Neuroendocrine response to psychological performance testing.

Neuroendocrine changes associated with performance testing requiring sustained attention were assessed in eight normal male subjects. To verify whether the hormonal pattern was modified by chronic stimulation of opiate receptors, eight heroin addicts also were studied. Reaction times were similar in normal and addict subjects. In normal individuals, consistent and significant increases in plasma ACTH and beta-endorphin and in urinary epinephrine and norepinephrine were observed, whereas serum prolactin (PRL) progressively decreased over the testing period. Despite maintained performance capabilities, heroin addicts showed a blunted response of ACTH and a paradoxical decrease in endorphin levels. As the normal subjects, both epinephrine and norepinephrine in urine showed the same significant increase over baseline values. Serum PRL showed a similar trend towards decreased values over the testing period in both groups.

Metyrapone effects on beta-endorphin, ACTH and cortisol levels after chronic opiate receptor stimulation in man.

The aim of this study was to evaluate beta-endorphin, ACTH, and cortisol plasma levels during metyrapone administration in man after chronic opioid receptor stimulation. Metyrapone (750 mg every 4 hr for 6 doses) was administered to ten male heroin addicts, who had been on a maintenance therapy with methadone for at least 6 months and to ten healthy sex- and age-matched volunteers. Before metyrapone administration the basal levels of cortisol and ACTH were significantly decreased in addicts as compared to normal controls, while plasma beta-endorphin was not different. The response of beta-endorphin and ACTH to metyrapone administration was significantly blunted in addicts (p less than 0.01). These results suggest that the chronic stimulation of opiate receptors can impair the function of the anterior pituitary gland.

Neurotransmitter and endocrine modulation of aggressive behavior and its components in normal humans.

Correlations between aggressiveness and its components and plasma concentrations of norepinephrine (NE), epinephrine (EPI), testosterone (T), cortisol (Cort) and prolactin (Prl) were studied in 158 physically and psychologically healthy male volunteers. Global aggressiveness, examined directly in the probands by the Buss-Durkee Hostility Inventory (BDHI), was not correlated with any of the biochemical parameters investigated, but reports by first-degree relatives and spouses showed positive correlations between global aggressiveness and NE and T levels. The BDHI scores for 'irritability' and 'resentment' were positively correlated with NE, T and Cort.

Hostility in heroin abusers subtypes: fluoxetine and naltrexone treatment.

1. Substance abusers subtypes have been identified considering underlying psychobiological disorder, familial factors, age of onset, legal problems and drug of choice. 2. In the present study the authors submitted 98 male heroin addicted individuals (age 19-28 y) to the Buss Durkee Hostility Inventory (Italian version) and a structured interview concerning social and clinical history; legal problems, age of onset of drug abuse, drug of choice. 3. Serotonergic system sensitivity was evaluated with fenfluramine challenge for PRL assay. 4. Thirty two patients (group A) showed high score for resentment and guilt at BDHI (hostility in), low rate of legal problems, late age of onset, preference for heroin and alcohol. Twenty nine patients (group B) showed high score for assault and irritability at BDHI (hostility out), high rate of legal problems, early age of onset, preference for heroin and cocaine. The other 37 patients (group C) showed aggression score in the normal range at BDHI, no legal problems, late onset of substance abuse, preference for heroin only. 5. PRL responses was blunted in group A (p < 0.001) and significantly decreased in group B (p < 0.05). PRL plasma levels were inversely correlated with HRSD scores. 6. All the patients were included in a treatment protocol with fluoxetine and naltrexone or placebo and naltrexone for 6 months. 7. The treatment was effective in group A with a significant improvement of BDHI results and decrease of craving score, lower level of drop out, lower level of positive urine controls. No significant differences between fluoxetine and placebo effects have been evidenced in patients of group B and C. The present findings suggest that psychopharmacological approach to addiction needs a diagnostic screening for specific subtypes.

Long-lasting impairment of neuroendocrine response to psychological stress in heroin addicts.

