Biomedical subjects

F Brambilla

Publications and source records attributed to F Brambilla.

At least 19 recordsLinked to original sources

PubMed2007

Perceived parenting behavior in the childhood of cocaine users: relationship with genotype and personality traits.

Low parental care during childhood, a pattern characteristic of an "affectionless control" rearing style was frequently reported in the history of addicted individuals. Parents' childrearing regimes and children's genetic predispositions, with their own behavioral characteristics, have been seen to be closely interwoven, probably affecting children's development and addictive behavior susceptibility. In the present study, parents care perception, aggressive personality traits, and genotype (serotonin transporter promoter gene--5-HTTLPR) have been investigated in cocaine users and healthy control subjects. PBI scores (maternal and paternal care) were lower and BDHI scores (aggressiveness) higher in cocaine users in comparison with controls and significant differences in the perception of either paternal or maternal care were observed between cocaine users and non-users. The short-short (SS) genotype frequency was significantly higher among cocaine users compared with control subjects (P = 0.04). Logistic regression proves that persons bearing the SS genotype have a risk of becoming cocaine user almost three times higher than those having the LL genotype. Estimations of the effects of other factors potentially affecting the risk of being cocaine addicted clearly prove the significant impact of aggressiveness: the highest the score, the highest the risk of becoming cocaine user. Moreover, paternal and maternal care perception significantly improve the fit of the model (the log likelihood decreases passing from -105.9 to -89.8, LR test = 32.17, P-value = 0.0000). Each unit increase in the PBI score yields a significant 12% and 10% decrease of the risk of becoming cocaine user, respectively for paternal and maternal care. Interestingly, once controlled for the PBI score, the relative risk associated to the SS genotype drops strikingly and becomes no longer statistically significant. On the whole, our preliminary data suggest that the association between 5-HT transporter polymorphism and psycho-stimulant use may be mediated by mother-child relationship and parental attachment perception, both being environmental and genetic factors involved in the proneness to substance use disorders, particularly in aggressive-antisocial individuals.

Adolescent↗

PubMed2005

Association of the serotonin transporter promoter polymorphism with smoking behavior among adolescents.

Serotonin transporter promoter polymorphism (5-HTTLPR) genotype was previously found associated with smoking behavior, difficulty in quitting smoking, and nicotine addiction; with non-replicated findings and contrasting results. Aim of the present study was to evaluate the possible association between 5-HTTLPR genotype and smoking behavior among adolescents, in relationship with psychological characteristics. Two hundred and ten Caucasian high school students (aged 14-19 years); 103 non-smokers, who have never smoked nicotine; and 107 tobacco smokers have been genotyped. Aggressiveness levels and temperamental traits were measured in both smokers and non-smokers, respectively, utilizing Buss-Durkee Hostility Inventory (BDHI) and Cloninger Three-Dimensional Personality Questionnaire (TPQ). Data about school performance have been also collected. The short-short (SS) genotype frequency was significantly higher among smokers compared with non-smokers (P = 0.023). The odds ratio for the SS genotype versus the long-long (LL) genotype frequency was 1.17 [95% CL (0.30-2.05)], when smokers were compared with non-smokers. The SS genotype frequency was significantly higher among heavy smokers with early onset, compared with moderate smokers with late onset (P = 0.042). BDHI irritability scores, NS scores at TPQ, and school failure frequency were significantly higher in smokers than in non-smokers. Multivariate model-fitting analysis evidenced a significantly greater relationship of genotype with irritability levels (BDHI scores) (0.34, P < 0.001) and temperament traits (NS scores) (0.36, P < 0.001), than with school performance (rate of school under-achievements) (0.18, P < 0.05) and nicotine smoking (number of cigarettes) (0.24, P < 0.01). Accordingly, factor-analysis showed that gene polymorphism contributes more directly to BDHI scores and NS scores (0.73; 0.71) than to smoking behavior and school under-achievement (0.54; 0.51). Our data suggest that a decreased expression of the gene encoding the 5-HTT transporter, due to "S" promoter polymorphism, may be associated with smoking behavior among adolescents and increased risk to develop nicotine dependence, possibly in relationship to personality traits, temperamental characteristics, and school under-achievements.

Achievement↗

PubMed2005

Serotonin transporter promoter polymorphism genotype is associated with temperament, personality traits and illegal drugs use among adolescents.

