title: Neuronal network of panic disorder: the role of the neuropeptide cholecystokinin.
abstract: 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.
authors.affiliation: Mood and Anxiety Disorders Research Unit, Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany. zwanzger@ukmuenster.de
authors.forename: P
authors.initials: P
authors.lastname: Zwanzger
authors.forename: K
authors.initials: K
authors.lastname: Domschke
authors.forename: J
authors.initials: J
authors.lastname: Bradwejn
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002766:Cholecystokinin / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009415:Nerve Net / Q000378:metabolism*; D016584:Panic Disorder / Q000209:etiology* / Q000378:metabolism; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*
chemical_list: D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin