Cognitive modulation of endocrine responses to CRH stimulation in healthy subjects.
BACKGROUND
The hypothalamic-pituitary adrenal (HPA) axis is critical for biobehavioral adaptation to challenge and appears dysregulated in a range of psychiatric disorders. Its precise role in psychopathology remains unclear and discrepant and difficult to explain findings abound in the clinical literature. Basic research suggests this system is sensitive to psychosocial cues, but psychosocial milieu factors are rarely controlled or examined in psychiatric studies using biological probes of the HPA axis. To test the hypothesis that psychological factors might complicate HPA study results even in direct, pharmacological challenge paradigms, endocrine responses to corticotropin-releasing hormone (CRH) were examined under two different cognitive preparation conditions.


METHODS
Healthy subjects (n=32) received standard instructions or a cognitive intervention (CI) prior to injection with CRH and placebo, given on separate days in random order. The CI combined access to control over drug exposure with novelty reduction and coping enhancement. Blood samples were obtained via intravenous catheter before and after CRH.


RESULTS
Cognitive intervention reduced corticotropin (ACTH) levels, but only when CRH was given first (intervention by order interaction). It did not reduce cortisol response. The CI and visit (1st or 2nd) both impacted cortisol levels on placebo day.


CONCLUSIONS
Modifiable psychological factors may amplify or inhibit HPA axis activity in pharmacological activation paradigms, including CRH stimulation tests. The factors manipulated by the CI (novelty/familiarity, control and coping) may have particular salience to the HPA axis. Differential sensitivity to such factors could impact results in studies applying biological HPA probes to psychiatric populations.
Abelson
James L
JL
University of Michigan Department of Psychiatry, Trauma, Stress and Anxiety Research Group, Molecular and Behavioral Neuroscience Institute, United States. jabelson@umich.edu
Khan
Samir
S
Young
Elizabeth A
EA
Liberzon
Israel
I
D000223:Adaptation, Psychological / Q000187:drug effects; D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism; D000328:Adult; D001007:Anxiety / Q000139:chemically induced; D003071:Cognition / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004703:Endocrine System / Q000187:drug effects* / Q000502:physiology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D006262:Health; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D010919:Placebos; D013268:Stimulation, Chemical; D013997:Time Factors; D055815:Young Adult
D010919:Placebos; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone