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

Frederico G Graeff,Francisco S Guimarães,Cybele Garcia-Leal,Cristina M Del-Ben

doi:10.1590/s0001-37652005000300009

Frederico G Graeff, Francisco S Guimarães + Show 2 more

Open Access

https://doi.org/10.1590/s0001-37652005000300009

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Abstract

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 hypothalamic-pituitary-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 alpha2-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 HPAaxis, in contrast to anticipatory anxiety.

Highlights

Starting with Hans Selye’s (1936) seminal work, a wealth of reported evidence established that different kinds of physical or psychological conditions that threaten the organism homeostasis elicit a stereotyped set of reactions named by Selye the “general adaptation syndrome”
The results of a large number of studies have consistently shown that the sympathetic nervous system and the HPA axis are activated by either novelty or environmental cues that signal the withholding of an expected reward or the delivery of punishment and generate anticipatory anxiety (Mason 1975)
Several publications were excluded on the basis of the following criteria: review articles, case reports, stress hormones measured during the quiescent period inbetween attacks, disorders other than panic disorder (PD) or healthy subjects not compared to PD patients

Summary

Introduction

Starting with Hans Selye’s (1936) seminal work, a wealth of reported evidence established that different kinds of physical or psychological conditions that threaten the organism homeostasis elicit a stereotyped set of reactions named by Selye the “general adaptation syndrome”. Most characteristic is the release of the adrenocorticotropic hormone (ACTH) and corticoids The neural circuits mediating neuroendocrine responses involve cortical activation of the basolateral amygdala, which in turn activates the central nucleus of the amygdala. The central amygdala activates hypothalamic neurons directly, indirectly through the bed nucleus of the stria terminalis, and/or via circuits involving brainstem serotonergic and catecholaminergic neurons. Neurons of the hypothalamic paraventricular nucleus secrete the corticotropic releasing hormone (CRH) into the portal circulation of the pituitary gland. CRH stimulates ACTH-secreting cells that release ACTH into the blood stream. ACTH acts on the adrenal cortex promoting cortisol secretion and release into the blood circulation. In addition to ACTH, prolactin is consistently released from the anterior pituitary in stressful situations. The primary function of this hormone is to promote lactation in pregnant females, it is considered as a stress hormone (van de Kar and Blair 1999)

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