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Controlled cross-over study in normal subjects of naloxone-preceding-lactate infusions; respiratory and subjective responses: relationship to endogenous opioid system, suffocation false alarm theory and childhood parental loss

Published online by Cambridge University Press:  06 May 2010

M. Preter ,
S. H. Lee ,
E. Petkova ,
M. Vannucci ,
S. Kim  and
D. F. Klein
M. Preter*
Affiliation:
Department of Psychiatry, Columbia University, and New York State Psychiatric Institute, New York, NY, and Department of Neurology, State University of New York, Downstate Medical Center, Brooklyn, NY, USA
S. H. Lee
Affiliation:
The Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA
E. Petkova
Affiliation:
Department of Child and Adolescent Psychiatry, New York University School of Medicine, New York, USA
M. Vannucci
Affiliation:
Department of Statistics, Rice University, Houston, TX, USA
S. Kim
Affiliation:
Department of Biostatistics, University of Michigan, Ann Harbor, MI, USA
D. F. Klein
Affiliation:
Phyllis Green and Randolph Cowen Institute for Pediatric Neuroscience, Department of Child and Adolescent Psychiatry, New York University Langone Medical Center; The Nathan S. Kline Institute for Psychiatric Research; Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA
*
*Address for correspondence: M. Preter, M.D., 1160 Fifth Avenue, Suite 112, New York, NY 10029, USA. (Email: [email protected])
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Abstract

Background

The expanded suffocation false alarm theory (SFA) hypothesizes that dysfunction in endogenous opioidergic regulation increases sensitivity to CO2, separation distress and panic attacks. In panic disorder (PD) patients, both spontaneous clinical panics and lactate-induced panics markedly increase tidal volume (TV), whereas normals have a lesser effect, possibly due to their intact endogenous opioid system. We hypothesized that impairing the opioidergic system by naloxone could make normal controls parallel PD patients' response when lactate challenged. Whether actual separations and losses during childhood (childhood parental loss, CPL) affected naloxone-induced respiratory contrasts was explored. Subjective panic-like symptoms were analyzed although pilot work indicated that the subjective aspect of anxious panic was not well modeled by this specific protocol.

Method

Randomized cross-over sequences of intravenous naloxone (2 mg/kg) followed by lactate (10 mg/kg), or saline followed by lactate, were given to 25 volunteers. Respiratory physiology was objectively recorded by the LifeShirt. Subjective symptomatology was also recorded.

Results

Impairment of the endogenous opioid system by naloxone accentuates TV and symptomatic response to lactate. This interaction is substantially lessened by CPL.

Conclusions

Opioidergic dysregulation may underlie respiratory pathophysiology and suffocation sensitivity in PD. Comparing specific anti-panic medications with ineffective anti-panic agents (e.g. propranolol) can test the specificity of the naloxone+lactate model. A screen for putative anti-panic agents and a new pharmacotherapeutic approach are suggested. Heuristically, the experimental unveiling of the endogenous opioid system impairing effects of CPL and separation in normal adults opens a new experimental, investigatory area.

Keywords

Affective neurosciencechildhood parental loss (CPL)endogenous opioidspanic disorder pathophysiology
Type
Original Articles
Information
Psychological Medicine , Volume 41 , Issue 2 , February 2011 , pp. 385 - 393
Copyright
Copyright © Cambridge University Press 2010

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