title: Cognitive modulation of the endocrine stress response to a pharmacological challenge in normal and panic disorder subjects.
abstract: BACKGROUND
  The hypothalamic-pituitary-adrenal (HPA) axis may mediate the deleterious effects of stress on health. It is sensitive to cognitive and emotional aspects of organism-environment interactions, such as familiarity, control, and social support. Scientific study of how such factors moderate human HPA axis activity has been limited. Their relevance to HPA axis disturbances in psychiatric patients is largely unexplored.
  
  
  OBJECTIVE
  To determine whether cognitive manipulation can alter HPA axis activity in laboratory studies and whether patients with panic disorder are differentially sensitive to the manipulated factors.
  
  
  METHODS
  Pharmacological activation paradigm (cholecystokinin-B agonist pentagastrin) by which we examined symptom and endocrine effects on subjects randomly assigned to a standard introduction or a cognitive intervention.
  
  
  METHODS
  Clinical research center.
  
  
  METHODS
  Recruited from university clinic and newspaper advertisements. Fourteen patients with panic disorder and 14 controls, individually matched for age and sex. Intervention Half of each group received a 9-minute cognitive intervention designed to reduce novelty, increase cognitive coping, and provide a sense of control.
  
  
  METHODS
  Corticotropin (ACTH) and cortisol levels.
  
  
  RESULTS
  The cognitive intervention significantly reduced cortisol (P = .02) and ACTH (P = .01) levels, despite pentagastrin's robust stimulation of both hormones (P<.001). The intervention effect was evident in patients and controls, who did not differ in basal HPA axis activity or response to pentagastrin. They did differ in panic symptom responses, which were unaffected by the intervention, and in ACTH effects of the intervention. Patients' exaggerated anxiety responses to pentagastrin were normalized by the intervention.
  
  
  CONCLUSIONS
  Cognitive/emotional manipulation can substantially modulate HPA axis responses to pharmacological activation in humans, and HPA disturbances in panic disorder may be secondary to manipulable cognitive/emotional sensitivities. Further study of such factors as novelty, control, and coping may help clarify the origins of HPA axis disturbance in psychiatric disorders and the mediators linking psychosocial stress to disease.
authors.affiliation: Department of Psychiatry and Mental Health Research Institute, Trauma, Stress and Anxiety Research Group, University of Michigan, Ann Arbor 48109-0118, USA. jabelson@umich.edu
authors.forename: James L
authors.initials: JL
authors.lastname: Abelson
authors.forename: Israel
authors.initials: I
authors.lastname: Liberzon
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Young
authors.forename: Samir
authors.initials: S
authors.lastname: Khan
mesh_terms: D000223:Adaptation, Psychological / Q000187:drug effects; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D001008:Anxiety Disorders / Q000139:chemically induced / Q000517:prevention & control; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D015928:Cognitive Behavioral Therapy; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D016584:Panic Disorder / Q000097:blood* / Q000139:chemically induced* / Q000628:therapy; D010418:Pentagastrin / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology; D043887:Receptor, Cholecystokinin B / Q000819:agonists; D013315:Stress, Psychological / Q000097:blood* / Q000523:psychology / Q000628:therapy
chemical_list: D043887:Receptor, Cholecystokinin B; D000324:Adrenocorticotropic Hormone; D010418:Pentagastrin; D006854:Hydrocortisone