Abstract: Pharmacological studies indicate a functional interaction between the serotonergic and oxytocinergic systems. In particular, some selective serotonin (5-HT) reuptake inhibitors, such as citalopram and fluvoxamine, seem to exert part of their antidepressant effects through oxytocin (OT) release. Further, the administration of fenfluramine, a serotonergic agonist, to healthy subjects increases plasma OT levels. Interestingly, immunocytochemical and double-immunofluorescent techniques revealed a high degree of overlap between 5-HT transporter (SERT)-labeled fibers and OT-containing cells in the paraventricular and supraoptic nuclei of primate hypothalamus. These findings suggest that the influence of 5-HT on OT system might be mediated by SERT. In this study, we explored the possible existence of a link between OT and SERT in human subjects, by means of two peripheral markers, the platelet SERT, as measured by [(3)H]-paroxetine ([(3)H]-Par) binding, and plasma OT levels. As far as [(3)H]-Par binding parameters are concerned, the Bmax (mean±SD, fmol/mg protein) was 1155+130 and the Kd (mean±SD, nM) was 1.31±0.61. The OT plasma levels (mean±SD, pg/ml) were 1.14±1.07. A significant and positive correlation was found between plasma OT levels and Kd values (correlation coefficient: r: 0.466, p=.038). This result represents the first evidence of an interaction between OT and SERT, as measured by [(3)H]-Par binding, at peripheral levels in humans. Given the several activities mediated by both OT and 5-HT, such a relationship might provide new perspectives and insights into psychiatric disorders and/or social relationship disturbances, as well as novel treatment strategies overcoming and/or integrating the serotonergic paradigm.
Abstract: The aim of this study was to explore the possible relationship between plasma clomipramine and its major metabolite (N-desmethylclomipramine) levels and related parameters, and clinical features in patients with obsessive-compulsive disorder (OCD). Twenty-six outpatients (13 men, 13 women), suffering from OCD were consecutively enrolled in this study. The severity of OCD was assessed by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The measurements were taken after 4 weeks and 6 months from the beginning of the treatment. The drug levels were measured by a high-performance liquid chromatography method developed by us. The correlations between biological and clinical parameters were analyzed by means of Spearman's correlation coefficient. The Mann-Whitney test was used for comparing biological and clinical variables between men and women. The results showed that clomipramine levels were related to the doses at the two assessment times. A significant and positive correlation was detected at the beginning between the N-desmethylclomipramine ratio and the Y-BOCS total score; however, this was true only for men, where the similar correlations were measured also with the Y-BOCS subscale. After 6 months of clomipramine, men showed a significant improvement of the compulsions. These findings would highlight the potential impact of assessing clomipramine plasma levels and their relationships with specific symptoms, as well as the influence of the sex on the drug response.
Abstract: In our previous study, we observed that the presence of autoimmune thyroid disease worsens fibromyalgia (FM) symptoms. The aims of this study are to evaluate whether there is a predisposition for the development of FM in patients with Hashimoto's thyroiditis (HT) with or without subclinical hypothyroidism (SCH) and in patients with SCH alone and what is the weight of antithyroid antibody positivity and SCH on FM comorbidity. Fifty-two patients, 39 affected by HT with or without SCH and 13 by SCH, were matched with 37 patients affected by FM and 25 healthy subjects. Blood samples were collected from all study subjects for the determination of serum TSH, free triiodothyronine, free thyroxine, antithyroperoxidase antibody (TPOAb), antithyroglobulin antibody (TgAb) and non-organ-specific autoantibodies. Clinical assessment of patients and controls included the "Fibromyalgia Impact Questionnaire" (FIQ), while pain severity was evaluated using a visual analogue scale (VAS). Patients and controls were also characterized by the presence of diffuse pain, fatigue, paresthesiae, muscle spasms, non-restful sleep, tension headache and presence of mood disorders. FM comorbidity resulted in twelve HT subjects (31%) and none in SCH patient. In particular, FM comorbidity in HT patients without SCH was 33.3% and in HT patients with SCH was 28.5%. Based on our data, we speculate that maybe there is more than a hypothesis regarding the cause-effect relation between thyroid autoimmunity and the presence of FM, thus suggesting a hypothetical role of thyroid autoimmunity in FM pathogenesis.