Performance in a vigilance task and the associated neuroendocrine changes during the performance in the task were examined in healthy subjects and in three groups of male heroin-addicts both before undergoing rehabilitation programmes and at various intervals from withdrawal (5 days, 1 to 2 mon, and 3 to 48 mon, respectively). Plasma levels of ACTH, beta-endorphin (EP) and prolactin (PRL) were measured every 10 min before and during performance. In drug addicts, simple reaction times never showed any significant difference as compared to control values. Despite similar baseline levels, ACTH exhibited a markedly depressed response to psychological testing in drug-addicts as compared to controls. Whereas a three-fold increase in ACTH was observed in 'normal' subjects during the performance (from 17 to 54 ng/l), mean values from drug-addicts remained unchanged. EP levels showed a wide scatter of individual values and inconsistent time courses over performance testing: after short-term abstinence, EP showed a three-fold increase over baseline control values but, contrary to what seen in 'normal' subjects, no changes over time were recorded. After long-term abstinence, basal EP was close to control values, but its increase during the testing period was still blunted. PRL levels decreased over the testing period both in controls and in heroin addicts. Thus, despite the lack of obvious signs of neurotoxicity, drug abusers show neuroendocrine changes consistent with a long-lasting selective impairment of the hypothalamic modulation of pituitary secretion.

Neurotransmitter-hormonal responses to psychological stress in peripubertal subjects: relationship to aggressive behavior.

The relationship between different degrees of normal aggressiveness (low, medium, high) and neurotransmitter-neuroendocrine responses to the administration of psychologically stressful tests (Mental Arithmetic, Stroop Color Word Interference task, Trial Social Stress test) was examined in thirty male peripubertal junior school adolescents. Plasma concentrations of norepinephrine (NE), epinephrine (EPI), ACTH, cortisol (CORT), growth hormone (GH), prolactin (PRL) and testosterone (T) were measured immediately before the beginning of the tests and at their end, 30 min later. High-normal aggressiveness have been found associated with significantly higher basal concentrations of NE, ACTH, PRL, and T and with a significant increase of GH responses to the stressful stimuli.

Intravenous flumazenil following prolonged exposure to lormetazepam in humans: lack of precipitated withdrawal.

The capacity of flumazenil to reverse benzodiazepine agonist effects has been widely demonstrated. In contrast, the role of flumazenil in precipitating withdrawal symptoms is unclear in humans: the inability of RO 15-1788 to induce benzodiazepine withdrawal seems to be related to the duration of exposure to the GABAergic drugs. In the present experiment we evaluated the effects of intravenous flumazenil or placebo in 36 healthy volunteers pretreated with lormetazepam for 30 days (2 mg/day) and 18 lormetazepam-dependent subjects (6-8 mg/day). Measurements of a balance task, subject- and observer-rated symptoms showed a reversal of lormetazepam effects induced by flumazenil without any significant withdrawal symptoms. Slight anxiety, increase in heart rate and perspiration were observed in a few subjects. Independent of benzodiazepine doses, long-term treatment seems to be responsible for tolerance development with consistent changes in GABA-benzodiazepine receptor sensitivity. Flumazenil could be able to normalize benzodiazepine receptor sensitivity and exert its weak agonist activity.

Serotonergic function after (+/-)3,4-methylene-dioxymethamphetamine ('Ecstasy') in humans.

(+/-)3,4-Methylene-dioxymethamphetamine (MDMA, or 'Ecstasy') effects on serotonin system function and behaviour in humans are unclear. Fifteen MDMA users, who did not have other drug dependencies or alcohol abuse, and had not used other drugs for prolonged periods, and 15 control individuals were included in a study to assess the biological and psychological changes after chronic use of MDMA. Prolactin and cortisol responses to D-fenfluramine challenge, clinical psychobehavioural changes, personality characteristics, including mood, aggressiveness and temperamental aspects, were evaluated 3 weeks after MDMA discontinuation. MDMA users had significantly reduced prolactin and cortisol responses in comparison with control individuals (p < 0.001 and p < 0.005, respectively). Dysphoria and mood changes were exhibited in seven individuals, tiredness in five and sensation-seeking behaviour in twelve at the clinical evaluation. Significantly higher scores were found in MDMA individuals than in control individuals for Minnesota Multiphasic Personality Inventory subscale for Depression, for Buss Durkee Hostility Inventory direct and guilt subscales, for Hamilton Depression Rating Scale and for novelty-seeking Tridimensional Personality Questionnaire subscale. Prolactin responses to D-fenfluramine stimulation area under the curve among MDMA users were negatively correlated with direct aggressiveness scores for Buss Durkee Hostility Inventory; a negative correlation between prolactin responses and novelty-seeking scores was also evidenced among MDMA users. These data suggest an association between serotonin system impairment and MDMA use in humans; in interpretation of these results, the possibility that serotonin deficit in MDMA individuals was partially related to a premorbid condition, in relationship with novelty-seeking behaviour and mood disorders, can not be excluded.

