The 35% carbon dioxide (CO2) challenge is a well-established model of panic. This study aimed to investigate 35% CO2 sensitivity in patients with social anxiety disorder (SAD) compared with patients with panic disorder (PD) and normal controls. First, a 35% CO2 challenge was conducted including 16 patients with generalized SAD, 16 with PD and 16 normal subjects. Outcome was assessed by a Visual Analogue Scale for Fear (VAS-F) and the Panic Symptom List (PSL). Second, meta-analyses of fear and panic scores were performed, including data from the present experiment and from previous 35% CO2 challenge studies in patients with SAD. The present 35% CO2 challenge found equal increases in VAS-F and PSL in patients with SAD compared with normal controls, whereas the CO2 response in patients with PD was significantly stronger than in controls. The meta-analyses confirmed the experimental data from this study, and in addition showed an intermediate panic rate in SAD patients, in between that of normal controls and patients with PD. In conclusion, neither our experiment nor the meta-analyses found evidence for a similarly exaggerated 35% CO2 sensitivity in SAD and PD, suggesting that the pathogenesis of SAD is different from PD, although patients with SAD may be slightly more sensitive than non-anxious controls.
American Psychiatric Association (2000) Diagnostic and Statistical Manual of Mental Disorders. Fourth edition, text revised. Washington, DC: American Psychiatric Association.
2.
AndersonERHopeDA (2009) The relationship among social phobia, objective and perceived physiological reactivity, and anxiety sensitivity in an adolescent population. J Anxiety Disord23: 18–26.
3.
BlechertJWilhelmFHMeuretAE. (2010) Respiratory, autonomic, and experiential responses to repeated inhalations of 20% CO(2) enriched air in panic disorder, social phobia, and healthy controls. Biol Psychol84: 8.
4.
CaldirolaDPernaGArancioC. (1997) The 35% CO2 challenge test in patients with social phobia. Psychiatry Res71: 41–48.
5.
ClarkDMWellsA (1995) A cognitive model of social phobia. In: HeimbergRGLiebowitzMRHopeDA. (eds) Social phobia: Diagnosis, assessment, and treatment. New York: Guilford Press, 41–68.
6.
ColasantiASalamonESchruersK. (2008) Carbon dioxide-induced emotion and respiratory symptoms in healthy volunteers. Neuropsychopharmacology33: 3103–3110.
7.
CraskeMG (1991) Phobic fear and panic attacks: the same emotional states triggered by different cues?Clin Psychol Rev11: 22.
8.
CraskeMGSipsasA (1992) Animal phobias versus claustrophobias: exteroceptive versus interoceptive cues. Behav Res Ther30: 569–581.
9.
DillonDJGormanJMLiebowitzMR. (1987) Measurement of lactate-induced panic and anxiety. Psychiatry Res20: 97–105.
10.
EsquivelGSchruersKRMaddockRJ. (2010) Acids in the brain: a factor in panic?J Psychopharmacol24: 639–647.
11.
FreireRCLopesFLValencaAM. (2008) Panic disorder respiratory subtype: a comparison between responses to hyperventilation and CO2 challenge tests. Psychiatry Res157: 307–310.
12.
FreireRCPernaGNardiAE (2010) Panic disorder respiratory subtype: psychopathology, laboratory challenge tests, and response to treatment. Harv Rev Psychiatry18: 220–229.
13.
FyerMRUyJMartinezJ. (1987) CO2 challenge of patients with panic disorder. Am J Psychiatry144: 1080–1082.
14.
GelernterCSSteinMBTancerME. (1992) An examination of syndromal validity and diagnostic subtypes in social phobia and panic disorder. J Clin Psychiatry53: 23–27.
15.
GibbonsRDHedekerDRDavisJM (1993) Estimation of effect size from a series of experiments involving paired comparisons. J Educ Stat18: 271–279.
16.
GormanJMPappLAMartinezJ. (1990) High-dose carbon dioxide challenge test in anxiety disorder patients. Biol Psychiatry28: 743–757.
17.
GraeffFGDel-BenCM (2008) Neurobiology of panic disorder: from animal models to brain neuroimaging. Neurosci Biobehav Rev32: 1326–1335.
18.
GriezEde LoofCPolsH. (1990) Specific sensitivity of patients with panic attacks to carbon dioxide inhalation. Psychiatry Res31: 193–199.
19.
GriezESchruersK (1998) Experimental pathophysiology of panic. J Psychosom Res45: 493–503.
20.
GriezESchruersK (2003) Mechanisms of CO2 challenges. J Psychopharmacol17: 260–262; discussion 267–268.
