Brain Functional Connectivity Correlates of Response in the 7.5% CO2 Inhalational Model of Generalized Anxiety Disorder: A Pilot Study

Overview

Journal Int J Neuropsychopharmacol

Publisher Oxford University Press

Specialty Psychiatry

Date 2020 Mar 15

PMID 32170303

Citations 4

Authors

Nathan T M Huneke

M John Broulidakis

Angela Darekar

David S Baldwin

Matthew Garner

Affiliations

Soon will be listed here.

Abstract

Background: The 7.5% CO2 inhalational model can be used to explore potential treatments for generalized anxiety disorder. However, it is unknown how inter-individual variability in the functional architecture of negative affective valence systems might relate to anxiogenic response in this model.

Methods: A total of 13 healthy volunteers underwent functional magnetic resonance imaging during a passive emotional face perception task. We explored task-evoked functional connectivity in the potential threat system through generalized psychophysiological interaction analysis. Within 7 days, these participants underwent prolonged 7.5% CO2 inhalation, and results from the generalized psychophysiological interaction analysis were correlated with CO2 outcome measures.

Results: Functional connectivity between ventromedial prefrontal cortex and right amygdala positively correlated with heart rate and subjective anxiety, while connectivity between midcingulate cortex and left amygdala negatively correlated with anxiety during CO2 challenge.

Conclusions: Response to CO2 challenge correlated with task-evoked functional connectivity in the potential threat system. Further studies should assess whether this translates into clinical populations.

Citing Articles

Characterising the anxiogenic network from functional connectivity analysis of the CO challenge model.

Graham D, Mathew S, Marsden J, Smith A, Smerdon G, Hall S Sci Rep. 2024; 14(1):29294.

PMID: 39592811 PMC: 11599608. DOI: 10.1038/s41598-024-80901-5.

Placebo Effects Are Small on Average in the 7.5% CO2 Inhalational Model of Generalized Anxiety.

Huneke N, Cross C, Fagan H, Molteni L, Phillips N, Garner M Int J Neuropsychopharmacol. 2024; 27(4).

PMID: 38577951 PMC: 11059817. DOI: 10.1093/ijnp/pyae019.

The impact of anxiety on postural control: CO challenge model.

Taylor A, Low D, Walsh G, Holt N Psychophysiology. 2022; 60(3):e14192.

PMID: 36200605 PMC: 10078562. DOI: 10.1111/psyp.14192.

The Association Between Adolescent Residential Mobility and Adult Social Anxiety, BDNF and Amygdala-Orbitofrontal Functional Connectivity in Young Adults With Higher Education.

Hasler G, Haynes M, Muller S, Tuura R, Ritter C, Buchmann A Front Psychiatry. 2021; 11:561464.

PMID: 33408651 PMC: 7779475. DOI: 10.3389/fpsyt.2020.561464.

References

Spitzer R, Kroenke K, Williams J, Lowe B . A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006; 166(10):1092-7. DOI: 10.1001/archinte.166.10.1092. View

Damasio A, Tranel D, Damasio H . Individuals with sociopathic behavior caused by frontal damage fail to respond autonomically to social stimuli. Behav Brain Res. 1990; 41(2):81-94. DOI: 10.1016/0166-4328(90)90144-4. View

Schneider S, Peters J, Bromberg U, Brassen S, Menz M, Miedl S . Boys do it the right way: sex-dependent amygdala lateralization during face processing in adolescents. Neuroimage. 2011; 56(3):1847-53. DOI: 10.1016/j.neuroimage.2011.02.019. View

Simpson Jr J, Drevets W, Snyder A, Gusnard D, Raichle M . Emotion-induced changes in human medial prefrontal cortex: II. During anticipatory anxiety. Proc Natl Acad Sci U S A. 2001; 98(2):688-93. PMC: 14649. DOI: 10.1073/pnas.98.2.688. View