Flumazenil effects on growth hormone response to gamma-hydroxybutyric acid.

Gamma-hydroxybutyric acid (GHBA) has been recently introduced for alcohol detoxication but few data are available concerning the central mechanism of action of this gamma-aminobutyric acid (GABA) catabolite. GHBA ability to stimulate growth hormone (GH) and prolactin (PRL) secretion has been reported: the involvement of GABA, dopamine or serotonin systems acting on pituitary hormones has been hypothesized. In the present study we investigated GH and PRL responses to GHBA with or without flumazenil (a benzodiazepine receptor antagonist) i.v. pretreatment. Our study included nine male healthy volunteers (aged 23.2 +/- 2.5 years) who were submitted to three tests in random order: (1) oral GHB administration; (2) oral GHBA and i.v. flumazenil administration; (3) oral placebo and i.v. saline administration. Blood samples for GH and PRL assays were collected during the three tests at -15, 0, 15, 30, 45, 60 and 90 min. GHBA induced a significant increase in GH plasma levels; flumazenil pretreatment antagonized GHBA action on GH secretion. No changes were obtained with placebo and saline administration. A subpopulation of GABA receptors or GHBA-specific receptors seems to be involved in GHBA action. The benzodiazepine receptor antagonist flumazenil was able to influence the sensitivity and the neuroendocrine consequences of GHBA binding site stimulation.

Naloxone and metergoline effects on growth hormone response to gamma-hydroxybutyric acid.

Gamma-hydroxybutyric acid (GHB) has been recently used in alcohol detoxification, but conflicting data are available concerning the central mechanism of action of this GABA catabolite. GHB ability to stimulate growth hormone (GH) secretion has been reported. Our previous studies revealed the ability of flumazenil (a benzodiazepine antagonist) to counteract GHB effects on GH secretion. Other hypotheses, including an opioid or serotonergic role of GHB, have been considered. In the present study we investigated GH responses to GHB with or without naloxone (an opiate receptor antagonist) or metergoline (a serotonin receptor antagonist) pretreatment. This study included 10 male healthy volunteers (aged 24.3 +/- 2.9 years) who were submitted to four tests in random order: (A) oral GHB administration; (B) oral GHB and i.v. naloxone administration; (C) oral GHB and oral metergoline administration; and (D) oral placebo and i.v. saline administration. Blood samples for GH assay were collected during the three tests at -15, 0, 15, 30, 45, 60 and 90 min. GHB induced a significant increase in GH plasma levels; naloxone pretreatment did not antagonize GHB action on GH secretion; metergoline significantly decreased GH response to GHB (p < 0.05). No changes were obtained with placebo and saline administration. The opioid system does not seem to be involved in GHB effects on GH-secreting pituitary cells; GHB effects on the serotonergic system influencing GH secretion, on the other hand, cannot be excluded.

ACTH and beta-endorphin responses to physical exercise in adolescent women tested for anxiety and frustration.

Thirty healthy adolescent women (age: 14 years), high school students without clinical signs of psychiatric or major affective disorders, received psychological and endocrinological examinations. Two psychological tests were used: the Anxiety Score Test for Adolescents and the Pictures Frustration Test for Adolescents of Rosenzweig. On the basis of the results of these tests, subjects were divided into two groups: A (n = 21), normal subjects; B (n = 9), subjects with evidence of anxiety (n = 1), frustration (n = 1), or both (n = 7). Plasma levels of adrenocorticotropic hormone (ACTH) and beta-endorphin were measured under basal conditions and after physical exercise (Step Test) in all subjects. Hormonal responses in groups A and B were compared. Basal concentrations of ACTH and cortisol were similar in the two groups, whereas basal beta-endorphin levels were significantly higher in group B than in group A. Exercise induced a slight but significant increase in plasma concentrations of both ACTH (32% increase) and beta-endorphin (60% increase) in group A. A striking increase in plasma ACTH (100% increment) and a slight increase of beta-endorphin (60% increment) levels were observed in group B after exercise. Absolute levels of ACTH and beta-endorphin after physical exercise were significantly higher in group B than in group A. These findings indicate increased levels of adrenocorticotropic and opioid activity in adolescent women with high scores on psychological measures of anxiety and frustration.

Neurotransmitter-neuroendocrine responses to experimentally induced aggression in humans: influence of personality variable.

