Panic induced by carbon dioxide inhalation and lack of hypothalamic–pituitary–adrenal axis activation

Sinha, Smit S.; Coplan, Jeremy D.; Gorman, Jack M.; Pine, Daniel S.; Martinez, Jose; Klein, Donald F.

doi:10.1016/s0165-1781(99)00029-3

Cited by 67 publications

(43 citation statements)

References 26 publications

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“…It has been shown that inhalation of low concentrations of CO 2 (5% or 7%) do not significantly increase cortisol release in panic disorder patients or normal controls, suggesting that this panicogenic agent does not activate the HPA axis. (41) However, there is evidence that inhalation of 35% CO 2 increases cortisol release in normal subjects. (42) Another hypothesis to explain the link between respiration and the HPA axis is that the HPA axis and respiratory control systems are both reactive to contextual cues such as novelty or anticipation of future challenge.…”

Section: Pharmacologic Implicationsmentioning

confidence: 99%

Respiratory manifestations of panic disorder: causes, consequences and therapeutic implications

et al. 2009

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Multiple respiratory abnormalities can be found in anxiety disorders, especially in panic disorder (PD). Individuals with PD experience unexpected panic attacks, characterized by anxiety and fear, resulting in a number of autonomic and respiratory symptoms. Respiratory stimulation is a common event during panic attacks. The respiratory abnormality most often reported in PD patients is increased CO 2 sensitivity, which has given rise to the hypothesis of fundamental abnormalities in the physiological mechanisms that control breathing in PD. There is evidence that PD patients with dominant respiratory symptoms are more sensitive to respiratory tests than are those who do not manifest such symptoms, and that the former group constitutes a distinct subtype. Patients with PD tend to hyperventilate and to panic in response to respiratory stimulants such as CO 2 , triggering the activation of a hypersensitive fear network. Although respiratory physiology seems to remain normal in these subjects, recent evidence supports the idea that they present subclinical abnormalities in respiration and in other functions related to body homeostasis. The fear network, composed of the hippocampus, the medial prefrontal cortex, the amygdala and its brain stem projections, might be oversensitive in PD patients. This theory might explain why medication and cognitive-behavioral therapy are both clearly effective. Our aim was to review the relationship between respiration and PD, addressing the respiratory subtype of PD and the hyperventilation syndrome, with a focus on respiratory challenge tests, as well as on the current mechanistic concepts and the pharmacological implications of this relationship.Keywords: Panic disorder; Anxiety; Respiration; Hyperventilation; Carbon dioxide. ResumoMúltiplas anormalidades respiratórias podem ser encontradas em pacientes com transtornos de ansiedade, particularmente no transtorno de pânico (TP). Indivíduos com TP experimentam ataques de pânico inesperados, caracterizados por ansiedade, medo e diversos sintomas autonômicos e respiratórios. A estimulação respiratória é um fenômeno comum durante os ataques de pânico. A anormalidade respiratória mais citada em pacientes com TP é a sensibilidade aumentada para o CO 2 , que originou a hipótese de uma disfunção fundamental nos mecanismos fisiológicos de controle da respiração no TP. Há evidências de que pacientes com TP com sintomas respiratórios predominantes são mais sensíveis a testes respiratórios do que aqueles sem a manifestação de tais sintomas, representando um subtipo distinto. Pacientes com TP tendem a hiperventilar e a reagir com pânico como resposta a estimulantes respiratórios como o CO 2 , gerando uma ativação de um circuito de medo hipersensível. Apesar de a fisiologia respiratória desses pacientes permanecer normal, algumas evidências recentes apontam a presença de disfunções subclínicas na respiração e em outras funções relacionadas à homeostase corporal. O circuito do medo, composto pelo hipocampo, córtex pré-frontal medial, amígd...

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Section: Pharmacologic Implicationsmentioning

confidence: 99%

Respiratory manifestations of panic disorder: causes, consequences and therapeutic implications

et al. 2009

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“…No or inconsistent cortisol response with laboratoryinduced panic attacks Charney et al, 1985 (caffeine); Liebowitz et al, 1985;Levin et al, 1987;Seier et al, 1997;Peskind et al, 1998 (lactate); Sinha et al, 1999;van Duinen et al, 2004 Curtis et al, 1982;Lieberman et al, 1983;Sheehan et al, 1983;Goldstein et al, 1987 Elevated nonsuppression rate with repeat testing, linked to severity of depression Coryell et al, 1989 Basal studies Normal UFC (in uncomplicated panic) Uhde et al, 1988;Kathol et al, 1988 Elevated ACTH increased afternoon or nocturnal cortisol Brambilla et al, 1992Goldstein et al, 1987Bandelow et al, 1997;Bandelow et al, 2000b''Natural'' panic Increased cortisol Bandelow et al, 2000aInconsistent response Cameron et al, 1987Woods et al, 1987 …”

