title: Copeptin - A potential endocrine surrogate marker of CCK-4-induced panic symptoms?
abstract: Intravenous cholecystokinin-tetrapeptide (CCK-4) administration reliably and dose-dependently provokes panic anxiety in man, accompanied by adrenocorticotropic hormone (ACTH) and cortisol release. Preclinical findings suggest that behavioral and endocrine effects of CCK-4 are mediated via corticotropin-releasing hormone (CRH) release. Anxiogenic stimulation of the central CCK-receptors in man was shown to increase as well vasopressin (AVP), which acts synergistically with CRH as pituitary-adrenocortical axis stimulator during stress. Copeptin (CoP), the C-terminal part of pre-pro-AVP, is released in an equimolar ratio to AVP. It is more stable in the circulation and easier to determine than AVP and it was found to closely mirror the production of AVP. So far, CoP secretion has not been characterized during panic provocation. In 30 healthy male human subjects, we repeatedly measured CoP in plasma during a panic challenge and studied its correlation to Acute Panic Inventory (API) ratings and plasma ACTH and cortisol. CoP levels correlated positively with the increase in API ratings (r=0.41, p=0.03), while ACTH or cortisol did not (r=0.08, p=0.68 and r=0.12, p=0.53, respectively). CoP levels correlated also positively with ACTH (r=0.48, p=0.009) and cortisol (r=0.48, p=0.01) concentrations throughout the CCK-4 challenge. As expected, we found a positive correlation between plasma ACTH and cortisol levels (r=0.57, p=0.001). A vasopressinergic activation during CCK-4 induced panic was demonstrated, which was correlated positively to panic symptoms and pituitary-adrenocortical release. Our findings suggest a role of CoP as a potential surrogate marker of CCK-4 panic symptoms. Further studies are needed to replicate our results and to further clarify the role of CoP as a stress-sensitive hormone in different panic paradigms as well as in panic patients.
authors.affiliation: University Hospital Hamburg-Eppendorf, Department of Psychiatry and Psychotherapy, Hamburg, Germany. Electronic address: c.demiralay@uke.de.
authors.forename: Cüneyt
authors.initials: C
authors.lastname: Demiralay
authors.affiliation: University Hospital Hamburg-Eppendorf, Department of Psychiatry and Psychotherapy, Hamburg, Germany.
authors.forename: Agorastos
authors.initials: A
authors.lastname: Agorastos
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Yassouridis
authors.affiliation: University Hospital Hamburg-Eppendorf, Department of Psychiatry and Psychotherapy, Hamburg, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Jahn
authors.affiliation: University Hospital Hamburg-Eppendorf, Department of Psychiatry and Psychotherapy, Hamburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Wiedemann
authors.affiliation: University Hospital Hamburg-Eppendorf, Department of Psychiatry and Psychotherapy, Hamburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kellner
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D001007:Anxiety / Q000139:chemically induced*; D015415:Biomarkers / Q000097:blood; D006020:Glycopeptides / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D010200:Panic / Q000502:physiology; D011949:Receptors, Cholecystokinin / Q000819:agonists*; D013758:Tetragastrin / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006020:Glycopeptides; D018377:Neurotransmitter Agents; D011949:Receptors, Cholecystokinin; C048197:copeptins; D013758:Tetragastrin; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone
keywords: CCK-4; Cholecystokinin; Copeptin; HPA-axis; Panic; Surrogate marker