Maurice Preter MD and Donald F. Klein, MD, DSc: Lifelong opioidergic vulnerability through early life separation: A recent extension of the false suffocation alarm theory of panic disorder.

Fresh off the [Epub] press. Of interest to some.

Keywords: Affective neuroscience; Childhood parental loss (CPL); Endogenous opioids; Panic disorder pathophysiology

From the conclusion:
“[…W]e objectively, experimentally showed a physiological link between endogenous opioid system deficiency and panic-like suffocation sensitivity in healthy adults. This is consonant with the expanded Suffocation-False Alarm Theory of panic suggesting an episodic functional endogenous opioid deficit (Preter and Klein, 1998). The specificity of the naloxone + lactate model of clinical panic should be tested using specific anti-panic components, possibly including opioidergic mixed agonist-antagonists such as buprenorphine. If specific, the naloxone + lactate effect in normal humans affords a screening method for testing putative anti-panic drugs which is currently not available. This could obviate the experimental treatment of panic disorder patients in drug development.
Our data also show for the first time that actual separations and losses during childhood, such parental death, parental separation or divorce (CPL), effect lifelong alterations in the physiological reactivity of the endogenous opioid system of healthy adults.
This result encourages epigenetic inquiry into the effects of CPL on endogenous opioid systems, and their role in resilience under extreme stress. In addition, a redefinition of what constitutes a (truly) healthy control in clinical research protocols may be called for.”

Neurosci Biobehav Rev. 2014 Apr 9. pii: S0149-7634(14)00082-7. doi:10.1016/j.neubiorev.2014.03.025.

 [Epub ahead of print]

Lifelong opioidergic vulnerability through early life separation: A recent extension of the false suffocation alarm theory of panic disorder.

Preter M1, Klein DF2.

Author information

1Corresponding Author. Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA. Electronic address:

2Phyllis Green and Randolph Cowen Institute for Pediatric Neuroscience, Department of Child and Adolescent Psychiatry, New York University Langone Medical Center 550 1(st) Ave, New York, NY 10016, USA. Electronic address:


The present paper is the edited version of our presentations at the “First World Symposium On Translational Models Of Panic Disorder”, in Vitoria, E.S., Brazil, on November 16-18, 2012. We also review relevant work that appeared after the conference. Suffocation-False Alarm Theory (Klein, 1993) 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. The expanded Suffocation-False Alarm Theory (Preter and Klein, 2008) hypothesizes that endogenous opioidergic dysregulation may underlie the respiratory pathophysiology and suffocation sensitivity in panic disorder. Opioidergic dysregulation increases sensitivity to CO2, separation distress and panic attacks. That sudden loss, bereavement and childhood separation anxiety are also antecedents of “spontaneous” panic requires an integrative explanation. Our work unveiling the lifelong endogenous opioid system impairing effects of childhood parental loss (CPL) and parental separation in non-ill, normal adults opens a new experimental, investigatory area.

Copyright © 2014. Published by Elsevier Ltd.


Affective neuroscience, Childhood parental loss (CPL), Endogenous opioids, Panic disorder pathophysiology



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