Neuroendocrine correlates of depression in abstinent heroin-dependent subjects.
The functions of the central alpha-adrenergic, serotoninergic and dopaminergic systems were investigated in 28 heroin-dependent subjects 6-8 weeks after detoxification, and in 22 healthy control subjects (group C). Fourteen heroin-dependent subjects with depressive comorbidity (group A), and 14 heroin-dependent subjects without other Axis I and II pathologies (group B) were included among abstinent substance abusers. Norepinephrine (NE) function was evaluated by growth hormone (GH) responses to acute stimulation with clonidine (clon); serotonin (5-HT) function by prolactin (PRL) and cortisol (CORT) responses to acute stimulation with D-fenfluramine (D-fen) and dopamine (DA) function by GH and PRL responses to acute administration of bromocriptine (brom). Central NE activity, as measured by the GH-clon test, seems to be well preserved both in A and B subjects. PRL and CORT responses to D-fen were significantly blunted both in A subjects and in B subjects, in comparison with control subjects (C); the PRL response in A subjects was significantly lower than in B subjects. The DA system of B subjects was found unimpaired; in contrast, a significantly higher GH response to brom in A subjects (depressed) could express D2 post-synaptic receptor hypersensitivity and, therefore, decreased pre-synaptic DA release. In sum, the study of central monoamine function revealed an alteration only of the 5-HT system in detoxified heroin-dependent subjects without psychiatric comorbidity, which might be a trait character of these subjects, possibly involved in the pathogenesis of the disorder. A more significant impairment of 5-HT function and the hypersensitivity of post-synaptic DA receptors in A subjects suggests that specific biological correlates of psychiatric comorbidity may characterize substance abuser subtypes.
Gerra
G
G
Centro Studi Farmacotossicodipendenze, Ser.T., AUSL, Via Spalato 2, 43100 Parma, Italy. pharmbeh@tin.it
Zaimovic
A
A
Zambelli
U
U
Delsignore
R
R
Baroni
M C
MC
Laviola
G
G
Macchia
T
T
Brambilla
F
F
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers; D001921:Brain / Q000378:metabolism; D001971:Bromocriptine / Q000494:pharmacology; D016022:Case-Control Studies; D003000:Clonidine / Q000494:pharmacology; D003863:Depression / Q000378:metabolism; D003865:Major Depressive Disorder / Q000378:metabolism* / Q000523:psychology; D017831:Diagnosis, Dual (Psychiatry); D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology; D006556:Heroin Dependence / Q000378:metabolism* / Q000523:psychology / Q000628:therapy; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011569:Psychiatric Status Rating Scales; D011941:Receptors, Adrenergic / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology; D015813:Substance Abuse Detection
D000316:Adrenergic alpha-Agonists; D015415:Biomarkers; D018491:Dopamine Agonists; D011941:Receptors, Adrenergic; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D018490:Serotonin Agents; D005277:Fenfluramine; D012701:Serotonin; D001971:Bromocriptine; D003000:Clonidine; D004298:Dopamine; D009638:Norepinephrine