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Biomedical subjects

F Brambilla

Publications and source records attributed to F Brambilla.

At least 19 recordsLinked to original sources

Psychopathological aspects of neuroendocrine diseases: possible parallels with the psychoendocrine aspects of normal aging.

Psychological impairments can occur during the course of major endocrine diseases. These impairments range from mild affective-cognitive-behavioral disturbances to frank psychoses. The former are rather specific for each hormonal disorder and disappear with the hormonal correction. The latter, instead, seem to be quite nonspecific and include depression, mania, schizophrenia-like and organic brain syndromes which appear at random in each endocrinopathy, not always regressing with hormonal recovery, and apparently correlating more with the severity than with the nosographic classification of the metabolic disturbances. It is suggested that age-related physiological changes of hormonal and psychological patterns mimic those occurring in neuroendocrine diseases and that, possibly, common brain biochemical changes may underlie the two phenomena.

Aging

Psychoimmunoendocrine aspects of panic disorder.

Immunological, neuroendocrine and psychological parameters were examined in 14 psychophysically healthy subjects and in 17 panic disorder patients before and after a 30-day course of alprazolam therapy. T lymphocyte proliferation in response to the mitogen phytohemagglutinin, lymphocyte beta-endorphin (beta-EP) concentrations, plasma ACTH, cortisol and beta-EP levels were examined in basal conditions and after corticotropin-releasing hormone (CRH) stimulation. Cortisol inhibition by dexamethasone (DST) and basal growth hormone (GH) and prolactin levels were also examined. Depression, state or trait anxiety, anticipatory anxiety, agoraphobia, simple and social phobias, severity and frequency of panic attacks were monitored by rating scales. The immune study did not reveal any significant difference between patients and controls, or any effect of alprazolam therapy. The hormonal data for the two groups were similar, except for higher than normal basal ACTH and GH plasma levels, lower than normal ratios between the ACTH and cortisol responses to CRH, and blunted DST in some patients. All the impairments improved after alprazolam therapy, in parallel with decreases in anxiety and in severity and frequency of panic attacks.

Adolescent

Peripheral opioid secretory pattern in anorexia nervosa.

The peripheral secretion of endogenous opioids was studied in 10 women with restrictive anorexia nervosa and 10 age- and sex-matched healthy controls. The circadian rhythm of beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH), and their responses to the administration of corticotropin releasing hormone (CRH, 1 micrograms/kg body weight, i.v.), clonidine (150 microgram, i.v.), domperidone (10 mg, i.v.), and 5-hydroxytryptophan (5-HTP, 200 mg, p.o.) were examined in patients and controls. The results revealed increased nocturnal secretion of beta-EP and diurnal-nocturnal secretion of beta-LPH with loss of circadian rhythmicity of both peptides, normal response to CRH stimulation, blunted response to clonidine and domperidine, and normal beta-EP and blunted beta-LPH response to 5-HTP stimulation. The data suggest a complex alteration of peripheral opioids and of central aminergic mechanisms that regulate proopiomelanocortin-derived peptide secretion and eating behavior.

5-Hydroxytryptophan

Modeling of biological and medical systems: a systemic strategy.

A strategy in the frame of General System Theory is proposed for the study of biological systems for medical purposes. Its definition and use requires in each experiment the collaboration between physician and system scientists and hence the definition of a common language, by which the real system under study is described. The strategy is based on three intermingled steps: first an ingenuous model is proposed, gathering all the medical knowledge about the studied system, organized within an informal frame derived from the state space approach. Next, a functional model is derived, enlightening the organization of the relations in the medical model. Finally, this organization is formalized by the most suitable algebraic tools, which are thereafter translated into APL programs. This last version is used for simulation, which is exploited not only as a tool to describe and make provisions on the dynamics of the models, but also to deepen and improve the knowledge about the observed system.

Computer Simulation

Hormonal circadian rhythms in eating disorders.