Abstract: Typical antipsychotics, potent D2 dopamine receptor
antagonists, are the most commonly used drugs in the
treatment of bipolar disorders. In the central nervous
system, the discovery of antagonistic interactions between
A2A adenosine receptors and D2 dopamine receptors
suggests that the adenosine system may be
involved in the pathogenesis of different psychiatric
disorders and in the therapeutic effectiveness of antipsychotic
drugs. Previously, we have demonstrated
an increase in A2A receptor expression and agonist
affinity in platelets from psychotic patients treated
with haloperidol. This result suggests that there is
also a structural and functional interaction between
A2A and D2 receptors in peripheral cells. In this work,
we investigated the effect of different doses of typical
drugs on A2A adenosine receptor binding and correlated
these parameters with the severity of symptoms.
We demonstrated, for the first time, that there was a
strong correlation between A2A receptor affinity constant
values (Kd) and drug doses in psychotic patients
with a moderate severity of illness and moderate
psychotic symptoms. The correlation was completely
lost in patients with severe illness and severe psychotic
symptoms. These results demonstrated that in platelets
of patients affected by psychosis, typical antipsychotics
modulated A2A receptor binding parameters;
this regulation is dependent on the degree of D2 receptor
occupancy in relation to the severity of psychotic
symptoms, suggesting A2A receptors are a peripheral
marker for individual therapy effectiveness.
Abstract: Abstract Objectives. The cyclic adenosine monophosphate responsive element binding (CREB) protein is a transcription factor involved in different neural processes, such as learning, neuroplasticity and the modulation of stress response. Alterations in the CREB pathway have been observed in the brains and lymphocytes of patients affected by depression and alcohol abuse. Given the lack of information, our study aimed at investigating the levels of total and activated CREB protein in lympho-monocytes of 20 drug-free patients suffering from post-traumatic stress disorders (PTSD), as compared with 20 healthy control subjects. Methods. Blood samples were collected from patients and healthy control subjects on the same time and lympho-monocytes were isolated according to standardized methods. CREB protein levels and activation were measured by means of immunoenzymatic techniques. Results. The results showed that PTSD patients had statistically lower levels of total CREB protein in lympho-monocytes than healthy control subjects. On the contrary, no difference in the activated CREB protein was detected. Conclusions. These findings, albeit preliminary, would suggest that the CREB pathway might be involved in the pathophysiology of PTSD. Future studies should clarify if specific PTSD symptom clusters might be related to the CREB pathway.
Abstract: On April 6th 2009, the town of L'Aquila, Italy, was struck by an earthquake (6.3 on the Richter scale) that lead large parts of the town to be destroyed and the death of 309 people. Significant losses in the framework of earthquakes have been reported as a major risk factor for PTSD development. Aim of this study was to investigate post-traumatic spectrum symptoms in a sample of adolescents exposed to the L'Aquila 2009 earthquake 21 months earlier, with particular attention to the impact of loss.
Abstract: Earthquakes are one of the most frequently occurring natural disasters and extensive research has been conducted on mental disorders on exposed populations, particularly on post-traumatic stress disorder (PTSD). On April 6th 2009, the town of L'Aquila (Abruzzo), in central Italy, was struck by an earthquake with a strength of 5.9 on the Richter scale. In the town of L'Aquila many buildings collapsed and large parts of the town were destroyed. Overall, 309 people were killed, 1600 injured among which 200 severely injured and hospitalized, more than 65,000 people were displaced.
Abstract: Orthorexia, from the Greek words orthos (straight, proper) and orexis (appetite), is a newly conceptualized disorder characterized by distorted eating habits and cognitions concerning supposedly healthy nutrition. In this article we present preliminary results of a wider research aimed to investigate the diffusion of Orthorexia in the general population and to highlight its characteristics and particularly the relationship with Eating Disorder and Obsessive-Compulsive Disorder.
Abstract: The present study explored the possible relationships between impulsivity, gender, and a peripheral serotonergic marker, the platelet serotonin (5-HT) transporter (SERT), in a group of 32 healthy subjects. The impulsivity was measured by means of the Barratt Impulsivity Scale, version 11 (BIS-11), a widely used self-report questionnaire, and the platelet SERT was evaluated by means of the specific binding of (3)H-paroxetine ((3)H-Par) to platelet membranes, according to standardized protocols. The results showed that women had a higher BIS-11 total score than men, and also higher scores of two factors of the same scale: the motor impulsivity and the cognitive complexity. The analysis of the correlations revealed that the density of the SERT proteins, as measured by the maximum binding capacity (B(max)) of (3)H-Par, was significantly and positively related to the cognitive complexity factor, but only in men. Men showed also a significant and negative correlation with the dissociation constant, Kd, of ((3)H-Par) binding, and the motor impulsivity factor. These findings suggest that women are generally more impulsive than men, but that the 5-HT system is more involved in the impulsivity of men than in that of women.
