Inhalation of 7.5% Carbon Dioxide Increases Threat Processing in Humans

Overview

Journal Neuropsychopharmacology

Date 2011 Apr 15

PMID 21490591

Citations 28

Authors

Matthew Garner

Angela Attwood

David S Baldwin

Alexandra James

Marcus R Munafo

Affiliations

Soon will be listed here.

Abstract

Inhalation of 7.5% CO(2) increases anxiety and autonomic arousal in humans, and elicits fear behavior in animals. However, it is not known whether CO(2) challenge in humans induces dysfunction in neurocognitive processes that characterize generalized anxiety, notably selective attention to environmental threat. Healthy volunteers completed an emotional antisaccade task in which they looked toward or away from (inhibited) negative and neutral stimuli during inhalation of 7.5% CO(2) and air. CO(2) inhalation increased anxiety, autonomic arousal, and erroneous eye movements toward threat on antisaccade trials. Autonomic response to CO(2) correlated with hypervigilance to threat (speed to initiate prosaccades) and reduced threat inhibition (increased orienting toward and slower orienting away from threat on antisaccade trials) independent of change in mood. Findings extend evidence that CO(2) triggers fear behavior in animals via direct innervation of a distributed fear network that mobilizes the detection of and allocation of processing resources toward environmental threat in humans.

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References

Stein M, Simmons A, Feinstein J, Paulus M . Increased amygdala and insula activation during emotion processing in anxiety-prone subjects. Am J Psychiatry. 2007; 164(2):318-27. DOI: 10.1176/ajp.2007.164.2.318. View

Sheehan D, Lecrubier Y, Sheehan K, Amorim P, Janavs J, Weiller E . The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1999; 59 Suppl 20:22-33;quiz 34-57. View

den Hout M, Griez E . Panic symptoms after inhalation of carbon dioxide. Br J Psychiatry. 1984; 144:503-7. DOI: 10.1192/bjp.144.5.503. View

Davis M, Whalen P . The amygdala: vigilance and emotion. Mol Psychiatry. 2001; 6(1):13-34. DOI: 10.1038/sj.mp.4000812. View

WATSON D, Clark L, Tellegen A . Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol. 1988; 54(6):1063-70. DOI: 10.1037//0022-3514.54.6.1063. View

Taylor S, Cox B . An expanded anxiety sensitivity index: evidence for a hierarchic structure in a clinical sample. J Anxiety Disord. 1998; 12(5):463-83. DOI: 10.1016/s0887-6185(98)00028-0. View

Bishop S . Neurocognitive mechanisms of anxiety: an integrative account. Trends Cogn Sci. 2007; 11(7):307-16. DOI: 10.1016/j.tics.2007.05.008. View

Monk C, Telzer E, Mogg K, Bradley B, Mai X, Louro H . Amygdala and ventrolateral prefrontal cortex activation to masked angry faces in children and adolescents with generalized anxiety disorder. Arch Gen Psychiatry. 2008; 65(5):568-76. PMC: 2443697. DOI: 10.1001/archpsyc.65.5.568. View

Ansari T, Derakshan N, Richards A . Effects of anxiety on task switching: evidence from the mixed antisaccade task. Cogn Affect Behav Neurosci. 2008; 8(3):229-38. DOI: 10.3758/cabn.8.3.229. View

10.

Bailey J, Kendrick A, Diaper A, Potokar J, Nutt D . A validation of the 7.5% CO2 model of GAD using paroxetine and lorazepam in healthy volunteers. J Psychopharmacol. 2006; 21(1):42-9. DOI: 10.1177/0269881106063889. View

11.

Colasanti A, Salamon E, Schruers K, van Diest R, van Duinen M, Griez E . Carbon dioxide-induced emotion and respiratory symptoms in healthy volunteers. Neuropsychopharmacology. 2008; 33(13):3103-10. DOI: 10.1038/npp.2008.31. View

12.

Poma S, Milleri S, Squassante L, Nucci G, Bani M, Perini G . Characterization of a 7% carbon dioxide (CO2) inhalation paradigm to evoke anxiety symptoms in healthy subjects. J Psychopharmacol. 2005; 19(5):494-503. DOI: 10.1177/0269881105056533. View

13.

Mogg K, Millar N, Bradley B . Biases in eye movements to threatening facial expressions in generalized anxiety disorder and depressive disorder. J Abnorm Psychol. 2001; 109(4):695-704. DOI: 10.1037//0021-843x.109.4.695. View

14.

Ettinger U, Ffytche D, Kumari V, Kathmann N, Reuter B, Zelaya F . Decomposing the neural correlates of antisaccade eye movements using event-related FMRI. Cereb Cortex. 2007; 18(5):1148-59. DOI: 10.1093/cercor/bhm147. View

15.

Browning M, Holmes E, Murphy S, Goodwin G, Harmer C . Lateral prefrontal cortex mediates the cognitive modification of attentional bias. Biol Psychiatry. 2009; 67(10):919-25. PMC: 2866253. DOI: 10.1016/j.biopsych.2009.10.031. View

16.

Paulus M, Stein M . An insular view of anxiety. Biol Psychiatry. 2006; 60(4):383-7. DOI: 10.1016/j.biopsych.2006.03.042. View

17.

Pineda J, Aghajanian G . Carbon dioxide regulates the tonic activity of locus coeruleus neurons by modulating a proton- and polyamine-sensitive inward rectifier potassium current. Neuroscience. 1997; 77(3):723-43. DOI: 10.1016/s0306-4522(96)00485-x. View

18.

Bailey J, Argyropoulos S, Lightman S, Nutt D . Does the brain noradrenaline network mediate the effects of the CO2 challenge?. J Psychopharmacol. 2003; 17(3):252-9. DOI: 10.1177/02698811030173002. View

19.

Grefkes C, Wang L, Eickhoff S, Fink G . Noradrenergic modulation of cortical networks engaged in visuomotor processing. Cereb Cortex. 2009; 20(4):783-97. DOI: 10.1093/cercor/bhp144. View

20.

Bailey J, Nutt D . GABA-A receptors and the response to CO(2) inhalation - a translational trans-species model of anxiety?. Pharmacol Biochem Behav. 2008; 90(1):51-7. DOI: 10.1016/j.pbb.2008.04.002. View