Serotonin transporter promoter polymorphism (5-HTTLPR) genotype was previously found associated with substance use disorders, particularly in the subjects with comorbid antisocial behavior, and with temperament and personality traits at risk for substance abuse. Aim of the present study was to evaluate the possible association between 5-HTTLPR genotype and the availability to experiment illegal drugs among adolescents, in relationship with psychological characteristics. 216 caucasian high school students (aged 14-19 ys), 125 abstinent subjects, who have never experimented psychotropic drugs, and 91 experimenters of illegal drugs have been genotyped. Aggressiveness levels and temperamental traits were measured in both abstinent subjects and experimenters utilizing respectively Buss-Durkee-Hostility-Inventory (BDHI) and Cloninger Three-dimensional Personality Questionnaire (TPQ). Data about school performance have been also collected. The short-short (SS) genotype frequency was significantly higher among experimenters compared with abstinent subjects (p = 0.001). The odds ratio for the SS genotype vs the long-long (LL) genotype frequency was 4.67, 95% Cl (1.97-11.04), when experimenters were compared with abstinent students. The SS genotype frequency was significantly higher among aggressive/novelty seeker (NS) experimenters with poor school achievements, compared with drugs experimenters without aggressiveness and school failure (p = 0.02). When evaluated on the entire sample, BDHI mean total scores, NS scores at TPQ and school failure frequency were significantly higher in SS individuals, in comparison with LL subjects. Our data suggest that a decreased expression of the gene encoding the 5-HTT transporter, due to "S" promoter polymorphism, may be associated with an increased availability to experiment illegal drugs among adolescents, particularly in the subjects with more consistent aggressiveness, NS temperament and learning disabilities.

Adolescent↗

PubMed2004

Association between low-activity serotonin transporter genotype and heroin dependence: behavioral and personality correlates.

In previous studies, serotonin (5-HT) system disturbance was found involved in a variety of behavioral disorders, psychopathologies, and substance use disorders. A functional polymorphism in the promoter region of the human serotonin transporter gene (5-HTTLPR) was recently identified and the presence of the short (S) allele found to be associated with a lower level of expression of the gene, lower levels of 5-HT uptake, type 2 alcoholism, violence and suicidal behavior. In the present study, 101 heroin addicts (males, West European, Caucasians) and 101 healthy control subjects matched for race and gender, with no history of substance use disorder, have been genotyped. Aggressiveness levels were measured in both heroin addicts and controls utilizing Buss-Durkee-Hostility-Inventory (BDHI). Data about suicide attempt and violent criminal behavior in subject history have been collected. The short-short (SS) genotype frequency was significantly higher among heroin dependent individuals compared with control subjects (P = 0.025). The odds ratio for the SS genotype versus the long-long (LL) genotype frequency was 0.69, 95% Cl (0.49-0.97), when heroin addicts were compared with healthy controls. The SS genotype frequency was significantly higher among violent heroin dependent individuals compared with addicted individuals without aggressive behavior (P = 0.02). BDHI mean total scores and suspiciousness and negativism subscales scores were significantly higher in SS individuals, in comparison with LL subjects, among heroin addicts. No association was found between SS genotype and suicide history. Our data suggest that a decreased expression of the gene encoding the 5-HTT transporter, due to "S" promoter polymorphism, may be associated with an increased risk for substance use disorders, particularly in the subjects with more consistent aggressiveness and impulsiveness.

Adult↗

PubMed2004

Analysis of monoamine oxidase A (MAO-A) promoter polymorphism in male heroin-dependent subjects: behavioural and personality correlates.

