E Romeo

Foundation Santa Lucia, Roma, Latium, Italy

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Publications (56)258.04 Total impact

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    ABSTRACT: Parkinson's disease (PD) is associated with a massive loss of dopaminergic cells in the substantia nigra leading to dopamine hypofunction and alteration of the basal ganglia circuitry. These neurons, are under the control, among others, of the excitatory glutamatergic and inhibitory γ-aminobutyric acid (GABA) systems. An imbalance between these systems may contribute to excitotoxicity and dopaminergic cell death. Neurosteroids, a group of steroid hormones synthesized in the brain, modulate the function of several neurotransmitter systems. The substantia nigra of the human brain expresses high concentrations of allopregnanolone (3α, 5αtetrahydroprogesterone), a neurosteroid that positively modulates the action of GABA at GABAA receptors and of 5α dehydroprogesterone, a neurosteroid acting at the genomic level. This article reviews the roles of NS acting as neuroprotectants and as GABAA receptor agonists in the physiology and pathophysiology of the basal ganglia, their impact on dopaminergic cell activity and survival, and potential therapeutic application in PD.
    Frontiers in Neuroendocrinology 04/2013; · 7.99 Impact Factor
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    ABSTRACT: The variable number of tandem repeat polymorphism in the 3'-untranslated region of the dopamine transporter gene (DAT) may influence the variability of the therapeutic response to methylphenidate (MPH) in Attention Deficit/Hyperactivity Disorder (ADHD). For this reason we evaluated the neuropsychological functioning after a prolonged period of MPH treatment and after a specific time from MPH suspension. Relationship between DAT VNTR genotypes and neurocognitive response to MPH was analyzed in a sample of 108 drug-naive ADHD patients. The performance of children with ADHD on measures of working memory, inhibition and planning was assessed at 4, 8 and 24 weeks and at 8 weeks after MPH withdrawal. Patients with 9/9 genotype evidenced an improvement in response inhibition and working memory only at 4 weeks of treatment, in planning at 24 weeks of therapy and after 8 weeks of MPH suspension. Patients with 9/10 showed an improvement in response inhibition at 4, 8 and 24 weeks of treatment, in planning at 24 weeks and after 8 weeks of MPH suspension. Patients with 10/10 evidenced an improvement in response inhibition and working memory at 4, 8 and 24 weeks of treatment and in planning at 4, 8 and 24 weeks of treatment and after 8 weeks of suspension. These results indicate that the 9/9 ADHD genotype has a different response at 24 weeks treatment with MPH. 10/10 DAT allele seems to be associated with an increased expression level of the dopamine transporter and seems to mediate the MPH treatment response in ADHD patients.
    European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 03/2013; · 2.01 Impact Factor
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    ABSTRACT: Anxiety disorders are the most common psychiatric disorders. They are frequently treated with benzodiazepines, which are fast acting highly effective anxiolytic agents. However, their long-term use is impaired by tolerance development and abuse liability. In contrast, antidepressants such as selective serotonin reuptake inhibitors (SSRIs) are considered as first-line treatment but have a slow onset of action. Neurosteroids are powerful allosteric modulators of GABA(A) and glutamate receptors. However, they also modulate sigma receptors and they are modulated themselves by SSRIs. Both pre-clinical and clinical studies have shown that neurosteroid homeostasis is altered in depression and anxiety disorders and antidepressants may act in part through restoring neurosteroid disbalance. Moreover, novel drugs interfering with neurosteroidogenesis such as ligands of the translocator protein (18 kDa) may represent an attractive pharmacological option for novel anxiolytics which lack the unwarranted side effects of benzodiazepines. Thus, neurosteroids are important endogenous neuromodulators for the physiology and pathophysiology of anxiety and they may constitute a novel therapeutic approach in the treatment of these disorders.
    Frontiers in Endocrinology 01/2011; 2:55.