GriezEJLousbergHvan den HoutMA. (1987) CO2 vulnerability in panic disorder. Psychiatry Res20: 87–95.
23.
HeimbergRGHopeDADodgeCS. (1990) DSM-III-R subtypes of social phobia. Comparison of generalized social phobics and public speaking phobics. J Nerv Ment Dis178: 172–179.
24.
HodgesMRRichersonGB (2010) Medullary serotonin neurons and their roles in central respiratory chemoreception. Respir Physiol Neurobiol173: 256–263.
25.
HofmannSGNewmanMGEhlersA. (1995) Psychophysiological differences between subgroups of social phobia. J Abnorm Psychol104: 224–231.
26.
HoltPEAndrewsG (1989a) Hyperventilation and anxiety in panic disorder, social phobia, GAD and normal controls. Behav Res Ther27: 453–460.
27.
HoltPEAndrewsG (1989b) Provocation of panic: three elements of the panic reaction in four anxiety disorders. Behav Res Ther27: 253–261.
28.
LeDouxJE (2000) Emotion circuits in the brain. Annu Rev Neurosci23: 155–184.
29.
MarenS (2009) An acid-sensing channel sows fear and panic. Cell139: 867–869.
30.
MarksIMMathewsAM (1979) Brief standard self-rating for phobic patients. Behav Res Ther17: 263–267.
31.
McTeagueLMLangPJLaplanteMC. (2009) Fearful imagery in social phobia: generalization, comorbidity, and physiological reactivity. Biol Psychiatry65: 374–382.
32.
PappLAKleinDFMartinezJ. (1993) Diagnostic and substance specificity of carbon-dioxide-induced panic. Am J Psychiatry150: 250–257.
33.
PernaGBertaniAArancioC. (1995a) Laboratory response of patients with panic and obsessive-compulsive disorders to 35% CO2 challenges. Am J Psychiatry152: 85–89.
34.
PernaGGabrieleACaldirolaD. (1995b) Hypersensitivity to inhalation of carbon dioxide and panic attacks. Psychiatry Res57: 267–273.
35.
PolsHVerburgKHauzerR. (1996) Alprazolam premedication and 35% carbon dioxide vulnerability in panic patients. Biol Psychiatry40: 913–917.
36.
RapeeRMBrownTAAntonyMM. (1992) Response to hyperventilation and inhalation of 5.5% carbon dioxide-enriched air across the DSM-III-R anxiety disorders. J Abnorm Psychol101: 538–552.
37.
RassovskyYKushnerMG (2003) Carbon dioxide in the study of panic disorder: issues of definition, methodology, and outcome. J Anxiety Disord17: 1–32.
38.
ReedVWittchenHU (1998) DSM-IV panic attacks and panic disorder in a community sample of adolescents and young adults: how specific are panic attacks?J Psychiatr Res32: 335–345.
39.
RichersonGB (2004) Serotonergic neurons as carbon dioxide sensors that maintain pH homeostasis. Nat Rev Neurosci5: 449–461.
40.
SalantiGHigginsJPAdesAE. (2008) Evaluation of networks of randomized trials. Stat Methods Med Res17: 279–301.
41.
SchruersKEsquivelGvan DuinenM. (2011) Genetic moderation of CO2-induced fear by 5-HTTLPR genotype. J Psychopharmacol25: 37–42.
42.
SchruersKKlaassenTPolsH. (2000) Effects of tryptophan depletion on carbon dioxide provoked panic in panic disorder patients. Psychiatry Res93: 179–187.
43.
SheehanDVLecrubierYSheehanKH. (1998) 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 Psychiatry59Suppl 20: 22–33;quiz 34–57.
44.
SpectorIPPecknoldJCLibmanE (2003) Selective attentional bias related to the noticeability aspect of anxiety symptoms in generalized social phobia. J Anxiety Disord17: 517–531.
45.
SpielbergerCD (1983) Manual for the State-Trait Anxiety Inventory. Palo Alto, CA: Consulting Psychologists Press.
46.
van DuinenMRickeltJGriezE (2008) Validation of the electronic Visual Analogue Scale of Anxiety. Prog Neuropsychopharmacol Biol Psychiatry32: 1045–1047.
47.
VerburgCGriezEMeijerJ (1994) A 35% carbon dioxide challenge in simple phobias. Acta Psychiatr Scand90: 420–423.
48.
ZiemannAEAllenJEDahdalehNS. (2009) The amygdala is a chemosensor that detects carbon dioxide and acidosis to elicit fear behavior. Cell139: 1012–1021.