The promoter of the monoamine oxidase A (MAO-A) gene was analysed to test whether length variation of the repeat polymorphism contributes to variation in individual vulnerability to aggressive-criminal behaviour, and liability to heroin dependence. The repeat number of the MAO-A polymorphism was assessed in 199 male subjects of Italian descent, a sample comprising 95 healthy subjects and 104 heroin-dependent subjects including 52 addicted individuals with violent behaviour and antisocial personality disorder. The frequency of the low-activity 3-repeat allele was significantly higher in violent offenders among heroin addicts, compared to addicted individuals without antisocial behaviour (34.6 vs. 15.4%; p<0.03) and controls (18.9%; p<0.05). No significant difference was evidenced in the frequencies of the MAO-A alleles between heroin-dependent subjects in general and control subjects. High activity 4-repeat allele frequency was significantly higher in addicted individuals without antisocial behavior compared to antisocial-aggressive heroin-dependent subjects (76.9 vs. 55.8%; p<0.02). Buss Durkee Hostility Inventory (BDHI) mean total scores were significantly higher in heroin addicts than in controls (p<0.001), and in antisocial-violent heroin addicts in comparison with addicted individuals without antisocial behaviour (p<0.005). Among heroin addicts BDHI irritability, suspiciousness and resentment subscales scores were found significantly higher in low activity 3-repeat allele subjects than in high activity alleles subjects (p<0.001; p<0.05; p<0.05, respectively). No association was found between MAO-A polymorphism and suicide history. Our findings suggest that the low-activity 3-repeat allele of the MAO-A promoter polymorphism confers increased susceptibility to antisocial-violent behavior and aggressiveness, rather than drug dependence per se, in heroin-dependent males.

Adult↗

PubMed2004

Interleukin-1beta and tumor necrosis factor-alpha in children with major depressive disorder or dysthymia.

BACKGROUND: Immune function is altered in adult depressed patients. The aim of our study was to see whether or not cytokine secretion is impaired at a very young phase of development of depressive disorders, possibly being pathogenetically involved in their course. METHODS: Basal plasma concentrations of interleukin-1beta (Il-1beta) and tumor necrosis factor-alpha (TNF-alpha) were measured radioimmunologically in 22 drug-free children-adolescents, 11 with recurrent major depressive disorders (MDD) and 11 with dysthymia (DYS), and in 11 psychophysically healthy age-sex matched controls. Depression was monitored using the Poznanski Rating Scale and Anxiety with the Reynold Rating Scale. RESULTS: Il-1beta levels were not significantly different in MDD from controls and significantly higher than normal in DYS subjects. TNF-alpha levels were not significantly different in MDD patients from controls and significantly lower than normal in DYS patients. Cytokine concentrations were correlated with anxious and depressive symptomatology in MDD but not in DYS patients. CONCLUSIONS: There is a cytokine pathology in depressive disorders of obscure etiopathogenetical significance.

Adolescent↗

PubMed2004

Intestinal permeability is decreased in anorexia nervosa.

Malnutrition and absence of exogenous luminal nutrients in the gastrointestinal tract affect intestinal permeability (IP) leading to an increased penetration of substances that passively cross intestinal epithelium via intercellular pathways. We hypothesised that an increase in IP could occur in patients with anorexia nervosa because of their prolonged fasting and chronic malnutrition. Therefore, we assessed IP in 14 drug-free anorexic women and 19 drug-free age-matched healthy women by means of the lactulose/mannitol (LA/MA) test. To this purpose, after an overnight fast, subjects ingested an oral solution containing 5 g lactulose and 2 g mannitol in 100 ml water. Urine specimens were collected immediately before and 30, 60, 120, 180, 240 and 300 min after the ingestion of the sugar solution. Urinary lactulose and mannitol were determined by high-performance anion exchange chromatography coupled with pulsed amperometric detection. We found that IP, as expressed by the 5-h LA/MA excretion ratio, was significantly decreased in anorexic women because of a lower urinary recovery of lactulose. Moreover, in patients, the time course of lactulose excretion significantly differs from healthy controls. These results do not confirm our hypothesis of increased IP in anorexia nervosa. Since IP reflects the anatomo-functional status of intestinal mucosa, the present findings support the idea that changes in the anatomo-physiology of intestinal mucosa occur in anorexia nervosa.

Adult↗

PubMed2003

Neuroendocrine responses to experimentally-induced emotions among abstinent opioid-dependent subjects.

