Dataset Information

Preliminary evidence for a role of the adrenergic nervous system in generalized anxiety disorder.

ABSTRACT: Generalized anxiety disorder (GAD) is a common chronic condition that is understudied compared to other psychiatric disorders. An altered adrenergic function has been reported in GAD, however direct evidence for genetic susceptibility is missing. This study evaluated the associations of gene variants in adrenergic receptors (ADRs) with GAD, with the involvement of stressful events. Data were obtained from 844 French community-dwelling elderly aged 65 or over. Anxiety disorders were assessed using the Mini-International Neuropsychiatry Interview, according to DSM-IV criteria. Eight single-nucleotide polymorphisms (SNPs) involved with adrenergic function were genotyped; adrenergic receptors alpha(1A) (ADRA1A), alpha(2A) (ADRA2A), and beta2 (ADRB2) and transcription factor TCF7L2. Questionnaires evaluated recent stressful life events as well as early environment during childhood and adolescence. Using multivariate logistic regression analyses four SNPs were significantly associated with GAD. A 4-fold modified risk was found with ADRA1A rs17426222 and rs573514, and ADRB2 rs1042713 which remained significant after Bonferroni correction. Certain variants may moderate the effect of adverse life events on the risk of GAD. Replication in larger samples is needed due to the small case number. This is the first study showing that ADR variants are susceptibility factors for GAD, further highlighting the critical role of the adrenergic nervous system in this disorder.

SUBMITTER: Zhang X

PROVIDER: S-EPMC5309880 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Preliminary evidence for a role of the adrenergic nervous system in generalized anxiety disorder.

Zhang Xiaobin X Norton Joanna J Carrière Isabelle I Ritchie Karen K Chaudieu Isabelle I Ryan Joanne J Ancelin Marie-Laure ML

Scientific reports 20170215

Generalized anxiety disorder (GAD) is a common chronic condition that is understudied compared to other psychiatric disorders. An altered adrenergic function has been reported in GAD, however direct evidence for genetic susceptibility is missing. This study evaluated the associations of gene variants in adrenergic receptors (ADRs) with GAD, with the involvement of stressful events. Data were obtained from 844 French community-dwelling elderly aged 65 or over. Anxiety disorders were assessed usin ...[more]

PMID: 28198454

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Project description:Hyperarousal symptoms in generalized anxiety disorder (GAD) are often incongruent with the observed physiological state, suggesting that abnormal processing of interoceptive signals is a characteristic feature of the disorder. To examine the neural mechanisms underlying interoceptive dysfunction in GAD, we evaluated whether adrenergic modulation of cardiovascular signaling differentially affects the heartbeat evoked potential (HEP), an electrophysiological marker of cardiac interoception, during concurrent electroencephalogram and functional magnetic resonance imaging (EEG-fMRI) scanning. Intravenous infusions of the peripheral adrenergic agonist isoproterenol (0.5 and 2.0 micrograms, μg) were administered in a randomized, double-blinded and placebo-controlled fashion to dynamically perturb the cardiovascular system while recording the associated EEG-fMRI responses. During the 0.5 μg isoproterenol infusion, the GAD group (n=24) exhibited significantly larger changes in HEP amplitude in an opposite direction than the HC group (n=24). In addition, the GAD group showed significantly larger absolute HEP amplitudes than HC during saline infusions, when cardiovascular tone did not increase. No significant group differences in HEP amplitude were identified during the 2.0 μg isoproterenol infusion. Using analyzable blood oxygenation level dependent fMRI data from participants with concurrent EEG-fMRI data (21 GAD and 21 HC), we found that the aforementioned HEP effects were uncorrelated with fMRI signals in the insula, ventromedial prefrontal cortex, dorsal anterior cingulate cortex, amygdala, and somatosensory cortex, brain regions implicated in cardiac signal processing according to prior fMRI studies. These findings provide additional evidence of dysfunctional cardiac interoception in GAD and identify neural processes at the electrophysiological level that may be independent from blood oxygen level-dependent responses during peripheral adrenergic stimulation.

Project description:OBJECTIVE:Accurate and prospective assessments of treatment-emergent suicidal thoughts and behaviors are essential to both clinical care and randomized clinical trials. The Sheehan Suicidality Tracking Scale is a prospective, patient self-report or clinician-administered rating scale that tracks both treatment-emergent suicidal ideation and behaviors. The Sheehan Suicidality Tracking Scale was incorporated into a multicenter, randomized, double-blind, placebo-controlled, and active comparator study examining the efficacy of an experimental corticotropin-releasing factor antagonist (BMS-562086) for the treatment of generalized anxiety disorder. METHOD:The Sheehan Suicidality Tracking Scale was administered to subjects at baseline, Week 2, Week 4, and Week 8 or early termination. Subjects completed theSheehan Suicidality Tracking Scale by self report. The Sheehan Suicidality Tracking Scale was designated as an exploratory outcome measure in the study protocol, and post-hoc analyses were performed to examine the performance of the Sheehan Suicidality Tracking Scale. RESULTS:A total of 82 subjects completed the Sheehan Suicidality Tracking Scale during the course of the study. Altogether, these subjects provided 297 completed Sheehan Suicidality Tracking Scale ratings across the study time points. Sixty-one subjects (n=25 placebo, n=24 BMS-562086, and n=12 escitalopram) had a baseline and at least one post-baseline Sheehan Suicidality Tracking Scale measurement. The mean change from baseline at Week 8 in the Sheehan Suicidality Tracking Scale total score was -0.10, -0.02, and -0.06 for escitalopram, placebo, and BMS-562086 groups, respectively. The sensitivity of the Sheehan Suicidality Tracking Scale and HAM-D Item #3 (suicide) for identifying subjects with suicidal thoughts or behaviors was 100 percent and 63 percent, respectively. CONCLUSIONS:The Sheehan Suicidality Tracking Scale may be a sensitive psychometric tool to prospectively assess for treatment-emergent suicidal thoughts and behaviors. Despite the small sample size and low occurrence of suicidal ideation during the course of this clinical trial, the self-reported Sheehan Suicidality Tracking Scale demonstrated increased sensitivity over the rater administered HAM-D Item #3 in identifying suicide related ideations and behaviors. Further research in larger study samples as well as in other psychiatric disorders are needed.

Dataset Information

Preliminary evidence for a role of the adrenergic nervous system in generalized anxiety disorder.

Publications

Preliminary evidence for a role of the adrenergic nervous system in generalized anxiety disorder.

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