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    ABSTRACT: Among the neuroactive steroids, 3alpha,5alpha-tetrahydrodeoxycorticosterone (3alpha,5alpha-THDOC) is at least in part produced in the adrenal gland and is therefore under the control of the hypothalamic-pituitary-adrenocortical (HPA) system. The antidepressant mirtazapine has been shown to attenuate HPA axis activity and to increase the concentrations of 3alpha-reduced metabolites of progesterone in depressed patients. In the present study, the impact of mirtazapine on 3alpha,5alpha-THDOC levels was investigated in relation to clinical response in depressed patients. A total of 23 drug-free inpatients suffering from a major depressive episode (DSM-IV criteria) underwent 5-week treatment with mirtazapine (45 mg/day). Plasma samples were taken weekly at 08:00 h and were quantified for 3alpha,5alpha-THDOC levels. 3alpha,5alpha-THDOC levels were not correlated with demographic and clinical parameters such as age and severity of depression. Moreover, 5-week treatment with mirtazapine did not influence the 3alpha,5alpha-THDOC in the depressed patients, neither in responders nor in non-responders. Putative increasing effects of mirtazapine on 3alpha-reduced neuroactive steroids such as 3alpha,5alpha-THDOC which may be mediated via an impact on the neurosteroidogenic enzyme 3alpha-hydroxysteroid dehydrogenase seem to be counterbalanced by the mirtazapine-induced inhibition of ACTH secretion which directly influences the 3alpha,5alpha-THDOC release of the adrenal cortex.
    The World Journal of Biological Psychiatry 01/2010; 11(2 Pt 2):308-13. · 3.57 Impact Factor
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    ABSTRACT: Summary Objective: The purpose of this study was to investigate the effects of fluoxetine (F) and indomethacine (I), two drugs that regulate the synthesis of the GABAergic neurosteroid 3α, 5α tetrahydroprogesterone (allopregnanolone, THP) on THP plasma levels and on symptoms of anxiety and depression in alcoholics during ethanol withdrawal. Method: Patients who met DSM-IV criteria for alcohol abuse were randomly assigned to treatment with F (40 mg/day) plus misoprostol (M) (500 mg/day) or I (100 mg/day) plus M or placebo (PL) plus M. Patients were rated with the Hamilton Anxiety (14-HAS) and Depression (17-HDS) scales on days 1, 5, 7, 15 and 28 of ethanol withdrawal and with a Visual Analogue Scale for Depression (VASD) and a Visual Analogue Scale for Anxiety (VASA) on days 1, 2, 4, 5, 7, 15 and 28 of withdrawal. On the same days a plasma sample was collected to measure the concentrations of THP by means of a very sensitive gas chromatographic mass spectrometric method. Results: During withdrawal at days 1, 2, 4 and 5, THP plasma values were lower and symptoms of anxiety and depression were significantly higher compared to the late withdrawal phase at days 15 and 28. In the F or I treatment, the depression and anxiety score, measured by VASD and VASA, decreased significantly at day 5-7 whereas THP plasma levels significantly increased compared to PL condition. Conclusions: Treatment of alcohol withdrawal either with F or I reduced the extent of anxiety and depression and normalised THP plasma levels that were decreased during withdrawal.
    The World Journal of Biological Psychiatry 07/2009; 1(2):101-104. · 3.57 Impact Factor
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    ABSTRACT: There is evidence that gamma-amino-butyric acid type A (GABA(A))-receptor modulating neuroactive steroids play a role in the pathophysiology of panic disorder. Antidepressant treatment has been suggested to stabilize the concentrations of neuroactive steroids. In this pilot study we investigated neuroactive steroid concentrations during GABAergic treatment, which might represent an alternative anxiolytic pharmacotherapeutic strategy. Neuroactive steroid concentrations were determined in 10 healthy subjects treated with tiagabine. To evaluate the anxiolytic effects of tiagabine a cholecystokinin-tetrapeptide (CCK-4) challenge was performed before and after treatment. Treatment with tiagabine led to a significant increase in 3alpha,5alpha-tetrahydrodeoxycorticosterone (3alpha,5alpha-THDOC) from 0.49 to 1.42 nmol/l (Z=-2.80, p=.005), which was significantly correlated with a decrease of panic symptoms in the CCK-4 challenge. Thus, it might be hypothesized that the anxiolytic effects of GABAergic treatment might in part be mediated by their influence on 3alpha,5alpha-THDOC concentrations.
