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Biomedical subjects

Donatella Marazziti

Publications and source records attributed to Donatella Marazziti.

At least 19 recordsLinked to original sources

Decreased density of peripheral benzodiazepine receptors in psychiatric patients after a suicide attempt.

To date, two main types of benzodiazepine (BDZ) receptors have been identified: one of these is the so-called central receptor which is found mainly in the cortex, limbic areas and cerebellum, and the other is known as the peripheral receptor, which is found in the kidneys, lungs, ovaries, testes, adrenal glands and blood cells, but is present also in the central nervous system (CNS), in particular in glial cells. Although for some time the peripheral BDZ receptor has been considered an acceptor site with no pharmacological activity, recent data have suggested that it may be involved in a variety of actions, such as the response to stress. The presence of these receptors in blood platelets, which are considered a reliable, peripheral mirror of the same structures located in the SNC, prompted us to evaluate them in a group of psychiatric patients after a suicide attempt, as compared with healthy control subjects, by means of the specific binding of 3H-PK 11195. Suicide, with no doubt, may be considered one of the most stressful situations occurring to humans. The results showed the presence of a significant decrease in the density of 3H-PK 11195 binding sites in the patients, as compared with healthy control subjects. This finding may represent a non-specific indicator of a condition of stress, since peripheral BDZ receptors are modulated by stress and hormones, or it may result more from an abnormal metabolism of steroid substances which could play a pivotal role in the development of vulnerability towards suicide.

Adolescent↗

Effectiveness of risperidone in psychogenic stiff neck.

A 48-year-old woman suffering from treatment-resistant psychogenic stiff neck and severe depression had been treated with a varied regimen of medications, including antidepressants, neuroleptics, and antiepileptics. These treatments did not result in improvement. Therefore, she was treated with a combination of sertraline and risperidone. Depressive symptoms decreased within a few weeks of treatment initiation. The psychogenic stiff neck, which had begun to improve within the first 2 weeks, had disappeared completely after 6 months of treatment with risperidone alone. This case report suggests that risperidone may be effective in some neurological motor disorders comorbid with mood disorders.

Antipsychotic Agents↗

Augmentation strategy with olanzapine in resistant obsessive compulsive disorder: an Italian long-term open-label study.

The present study reports the results of an open-label trial on the use of the combination of olanzapine (an atypical antipsychotic) serotonin reuptake inhibitors (SRIs) in 26 resistant outpatients affected by resistant obsessive-compulsive disorder (OCD). All patients had been suffering from OCD, according to DSM IV criteria, for at least 2 years and had different comorbid disorders; they had been treated with an SRI at adequate dosages for at least 6 months, or had tried different augmentation strategies with no or poor response. As a result, olanzapine was added and continued for 1 year. After 12 weeks of this regimen, most of the patients (17) had shown a reduction in OC symptoms, as assessed by a decrease in the Yale-Brown Obsessive Compulsive Scale total score, which continued throughout subsequent months. Only mild side-effects were recorded and no patient halted the treatment. The addition of olanzapine would appear to be a useful short- and long-term strategy for augmenting SRI effectiveness in resistant OCD patients, especially in those presenting comorbidity with bipolar disorders.

Adult↗

Hormonal changes when falling in love.

To fall in love is the first step in pair formation in humans and is a complex process which only recently has become the object of neuroscientific investigation. The little information available in this field prompted us to measure the levels of some pituitary, adrenal and gonadal hormones in a group of 24 subjects of both sexes who had recently (within the previous six months) fallen in love, and to compare them with those of 24 subjects who were single or were part of a long-lasting relationship. The following hormones were evaluated by means of standard techniques: FSH, LH, estradiol, progesterone, dehydroepiandrosterone sulphate (DHEAS), cortisol, testosterone and androstenedione. The results showed that estradiol, progesterone, DHEAS and androstenedione levels did not differ between the groups and were within the normal ranges. Cortisol levels were significantly higher amongst those subjects who had recently fallen in love, as compared with those who had not. FSH and testosterone levels were lower in men in love, while women of the same group presented higher testosterone levels. All hormonal differences were eliminated when the subjects were re-tested from 12 to 24 months later. The increased cortisol and low FSH levels are suggestive of the "stressful" and arousing conditions associated with the initiation of a social contact. The changes of testosterone concentrations, which varied in opposite directions in the two sexes, may reflect changes in behavioural and/or temperamental traits which have yet to be clarified. In conclusion, the findings of the present study would indicate that to fall in love provokes transient hormonal changes some of which seem to be specific to each sex.

Adult↗

Platelet alpha2-adrenoreceptors in obsessive-compulsive disorder.

