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Neurosci Biobehav Rev. 2014 Oct;46 Pt 3:345-51. doi: 10.1016/j.neubiorev.2014.03.025. Epub 2014 Apr 13.

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

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Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA. Electronic address:
Phyllis Green and Randolph Cowen Institute for Pediatric Neuroscience, Department of Child and Adolescent Psychiatry, New York University Langone Medical Center, 550 1st 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.


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

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