Grosbras M, Paus T . Brain networks involved in viewing angry hands or faces. Cereb Cortex. 2005; 16(8):1087-96. DOI: 10.1093/cercor/bhj050. View

Ainsworth B, Marshall J, Meron D, Baldwin D, Chadwick P, Munafo M . Evaluating psychological interventions in a novel experimental human model of anxiety. J Psychiatr Res. 2015; 63:117-22. PMC: 4406751. DOI: 10.1016/j.jpsychires.2015.02.001. View

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

WATSON D . Intraindividual and interindividual analyses of positive and negative affect: their relation to health complaints, perceived stress, and daily activities. J Pers Soc Psychol. 1988; 54(6):1020-30. DOI: 10.1037//0022-3514.54.6.1020. View

Prater K, Hosanagar A, Klumpp H, Angstadt M, Phan K . Aberrant amygdala-frontal cortex connectivity during perception of fearful faces and at rest in generalized social anxiety disorder. Depress Anxiety. 2012; 30(3):234-41. PMC: 3987867. DOI: 10.1002/da.22014. View

10.

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

11.

Mochcovitch M, Freire R, Garcia R, Nardi A . A systematic review of fMRI studies in generalized anxiety disorder: evaluating its neural and cognitive basis. J Affect Disord. 2014; 167:336-42. DOI: 10.1016/j.jad.2014.06.041. View

12.

Kienast T, Hariri A, Schlagenhauf F, Wrase J, Sterzer P, Buchholz H . Dopamine in amygdala gates limbic processing of aversive stimuli in humans. Nat Neurosci. 2008; 11(12):1381-2. DOI: 10.1038/nn.2222. View

13.

Rabany L, Diefenbach G, Bragdon L, Pittman B, Zertuche L, Tolin D . Resting-State Functional Connectivity in Generalized Anxiety Disorder and Social Anxiety Disorder: Evidence for a Dimensional Approach. Brain Connect. 2017; 7(5):289-298. DOI: 10.1089/brain.2017.0497. View

14.

Garner M, Attwood A, Baldwin D, James A, Munafo M . Inhalation of 7.5% carbon dioxide increases threat processing in humans. Neuropsychopharmacology. 2011; 36(8):1557-62. PMC: 3138667. DOI: 10.1038/npp.2011.15. View

15.

Vogt B . Submodalities of emotion in the context of cingulate subregions. Cortex. 2014; 59:197-202. DOI: 10.1016/j.cortex.2014.04.002. View

16.

Olatunji B, Wolitzky-Taylor K, Babson K, Feldner M . Anxiety sensitivity and CO2 challenge anxiety during recovery: differential correspondence of arousal and perceived control. J Anxiety Disord. 2008; 23(4):420-8. DOI: 10.1016/j.janxdis.2008.08.006. View

17.

Fluharty M, Attwood A, Munafo M . Anxiety sensitivity and trait anxiety are associated with response to 7.5% carbon dioxide challenge. J Psychopharmacol. 2015; 30(2):182-7. PMC: 4724859. DOI: 10.1177/0269881115615105. View

18.

Keogh E, Dillon C, Georgiou G, Hunt C . Selective attentional biases for physical threat in physical anxiety sensitivity. J Anxiety Disord. 2001; 15(4):299-315. DOI: 10.1016/s0887-6185(01)00065-2. View

19.

Goossens L, Leibold N, Peeters R, Esquivel G, Knuts I, Backes W . Brainstem response to hypercapnia: a symptom provocation study into the pathophysiology of panic disorder. J Psychopharmacol. 2014; 28(5):449-56. DOI: 10.1177/0269881114527363. View

20.

Rao H, Di X, Chan R, Ding Y, Ye B, Gao D . A regulation role of the prefrontal cortex in the fist-edge-palm task: evidence from functional connectivity analysis. Neuroimage. 2008; 41(4):1345-51. DOI: 10.1016/j.neuroimage.2008.04.026. View