The circadian rhythm of several plasma hormones (prolactin, growth hormone, adrenocorticotropic hormone (ACTH), cortisol, and melatonin) was simultaneously evaluated in 23 women with anorexia nervosa (AN), in 27 obese (OB) women, and in gender and age-matched healthy controls. A trend toward similar alterations of the circadian pattern of the different hormones was observed in the two groups of patients, with the exception of plasma growth hormone (GH), which exhibited nutrition-dependent impairments. The timing of the peaks for each hormonal rhythm revealed the existence of an internal desynchronization in both eating disorders.

Adult

Tonic and dynamic gonadotropin secretion in depressive and normothymic phases of affective disorders.

Baseline follicle stimulating hormone (FSH) and luteinizing hormone (LH) plasma levels and their responses to luteinizing hormone releasing hormone (LHRH) stimulation were investigated in 72 patients who met Research Diagnostic Criteria for affective disorders and in 72 healthy volunteers. Fifty-six patients were examined during a depressive phase and 16 during a normothymic phase. LH-FSH basal levels were significantly lower in postmenopausal depressed and normothymic women than in controls. In fertile women and men, concentrations of the two gonadotropins were also lower in patients than in controls, but the phenomenon did not generally reach statistical significance. LHRH-induced LH rises were lower in postmenopausal and fertile depressed and normothymic women than in controls, while FSH rises were reduced only in postmenopausal depressive women in both depressed and normothymic phases. The impairment underlying the gonadotropin secretory deficiency remains to be elucidated.

Adult

Effects of phosphatidylserine therapy in geriatric patients with depressive disorders.

The effects of phosphatidylserine (BC-PS) on cognitive, affective and behavioural symptoms were studied in a group of 10 elderly women with depressive disorders. Patients were treated with placebo for 15 days, followed by BC-PS (300 mg/day) for 30 days. The Hamilton Rating Scale for Depression, Gottfries-Bråne-Steen Rating Scale, Nurse's Observation Scale for Inpatient Evaluation and Buschke Selective Reminding Test were administered before and after placebo and after BC-PS therapy, to monitor changes in depression, memory and general behaviour. At the same time, basal plasma levels of noradrenaline, MHPG, DOPAC, HVA and 5-HIAA, and GH/beta-endorphin/beta-lipotropin responses to clonidine stimulation were measured. BC-PS induced consistent improvement of depressive symptoms, memory and behaviour. No changes in amine metabolite levels or in hormonal responses to alpha 2-adrenoceptor stimulation were observed.

3,4-Dihydroxyphenylacetic Acid

Effects of alpha- and beta-adrenergic agonists and antagonists on growth hormone secretion in man.

The adrenergic system is involved in the neural control of GH secretion with both stimulatory and inhibitory influences mainly mediated via GHRH and/or somatostatin modulation. To throw further light on adrenergic neuroregulation of somatotrophic function in man, the effect of various catecholamine agonists and antagonists on basal or GHRH-stimulated GH secretion was studied. Twenty-one adult males aged 20-30 years underwent the following studies: 1. clonidine (CLON), alpha 2-agonist, (15 micrograms/min infused i.v. from 0 to +10 min) alone and preceded by yohimbine (YOH), alpha 2-antagonist, (30 mg orally at -50 min); 2. GHRH (GHRH 44, 1 microgram/kg i.v. bolus at 0 min) alone and preceded by YOH; 3. CLON alone and combined with methoxamine (METHOX), alpha 1-agonist, (1 mg/min infused i.v. from -10 to +10 min); 4. GHRH alone and combined with i.v. infusion of phentolamine (PHEN), alpha 1/alpha 2-antagonist, (0.5 mg/min from -60 to +30 min); 5. GHRH alone and combined with i.v. infusion of salbutamol (SAL), beta 2-agonist, (10 micrograms/min from -5 to +15 min). The GH response to CLON was inhibited by YOH (area under the response curve, mean +/- S.E.: 672.6 +/- 143.0 vs. 219.6 +/- 16.7 micrograms/l/h, P less than 0.05) but was not modified by METHOX (278.4 +/- 94.1 vs. 216.7 +/- 115.5 micrograms/l/h). On the other hand, YOH was unable to affect the GH response to GHRH (339.3 +/- 19.1 vs. 518 +/- 172.8 micrograms/l/h).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists

Alpha 2-adrenoceptor sensitivity in anorexia nervosa: GH response to clonidine or GHRH stimulation.

