the AN group between central autonomic network regions and motor, premotor, frontal, parietal, and visual brain regions. Across both groups, these FC changes were inversely associated with trait anxiety (State-Trait Anxiety Inventory-Trait), trait depression (9-item Patient Health Questionnaire), and negative body image perception (Body Shape Questionnaire) measures, but not with changes in resting heart rate. These results were not accounted for by baseline group FC differences.
Weight-restored females with AN show a widespread state-dependent disruption of signaling between central autonomic, frontoparietal, and sensorimotor brain networks that facilitate interoceptive representation and visceromotor regulation. Additionally, trait associations between central autonomic network regions and these other brain networks suggest that dysfunctional processing of interoceptive signaling may contribute to affective and body image disturbance in AN.
Body image disturbance and anxiety are core features of anorexia nervosa (AN), a psychiatric disorder with one of the highest mortality rates. This study examined the efficacy of a novel ...non-pharmacological treatment, floatation-REST (Reduced Environmental Stimulation Therapy) on body image disturbance and anxiety in inpatients with AN.
This parallel group randomised controlled trial compared floatation-REST vs. care as usual in women and girls hospitalised for treatment of AN in Tulsa, Oklahoma, USA. Participants were randomised on a 2:1 ratio to receive eight, twice-weekly, 60-min floatation-REST sessions for 4 weeks, in addition to care as usual, or to receive care as usual. The primary outcome was the average change in body dissatisfaction from pre- to post-float as measured by the Photographic Figure Rating Scale. The secondary outcome was the average change in anxiety from pre- to post-float as measured by the state version of the State Trait Anxiety Inventory. Longitudinal effects of floatation-REST on body dissatisfaction were also examined. All analyses were conducted using the intention-to-treat principle. Planned linear mixed models tested the effect of floatation-REST vs. care as usual. The trial was preregistered (clinicaltrials.govNCT03610451).
Between March 16, 2018 and February 25, 2021, 133 participants were screened for eligibility, and 86 were consented. Eighteen were excluded after consent, for a final randomisation sample of 68 participants (45 floatation-REST; 23 care as usual). There were two session by condition interactions on body dissatisfaction (p = 0.00026) and state anxiety (p < 0.0001), such that the floatation-REST group exhibited acute (i.e., pre- to post-session) reductions in body dissatisfaction (floatation-REST group mean change (Δm) = −0.43; 95% CI −0.56 to −0.30, p < 0.0001, Cohen’s d = 0.23), and acute reductions in anxiety (floatation-REST group Δm = −15.75; 95% CI −17.95 to −13.56, p < 0.0001, Cohen’s d = 1.52); however, the care as usual group exhibited no significant changes. With regard to longitudinal results, there was a significant time by treatment interaction between baseline and immediately post intervention (p = 0.012) and baseline and six-month follow up (p = 0.0019). At immediately post intervention, there was a trending reduction in body dissatisfaction for the floatation-REST group (Δm = −0.41, 95% CI −0.86 to 0.03, p = 0.068) and care as usual group (Δm = 0.61; 95% CI −0.04 to 1.27, p = 0.070). At six-months post-intervention, the floatation-REST group exhibited lower body dissatisfaction (Δm = −0.91; 95% CI −1.37 to −0.45, p = 0.0020, Cohen’s d = 0.53) whereas the care as usual group reported no change in body dissatisfaction (Δm = 0.35; 95% CI −0.28 to 0.98, p = 0.96) relative to baseline. There were no adverse events related to the trial during the study.
Our findings suggest that Floatation-REST decreased body dissatisfaction compared to care as usual acutely after each float session and at six-month follow-up. Floatation-REST has potential utility for the treatment of body image disturbance and anxiety in AN. These results may be limited by some generalisability concerns given the recruitment of a modest sample receiving inpatient treatment at a single site.
The William K. Warren Foundation.
Anemia and cough are common problems with adolescent females. We present a case where these common symptoms led to the discovery of an uncommon entity, Goodpasture's Syndrome. The purpose of this ...report is to review the clinical manifestations, treatment and pathology of Goodpasture's Syndrome.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK