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Biomedical subjects

F Brambilla

Publications and source records attributed to F Brambilla.

At least 37 records · Page 2Linked to original sources

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.

Adrenergic alpha-Agonists↗

Psychoneurendocrinology: a science of the past or a new pathway for the future?

Psychoneuroendocrinology is a branch of neuroscience that developed in the beginning of the last century, which investigates the possibility of a cause-effect link between endocrinopathies and mental disorders - with these studies ending in negative results. Psychoneuroendocrinology was then used as a methodological approach for the investigation of neurotransmitter function, on the basis of the observation that neurotransmitters regulate neurohormone and peripheral hormone secretions. Data were obtained for hypothalamic noradrenergic, serotoninergic, dopaminergic, gabaergic and acetylcholinergic functions, which could not be automatically extended to higher brain centers whose impairments might be etiopathogenetically involved in the development of mental disorders. Future studies should focus on new methodological approaches to brain biochemistry, on investigation of genetic, molecular biology, brain imaging, psychoneuroimmunoendocrinology, neuropeptide and neurosteroid secretion in relation to brain endocrine function in mental diseases.

Animals↗

Long-lasting effects of (+/-)3,4-methylenedioxymethamphetamine (ecstasy) on serotonin system function in humans.

BACKGROUND: Fifteen (+/-)3,4-Methylenedioxymethamphetamine (MDMA) users, who did not show other drug dependencies or prolonged alcohol abuse, and 15 control subjects were included in the study. METHODS: Prolactin (PRL) and cortisol (CORT) responses to the serotonergic agonist d-fenfluramine (D-fen), clinical psychobehavioral changes, and psychometric measures were evaluated 3 weeks and then 12 months after MDMA discontinuation. RESULTS: MDMA users showed significantly reduced PRL and CORT responses in comparison with control subjects at 3 weeks (respectively, p < .001; p < .005). The responses of PRL to D-fen were unmodified at 12 months after prolonged abstinence and were significantly reduced in comparison with controls (p < .001). In contrast, CORT responses in MDMA users were restored after 12 months of abstinence, with significantly higher responses to D-fen, in comparison with 3-week responses (p < .05). MDMA users' high scores on the Novelty Seeking (NS) scale on the Tridimensional Personality Questionnaire (TPQ) appeared unchanged by long-term abstinence. In contrast, Buss Durkee Hostility Inventory (BDHI) (Buss and Durkee 1957) direct and guilt scores decreased significantly after 12 months of abstinence. PRL AUCs at 12 months were inversely correlated with the measures of MDMA exposure (r = -.538). CONCLUSIONS: Our data indicate long-lasting 5-HT system impairment in abstinent MDMA users although the hypothesis of serotonergic changes attributable to a premorbid condition cannot be excluded. CORT restored responses to D-fen at 12 months, and the correlation of neuroendocrine changes with MDMA exposure suggest that the neuroendocrine impairment may be due to a partially reversible neurotoxic action of MDMA on the human brain.

Adolescent↗

Neuroendocrine correlates of temperamental traits in humans.

Studies investigating temperament traits in humans and their biological correlates have found high levels of novelty seeking (NS) linked with dopaminergic system changes, and particularly a deficit of dopamine transporter. Harm avoidance and reward dependence, on the other hand, appeared to be associated, respectively with serotonin and noradrenaline changes. In the present study, we have investigated the dopaminergic (DA), serotonergic (5-HT), and noradrenergic (NE) functions in healthy volunteers by challenging the monoamine systems with the DA agonist bromocriptine, the 5-HT agonist D-fenfluramine, and the NE agonist clonidine, respectively. Parallel to this investigation, we examined the temperament traits of our subjects by measuring NS, harm avoidance (HA) and reward dependence (RD) using the 'Three-dimensional Personality Questionnaire' (TPQ). The aims of the study were to see whether or not the monoamine functions were correlated with temperament traits. Bromocriptine challenge induced a significant GH increase and a significant suppression of PRL. D-fenfluramine test significantly increased PRL and cortisol plasma levels and Clonidine test induced a significant rise in GH values. NS scores showed a significant direct correlation with brom-stimulated GH values (r=0.426, P<0.05) and a significant inverse correlation with brom-inhibited PRL values (r=-0.498, P<0.01). HA scores correlated significantly with D-fen-stimulated PRL and CORT AUCs, (PRL: r=0.424, P<0.05; CORT: r=0. 595, P<0.005). RD scores correlated positively with clon-stimulated GH values (r=0.55; F=8.6; P<0.01) and negatively with brom-inhibited-PRL AUCs (r=-0.439, P<0.05). Our data support Cloninger theory concerning the biological correlates of temperamental traits, and evidence the link between the neuroendocrine responses to dynamic challenges and stable temperament features.