The need for new therapeutic targets in obsessive-compulsive disorder (OCD) prompted us to investigate the putative involvement of the norepinephrine system by means of platelet alpha(2)-adrenoreceptors in a group of 20 OCD patients and healthy control subjects, matched for sex and age. Platelet membranes were prepared according to standard protocols, and the alpha(2)-adrenoreceptors were measured by means of the specific binding of [(3)H]rauwolscine, a highly selective antagonist for this receptor subtype. The results, which showed no difference between patients and controls in the binding parameters of [(3)H]rauwolscine, suggest that the role of alpha(2)-adrenoreceptors, as reflected by the platelet model, is quite limited in OCD and may, perhaps, be restricted purely to some symptoms or dimensions such as motricity, as suggested by the higher density of alpha(2)-adrenoreceptors found in patients concomitantly affected by motor tics.

Adolescent↗

Absence of NK1 receptors in human blood lymphocytes and granulocytes.

Substance P is a peptide that exerts its activity through the interaction with specific receptors that are distributed in different brain areas. Given the potential of NK1 receptor antagonists as antidepressants, the availability of a peripheral model of NK1 receptors would be particularly relevant for the possibility to perform studies in samples of patients. Therefore, with the present study we aimed to explore the possible existence of NK1 receptors by means of [3H]SR140333 and [125I]BHSP that behave as, respectively, antagonist and agonist, at this level, in human blood lymphocytes and granulocytes of healthy donors. The results of the present study failed to detect the presence of a high-affinity and saturable binding of [3H]SR140333 and [125I]BHSP in human blood cells, whereas a specific binding for both compounds was found in rat cerebral cortex that was used as the control tissue. These findings would question the presence of NK1 receptors in human circulating cells.

Adult↗

Serotonergic activity measured by platelet [3H]paroxetine binding in patients with eating disorders.

Most of the evidence from pharmacological studies supports the hypothesis of a serotonergic (5-HT) dysregulation in eating disorders (ED), though a specific alteration related to the major ED subtypes, anorexia (AN) and bulimia nervosa (BN), has not been identified yet, possibly because of changes over time in ED nosology. The aim of the present study was to verify whether differences in serotonergic activity, measured by platelet [3H]paroxetine binding, would validate current ED classification. Platelet [3H]paroxetine binding was investigated in 26 patients with eating disorders diagnosed in accord with DSM-IV criteria (AN, n=11; BN, n=15) and 26 normal weight controls of comparable age; ED symptomatology was assessed by the Diagnostic Schedule for Eating Disorders. ED patients had significantly lower B(max) values than controls (288.5+/-109.2 vs. 1396.8+/-251.3 fmol/mg), whereas the K(d) was not significantly altered (0.12+/-0.13 and 0.12+/-0.05 nM, respectively). Among patients, differences in B(max) were related neither to DSM-IV subtypes nor to clinical variables such as presence of binge-eating, purging, impulsive behaviors, or symptoms of depression. Although ED patients share a dysregulation in serotonergic activity, DSM-IV subtype classification was not validated by [3H]paroxetine binding, and hence does not correspond to a specific 5-HT profile.

Adult↗

[3H]-ketanserin binding sites in different psychiatric disorders.

The results of the present study showed the presence of a high-affinity and saturable binding of [3H]-ketanserin to frontal and parietal brain membranes obtained postmortem from bipolar, depressed, schizophrenic patients and normal controls. The human brain samples (60 frontal cortex and 51 parietal cortex), were donated by the Stanley Foundation Brain Collection. The overall data showed that normal controls, depressed and schizophrenic patients had a higher density in the frontal than in the parietal cortex, while bipolar patients did not show any difference. When the data were analysed according to the two hemispheres, some additional, intriguing observations were made: it emerged that [3H]-ketanserin binding sites did not show any difference in the two frontal cortices, while they were less represented in the right parietal cortex of normal and bipolar patients and more dense in schizophrenic patients. In conclusion, our study has demonstrated the presence of heterogenous alterations of [3H]-ketanserin binding sites in healthy controls and different psychiatric disorders that may be of help in a further elucidation of the specific role that 5-HT(2A) receptors may play in these disorders.

Binding Sites↗

Normal and obsessional jealousy: a study of a population of young adults.