Abstract: There is increasing evidence that the brain-derived neurotrophic factor (BDNF) is involved in the pathophysiology of mood disorders and that its peripheral levels represent a reliable mirror of its concentration in the brain. The aim of the present study was to measure BDNF plasma levels in patients affected by major depression and to explore the possible relationship between the biological parameter and characteristics of the illness.
Abstract: To assess the roles of instrument diameter (5.0- or 3.5-mm external sheath), uterine distention medium (carbon dioxide [CO(2)] or saline solution), and hysteroscopist experience in diagnostic hysteroscopy.
Abstract: The presence of functional pheromones in axillary extracts in humans is still matter of debate. Scattered data suggest that unidentified human axillary compounds with pheromonal activity may influence mood and this may occur, perhaps, through the modulation of the serotonin (5-HT) system that has been linked to mood by several findings. Therefore, the aim of this study was to assess the possible changes of a peripheral marker of the 5-HT system, i.e., the platelet 5HT transporter, and of some psychological tests, in a group of women who were exposed to male axillary extracts (group 1). A matched group of women who underwent an exposure to a neutral solution, were used as control subjects (group 2). The 5-HT transporter was evaluated by means of the specific binding of (3)H-paroxetine ((3)H-Par) to platelet membranes, as well as by means of (3)H-5-HT reuptake in whole platelets, at baseline (T0) and 1h after the stimulation (T1). The following tests were used: the "Experiences in Close Relationships" questionnaire (ECR), the latest version of the Barratt Impulsiveness Scale (BIS-11) and the Structured Clinical Interview for Mood Spectrum, self-reported version. The dissociation constant (Kd) of (3)H-Par binding showed a significant decrease at T1 only in the women exposed to male axillary extracts, as compared with baseline values, while the Bmax and (3)H-5-HT reuptake parameters did not show any change in both groups. The correlation analyses showed that at T0, the Kd values correlated significantly and positively with the factor of motor impulsiveness in all subjects. Two factors of the BIS-11, in particular, the attentional and the motor impulsiveness were significantly lower at T1 in the group 1. Further, at T1 and still in the group 1, a significant and positive correlation was measured between the Kd values and two ECR attachment styles, the secure and preoccupied, as well as with the ECR anxiety scale. Taken together, these findings suggest that the application of male axillary extracts to women may modify the affinity of their platelet 5-HT transporter, as well as of some impulsiveness and romantic attachment characteristics. The substances responsible for this effect remain to be identified.
Abstract: Recent data have shown the presence of immunological alterations in adult patients suffering from obsessive-compulsive disorder (OCD). The objective of this study was to examine the possible effects of 12 months of treatment with different serotonergic drugs, such as clomipramine and selective serotonin reuptake inhibitors (SSRIs) on peripheral immunological cells of 18 OCD patients. Both the absolute number and percent of CD4+, CD8+, CD3+, CD19+ and CD56+ cells were measured in peripheral blood before and after treatment by means of a Facstar Flow Sorter apparatus. At baseline, all patients showed a significant increase of CD8+ and decrease of CD4+ lymphocytes when compared with a similar group of healthy control subjects; after the treatment, CD8+ and CD4+ cells, respectively, decreased and increased significantly, and the CD4+/CD8+ ratio increased, when compared with baseline values, in parallel with the clinical improvement. These data suggest that the alterations of immune cells reported in patients with OCD at baseline may be reverted by treatment with SRIs and should be considered a state-dependent marker, perhaps related to a condition of stress.
Abstract: There are concerns about the quality of generic drugs in the postmarketing setting. The aim was to establish whether two generic formulations of amoxicillin, available on the Italian market, fulfil the criteria for clinical pharmacokinetic bioequivalence vs. the branded drug.
Abstract: Aim of the study was to investigate caffeine use in different types of eating disorders (ED) patients either using a categorical approach [Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition - Text Revision (DSM-IV-TR) diagnostic criteria] or a dimensional perspective.
Abstract: In both animals and humans, stress has been demonstrated to reduce the expression of the Brain-Derived Neurotrophic Factor (BDNF), a neurotrophin (NT) which promotes the proliferation, survival and differentiation of neurons. Although traumatic events have been found to be associated with lower BDNF plasma levels in affective disorders, no study has explored this parameter in patients with post-traumatic stress disorder (PTSD). We, therefore, measured BDNF plasma level in 18 patients with PTSD and in 18 healthy control subjects. Diagnoses were assessed by the Structured Clinical Interview for DSM-IV, while the specific symptoms were examined in the patients by means of the Impact of Event Scale for PTSD and the traumas experienced were assessed by using the Life Events Checklist. BDNF plasma levels were evaluated by means of a standardized Elisa method. The results, while showing significantly lower BDNF levels in PTSD patients, as compared with those of healthy subjects (p=0.001), although obtained in a small sample size, would suggest that this NT may be involved in the pathophysiology of PTSD.
