Conflict of Interest Disclosure: All affiliations mentioned below have no relevance to the work covered in the manuscript: PZ has received speaker fees from Pfizer, Servier, Lilly, Astra Zeneca, and Bristol-Myers Squibb, he was on the advisory board of Pfizer, was a consultant for Ironwood Pharmaceuticals, and has received funding from AstraZeneca. KD has received speaker fees from Pfizer, Lilly, and Bristol-Myers Squibb, she is a consultant for Johnson & Johnson and has received funding by Astra Zeneca. JB was a consultant for Ironwood Pharmaceuticals and has received speaker fees from Servier.
NEURONAL NETWORK OF PANIC DISORDER: THE ROLE OF THE NEUROPEPTIDE CHOLECYSTOKININ
Article first published online: 2 MAY 2012
© 2012 Wiley Periodicals, Inc.
Depression and Anxiety
Volume 29, Issue 9, pages 762–774, September 2012
How to Cite
Zwanzger, P., Domschke, K. and Bradwejn, J. (2012), NEURONAL NETWORK OF PANIC DISORDER: THE ROLE OF THE NEUROPEPTIDE CHOLECYSTOKININ. Depress. Anxiety, 29: 762–774. doi: 10.1002/da.21919
- Issue published online: 4 SEP 2012
- Article first published online: 2 MAY 2012
- Manuscript Accepted: 13 JAN 2012
- Manuscript Revised: 9 JAN 2012
- Manuscript Received: 8 SEP 2011
- panic disorder;
Panic disorder (PD) is characterized by panic attacks, anticipatory anxiety and avoidance behavior. Its pathogenesis is complex and includes both neurobiological and psychological factors. With regard to neurobiological underpinnings, anxiety in humans seems to be mediated through a neuronal network, which involves several distinct brain regions, neuronal circuits and projections as well as neurotransmitters.
A large body of evidence suggests that the neuropeptide cholecystokinin (CCK) might be an important modulator of this neuronal network. Key regions of the fear network, such as amygdala, hypothalamus, peraqueductal grey, or cortical regions seem to be connected by CCKergic pathways. CCK interacts with several anxiety-relevant neurotransmitters such as the serotonergic, GABA-ergic and noradrenergic system as well as with endocannabinoids, NPY and NPS. In humans, administration of CCK-4 reliably provokes panic attacks, which can be blocked by antipanic medication. Also, there is some support for a role of the CCK system in the genetic pathomechanism of PD with particularly strong evidence for the CCK gene itself and the CCK-2R (CCKBR) gene. Thus, it is hypothesized that genetic variants in the CCK system might contribute to the biological basis for the postulated CCK dysfunction in the fear network underlying PD.
Taken together, a large body of evidence suggests a possible role for the neuropeptide CCK in PD with regard to neuroanatomical circuits, neurotransmitters and genetic factors. This review article proposes an extended hypothetical model for human PD, which integrates preclinical and clinical findings on CCK in addition to existing theories of the pathogenesis of PD.