It has been known since at least the 1920’s that inhaling high amounts of CO2 (20%) induces panic attacks in healthy individuals. There is a remarkable literature deriving from diving and respiratory physiology in submariners available treating this topic. The great father and son team [John Scott Haldane (the physiologist and polymath) and J. B. S. Haldane (the physiologist, geneticist, evolutionary biologist, biomathematician and wit)] contributed many papers examining the effects of such CO2 inhalation (e.g., e.g.). Those involved in the drafting of Torture Memos cite waterboarding as causing elevations in blood carbon dioxide levels (hypercapnia; see this and this for a further discussion). Panic disorder patients show panic response to even small doses of CO2 inhalation. Patients with anxiety disorders or a family history of anxiety disorder are also more susceptible to show panic response to CO2 inhalation. Inhaling hypercapnic gases, such as various concentrations of CO2, has been hypothesized to trigger a biological alarm system that has evolved to serve as a suffocation monitor. Earlier studies have tried to infer the neural circuit involved in this panic response. The hippocampus, amygdala and cortex have all been hypothesized to play a vital role in CO2-induced panic response. Here, we examine the interaction between the induction of prior chronic stress and the panic response induced by breath differing concentrations of CO2. [Download the paper]
Chronic immobilization stress occludes in vivo cortical activation in an animal model of panic induced by carbon dioxide inhalation*
Mohammed Mostafizur Rahman, Christian M. Kerskens, Sumantra Chattarji and Shane M. O‘Mara
Breathing high concentrations of carbon dioxide (CO2) can trigger panic and anxiety in humans. CO2 inhalation has been hypothesized to activate neural systems similar to those underlying fear learning, especially those involving the amygdala. Amygdala activity is also upregulated by stress. Recently, however, a separate pathway has been proposed for interoceptive panic and anxiety signals, as patients exhibited CO2-inhalation induced panic responses despite bilateral lesions of the amygdala. This paradoxical observation has raised the possibility that cortical circuits may underlie these responses. We sought to examine these divergent models by comparing in vivo brain activation in unstressed and chronically-stressed rats breathing CO2. Regional cerebral blood flow measurements using functional Magnetic Resonance Imaging (fMRI) in lightly-anaesthetized rats showed especially strong activation of the somatosensory cortex by CO2 inhalation in the unstressed group. Strikingly, prior exposure to chronic stress occluded this effect on cortical activity. This lends support to recent clinical observations and highlights the importance of looking beyond the traditional focus on limbic structures, such as the hippocampus and amygdala, to investigate a role for cortical areas in panic and anxiety in humans.
*I am delighted to have conducted this work in collaboration with my colleagues at the National Centre for Biological Sciences (NCBS), Bangalore (Shona Chatterji and his PhD student Mohammed Mostafizur Rahmen). Our collaboration was supported by a Science Foundation Ireland – Short-Term Travel Fellowship.