The aim of this study was to evaluate the effect on the activity of the hypothalamic-pituitary dopaminergic system of two new atypical antipsychotic drugs: the ergoline derivative SDZ HDC-912, which is a dopamine (DA) D2 receptor partial agonist; and the quinolinone derivative OPC-4392, which acts as an agonist at presynaptic DA autoreceptors and as an antagonist at post-synaptic D2 receptors. The effects of both compounds were compared to the effects of the benzamide derivative amisulpride. Prolactin (PRL) and growth hormone (GH) levels before and after challenge with apomorphine (Apo), a dopaminergic agonist, were determined after at least 2 weeks washout and again after 1 month of treatment in DSM-III-R schizophrenic inpatients. SDZ HDC-912 significantly decreased Apo-induced PRL inhibition, and tended to decrease PRL secretion and Apo-induced GH stimulation. OPC-4392 induced a significant decrease in baseline PRL and in Apo-induced PRL suppression, and a non-significant decrease in Apo-induced GH stimulation. The neuroendocrine profiles of these two compounds agree with their dopaminergic properties; however, the decrease in PRL basal level differentiates the two drugs from neuroleptic agents.
SummaryThis study evaluates the relationship between stress of captivity and subsequent presence of Post Traumatic Stress Disorder (PTSD) has been evaluated in a homogeneous population of 817 Alsatian World War II veterans who were imprisoned in the USSR during and after the war. Data were collected in 1988 by a questionnaire structured to investigate the presence of DSM-III-R criteria for PTSD as well as events experienced in captivity. The presumptive diagnosis of PTSD was found to be significantly associated with longer internment and with higher scores on a severity of POW experience index.
One of the axes of research in our department is oriented on the study of the action of psychotropic drugs on the Central Nervous System by the means of the non invasive and direct techniques of cerebral imagery. First approach: EEG mapping In depressive states, the modification of nocturnal wakefulness states observed under lithium therapy begins to be well known. However, under lithium monotherapy, few diurnal studies have been performed. EEG mapping, based on a protocol and a strict methodology, could represent an interesting technique to approach the mechanisms of lithium action in psychopathological states concerned by this type of therapy. Second approach: Nuclear Magnetic Resonance (NMR) We studied the manic-depressive states in man before and after chronic administration of lithium salts. This research is performed in fundamental molecular studies, in vitro, and from modification of certain parameters in protonic NMR imagery that can be observed in these pathological states. We are participating in a research program and we preliminarily present: 1. the study by protonic NMR of the in vitro interaction between the lithium ion and water which is free or bound to the total cerebral tissue of rats (acute intravenous treatment by Li+ in different doses and at different times of tissular penetration). 2. the study by lithium NMR of the in vitro kinetics of the erythrocyte's lithium penetration in man, for the plasmatic concentrations (acute intravenous dose) considered as therapeutic in manic-depressive states. These measures performed by spectroscopic NMR are coupled with a classical dosage of lithium made with a flame spectrophotometer.(ABSTRACT TRUNCATED AT 250 WORDS)
The present study was conducted in order to investigate the relationships between central noradrenergic (NA) and serotonergic (5-HT) function and clinical characteristics of a major depressive episode according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. We measured growth hormone response (ΔGH) to clonidine (CLO) (an α2 NA agonist), as an index of central NA function, and prolactin response (APRL) to d-fenfluramine (d-FEN) (a specific 5-HT releaser/uptake inhibitor), as an index of central 5-HT function, in 53 medication-free depressed inpatients. On the basis of their CLO and d-FEN test responses, patients were classified into 4 groups. Group 1 (blunted ΔPRL(d-FEN) alone [11 %]) was characterized by a recent violent suicide attempt, a high degree of medical damage, and mild anxiety. Group 2 (blunted ΔGH(CLO) alone [32%]) was characterized by an absence of a history of suicide attempt and by severe anxiety. Group 3 (combination of blunted ΔGH(CLO) and APRL(d-FEN) [18%]) was characterized by a history of suicide attempts, total duration of the illness of over W years, age over 40 years, and more than 3 previous hospitalizations. Group 4 (no abnormality [39%]) had no specific clinical profile. These results suggest that, in depression, specific psychopathological features may be linked to 5-HT and/or NA dysfunction. However, our results also suggest that NA and/or 5-HT dysfunction are less likely to be the primary cause of mood disorders but are more indicative of failure of compensatory mechanisms involved in affective homeostatic processes.
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