Adrenergic alpha-Agonists↗

Dopamine function in obsessive compulsive disorder: cortisol response to acute apomorphine stimulation.

Central dopaminergic dysfunction has been suggested to be involved in the pathogenesis of obsessive compulsive disorder (OCD). In 15 patients with OCD and in 15 age-sex matched controls we evaluated the dopamine (DA) function by measuring the cortisol (CORT) responses to stimulation with the DA agonist apomorphine (APO). The CORT response to acute saline administration was also measured, to exclude the existence of a pathology of the circadian secretion of the hormone which could obscure the significance of the CORT response to APO stimulation. Basal levels of CORT were the same in patients and controls, but the values after saline administration were significantly higher in patients than in controls. APO stimulation-induced CORT rises were significantly higher in patients than in controls, but when the data after APO were corrected for those after saline, there were no significant difference between the two groups of subjects. Our data suggest that there are no alterations of the central dopaminergic function connected with the regulation of the hypothalamo-pituitary-adrenal axis in OCD.

Adolescent↗

Neuroendocrine correlates of temperament traits in abstinent opiate addicts.

PURPOSE: Studies investigating temperament traits of drug abusers and their biological correlates have disclosed high rates of novelty seeking (NS) in opiate addicts, possibly based on dysfunctions of the dopaminergic (DA) system. The aims of the present study were to see whether or not the monoamine functions were impaired in detoxified addicts and whether or not these alterations were correlated with temperament traits, given the possibility that impairment of the biological and temperament parameters might be responsible for the development of addiction. METHODS: We have investigated the DA, serotonergic (5-HT), and noradrenergic (NE) functions in 22 abstinent heroin addicts and 22 healthy controls by challenging the monoamine systems with the DA agonist bromocriptine (brom), the 5-HT agonist D-fenfluramine (D-fen), and the NE agonist clonidine (clon), respectively. We examined the temperament traits by measuring NS, harm avoidance (HA), and reward dependence (RD) using the "Three-Dimensional Personality Questionnaire" (TPQ). RESULTS: Addicts showed higher than normal NS scores at TPQ blunted 5-HT function, and normal DA and NE activities, in response to the neuroendocrine challenges. NS correlated negatively with the DA function in both addicts and controls, and negatively with the 5-HT function only in addicts. HA correlated positively with 5-HT function in controls but not in addicts. IMPLICATIONS: The impairment in 5-HT function observed in heroin addicts and the changes in the biological correlates of temperamental traits could increase the proneness to addiction and possible comorbid psychiatric disorders.

Adult↗

Serotonergic dysfunction across the eating disorders: relationship to eating behaviour, purging behaviour, nutritional status and general psychopathology.