Aggressiveness was experimentally induced in 30 psychophysically healthy male subjects, 18-19 years old, divided into 15 cases with low normal and 15 with high normal basal aggressivity. Plasma norepinephrine (NE), epinephrine (EPI), growth hormone (GH), prolactin (PRL), cortisol (CORT) and testosterone (Te) concentrations were measured in basal conditions and during experimentally induced aggressiveness. Basal Te and stimulated NE, GH and Cort levels were higher in subjects with high-normal than in those with low-normal aggressiveness, suggesting that the functional tonus of the NE system and of the NE-dependent hormonal axes might be a modulator of the behavioral parameter.

Serotonin function in detoxified heroin abusers: prolactin and cortisol responses to fenfluramine challenge.

The function of the central serotonergic system was examined indirectly through the measurement of prolactin (PRL) and cortisol responses to fenfluramine challenges in 27 heroin addicts 2 months after detoxification and in nine healthy volunteers. Heroin abusers included nine addicts with comorbid depressive disorders (Group A), nine with aggressive behavior and antisocial personality (Group B), and nine with heroin addiction uncomplicated by other Axis I and II psychiatric disorders (Group C). PRL and cortisol responses of patients in Group A were blunted, while those of patients in Groups B and C did not differ from those of the healthy volunteers. Cortisol responses in Group A differed significantly from those in the other patient groups and in the normal comparison group for AUC analyses, but the diagnosis x time interaction showed a significant difference only between Group A and the normal group. Our data suggest that the function of the serotonergic system is impaired in heroin addicts with comorbid depression but not in heroin addicts who are not clinically depressed. Thus, the serotonergic system does not appear to be impaired by prolonged opioid exposure, per se.

Neuroendocrine responses of healthy volunteers to 'techno-music': relationships with personality traits and emotional state.

A variety of studies reported psychological and physiological effects of music. Different types of music have been found to induce different neuroendocrine changes. The aim of the present experiment was to investigate the possible combination of emotional and endocrine changes in response to techno-music and to define personality variables as predictors of respective changes. Sixteen psychosomatically healthy subjects (18- to 19-year-olds, eight males and eight females) were exposed, in random order, to techno-music or to classical music (30 min each). Plasma norepinephrine (NE), epinephrine (EPI), growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH) cortisol (CORT), beta-endorphin (beta-EP) concentrations and changes of emotional state were measured in basal conditions and after the experimental trials with two different types of music. Techno-music was associated with a significant increase in heart rate, systolic blood pressure and significant changes in self-rated emotional states. A significant increase was observed in beta-EP, ACTH, NE, GH and CORT after listening to techno-music. Classical music induced an improvement in emotional state, but no significant changes in hormonal concentrations. No differences between male and female subjects' responses to music have been found. Plasma levels of PRL and EPI were unaffected by techno- and classical music. Changes in emotional state and NE, beta-EP and GH responses to techno-music correlated negatively with harm avoidance scores and positively with the novelty-seeking temperament score on the Cloninger scale. Listening to techno-music induces changes in neurotransmitters, peptides and hormonal reactions, related to mental state and emotional involvement: personality traits and temperament may influence the wide inter-individual variability in response to music.

Clonidine and opiate receptor antagonists in the treatment of heroin addiction.

Good results in detoxification methods have been reached using both together clonidine and opiate receptors antagonists. One hundred fifty-two heroin-abusing patients were studied evaluating withdrawal symptoms after therapy with (a) clonidine only, (b) clonidine and naltrexone, (c) clonidine and naloxone, and (d) placebos. Treatment results, emotional and behavioral changes, and involvement in psychosocial programs were evaluated after a 6-month follow-up. Although opiate antagonists were able to induce slight and transient withdrawal signs and symptoms, there was, in the group of patients treated with clonidine and naltrexone together, a low percentage of catabolites in urine and an improvement in mood and family relationships. Furthermore, the patients that underwent longer naltrexone treatment showed a stronger involvement in psychosocial programs, and even their relatives demonstrated more interest in the recovery program. A decrease in the difficulties of accepting an opiate antagonists treatment and a different evaluation of withdrawal syndrome were the results of an early use of naltrexone.

[Homeostasis of blood glucose and abuse of exogenous opiates: evaluation of fructosamine and glycosylated hemoglobin]. / Omeostasi glicemica ed abuso di oppioidi esogeni: valutazione della fruttosamina e dell'emoglobina glicosilata.

