Effects of acute metabolic stress on the dopaminergic and pituitary-adrenal axis activity in patients with schizotypal personality disorder.
BACKGROUND
Stress has been associated with the onset of schizophrenia and exacerbation of psychotic symptoms. Patients with schizotypal personality disorder (SPD), the prototypic schizophrenia spectrum disorder, do not develop the frank psychosis of schizophrenia and appear clinically to be less reactive to stress than schizophrenic patients. Schizophrenic patients demonstrate increased dopaminergic (DA) and hypothalamic-pituitary-adrenal-axis (HPA) activation following 2-deoxyglucose (2-DG), an acute metabolic (glycopyruvic) stressor, compared to healthy volunteers (HV). We hypothesized that SPD patients would demonstrate comparable or lower DA and HPA responses after 2-DG to HV.


METHODS
Fifteen SPD patients and 13 HV were administered 2-DG (40 mg/kg, i.v.) in a double-blind, placebo-controlled, randomized protocol. The area under the curve (AUC) was determined for plasma HVA, ACTH and cortisol (utilizing baseline and post infusion indices).


RESULTS
2-DG induced significant increases in ACTH, cortisol and HVA concentrations in both groups and cortisol elevations were significantly lower in patients with SPD than in HV.


CONCLUSIONS
Patients with SPD have a blunted cortisol and a normal dopaminergic response to 2-DG. These results are consistent with the hypothesis that SPD patients are better buffered against DA and HPA overactivation in response to stress.
Mitropoulou
Vivian
V
Department of Psychiatry, Mt. Sinai School of Medicine Clinical Reseach Center, New York, NY 10029, USA. vivian.mitropoulou@mssm.edu
Goodman
Marianne
M
Sevy
Serge
S
Elman
Igor
I
New
Antonia S
AS
Iskander
Elisabeth G
EG
Silverman
Jeremy M
JM
Breier
Alan
A
Siever
Larry J
LJ
D000208:Acute Disease; D000328:Adult; D000963:Antimetabolites / Q000008:administration & dosage / Q000494:pharmacology*; D003847:Deoxyglucose / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005947:Glucose / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism*; D007262:Infusions, Intravenous; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism*; D019289:Pyruvic Acid / Q000378:metabolism; D012569:Schizotypal Personality Disorder / Q000378:metabolism*
D000963:Antimetabolites; D019289:Pyruvic Acid; D003847:Deoxyglucose; D005947:Glucose; D004298:Dopamine; D006854:Hydrocortisone; D006719:Homovanillic Acid