BACKGROUND: Several recent studies have pointed to a dysfunction of serotonin transmission in patients with eating disorders. Notwithstanding, it is not known whether serotonergic abnormalities are related primarily to eating and/or purging behaviour, nutritional status or general psychopathological dimensions. Therefore, by using a validated neuroendocrine strategy, we investigated central serotonergic function in patients with anorexia nervosa, bulimia nervosa or binge-eating disorder who differ on the above parameters. METHODS: Plasma prolactin response to D-fenfluramine (30 mg p.o.) or placebo was measured in 58 drug-free female volunteers, comprising 15 underweight anorexic women, 18 bulimic women, 10 women with binge-eating disorder and 15 female healthy controls. Behavioural assessment included ratings of eating disorder symptoms, depression, aggression and food-related obsessions and compulsions. RESULTS: A significantly decreased prolactin response to D-fenfluramine was found in underweight anorexic women and in bulimics with high frequency bingeing ( > 2 binge episodes/day), but not in patients with binge-eating disorder or in bulimics with low frequency bingeing (< I binge episode/day). In the whole bulimic group, a negative correlation emerged between frequency of bingeing and prolactin response. No significant correlation was found between physical or psychopathological measures and the hormonal response in any group. CONCLUSIONS: These results confirm our previous findings of an impaired serotonergic transmission in underweight anorexics and in bulimics with high frequency bingeing, but not in patients with less severe bulimia nervosa. Moreover, they show, for the first time, that the hypothalamic serotonergic system is not altered in women with binge-eating disorder.

Adult↗

Neuroendocrine responses to psychological stress in adolescents with anxiety disorder.

Neurotransmitter-neuroendocrine and cardiovascular responses to the administration of a psychologically stressful mixed-model test (Mental Arithmetic, Stroop Color Word Interference Task, Trier Social Stress Test) were examined in 20 male peripubertal subjects affected by anxiety disorder (group A: 14 with generalized anxiety disorder, 6 with generalized anxiety disorder and separation anxiety disorder) and 20 junior school adolescents, matched for age, without overt psychological disorders (group B). Plasma levels of norepinephrine (NE), epinephrine (EPI), adrenocorticotropic hormone (ACTH), beta-endorphin (beta-EP), cortisol (CORT), growth hormone (GH), prolactin (PRL) and testosterone (Te) were measured immediately before the beginning of the tests and 30 min later at their end. Mean prestress values of GH, PRL, beta-EP and ACTH were significantly higher in anxious subjects than in controls. There was no difference in NE, EPI, CORT and Te prestress levels in the two groups. After the psychological stress session NE, GH and Te concentrations increased significantly in anxious subjects (A), but not in controls. In contrast, beta-EP and PRL decreased significantly during the psychological stress session in anxious subjects, and were unaffected by stress in the subjects without anxiety. No significant changes were found in ACTH, CORT and EPI during the challenge either in anxious subjects or in controls, which may be attributed to the late time of poststress blood sampling. In contrast to controls, heart rate and systolic blood pressure increased significantly in anxious subjects after psychological stress testing. Our data support the hypothesis that the hyperactivity of the noradrenergic system in response to stress is associated with anxiety disorders in adolescents and might influence the responses of GH and Te. High prestress basal values of stress hormones seem to be induced in anxious subjects by the anticipation of the task or by a persistent hyperactivity of the noradrenergic system. Further studies are needed to investigate in more detail the involvement of the HPA axis in anxious adolescents by a more refined resolution of time points of blood sampling.

Adolescent↗

Plasma levels of tumor necrosis factor-alpha in patients with panic disorder: effect of alprazolam therapy.

Plasma concentrations of tumor necrosis factor-alpha (TNF-alpha) were measured in 10 outpatients with panic disorder, twice (at a 48-h interval) before and twice on days 30-32 of treatment with alprazolam (2-2.5 mg/day), and twice in 10 age- and sex-matched healthy controls. TNF-alpha concentrations did not differ in patients and control subjects, either before therapy or at days 30-32 of therapy. In five patients before therapy, and in three of them after therapy, TNF-alpha values were higher than the maximal concentrations of the cytokine in controls.

Adult↗

Neurotransmitters, neuroendocrine correlates of sensation-seeking temperament in normal humans.