The present study investigated neuroendocrine and cardiovascular changes during experimentally-induced affective states in abstinent heroin-dependent subjects and healthy controls. The procedure for eliciting emotions in all subjects used pleasant and unpleasant stimuli that did not differ in subjective arousal properties. We investigated whether the valence of the stimuli differentially affected neuroendocrine responses by comparing neutral, pleasant and unpleasant pictures on heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP), methyl-OH-phenyl-glycol (MHPG), norepinephrine (NE), epinephrine (EPI), adrenocorticotrophic hormone (ACTH) and cortisol (CORT) plasma levels. Twelve abstinent heroin-dependent subjects, in comparison with 12 control subjects, were submitted to three experimental sessions, each on one of three experimental days a week apart, in counterbalanced order: day 1=unpleasant pictures, day 2=pleasant pictures, day 3=neutral pictures. In the rating of subjective arousal pleasant and unpleasant stimuli received the same high score in comparison with neutral stimuli; a different cardiovascular and neuroendocrine pattern was obtained in healthy subjects: unpleasant stimuli elicited increases in HR, SBP, MHPG, NE, ACTH, CORT, whereas neutral and pleasant stimuli did not induce any significant response in hormonal levels. In contrast, in heroin addicts, despite increased perceptions of unpleasantness, HR, SBP, MHPG and NE levels did not increase after disliked stimuli; these subjects also reported increased arousal during exposure to neutral stimuli. In comparison with controls, addicted individuals showed higher CORT and ACTH basal levels, and a consequent lack of response to unpleasant stimuli. The results indicate that neuroendocrine and cardiovascular systems respond selectively to affective, motivationally relevant stimuli, and that substance use disorders may be associated with dysregulation of emotion-processing mechanisms.

Adrenocorticotropic Hormone↗

PubMed2003

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↗

PubMed2001

Aggressive responding of male heroin addicts under methadone treatment: psychometric and neuroendocrine correlates.

Objective measures of experimentally-induced aggressiveness were evaluated in 20 methadone-treated heroin addicts, in comparison to 20 normal healthy male subjects. All the subjects were submitted to preliminary DSM IV interviews, Buss Durkee Hostility Inventory (BDHI) and Minnesota Multiphasic Personality Inventory (MMPI II). During a laboratory task, the point subtraction aggression paradigm (PSAP), subjects earned monetary reinforcers with repeated button presses, and were provoked by the subtraction of money, which was attributed to a fictitious other participants. Subjects could respond by ostensibly subtracting money from the fictitious subject (the aggressive response), or protecting their counter (escape response). Money-earning responses were significantly lower (t=4.38, P<0.001) and aggressive responses significantly higher (t=5.45; P<0.001) in methadone patients in comparison to controls. During the experimentally-induced aggressiveness, plasma adrenocorticotropic hormone (ACTH), cortisol (CORT) and growth hormone (GH) concentrations increased significantly less and norepinephrine (NE) and epinephrine (EPI) levels, together with heart rate (HR), significantly more in methadone subjects than in healthy subjects. PSAP aggressive responses positively correlated with catecholamines changes, BDHI 'direct' and 'irritability' scores, MMPI 'psychopathic deviate' scores both in methadone subjects and controls, and with CORT responses only in healthy subjects. No correlation was found between methadone doses, or exposure extent, and aggressiveness levels. Our findings suggest that heroin dependent patients have higher outward-directed aggressiveness than healthy subjects, in relationship with monoamines hyper-reactivity, also under methadone medication. Aggressiveness in methadone patients seems to be related more to the personality traits than to drug effects. Hypothalamus-pituitary-adrenal (HPA) axis responses, unexpectedly dissociated from catecholamines rise among methadone patients, could be due to a long-lasting inhibitory action exerted by opiates on pro-opio-melanocortin (POMC), or to a premorbid psychobiological condition that exhausted hormonal reactivity.

Adult↗

PubMed2001

Plasma concentrations of interleukin-1-beta, interleukin-6 and tumor necrosis factor-alpha, and of their soluble receptors and receptor antagonist in anorexia nervosa.

Interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) induce anorexia, and multiple behavioral and biochemical alterations that mimic those of anorexia nervosa. Reports in the literature, however, contain contrasting data on the pattern of secretion of the three cytokines and on the downstream activities of their receptors and receptor antagonists in anorexia nervosa. We measured plasma concentrations of IL-1beta, IL-6, TNF-alpha, soluble IL-6 receptor (sIL-6-R), soluble TNF-alpha receptors I and II (s-TNF-alpha-R-I and II), and soluble IL-1beta receptor antagonist (s-IL-1beta-R-A) in 14 female patients with anorexia nervosa (nine restricters, five binge/purgers) and in 13 age- and sex-matched healthy control subjects to see whether the circulating cytokine concentrations and the downstream steps of cytokine activity were impaired, and if these alterations were correlated with some aspects of the disease. Concentrations of IL-1beta, IL-6, TNF-alpha, s-TNF-alpha-R-I and -II and sIL-1beta-RA in plasma did not differ significantly in patients with anorexia nervosa compared with control subjects. Concentrations of sIL-6-R were significantly lower in the patients than in the control subjects, but there were no differences between the two sub-types of anorexia nervosa. The etiopathogenetic significance of the sIL-6-R alteration is not clear, but together with recent data in the literature on cytokine function, the finding suggests that an impairment of the pro-inflammatory cytokine pathway might be involved in the development of anorexia nervosa.

