Brainstem response to hypercapnia: A symptom provocation study into the pathophysiology of panic disorder
Abstract
Background: The biological basis of uncued panic attacks is not yet understood. An important theory concerning the nature and cause of panic disorder is the ‘suffocation false alarm theory’. This alarm is supposed to be over-sensitive in panic disorder patients and can be triggered by CO 2 . No neurobiological substrate has been identified for such an alarm. The present study investigates differences in brain activation in panic patients, healthy individuals and experienced divers in response to CO 2 , representing three groups with descending sensitivity to CO 2 . Method: Brain activation was measured with functional magnetic resonance imaging. Subjects breathed through a mouthpiece delivering a continuous flow of 100% oxygen for two minutes, followed by a hypercapnic gas mixture (7% CO 2 ) for the next two minutes. Statistical analysis was performed using SPM8. Results: There was a significant main effect of group in response to the CO 2 . Patients show increased brainstem activation in response to hypercapnia compared to controls and divers. Subjective feelings of breathing discomfort were positively correlated with brain activation in the anterior insula in all groups. Conclusion: This is the first study showing that the behavioural response to CO 2 that characterises panic disorder patients is likely due to increased neural sensitivity to CO 2 at brainstem level.
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Studies of panic disorder specifically reported increased brainstem activation during CO2 reactivity tasks.
“Additionally, studies of PD specifically reported increased brainstem activation during CO2 reactivity tasks [44, 45].”
From Neural correlates of altered interoception in depressive and anxiety disorders: a systematic review and meta-analysis (2026) · cites this paper as [44]
Goossens et al. found increased activation in the brainstem in panic disorder patients compared with controls.
“Conversely, Goossens et al. found increased activation in the brainstem in PD patients compared to controls [44].”
From Neural correlates of altered interoception in depressive and anxiety disorders: a systematic review and meta-analysis (2026) · cites this paper as [44]
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“Conversely, Goossens et al. found increased activation in the brainstem in PD patients compared to controls [44].”
- Authors
- Goossens, L., Leibold, N., Peeters, R., Esquivel, G., Knuts, I., Backes, W., Marcelis, M., Hofman, P., Griez, E., & Schruers, K.
- Affiliations
- Maastricht University (NL)
- KU Leuven (BE)
- Maastricht University Medical Centre (NL)
- ORCID
- Venue
- Journal of Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 2014-03-19
- Volume
- 28
- Issue
- 5
- Pages
- 449-456
- ISSN
- 0269-8811 (ISSN-L)
- 1461-7285
- OpenAlex
- W2149143470
- Cited by
- 61
- References
- 47
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2023: 7 · 2022: 2 · 2021: 4 · 2020: 7 · 2019: 4 · 2018: 7 · 2017: 6 · 2016: 7 · 2015: 4 · 2014: 1
- FWCI
- 8.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
- Keywords
- panic disorder, hypercapnia, brainstem activation, CO2 sensitivity, breathing discomfort, anterior insula, divers, functional MRI
- MeSH terms
- Adult, Brain Stem, Carbon Dioxide, Female, Humans, Hypercapnia, Male, Respiration, Panic Disorder
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