Correlations between sensation-seeking (SS) personality dimension and plasma concentrations of norepinephrine (NE), epinephrine, and NE-dependent testosterone (T), cortisol and prolactin (PRL) were studied in 74 physically and psychologically healthy male volunteers, in order to see whether or not the noradrenergic system is involved in the modulation of this personality trait. Novelty-seeking scores by the Temperament and Character Inventory and SS scores on a Visual Analog Scale were positively correlated with plasma NE, T and PRL levels, suggesting that NE and the downstream cascade of NE-dependent hormones, together with other monoaminergic changes, might be responsible for the development and the degree of this temperamental character.

Adult↗

Experimentally induced aggressiveness in adult children of alcoholics (ACOAs): preliminary behavioral and neuroendocrine findings.

OBJECTIVE: This study was conducted to determine the nature of the reaction of nonalcoholic adult children of alcoholic (ACOA) fathers to the experimental induction of aggression. Of particular interest was the relationship between biochemical factors and personality traits during a stressful event experienced by persons at risk for alcoholism. METHOD: Aggression was induced by a modified free-operant procedure in 14 ACOA and 14 non-ACOA subjects between 18 and 19 years of age with men and women represented in equal numbers. Neurotransmitter-hormonal assays from blood drawn immediately before, and 20 and 30 minutes after, starting the test included norepinephrine (NE), epinephrine (EPI), prolactin (PRL), growth hormone (GH) and cortisol (Cort). Personality traits were assessed by the Minnesota Multiphasic Personality Inventory (MMPI) Tridimensional Personality Questionnaire (TPQ) and the Buss-Durkee Hostility Inventory (BDHI). RESULTS: During the aggression induction session, ACOAs gained (F = 4.6, 1/13 df, p < .05) and subtracted (F = 9.2, 1/13 df, p < .005) significantly less money than non-ACOAs, evidence of lower outward-directed aggressiveness among ACOAs. Higher baseline plasma levels of Cort (F = 9.8, 1/13 df, p < .01) and PRL (F = 4.0, 1/13 df, p < .05) and decreased NE (F = 8.5, 1/13 df, p < .005) and GH (F = 10.9, 1/13 df, p < .001) responses during the experimental session were observed. On personality measures ACOAs scored higher than non-ACOAs on MMPI hysteria (F = 10.8, 1/13 df, p < .005), hypochondria (F = 20.1, 1/13 df, p < .001) and paranoia (F = 4.7, 1/13 df, p < 0.5) subscales, on the TPQ reward dependence (F = 10.9, 1/13 df, p < .005) subscale and on BDHI guilt (F = 15.7, 1/13 df, p < .001) and resentment (F = 6.4, 1/13 df, p < .05) subscales. CONCLUSION: These findings, preliminary in nature, support a hypothesis of inhibition of state and trait aggression in ACOAs in association with monoaminergic and endocrine changes.

Adolescent↗

Growth hormone response to growth hormone-releasing hormone stimulation in obsessive-compulsive disorder.

Two groups of 30 patients with obsessive-compulsive disorder and 30 age- and sex-matched healthy control subjects were given a growth hormone-releasing hormone (GHRH) stimulation test to determine: (1) whether the downstream function of the somatotropic axis (growth hormone = GH, somatomedin-C = SMD-C) was impaired; (2) what might be the central alteration responsible for such impairment; and (3) whether alterations might be linked to the etiopathogenesis of the disease. Basal values of GH and SMD-C were the same in patients and control subjects, but GH responses to GHRH stimulation were significantly lower in patients than in control subjects. The absence of a pathology of basal GH and SMD-C concentrations indicates that the blunted GH responses to GHRH stimulation are not due to a negative feedback mechanism and suggests that a central neurotransmitter-neuropeptide pathology might be involved in the phenomenon.

Adolescent↗

GABAergic function in detoxified heroin addicts: relationship to anxiety disorders.

