| Progress in Neuro-Psychopharmacology and Biological Psychiatry Article in Press, Accepted Manuscript – Note to users |
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doi:10.1016/j.pnpbp.2007.07.029 
Copyright © 2007 Elsevier Inc. All rights reserved.
Panic, Suffocation False Alarms, Separation Anxiety and Endogenous Opioids
Maurice Pretera, 
, 
and Donald F. Kleinb, 1,
aNew York State Psychiatric Institute Columbia University College of Physicians and Surgeons, 1160 Fifth Avenue, Suite 112 New York, NY 10029, USA
bNew York State Psychiatric Institute Columbia University College of Physicians and Surgeons 1051 Riverside Drive, New York, NY 10032, USA
Received 23 February 2007; revised 24 July 2007; accepted 24 July 2007. Available online 9 August 2007.
Corresponding author. Tel.: 
+1 212 713 5336
; fax: +1 212 713 5336.1 Tel.:
+1 212 543 6249.
Review article
Panic, suffocation false alarms, separation anxiety and endogenous opioids
Maurice Preter a,⁎, Donald F. Klein b,1
a New York State Psychiatric Institute, Columbia University College of Physicians&Surgeons, 1160 Fifth Avenue, Suite 112, New York, NY 10029, USA
b New York State Psychiatric Institute, Columbia University College of Physicians&Surgeons, 1051 Riverside Drive, New York, NY 10032, USA
Received 23 February 2007; received in revised form 24 July 2007; accepted 24 July 2007
Abstract
This review paper presents an amplification of the suffocation false alarm theory (SFA) of spontaneous panic [Klein DF (1993). False suffocation alarms, spontaneous panics, and related conditions. An integrative hypothesis. Arch Gen Psychiatry; 50:306-17.]. SFA postulates the existence of an evolved physiologic suffocation alarm system that monitors information about potential suffocation. Panic attacks maladaptively
occur when the alarm is erroneously triggered. That panic is distinct from Cannon’s emergency fear response and Selye’s General Alarm Syndrome is shown by the prominence of intense air hunger during these attacks. Further, panic sufferers have chronic sighing abnormalities outside of the acute attack. Another basic physiologic distinction between fear and panic is the counter-intuitive lack of hypothalamic–pituitary–adrenal (HPA) activation in panic. Understanding panic as provoked by indicators of potential suffocation, such as fluctuations in pCO2 and brain lactate, as well as environmental circumstances fits the observed respiratory abnormalities. However, that sudden loss, bereavement and childhood separation anxiety are also antecedents of “spontaneous” panic requires an integrative explanation. Because of the opioid system’s central regulatory role in both disordered breathing and separation distress, we detail the role of opioidergic dysfunction in decreasing the suffocation alarm threshold. We present results from our laboratory where the naloxone-lactate challenge in normals produces supportive evidence for the endorphinergic defect hypothesis in the form of a distress episode of specific tidal volume hyperventilation paralleling challenge-produced and clinical panic.
© 2007 Elsevier Inc. All rights reserved.
Keywords: Affective neuroscience; Endogenous opioids; Panic disorder; Respiratory physiology; Separation anxiety
