Dopamine and serotonin function in untreated schizophrenia: clinical correlates of the apomorphine and d-fenfluramine tests.
This study examined the prolactin (PRL), adrenocorticotropin (ACTH) and cortisol responses to the direct DA receptor agonist apomorphine (APO) and the selective 5HT-releasing agent d-fenfluramine (d-FEN) in 20 untreated inpatients with DSM-IV schizophrenia and without a history of suicide attempt, compared to 23 hospitalized healthy controls. We hypothesized that different patterns of responsiveness of the DA and 5-HT systems might be associated with specific schizophrenic symptom clusters. A positive correlation was observed between pituitary-adrenal response to APO and d-FEN tests (i.e. deltaACTH and deltacortisol) in the overall population and in schizophrenic patients. Pituitary-adrenal response to APO was lower in patients than in normal controls. Moreover, lower pituitary-adrenal response to APO and d-FEN was associated with increased severity of BPRS thought disturbance score. Lower pituitary-adrenal responses to APO (and to a lesser degree to d-FEN) differentiated paranoid from disorganized schizophrenic patients. Neither PRL suppression to APO, nor PRL stimulation to d-FEN were altered in schizophrenic patients. Our results suggest that decreased hypothalamic DA receptor activity (possibly secondary to increased presynaptic DA release) together with relatively decreased 5-HT tone characterize paranoid SCH, while normal hypothalamic DA receptor activity together with relatively increased 5-HT tone characterize the disorganized SCH subtype.
Centre Hospitalier, Secteur VIII, 68250 Rouffach, France. fabrice.duval@forenap.asso.fr
Fabrice
F
Duval
Marie-Claude
MC
Mokrani
José
J
Monreal
Paul
P
Bailey
Marcelo
M
Valdebenito
Marc-Antoine
MA
Crocq
Jean-Paul
JP
Macher
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D001058:Apomorphine; D010054:Brief Psychiatric Rating Scale; D003937:Diagnosis, Differential; D004298:Dopamine / Q000097:blood*; D018491:Dopamine Agonists; D005260:Female; D005277:Fenfluramine; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology; D011388:Prolactin / Q000097:blood; D012559:Schizophrenia / Q000097:blood / Q000175:diagnosis*; D012562:Schizophrenia, Disorganized / Q000097:blood / Q000175:diagnosis / Q000523:psychology; D012563:Schizophrenia, Paranoid / Q000097:blood / Q000175:diagnosis / Q000523:psychology; D012565:Schizophrenic Psychology; D012701:Serotonin / Q000097:blood*; D018490:Serotonin Agents
D018491:Dopamine Agonists; D018490:Serotonin Agents; D005277:Fenfluramine; D012701:Serotonin; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D001058:Apomorphine; D004298:Dopamine; D006854:Hydrocortisone