The function of the GABAergic system was examined in 20 subjects with heroin dependence and abuse, 2 months after detoxification, and in 10 healthy volunteers, by measuring the growth hormone (GH) response to a challenge with the GABA B receptor agonist baclofen. Ten heroin addicts had comorbid anxiety disorder (Group A), while the other ten had heroin addiction uncomplicated by Axis I and II psychopathologies (Group B). GH responses to baclofen stimulation of Group A patients were significantly blunted, while those of Group B subjects did not differ from responses of healthy volunteers. Our data show that the function of the GABAergic system is impaired only in heroin addicts with comorbid anxiety disorders (anxious cluster), suggesting that the GABA system is not persistently influenced by prolonged exposure to opioid receptor stimulation.

Adult↗

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↗

Plasma concentrations of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha in anorexia and bulimia nervosa.

Plasma interleukin-1 beta (Il-1 beta) interleukin-6 (Il-6) and tumor necrosis factor-alpha (TNF-alpha) concentrations were measured in 26 women with Anorexia Nervosa (AN), nine of the restricted type (AN-R) and 17 of the binge-eating/purging type (AN-BP), in 24 women with Bulimia Nervosa (BN) and in 26 healthy age- and sex-matched controls. Concentrations of the cytokines were measured at the beginning of the study before starting any treatment and then after 1 and 3 months of combined cognitive-behavioral and pharmacological therapy (fluoxetine for AN-R and AN-BP, amineptine for AN-BP and BN, and fluvoxamine for BN). Basal values of Il-1 beta, Il-6 and TNF-alpha, were the same in patients and controls and did not change during treatments, in spite of the improvement of the mental disorders. This seems to exclude the possibility that alterations of basal plasma cytokine secretion are involved in the etiopathogenesis of AN and BN.

Adolescent↗

Plasma prolactin response to D-fenfluramine is blunted in bulimic patients with frequent binge episodes.

BACKGROUND: Abnormalities of brain serotonin (5-HT) transmission have been implicated in the pathophysiology of bulimia nervosa (BN), but no conclusive data have yet been provided. The purpose of this study was to assess 5-HT transmission via the measurement of the prolactin (PRL) response to the specific 5-HT releasing agent D-fenfluramine (D-FEN) in both patients with BN and comparison subjects. METHODS: According to a double-blind placebo-controlled design, plasma PRL response to D-FEN was measured in 14 drug-free bulimics and 14 matched healthy controls. In both patients and controls, eating-related psychopathology, depressive and obsessive-compulsive symptoms, and aggressiveness were measured by rating scales. RESULTS: Baseline plasma levels of PRL and 17 beta-oestradiol were significantly reduced in bulimic patients, whereas basal plasma levels of cortisol did not significantly differ from healthy controls. PRL response to D-FEN was not different between patients and controls as groups, but it was significantly blunted in bulimics with high frequency bingeing (> or = 2 binge episodes per day; N = 7) as compared to both those with low frequency bingeing (< or = 1 binge episode per day; N = 7) and matched controls. A significant negative correlation emerged between the frequency of binge episodes and the hormone response to D-FEN. Moreover, although patients scored higher than healthy subjects on rating scales assessing depressive and obsessive-compulsive symptoms and aggressiveness, no significant correlation was found between these measures and the PRL response to D-FEN. CONCLUSIONS: These results support the idea that serotonin transmission is impaired in bulimic patients with frequent binge episodes.

Adult↗

Blood levels of cytokines in elderly patients with major depressive disorder.

Plasma concentrations of interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNFalpha) were measured in 10 elderly women with major depressive disorder (MDD) and in two groups of controls, one consisting of 10 age-matched healthy female volunteers and one consisting of 10 young healthy female volunteers. The cytokine concentrations were measured in MDD patients before and after 30 days of treatment with phosphatidylserine (BC-PS), 600 mg daily p.o. The plasma IL-Ibeta, IL-6 and TNFalpha concentrations did not differ significantly in young controls, elderly controls and MDD patients. BC-PS therapy, while significantly improving the depressive symptoms, did not alter the cytokine concentrations.

Administration, Oral↗