BACKGROUND: Jealousy is a heterogenous emotion ranging from normality to pathology. Several problems still exist in the distinction between normal and pathological jealousy. AIM OF THE STUDY: With the present study, we aimed to contribute to the definition of the boundary between obsessional and normal jealousy by means of a specific self-report questionnaire developed by us. METHOD: The questionnaire called "Questionnaire on the Affective Relationships" (QAR) and consisting of 30 items, was administered to 400 university students of both sexes and to 14 outpatients affected by obsessive-compulsive disorder (OCD) whose main obsession was jealousy. The total scores and single items were analysed and compared. RESULTS: Two hundred and forty-five, approximately 61% of the questionnaires, were returned. The statistical analyses showed that patients with OCD had higher total scores than healthy subjects; in addition, it was possible to identify an intermediate group of subjects, corresponding to 10% of the total, who were concerned by jealousy thoughts around the partner, but at a lower degree than patients, and that we called "healthy jealous subjects" because they had no other psychopathological trait. Significant differences were also observed for single items in the three groups. CONCLUSIONS: Our study showed that 10% of a population of university students, albeit normal, have jealousy thoughts around the partner, as emerged by the specific questionnaire developed by us. This instrument permitted to clearly distinguish these subjects from patients with OCD and healthy subjects with no jealousy concern.

Adult↗

WCA recommendations for the long-term treatment of obsessive-compulsive disorder in adults.

What are the latest psychotherapeutic and pharmacotherapeutic treatment recommendations for obsessive-compulsive disorder (OCD)? OCD is a relatively common disorder with a lifetime prevalence of approximately 2% in the general population. It often has an early onset, usually in childhood or adolescence, and frequently becomes chronic and disabling if left untreated. High associated healthcare utilization and costs, and reduced productivity resulting in loss of earning, pose a huge economic burden to OCD patients and their families, employers, and society. OCD is characterized by the presence of obsessions and compulsions that are time-consuming, cause marked distress, or significantly interfere with a person's functioning. Most patients with OCD experience symptoms throughout their lives and benefit from long-term treatment. Both psychotherapy and pharmacotherapy are recommended, either alone or in combination, for the treatment of OCD. Cognitive-behavioral therapy is the psychotherapy of choice. Pharmacologic treatment options include the tricyclic antidepressant clomipramine and the selective serotonin reuptake inhibitors (SSRIs) citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline. These have all shown benefit in acute treatment trials; clomipramine, fluvoxamine, fluoxetine, and sertraline have also demonstrated benefit in long-term treatment trials (at least 24 weeks), and clomipramine, sertraline, and fluvoxamine have United States Food and Drug Administration approvals for use in children and adolescents. Available treatment guidelines recommend first-line use of an SSRI (ie, fluoxetine, fluvoxamine, paroxetine, sertraline, or citalopram) in preference to clomipramine, due to the latter's less favorable adverse-event profile. Further, pharmacotherapy for a minimum of 1-2 years is recommended before very gradual withdrawal may be considered.

Adult↗

Venlafaxine treatment of obsessive-compulsive disorder: case reports.

About one-third of patients affected by obsessive-compulsive disorder fail to respond to serotonergic drugs and different strategies have been proposed for these resistant cases. This article reports experiences with venlafaxine in patients with obsessive-compulsive disorder who did not respond or did not tolerate serotonergic drugs.

Adult↗

Platelet serotonin transporter in patients with diarrhea-predominant irritable bowel syndrome both before and after treatment with alosetron.

OBJECTIVES: Serotonin reuptake is mediated by a transporter protein (SERT), and its dysfunctions can alter serotonergic transmission. The present study examines the binding profile of platelet SERT in healthy volunteers as well as in patients with diarrhea-predominant irritable bowel syndrome (D-IBS), both before and after treatment with the 5-HT(3) receptor antagonist alosetron. METHODS: Binding of [(3)H]paroxetine to SERT was assayed in platelet membranes collected from D-IBS patients (12 women, age 21-73 yr) and healthy volunteers (12 women, age 24-68 yr). Both maximal binding capacity (B(max)) and dissociation constant (K(d)) were estimated. In D-IBS patients, binding parameters and symptom severity score were evaluated at baseline and after treatment with alosetron (1 mg b.i.d. for 8 wk). RESULTS: At baseline, B(max) and K(d) values of [(3)H]paroxetine binding were respectively lower and higher in D-IBS patients than in healthy volunteers (B(max): 518.7 +/- 155.9 vs 1151.9 +/- 187.4 fmol/mg, p < 0.001; K(d): 0.19 +/- 0.05 vs 0.06 +/- 0.02 nmol/L, p < 0.001). Symptom severity score in D-IBS patients (50.9 +/- 18.8) was negatively correlated with B(max) (r = -0.964; p < 0.001) but not K(d) values (r = -0.164; p = 0.609). After treatment with alosetron, symptom severity score decreased significantly (14.4 +/- 3.7; p < 0.001), whereas B(max) (522.7 +/- 39.7 fmol/mg) and K(d) values (0.17 +/- 0.07 nmol/L) did not change. CONCLUSIONS: The present results indicate that SERT expressed on platelet membranes of D-IBS patients is characterized by low density and binding affinity and suggest a possible correlation between the reduced capacity of serotonin reuptake and the severity of D-IBS symptoms.