    Psychoneuroendocrinology 07/2009; 34(10):1586-9. · 5.59 Impact Factor
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    ABSTRACT: The role of neurosteroids in neuropsychiatric disorders has been thoroughly investigated in many research studies that have stressed their significant pathophysiological function in neuropsychiatry. In this review, we will focus mainly on the steroids active on the GABA(A) receptors studied in anxiety and depression. The aim is to discuss the controversial results reported in research on anxiety and depressive disorders. We suggest the combined use of biological parameters linked to psychopathological dimensions to make more homogeneous diagnoses and to develop more precise therapies for the treatment of depression and anxiety disorders. We discuss the role of neurosteroids in the pathophysiology and therapy of anxiety and depression. Finally, we consider the possibility of using quantification of mRNA expression of steroidogenic enzymes from peripheral sources in neuropsychiatry.
    Neurochemistry International 01/2008; 52(4-5):596-601. · 2.66 Impact Factor
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    ABSTRACT: Background. Among the neuroactive steroids, 3alpha,5alpha-tetrahydrodeoxycorticosterone (3alpha,5alpha-THDOC) is at least in part produced in the adrenal gland and is therefore under the control of the hypothalamic-pituitary-adrenocortical (HPA) system. The antidepressant mirtazapine has been shown to attenuate HPA axis activity and to increase the concentrations of 3alpha-reduced metabolites of progesterone in depressed patients. In the present study, the impact of mirtazapine on 3alpha,5alpha-THDOC levels was investigated in relation to clinical response in depressed patients. Method. A total of 23 drug-free inpatients suffering from a major depressive episode (DSM-IV criteria) underwent 5-week treatment with mirtazapine (45 mg/day). Plasma samples were taken weekly at 08:00 h and were quantified for 3alpha,5alpha-THDOC levels. Results. 3alpha,5alpha-THDOC levels were not correlated with demographic and clinical parameters such as age and severity of depression. Moreover, 5-week treatment with mirtazapine did not influence the 3alpha,5alpha-THDOC in the depressed patients, neither in responders nor in non-responders. Conclusion. Putative increasing effects of mirtazapine on 3alpha-reduced neuroactive steroids such as 3alpha,5alpha-THDOC which may be mediated via an impact on the neurosteroidogenic enzyme 3alpha-hydroxysteroid dehydrogenase seem to be counterbalanced by the mirtazapine-induced inhibition of ACTH secretion which directly influences the 3alpha,5alpha-THDOC release of the adrenal cortex.
    The World Journal of Biological Psychiatry 11/2007; · 3.57 Impact Factor
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    ABSTRACT: Antidepressants such as SSRIs or mirtazapine have been demonstrated to increase the concentrations of 3alpha-reduced neuroactive steroids throughout several weeks of treatment. However, no data are available on the impact of mood stabilizers such as lithium or carbamazepine on neuroactive steroid levels in depressed patients. Study 1 was performed in 26 drug-free depressed inpatients who were treated with either mirtazapine monotherapy (n=13) or combination therapy with mirtazapine and addition of lithium (n=13). Twenty drug-free depressed inpatients were included in study 2, receiving either mirtazapine monotherapy (n=10) or combination treatment with mirtazapine and carbamazepine (n=10). Plasma samples were taken weekly at 0800 h in the morning and quantified for neuroactive steroids by means of combined gas chromatography/mass spectrometry analysis. In study 1, the mirtazapine-induced rises in 3alpha,5alpha-tetrahydroprogesterone and 3alpha,5beta-tetrahydroprogesterone were abolished by additional lithium administration, as compared to mirtazapine monotherapy. In study 2, the mirtazapine-evoked increase in 3alpha,5alpha-tetrahydroprogesterone was reversed after additional administration of carbamazepine, presumably due to lowered mirtazapine levels after induction of cytochrome P450 enzymes. Apparently, the mood stabilizers lithium and carbamazepine do not enhance but rather reverse the increase in plasma concentrations of 3alpha-reduced neuroactive steroids in depressed patients pretreated with antidepressants such as mirtazapine.