Abstract: Scant information is available on the diurnal variation of peripheral neurotrophic factors, including brain-derived neurotrophic factor (BDNF), in human beings. We explored plasma and serum BDNF levels at three different clock times in a study of 28 healthy subjects of both sexes. Statistically significant diurnal variation in plasma BDNF level was detected in men, with the peak at 08:00 h and nadir at 22:00 h. At this time, the plasma BDNF concentration of men was significantly lower than that of women (p=.02). However, no diurnal variation was found either in plasma BDNF of women, in either the follicular or luteal phases of the menstrual cycle, or in serum BDNF level in both men and women. These findings support the concept of rhythmic variation in plasma BDNF regulation that seems to be sex-related.
Abstract: To investigate obese people with/without binge-eating Disorder (BED) in terms of shared psychopathological features pertaining to spectrum of eating disorders.
Abstract: Brain-derived neurotrophic factor (BDNF) has been hypothesized to be involved in the neurobiology of major depression. The aim of this study was to assess the possible relationships between depressive symptoms and serum and/or plasma BDNF levels during 1 year of antidepressant treatment.
Abstract: To examine the possible role of the soluble factor in fibromyalgia (FM) by studying the correlation of cytokine levels with the patients' clinical and psychiatric profile.
Abstract: Controversies exist regarding the impact of psychological stress on the functioning of the immune system in humans. The aim of the present study, therefore, was to evaluate whether the condition of a pre-exam stress may or not modify resting lymphocyte subsets, as well as blood pressure and heart rate. About 22 medical residents of both sexes not suffering from any medical or psychiatric disorder were included in the study. Anxiety levels were measured by means of the Hamilton rating scale for anxiety (HRSA) and anxiety traits by means of the panic-agoraphobic spectrum self-report (PAS-SR) version and the obsessive-compulsive spectrum self-report (OBS-SR) version. The results showed that systolic blood pressure and heart rate increased significantly just before sitting an examination (t(1)) in all subjects, as compared with a calm situation (t(2)), in parallel with the increase in the HRSA total score, while no significant difference was observed in lymphocyte subsets at the two assessment times. However, men had a higher number of CD4+ cells than women at t(1) and t(2), while women showed a higher heart rate at t(1). In addition, significant correlations between CD4+ lymphocyte count and heart rate at t(1) or HRSA at t(2) were detected. These findings indicate that the acute stress determined by sitting for examination provokes changes in autonomic nervous system parameters, such as blood pressure and heart rate, as well as in the subjective feeling of anxiety, as shown by the increased HRSA total scores, which were not paralleled by modifications of lymphocyte subsets. However, individual differences, related to both sex and personality traits yet to be identified, seem to have an impact in shaping the stress response.
Abstract: Although the beneficial effects of balneotherapy have been recognized since a long time, a few information is available on the biological mechanisms underlying them and the subjective feelings of increased well-being and mood. The links between the serotonin (5-HT) system and mood prompted us to investigate the 5-HT platelet transporter (SERT), which is considered a reliable, peripheral marker of the same structure present in presynaptic neurons, in 20 healthy volunteers before (t0) and 30 min after (t1) thermal balneotherapy with ozonized water of Montecatini spa, as compared with a similar group who underwent a bath in non-mineral water. The SERT was evaluated by means of the specific binding of (3)H-paroxetine ((3)H-Par) to platelet membranes. Equilibrium-saturation binding data, the maximal binding capacity (Bmax) and the dissociation constant (Kd), were obtained by means of the Scatchard analysis. The results showed that, while Bmax values did not change in both groups, the Kd values decreased significantly at t1 only in those subjects who bathed in ozonized water. The results of this study, while showing a decrease of the dissociation constant (Kd) which is the inverse of affinity constant, of (3)H-Par binding to SERT in all subjects after balneotherapy and not in those bathing in normal water, suggest that SERT modifications may be related to a specific effect of ozonized water and, perhaps, also to the increased sense of well-being.
