Thursday, November 21, 2024
11/21/2024
There is a fundamental gap in our understanding of how chronic hyperventilation (HV), which is present in approximately half of anxious patients and is a significant barrier to treatment response, affects brain function and anxiety-related symptoms. This gap represents an important problem because, until it is filled, the field will not be able to precisely identify mechanistic targets for new treatment development. The long-term goal is to improve treatment efficacy for anxiety disorders by targeting specific biomarkers of illness and recovery, and by matching patients to specific interventions based on these biomarkers. The objective here is to examine differences in brain function between hypocapnic (hyperventilating) and normocapnic anxious patients, as well as healthy control subjects; and to determine the extent to which parameters of voluntary HV are similar to or different from the chronic and non-volitional HV seen in patients with anxiety disorders. The central hypothesis is that chronic, anxiety-related HV is associated with persistent changes in electrocortical activity, and that HV and its associated CNS sequelae lead to greater anxiety sensitivity and further HV in a vicious cycle. The rationale for the proposed research is that (a) current treatments, though effective, do not benefit half of the patients who receive them; (b) HV may be a critical reason for this nonresponse; and (c) by examining the relationship between anxiety, chronic HV, and CNS changes, and by determining the causal relationship between HV and indices of anxiety, we will be able to identify meaningful biological targets that would allow us, for the first time, to pursue clinical trials of anxious patients with assignment to different treatments based on the presence or absence of a particular transdiagnostic biomarker. The proposed pilot study will test this hypothesis by pursuing three specific aims: (1) to determine the relationship between baseline hypocapnia and physiologic, CNS, and self-report indices of HV and anxious responding in adults with anxiety disorders; (2) to examine the causal relationship between voluntary HV and physiologic, CNS, and self-report indices of HV and anxious responding in adults with and without anxiety disorders; and (3) to explore similarities and differences between the relationship between voluntary and chronic HV. Participants will be examined under conditions of normal breathing and voluntary HV. EEG and electrodermal activity will be used to measure CNS and physiologic indices of both HV and anxiety, allowing the examination of interactions between respiratory- and anxiety-related factors and thereby clarify effects that have thus far been confounded in research. The approach is innovative, because it uses multi-level analysis and will compare, for the first time, voluntary and naturally-occurring HV. The proposed research is significant, because it is expected to advance the field's understanding of the role of HV in chronic anxiety, will help clarify why hypocapnic patients respond less well to treatment, and will generate targets for novel treatment development.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