Adolescent↗

PubMed2001

Social stress in anorexia nervosa: a review of immuno-endocrine relationships.

Anorexia nervosa (AN) patients have difficulty in establishing social contacts, leading to tension, anxiety and full-blown stress reactions. Stress hormones are chronically increased in AN, while immune function, which is involved in physical and psychological coping capacities, is mostly unimpaired. We examined immune function in a group of anorexics by measuring the T-lymphocyte proliferative response to stimulation with phytohemagglutinin (PHA), before and after in vivo acute administration of corticotropin-releasing hormone (CRH), to mirror a stress reaction. The responses of anorexics, before and after CRH stimulation, did not differ from those of controls. In a second group of anorexics, we measured plasma concentrations of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) before and after psychopharmacological (fluoxetine, amineptine) therapy. Basal values of the cytokines were not different in patients and controls, and did not change during therapy. In the same patients, we measured basal concentrations of soluble IL-1 beta receptor antagonist (s-IL-1 beta-RA), soluble IL-6 receptor (sIL-6-R) and soluble TNF-alpha receptors I and II (sTNF-alpha-R-I and -II). S-IL-1 beta-RA and sTNF-alpha-R-I and -II levels were not different in patients and controls, while those of s-IL-6-R were lower than normal in anorexics. The normality of most of the immune parameters in our anorexics, in basal conditions, after a stressful stimulation and after pharmacological manipulation of neurotransmitters suggests that the well-known interrelation among immune, neuroendocrine and central nervous system functions is not maintained in AN, the immune system being somehow unresponsive to stimuli.

Adaptation, Psychological↗

PubMed2001

Pivagabine effects on neuroendocrine responses to experimentally-induced psychological stress in humans.

Neuroendocrinology of chronic stress seems to be characterized by HPA axis hyperactivity and early childhood stressors have been hypothesized to predispose individuals to adult onset depression by means of dysregulation of the HPA axis. Pivagabine (PVG), a hydrophobic 4-aminobutyric acid derivative, has been used experimentally recently in the treatment of different disorders related to stress-maladaptation, because of its possible inhibitory action on corticotrophin releasing factor secretion and HPA axis function. In the present study, 20 healthy male subjects were each exposed twice to the same psychosocial stressor (stroop color-word interference task, public speaking and mental arithmetic in front of an audience) during a first session (day 1) and a second session (day 8). Plasma concentrations of norepinephrine (NE), epinephrine (EPI), adrenocorticotropic hormone (ACTH) and cortisol (CORT), heart rate (HR) and systolic blood pressure (SBP) were measured immediately before the beginning of the tests and at their end, 30 min later, on both experimental days. Utilizing a double blind schedule, the subjects received pivagabine (900 mg, twice a day)(PVG group: nine subjects) or placebo (PBO group: 11 subjects) during the 7 days between the two stress sessions. NE, EPI, ACTH, and CORT levels were significantly elevated after stress exposure on day 1 and day 8 in PBO group subjects. After PVG treatment, on day 8, ACTH, CORT, NE and EPI responses to stress were significantly blunted, together with HR and SBP, in PVG group subjects. These results add to the evidence concerning PVG capacity to inhibit the HPA axis in humans, in response to stressful stimuli, and suggest that the action of PVG may be mediated not only by GABAergic receptors, but also by the suppression of catecholamines response. PVG treatment could modulate HPA hyper-responsiveness to stress in subjects with negative affectivity and depressive traits.

Adrenocorticotropic Hormone↗

PubMed2001

Neuroendocrine responses to experimentally-induced psychological stress in healthy humans.