Adult↗

Jealousy and subthreshold psychopathology: a serotonergic link.

BACKGROUND: A few studies suggest that different neurotransmitters may play a role in the expression of jealousy. Our study aimed to explore the serotonergic system by means of the specific binding of (3)H-paroxetine ((3)H-Par) to platelet membranes of healthy subjects with and without excessive jealousy concerns, according to a specific self-administered questionnaire [Questionnaire for affective relationships (QAR)]. SUBJECTS AND METHODS: The study sample includes 21 subjects concerned by jealousy thoughts and 21 control subjects without jealousy concerns, as shown by their QAR scores. Subjects of the first group were administered a battery of self-report instruments designed to detect the presence of typical, atypical and subthreshold psychopathology. Platelet membranes and (3)H-Par binding were carried out according to standardized protocols. RESULTS: Subjects with excessive jealousy concerns had a reduced density of (3)H-Par binding as compared with control subjects without jealousy concerns and had one or more psychiatric spectrum conditions. CONCLUSIONS: Our findings suggest that excessive jealousy is associated with various forms of psychopathology and may be underlain by alteration of the serotonergic system, as reflected by the lower density of the platelet serotonin transporter.

Adult↗

Decreased lymphocyte 3H-paroxetine binding in obsessive-compulsive disorder.

The pathophysiology of obsessive-compulsive disorder (OCD) is mainly focused on the serotonin (5-HT) system and transporter. The presence of this structure in blood lymphocytes prompted us to investigate it, by means of the specific binding of (3)H-paroxetine ((3)H-PAR), in a group of drug-free OCD patients as compared with healthy control subjects matched for sex and age. Lymphocyte membranes and (3)H-PAR binding were carried out according to standard protocols. The results showed that the patients had a statistically significant lower density of (3)H-PAR-binding sites than the control subjects. On one hand, this finding confirms previous data of an abnormal platelet 5-HT transporter in OCD, on the other it provides the possibility to explore the regulation of this structure in this and other disorders, since lymphocytes are nucleate cells.

Adult↗

Do animal models of anxiety predict anxiolytic-like effects of antidepressants?

Chronically administered antidepressant drugs, particularly selective serotonin (5-HT) reuptake inhibitors (SSRIs), are clinically effective in the treatment of all anxiety disorders, while the clinical effectiveness of "traditional" anxiolytics, such as benzodiazepines (BDZs), is limited to generalised anxiety disorder or acute panic attacks. This implies that animal models of anxiety should be sensitive to SSRIs and other antidepressants in order to have predictive validity. We reviewed the literature on the effects of antidepressants in the so-called animal models of anxiety and found that only the isolation-induced calls in guinea-pig pups may reveal anxiolytic-like action of all antidepressant classes after acute administration. Some other models, such as marble-burying or conditioned-freezing behaviours, and isolation- or shock-induced ultrasonic vocalisation models, may detect anxiolytic-like activity of acutely administered antidepressants, although the sensitivity of these models is usually limited to SSRIs and other drugs affecting 5-HT uptake. The predictive validity of models of "anxiety", such as the plus-maze and light-dark transition tests or stress-induced hyperthermia, appears to be limited to BDZ-related drugs. Far less work has been done on chronic administration of antidepressants in animal anxiety models. Unless and until such studies have been undertaken, the true predictive value of the anxiety models will remain unknown.

Animals↗

Decreased inhibitory activity of PKC in OCD patients after six months of treatment.

We investigated 5-HT reuptake and protein kinase of type C (PKC) activation in platelets of 14 OCD patients at baseline and after six months of treatment with different serotonin (5-HT) reuptake inhibitors (SRIs). The results showed that all SRIs provoked a significant increase in both the maximal velocity (V(max)) and the Michaelis-Menten constant (K(m)) of 5-HT reuptake, as compared with baseline values. The activation of PKC by means of 4-beta-12-tetradecanoylphorbol 13-acetate provoked a significant decrease in V(max) values, but the effect was not as evident as at baseline. These findings could indicate that, in OCD patients, SRIs increase the rate of reuptake and decrease the inhibitory effect of PKC and that the two phenomena may be linked, the first perhaps depending upon the second.

Adolescent↗