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R Caccavari

Publications and source records attributed to R Caccavari.

At least 19 recordsLinked to original sources

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.

Adrenergic alpha-Agonists↗

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.

Adolescent↗

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.

Adolescent↗

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.

Adolescent↗

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.

Adolescent↗

Serotonergic function in mothers of opioid addicts: correlation with comorbid depression.

The serotonergic (5-HT) function of 36 mothers of heroin addicts, of whom 16 subjects were without psychopathological features (group A) and 20 subjects had major depressive disorders (group B), as well as 10 age- and sex-matched healthy controls, was examined by L-D-fenfluramine stimulation of secretion of prolactin (PRL) and cortisol. The subjects' addict relatives were also tested for personality features and hormonal responses to L-D-fenfluramine. The PRL and cortisol responses to the stimulus were normal in mothers of group A, and blunted in mothers of group B. A high frequency (70%) of heroin addicts with comorbid depression was found among the sons of group B mothers. The sons of depressed mothers showed reduced PRL and cortisol responses to fenfluramine. A significant direct correlation has been demonstrated between the PRL areas under curves (AUC) of mothers and sons in response to the 5-HT agonist. Our data suggest that genetic 5-HT impairment is not involved in the pathogenesis of heroin addiction or codependence per se, and is probably linked to the presence of familial depression in comorbidity with the addictive disorder.

Adult↗

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.

Adolescent↗

Neuroendocrine responses to emotional arousal in normal women.

The neuroendocrine effects of many stressful challenges and experimentally induced emotional states have been investigated in humans, but few data are available concerning the psychobiological correlates of the emotional arousal induced by TV violence, fear and conflictual emotions. In this study we evaluated cardiovascular, hormonal and mood changes induced by the view of a violent or, in random order, neutral movie in 20 healthy young women. The emotional arousal was associated with a significant increase in heart rate, systolic blood pressure and significant changes in self-evaluated mood states. beta-Endorphin, adrenocorticotrophic hormone, epinephrine and growth hormone showed a significant increase during emotional arousal, with a significant interaction mood-time. Cortisol increased significantly during the violent movie (areas under curves analysis), but not significant interaction mood-time has been demonstrated. Prolactin and norepinephrine levels did not show a significant change during the emotional stimulus. Our data evidence the existence of neuroendocrine changes associated with the defence mechanism and aroused by movie violence and conflictual situations.

Adult↗

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.

Adult↗

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.

Adult↗

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.

Adult↗

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.

Adult↗

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.

Administration, Oral↗

Alpha-1- and 2-adrenoceptor subsensitivity in siblings of opioid addicts with personality disorders and depression.

Noradrenergic receptor sensitivity of 16 healthy male siblings of heroin addicts and of 8 age and sex-matched controls was examined by administering a clonidine stimulation test and by measuring the resulting growth hormone (GH) (alpha-2-adrenoceptors) and beta-endorphin (beta-endorphin) (alpha-1-adrenoceptors) responses. Siblings were divided into two groups: A = siblings of heroin addicts with personality disorders and high aggressivity and B = siblings of heroin addicts without mental disorders. The GH and beta-endorphin responses to clonidine were blunted in group A subjects compared with controls and normal in group B.

Adult↗

Alpha-2-adrenoceptor sensitivity in heroin addicts with and without previous attention deficit disorder/hyperactivity and conduct disorder.

Growth hormone (GH) and beta-endorphin (beta-EP) responses to clonidine stimulation were examined in 18 male heroin addicts, 9 with and 9 without previous histories of attention deficit disorder with hyperactivity (ADD-H) and conduct disorder (CD). Ten psychophysically healthy volunteers were used as controls. ADD-H/CD addicts had blunted GH and beta-EP responses as compared to controls while those of non-ADD-H/CD addicts were normal. This suggests that postsynaptic adrenoceptor sensitivity is decreased and, possibly, that presynaptic noradrenaline secretion is increased in ADD-H/CD patients with heroin addiction.

Adolescent↗

Parental divorce and neuroendocrine changes in adolescents.

Plasma noradrenaline (NE), adrenocorticotrophic hormone (ACTH), growth hormone (GH), prolactin (PRL) and luteinizing hormone (LH) concentrations were examined in basal conditions and after stimulation by the step test in two groups of psychophysically healthy adolescent girls, 18 from divorced families and 16 from non-divorced families. Basal NE, ACTH, GH, PRL values did not differ in the two groups, whereas those of LH were significantly lower in the adolescents from divorced parents than in those from non-divorced families. Responses of NE and ACTH to the stimulus were normal, of GH and PRL were weaker, and of LH slightly weaker in children of divorced parents. An impaired catecholaminergic and serotoninergic tonus in children of disrupted families might underly the hormonal alterations.

Adolescent↗

Noradrenergic and hormonal responses to physical exercise in adolescents. Relationship to anxiety and tolerance to frustration.

Seventy physically healthy 14-year-old adolescents, 40 boys and 30 girls, were evaluated psychologically and endocrinologically. After the psychological tests (Anxiety Score Test for Adolescents, Rosenzweig, Pictures Frustration Test for Children), subjects were divided into group A, with low anxiety/sense of guilt and high self-esteem/tolerance to frustration and group B with the opposite. In both groups, we measured basal plasma levels of noradrenaline (NE), growth hormone (GH), prolactin (PRL), melatonin (MT) and luteinizing hormone (LH) and their response to physical exercise (the Harvard step test). Basal levels of the hormones and of NE were not different in the two groups. After the physical stimulus, NE levels rose significantly more in B girls than in A and significantly less in B than in A boys. GH and PRL levels increased only in A girls and MT in B boys, while LH levels decreased in A boys and girls but not in B subjects.

Adolescent↗

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.

Adolescent↗