Previous studies of hormonal and neurophysiological changes in response to psychological stress in humans have produced contrasting findings due to differing experimental procedures and consistent individual variability. Habituation effects, which influence physiological coping in response to exposure to repeated stress, need to be investigated more extensively. In the present study, twenty healthy male subjects were each exposed twice to the same psychosocial stressor (Stroop Color Word Interference task, public speaking and mental arithmetic in front of an audience) during a first session (day 1) and a second session (day 8). Plasma concentrations of norepinephrine (NE), epinephrine (EPI), adrenocorticotropic hormone (ACTH), cortisol (CORT) and prolactin (PRL) were measured immediately before the beginning of the tests and at their end, 30 min later, on both experimental days. For the total group, NE, EPI, ACTH, and CORT levels were significantly elevated, and PRL levels were significantly decreased, after stress exposure on day 1. ACTH and CORT levels showed less significant increases after stress on day 8. In contrast, NE and EPI responses to stress were not significantly blunted, and PRL response was unchanged on day 8. Cluster analysis revealed two groups of subjects who showed different habituation patterns for ACTH and CORT. The first group (n=12) of subjects showed a reduction of ACTH and CORT responses to stress on day 8. The subjects of the second group (n=8) displayed a significant increase of ACTH and cortisol in response to stress on day 8, without any habituation effect. These results increase the evidence concerning the involvement of the HPA axis and catecholamines in response to psychological stress, and suggest that possible individual differences in the neuroendocrine coping mechanisms may affect mood regulation and the state of health.

Adrenocorticotropic Hormone↗

PubMed2001

Central dopaminergic function in anorexia and bulimia nervosa: a psychoneuroendocrine approach.

Data on central dopamine (DA) function in patients with Anorexia Nervosa (AN) and Bulimia Nervosa (BN) are contradictory. To tentatively clarify the brain secretory state of the amine and its relationship with the nutritional impairments and/or the psychopathological aspects of the two disorders, we measured the responses of growth hormone (GH) to acute stimulation with apomorphine (APO), a selective D-1 and D-2 receptor agonist, in 16 AN patients, 8 restricted (AN-R) and 8 bingeing-purging (AN-BP), in 7 BN patients and in 8 healthy controls (CTR). Interference of impairment of the somatotropic axis in the GH response to APO stimulation was excluded by measuring the GH and insulin-like growth factor-1 (IGF-1) basal levels and GH responses to growth hormone-releasing hormone (GHRH) stimulation. Psychological aspects of patients and controls were investigated by the rating scales Eating Disorder Inventory (E.D.I.), Bulimic Investigation Test Edinburgh (B.I.T.E)., and Yale-Brown Cornell Eating Disorder Scale (YBC-ED). Basal GH levels were significantly higher and those of IGF-1 lower in AN-R than in AN-BP, BN and CTR subjects. GH responses to GHRH stimulation were significantly higher in AN-R than in AN-BP and BN patients and in CTR. GH responses to APO stimulation were significantly lower in AN-R and AN-BP than in BN and CTR subjects, suggesting that at the hypothalamic level there is a subsensitivity of postsynaptic D-2 receptors and possibly a presynaptic DA hypersecretion. The altered GH responses to APO stimulation did not correlate with the Body Mass Index, while they correlated negatively with E.D.I. scores.

Adolescent↗

PubMed2001

Experimentally induced aggressive behavior in subjects with 3,4-methylenedioxy-methamphetamine ("Ecstasy") use history: psychobiological correlates.

PURPOSE: Objective measures of experimentally induced aggressiveness were evaluated in 12 male 3,4-methylenedioxy-methamphetamine (MDMA, "Ecstasy") users, in comparison with 20 healthy male subjects. METHODS: All the subjects were preliminarily submitted to DSM-IV interviews and Buss-Durkee Hostility Inventory (BDHI). During a laboratory task, the Point Subtraction Aggression Paradigm (PSAP), subjects earned monetary reinforcers with repeated button presses, and were provoked by the subtraction of money that was attributed to a fictitious other participant. Subjects could respond by ostensibly subtracting money from the fictitious subject (the aggressive response). Escape responses were also possible protecting the counter from monetary subtractions. RESULTS: Money-earning responses were not different in Ecstasy users and controls; aggressive responses were significantly higher in Ecstasy users in comparison with control subjects (F=20.74, P<.001). Baseline adrenocorticotropic hormone (ACTH) and cortisol (CORT) levels were higher in Ecstasy users than in controls. No difference was found in norepinephrine (NE) and epinephrine (EPI) basal levels of the two groups. During the experimentally induced aggressiveness, plasma ACTH concentrations increased significantly less and NE and EPI levels, together with heart rate (HR), increased significantly more in Ecstasy users than in healthy subjects. Despite ACTH-blunted responses, CORT did not increase differently from controls in Ecstasy users. PSAP aggressive responses positively correlated with catecholamines and CORT changes, BDHI Direct Aggression and Irritability scores, both in Ecstasy users and controls. A significant correlation was found between Ecstasy exposure extent and aggressive responses (r=.78, P<.001). IMPLICATIONS: Our findings suggest that Ecstasy users have higher outward-directed aggressiveness than healthy subjects. Aggressiveness in MDMA subjects seems to be associated more with MDMA pharmacological effects than with personality traits: Nevertheless, a premorbid psychobiological proneness to aggressive behavior cannot be excluded. Increased catecholamines reactivity, basal hypothalamus-pituitary-adrenal (HPA) axis hyperactivity, and blunted ACTH responses could be due to MDMA action on monoaminergic pathways and adrenal function.