The study was designed to assess glycaemic homeostasis in different situations of chronic stimulation of the opiate receptors by exogenous opiates. After an OGTT, levels of glycosylated haemoglobin (HbA1c) and serum fructosamine were measured in 3 groups of male drug addicts of comparable age. Group A consisted of 10 subjects undergoing substitution treatment with oral methadone. Group B consisted of 10 subjects addicted to intravenous injection of the syrup based methadone intended for oral administration. Group C consisted of 10 heroin addicts. Ten healthy subjects of the same age and sex were used as controls. Analysis of the results showed normal glucose tolerance in all groups with tendentially higher basal glycaemia levels in group B. HbA1c levels were significantly higher, though within normal limits, in group B than in either those receiving oral methadone (p less than 0.01) or the heroin addicts (p less than 0.01). The group B subjects also showed the highest fructosamine levels that were both well above normal limits and higher than those in the other groups in whom fructosamine levels were normal. The data therefore confirm normal glycaemia compensation in those taking oral methadone and in heroin addicts during the period considered. A new type of drug addiction involving the intravenous injection of methadone was also encountered. This produces an outstanding short-term change in glycaemic homeostasis and may well lead to future alterations in glucose tolerance.

[Risk of accidents to hospital personnel]. / Rischio infortunistico del personale ospedaliero.

The industrial accident phenomenon among personnel on duty in the hospital ambit requires further studies, also for the distinctive aspects that it presents as regards that may be found in the factory. The authors, for this end, have conducted an analysis about industrial accidents happened in the hospitals of Parma in 1977 and in 1978, with reference to the different working qualifications, the sex and the age of the staff, the kind of the suffered lesion, the affected bodily seat and the traumatic event on the occasion of which the injury happened. Moreover distribution per hour of industrial accidents, in relation to shifts as well, their monthly and weekly incidence, compatibly with the difficulties of treatment of the analysis in connection with the heterogeneity, chronological too, of various working services, have been calculated. The above-mentioned survey indicates that the factors that cause a bigger risk of accident are individual factors - sex, age and job - and factors connected both with the kind of internal organization of work and with the structures of working place.

[Clinico-criminological aspects of tattoo removal]. / Aspetti clinico-criminologici in un caso di detatuaggio.

The desire to remove one's tattooes in prison surroundings is unanimously recognized as a positive sign of maturity and rehabilitation. A case of attempted tattoo removal serves to draw attention to some aspects of the motives which underlie such behaviour in order to determine a correct forecast of the real possibilities of the prisoner's recovery. The behavioural and psychological analysis of the case under study confirms the predictive value of the act in that it was coupled with a real request for help on the part of the subject regarding his personal wants and needs. Tattoo removal carried out surgically is concluded to be a useful therapeutic operation with the aim of safeguarding the mental health and rehabilitation of the prisoner.

Neuroendocrine correlates of antisocial personality disorder in abstinent heroin-dependent subjects.

The function of the central alpha-adrenergic, serotoninergic and dopaminergic systems was investigated in 30 heroin-dependent subjects, 6 - 8 weeks after detoxification and in 22 psychophysically healthy controls (group C). Twelve heroin-dependent subjects with antisocial personality disorder (ASPD) (group A), 18 heroin-dependent subjects without other Axis I and II pathologies (group B) were included among abstinent substance abusers. The norepinephrine (NE) function was evaluated by the GH responses to acute stimulation with clonidine (clon); the serotonin (5-HT) function by the PRL and cortisol (CORT) responses to acute stimulation with d-fenfluramine (d-fen) and the dopamine (DA) function was investigated by growth hormone (GH) and prolactin (PRL) responses to acute administration of bromocriptine (brom). Alpha-adrenergic sensitivity, as measured by the GH-clon test, was found significantly reduced in A subjects (ASPD), in comparison with B subjects and controls. PRL and CORT responses to d-fen were significantly blunted both in A and B subjects, in comparison with control subjects. DA receptors sensitivity seems to be reduced significantly in ASPD (A subjects); in contrast, heroin addicts without open psychiatric co-morbidity showed unimpaired responses to brom challenge; a significantly lower GH response to brom and a lack of PRL suppression in ASPD subjects could express D2 postsynaptic receptor hyposensitivity possibly related to DA gene variants associated to co-morbid disorder. In sum, the study of central monoamine function revealed an alteration of the 5-HT system in all detoxified heroin-dependent subjects. A significant reduction of alpha-adrenergic receptors sensitivity and the hyposensitivity of postsynaptic DA receptors in ASPD subjects suggest once again that specific biological correlates of psychiatric co-morbidity may characterize substance abusers subtypes.