Growth hormone (GH) response to clonidine and growth hormone-releasing hormone (GHRH) stimulation, together with baseline somatomedin C (SmC) levels, were examined in parallel in a group of 21 patients with anorexia nervosa (AN) and in 10 controls. In addition, the Hamilton Rating Scale for Depression (HRS) was administered to the patients. Clonidine (2.5 micrograms/kg body weight, iv) induced GH elevations that were not significantly different between patients and controls. In contrast, GHRH (1 microgram/kg body weight, iv) produced a significantly higher GH response in anorectics than in controls. The ratio between GH responses (area under the curve, or AUC) to GHRH and to clonidine was significantly higher in patients than in controls. Baseline SmC levels (6 patients) were significantly lower in anorectics than in controls. Minor depressive symptomatology was present in all patients. When viewed in relation to the GH hyperresponsiveness to GHRH, the apparent normality of the response to clonidine in anorectics reflects the existence of an actual alpha 2-adrenoceptor subsensitivity. As clonidine reportedly acts via release of endogenous GHRH, an excessive, rather than a normal, GH response to clonidine was to be anticipated.

Adolescent

Melatonin and pituitary-gonadal function in disorders of eating behavior.

In order to study the possible relationships between melatonin secretion and pituitary-gonadal function, the circadian rhythm of plasma melatonin, the basal levels of estradiol-17beta and testosterone and the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) response to luteinizing hormone-releasing hormone (LH-RH) stimulation were evaluated in normally cycling healthy women and in two groups of women with menstrual dysfunctions related to eating disorders (19 patients with anorexia nervosa and 16 with primary obesity). The circadian rhythm of plasma melatonin reached statistical significance in anorectic patients but not in obese patients. The mean 24 h melatonin level was significantly higher in anorectic than in obese patients and in control subjects. However, both groups of patients shared some abnormalities of melatonin circadian pattern, such as increased ratio between day and night melatonin levels, abnormal secretory peaks during the light hours and great interindividual variability for timing, amplitude, and duration of melatonin nocturnal peak. A selective impairment of LH secretion was observed in both anorectic and obese patients. By considering together the two groups of patients and controls, a linear inverse correlation between the circadian mesor of plasma melatonin and the basal and LH-RH stimulated LH levels was found. The persistence of a certain melatonin secretion during the light hours in both anorectic and obese patients could play an inhibitory role on the pituitary gonadal function in these subjects.

Adolescent

Vasopressin (DDAVP) therapy in chronic schizophrenia: effects on negative symptoms and memory.

Ten chronic undifferentiated schizophrenics, 6 men and 4 women, aged 28-63, with 6- to 31-year histories of the disease were given DDAVP to observe the effects of this neuropeptide on the prevalent negative symptoms of their illness. Patients were maintained on neuroleptic therapy and first given a 20-day course of placebo followed by 20 days of DDAVP i.m., 4 micrograms Andreasen Scale for assessment of negative symptoms, the Brief Psychiatric Rating Scale, the NOSIE Rating Scale and the Luria-Nebraska Rating Scale were administered to monitor negative symptomatology, behavior and memory before the study began, after placebo and after DDAVP administration. Patients were also given a growth hormone-clonidine test and in addition plasma basal concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) were measured at the same intervals. DDAVP therapy induced a significant improvement of negative symptomatology and a trend toward improvement of short- to medium-term memory. No changes in homovanillic acid, MHPG, 5-HIAA and DOPAC, nor of growth hormone response to clonidine stimulation were observed.

Adult

Effect of lithium treatment on the GH-clonidine test in affective disorders.