Adolescent↗

PubMed2001

Neurotransmitter and hormonal background of hostility in anorexia nervosa.

Marked hostility toward relatives, therapists and friends is very frequently observed in anorexia nervosa (AN) as expression of outward-directed aggressiveness which interferes with the therapeutic programs of the patients. With the purpose to investigate this aspect of the disorder and its biological background, we studied in anorexics some neurotransmitter-hormonal secretions which are known to modulate aggressivity-hostility by measuring plasma concentrations of total (TT) and free testosterone (FT), total estrogens (TE), the TT/E and FT/TE ratios, and the serotonergic function by measuring basal prolactin (PRL) levels and responses to stimulation with the specific serotonin (5-HT)-releasing agent D-fenfluramine (D-Fen). In 13 women with AN, 5 of the restricted (AN-R) and 8 of the bingeing/purging type (AN-BP) in an active phase of the disease, and in 13 healthy controls matched for sex and age, we measured hostility by the SCL-90 scale (subscale items 11, 24, 63, 67, 74, 81). Basal TT, FT, TE, TT/TE, FT/TE, PRL values and PRL responses to D-Fen and to saline administration were measured radioimmunologically in AN patients and controls. Hostility was significantly higher in AN patients than in controls, TT, FT and TE concentrations were significantly lower in AN patients than in controls, TT/TE ratio was significantly higher in AN patients than in controls, and FT/TE ratio was not different in the two groups. In AN patients and controls, hostility correlated positively with TT and FT values. Basal PRL values and responses to D-Fen administration were significantly lower in anorexics than in controls, but they did not correlate with the degree of hostility in either patients or controls. In conclusion, hostility is higher than normal in anorexics, and its severity seems to be linked to the secretion of FT and not to the alterations in the 5-HT function.

Adolescent↗

PubMed2001

Aetiopathogenesis and pathophysiology of bulimia nervosa: biological bases and implications for treatment.

Bulimia nervosa is an eating disorder characterised by recurrent episodes of binge eating and associated efforts to purge the ingested calories through self-induced vomiting, laxative or diuretic abuse, fasting or intensive exercise. The aetiopathogenesis and pathophysiology of the disorder are currently unclear. Biological bases have been proposed repeatedly, based on several lines of evidence: hunger, satiety and food choice are regulated by neurotransmitters and neuropeptides, and impairment of eating habits may be related to alterations in the secretion of these chemicals; genetic studies suggest that these neurotransmitter systems are dysfunctional in individuals with bulimia nervosa; and the frequent comorbidity of bulimia nervosa with major depressive and obsessive-compulsive disorders, conditions in which multiple alterations of brain biochemical functions have been demonstrated. Data in the literature suggest that levels of noradrenaline (norepinephrine) and serotonin (5-hydroxytryptamine; 5-HT) are lower in individuals with bulimia nervosa than in healthy controls. Levels of dopamine are similar to, or lower than, those in controls. After remission of the disorder, noradrenergic function returns to that seen in controls, whereas dopaminergic and serotonergic function rebound to levels higher than in controls. Among the neuropeptides, alterations in the levels of neuropeptide Y, peptide YY, beta-endorphin, corticotrophin-releasing hormone, somatostatin, cholecystokinin and vasopressin have been found in the symptomatic phase of bulimia nervosa, with a return to levels seen in controls after remission. Pharmacological treatment of bulimia nervosa that is directed at correction of the neurochemical alterations observed is difficult because of the complexity of the impairments. However, such treatment is necessary and should be continued long after symptomatic remission to ensure reinstitution of cerebral biochemical homeostasis.

Bulimia↗