Section: Paradigmsmentioning

confidence: 99%

HPA axis activity in patients with panic disorder: review and synthesis of four studies

et al. 2006

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Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis may play a role in panic disorder. HPA studies in patients with panic disorder, however, have produced inconsistent results. Seeking to understand the inconsistencies, we reexamined endocrine data from four studies of patients with panic disorder, in light of animal data highlighting the salience of novelty, control, and social support to HPA axis activity. Patients with panic disorder were studied (1) at rest over a full circadian cycle, (2) before and after activation by a panicogenic respiratory stimulant (doxapram) that does not directly stimulate the HPA axis, and (3) before and after a cholecystokinin B (CCK-B) agonist that is panicogenic and does directly stimulate the HPA axis. Patients with panic disorder had elevated overnight cortisol levels, which correlated with sleep disruption. ACTH and cortisol levels were higher in a challenge paradigm (doxapram) than in a resting state study, and paradigm-related ACTH secretion was exaggerated in patients with panic disorder. Panic itself could be elicited without HPA axis activation. Patients with panic disorder showed an exaggerated ACTH response to pentagastrin stimulation, but this response was normalized by prior exposure to the experimental context or psychological preparation to reduce novelty and enhance sense of control. Novelty is one of a number of contextual cues known from animal work to activate the HPA axis. The HPA axis abnormalities seen in patients with panic disorder in the four experiments reviewed here might all be due to exaggerated HPA axis reactivity to novelty cues. Most of the published panic/HPA literature is consistent with the hypothesis that HPA axis dysregulation in panic is due to hypersensitivity to contextual cues. This hypothesis requires experimental testing. Depression and Anxiety 24:66-76,

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“…In three of them (Woods et al 1988, Sasaki et al 1996, Sinha et al 1999) the 5% CO 2 challenge was used, while in the fourth (van Duinen et al 2004) single inhalation of 35% CO 2 was employed. Woods et al (1988) and Sinha et al (1999) used a canopy to administer two CO 2 concentrations, 5 and 7.5% in the first one, and 5 and 7% in the second study. Sasaki et al (1996) used only the 5% CO 2 concentration administered through a breathing mask.…”

Section: Carbon Dioxide (Co 2 )mentioning

confidence: 99%

Does the panic attack activate the hypothalamic-pituitary-adrenal axis?

Graeff

Garcia-Leal

Del-Ben

et al. 2005

An. Acad. Bras. Ciênc.

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A bibliographic search has been performed in MEDLINE using cortisol and panic as key-words, occurring in the title and/or in the abstract. Human studies were selected, with no time limit. The following publications were excluded: review articles, case reports, panic attacks in disorders other than panic disorder, and studies on changes that occurred in-between panic attacks. The results showed that real-life panic attacks as well as those induced by selective panicogenic agents such as lactate and carbon dioxide do not activate the hypothalamicpituitary-adrenal (HPA) axis. Agonists of the colecystokinin receptor B, such as the colecystokinin-4 peptide and pentagastrin, increase stress hormones regardless of the occurrence of a panic attack and thus, seem to activate the HPA axis directly. The benzodiazepine antagonist flumazenil does not increase stress hormones, but this agent does not reliably induce panic attacks. Pharmacological agents that increased anxiety in both normal subjects and panic patients raised stress hormone levels; among them are the α 2 -adrenergic antagonist yohimbine, the serotonergic agents 1-(m-chlorophenyl) piperazine (mCPP) and fenfluramine, as well as the psychostimulant agent caffeine. Therefore, the panic attack does not seem to activate the HPA axis, in contrast to anticipatory anxiety.

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Panic induced by carbon dioxide inhalation and lack of hypothalamic–pituitary–adrenal axis activation

Cited by 67 publications

References 26 publications

Respiratory manifestations of panic disorder: causes, consequences and therapeutic implications

Respiratory manifestations of panic disorder: causes, consequences and therapeutic implications

HPA axis activity in patients with panic disorder: review and synthesis of four studies

Does the panic attack activate the hypothalamic-pituitary-adrenal axis?

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