The effects of short-term lithium (Li) administration on alpha 2-adrenoceptor sensitivity was studied in 10 healthy volunteers and in 15 patients with normothymic, phasic depressive disorders. The GH-clonidine test was used to examine alpha 2-adrenoceptor sensitivity, administered before and after Li treatment (600 mg/day for 7 days in controls and for 15 days in patients). Before treatment, the GH response to clonidine in the patients was blunted, and afterwards it tended to increase in the patients and it was significantly decreased in the controls. The difference between the response in the two groups was significant and was correlated both with the diagnosis and the pretreatment GH response to the stimulus. The opposing pattern of the response in patients and controls to Li administration suggests that the drug exerts a modulatory effect on alpha 2-adrenoceptor sensitivity, with up or down regulation inversely correlated with pretreatment status.

Adolescent

Melatonin circadian rhythm in anorexia nervosa and obesity.

The mean 24-hour secretion and circadian rhythm of melatonin were studied in 12 female subjects with anorexia nervosa (AN), 13 massively obese (OB) women, and 9 normal weight healthy volunteers to investigate the relationship between type of feeding behavior and hormonal secretory pattern. Blood samples for melatonin were drawn every 4 hours from 0400 h to 2400 h and every 2 hours from 2400 h to 0400 h. Mean 24-hour melatonin secretion was significantly higher in AN than in OB patients and controls. Melatonin circadian rhythms were disrupted in 8 of the 12 AN patients and in 9 of the 13 OB subjects, with phase-advanced nocturnal rises, abnormal diurnal peaks, or no nocturnal rises. The population mean cosinor analysis validated the existence of a significant circadian rhythm of the hormone in AN but not in OB subjects. No significant correlation between mean 24-hour secretion or type of circadian alterations and degree of weight deficit or excess was observed. The circadian alterations of melatonin in AN and OB may be linked to impaired secretory tonus of noradrenalin in the central nervous system, possibly unrelated to feeding patterns.

Adolescent

Plasma opioids in alcoholics after acute alcohol consumption and withdrawal.

Beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) plasma concentrations were examined in ten chronic alcohol abusers, eight men and two women aged 25-56 years with histories of continuously elevated ethanol consumption dating from 5-30 years. Plasma levels of the two peptides were measured after acute alcohol consumption and then after 3, 6 and 9 days of forced abstinence, during chlordiazepoxide treatment. Beta-EP and beta-LPH concentrations were normal on all four occasions. A reduced sensitivity of opioid receptors to acute alcohol administration due to chronic alcohol consumption is suggested.

Adult

Clonidine stimulation in anorexia nervosa: growth hormone, cortisol, and beta-endorphin responses.

Clinical and biochemical findings link anorexia nervosa (AN) and primary effective disorders (PAD). Clonidine, an alpha 2-adrenoceptor agonist, has been shown to blunt growth hormone (GH) response and greatly lower plasma cortisol in PAD patients. We examined the GH, cortisol, and beta-endorphin (beta-EP) responses to an acute clonidine challenge (150 micrograms i.v. as a bolus) before and after 30 days of treatment with desmethylimipramine in 14 women with AN. Both before and after treatment, the AN patients showed normal plasma GH and cortisol responses, but an increased plasma beta-EP response. The increased beta-EP response in AN was independent of weight and depressive symptomatology. Our data indicate that alpha 2-adrenoceptors involved in the control of GH and adrenocorticotropic hormone are not altered in AN. The increased beta-EP response may indicate elevated opioid activity in the hypothalamo-pituitary system of AN patients.

Adolescent

Biological heterogeneity of major depressive disorder: indications by sleep EEG and TRH stimulation test findings.

A group of 27 patients with definite (n = 20) or probable (n = 7) RDC major depressive disorder underwent 2 sleep EEGs and 1 TRH test while in a drug-free depressive phase. A short mean REM latency (less than 60 min) identified 55.5% of major depressives while added use of blunted TSH responses (delta max. less than 5 microU/ml) increased that percentage by 11%. When patients were subdivided into RDC endogenous and nonendogenous, mean REM latency and global depression scores distinguished the 2 groups, while delta TSH did not. A short mean REM latency identified endogenous depression with 80% specificity and 76% sensitivity. The combination of REM latency and delta TSH reduced the specificity to 60%, and therefore cannot be recommended for differentiating endogenous from nonendogenous depression.

Adult