Abstract: Recent literature demonstrates the relationship between psychopathology and medically unexplained pain, even if the results of several studies show a high degree of variability. The present study was planned with the aim of analysing both the possible relationship between the level (low/high) of organicity and the presence of psychopathology, and the degree to which these differences are related to methodological problems. Between 1998 and 2000, four hundred and thirty six consecutive patients seen at the Pisa Pain Therapy and Palliative Care Unit were requested to fill in a questionnaire, the GHQ-12, to screen the subjects probably with (GHQ-12>3) or without (GHQ-12</=3) psychopathology. All the patients scoring above the GHQ-12 threshold (score of 3), and a randomised sample of those scoring below the GHQ-12 threshold, were included in the study. These patients were then interviewed using three different instruments: the Mini International Neuropsychiatric Interview (MINI) for a standardised psychiatric diagnosis, the Semistructured Interview for Depression (SID) for the characterisation of temperament, and the Italian Pain Questionnaire (IPQ) for the evaluation of pain. Our results suggest that Somatisation Disorders are more frequent in the medically unexplained pain group than in the medically explained pain group, whereas the other psychiatric disorders have a similar prevalence in the two pain groups. Mood and anxiety disorders are correlated with high scores on GHQ-12 and medically explained pain has a higher prevalence of GHQ-12>3 than the medically unexplained pain group. These results confirm that methodology is an important factor that could modify results in psychiatric research. Both medically unexplained pain and the presence of psychopathology are significantly correlated with sex, and age: females and young patients have a higher prevalence of psychopathology and of medically unexplained pain. Our results suggest that in the correlation between the low organicity of pain and psychopathology, the age and sex play a relevant role.
Abstract: Assessing the quality of life should be an essential part of the long-term results of surgery, particularly for those procedures that may influence a patient's lifestyle and body image. Eliminating the need for dependence on chronic hemodialysis, kidney transplantation improves the patient's autonomy but exposes them to the side-effects of immunosuppression and the constant threat of rejection. The purpose of this study was to compare the quality of life of patients on the waiting list for a kidney transplantation to that of those already transplanted at our Center to quantify carefully the impact of this therapy on the patient's physical, emotional, and social well-being. Computer analysis of the data collected from self-administered questionnaires revealed that the vast majority of successfully transplanted patients experience a significant improvement in almost all the areas investigated compared with the pretransplant group. In addition, we tried to use the questionnaire to predict which type of patient will adjust more fully to the impact of a kidney transplantation and which will probably need posttransplant psychological care and social support. Aside from clinical factors such as the time spent on hemodialysis before transplantation, the gender, the age, as well as the source of the organ (living vs. cadaver donor) seem to play a role in the final outcome of a successful kidney transplantation.
Abstract: A randomized double-blind study was performed to compare the therapeutic effects of lithium and carbamazepine (CBZ) each administered in combination with chlorpromazine (CPZ) for 3 weeks in women with acute psychosis. Thirty patients were studied. The initial dose was 1200 mg/day for CBZ and 900 mg/day for lithium, and it was subsequently modified according to plasma levels and clinical indications. The dose of CPZ was free and depended on the severity of symptomatology. Both treatments produced a significant improvement in psychotic symptoms without significant differences between the treatment groups. Also, as regards tolerability no clinically relevant differences were found between the two groups. During the first week of treatment the CPZ dose required in the CBZ group was significantly lower than that administered to the lithium group, indicating that CBZ had a greater sedative action; however, this difference decreased as treatment continued. These results confirm that CBZ is a valid alternative to lithium in the treatment of acute psychosis.
Abstract: The indications and the characteristics of the multicenter clinical trials are considered and the BLIPS/BDP system is showed in detail as developed at the Institute of Clinical Psychiatry of the University of Pisa within the cooperation with the National Institute of Mental Health (NIMH-USA) at the Center for Clinical Psychopharmacology Data Documentation (CCPDD). The characteristics of the BLIPS/BDP system in the storage, retrieval and documentation of data derived from clinical trials on psychotropic drugs are reported. Finally, examples are given of the large number of possible utilizations of the BLIPS/BDP Data Bank documenting its flexibility and versatility and the extent of its possibilities.
Abstract: This article describes a controlled clinical trial comparing nomifensine and amitriptyline in endogenously depressed inpatients. It is also the first trial of the ICPP-BLIPS, a computer based clinical trial data documentation system. Using strict methodological criteria, careful quality control and comprehensive and systematic data display and data analysis, we have been able to show clearcut efficacy differences between nomifensine and amitriptyline (favouring the later) and clearcut differences in the profile of side effects between these drugs. Future studies utilizing this methodology are recommended were definitive and documented results of clinical trials are desired.