    Psychoneuroendocrinology 08/2007; 32(6):669-80. · 5.59 Impact Factor
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    ABSTRACT: Neuroactive steroids modulate neurotransmission through modulation of specific neurotransmitter receptors such as gamma-aminobutyric acid type A (GABA(A)) receptors. Preclinical studies suggested that neuroactive steroids may modulate anxiety and depression-related behaviour and may contribute to the therapeutical effects of antidepressant drugs. Attenuations of such neuroactive steroids have been observed during major depression and in several anxiety disorders, suggesting a pathophysiological role in such psychiatric conditions. In panic disorder patients a dysequilibrium of neuroactive steroid composition has been observed, which may represent a counterregulatory mechanism against the occurrence of spontaneous panic attacks. Furthermore, alterations of 3alpha-reduced pregnane steroids during major depression were corrected by successful treatment with antidepressant drugs. However in contrast, non-pharmacological antidepressant treatment strategies did not affect neuroactive steroid composition. In addition, changes in neuroactive steroid concentrations after mirtazapine therapy occurred independently from the clinical response, thereby suggesting that changes in neuroactive steroid concentrations more likely reflect direct pharmacological effects of antidepressants rather than clinical improvement in general. Nevertheless, the effects of antidepressant pharmacotherapy on the composition of neuroactive steroids may contribute to the alleviation of certain depressive symptoms, such as amelioration of anxiety, inner tension or sleep disturbances. Moreover, first studies investigating the therapeutical effects of dehydroepiandrosterone revealed promising results in the treatment of major depression. In conclusion, neuroactive steroids are important endogenous modulators of depression and anxiety and may provide a basis for development of novel therapeutic agents in the treatment of affective disorders.
    Pharmacology Biochemistry and Behavior 09/2006; 84(4):656-66. · 2.82 Impact Factor
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    ABSTRACT: Neuroactive steroids modulate neurotransmission through modulation of specific neurotransmitter receptors such as gamma-aminobutyric acid type A (GABAA) receptors. Preclinical studies suggested that neuroactive steroids may modulate anxiety- and depression-related behaviour and may contribute to the therapeutical effects of antidepressant drugs. Attenuations of 3alpha-reduced neuroactive steroids have been observed during major depression. This disequilibrium can be corrected by successful treatment with antidepressant drugs. However, non-pharmacological antidepressant treatment strategies did not affect neuroactive steroid composition independently from the clinical response. Further research is needed to clarify whether enhancement of neuroactive steroid levels might represent a new therapeutical approach in the treatment of affective disorders. Nevertheless, the first studies investigating the therapeutical effects of exogenously administered dehydroepiandosterone revealed promising results in the treatment of major depression. In addition, in various anxiety disorders alterations of neuroactive steroid levels have been observed. In panic disorder, in the absence of panic attacks, neuroactive steroid composition is opposite to that seen in depression, which may represent counter-regulatory mechanisms against the occurrence of spontaneous panic attacks. However, during experimentally induced panic attacks, there was a pronounced decline in GABAergic neuroactive steroids, which might contribute to the pathophysiology of panic attacks. In conclusion, neuroactive steroids contribute to the pathophysiology of affective disorders and the mechanisms of action of antidepressants. They are important endogenous modulators of depression and anxiety and may provide a basis for the development of novel therapeutic agents in the treatment of affective disorders.
    Psychopharmacology 07/2006; 186(3):373-87. · 4.06 Impact Factor
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    ABSTRACT: Polymerase chain reaction (PCR) is a powerful tool for qualitative evaluation of nucleic acid expression. PCR has been widely applied to measure DNA and RNA messages expression. Neurosteroids synthesized in the nervous system are potent modulators of synaptic activity and have been implicated in several neuropsychiatric disorders. To examine the possibility of an altered expression of the neurosteroidogenic metabolic enzymes in neurological diseases (like Parkinson's disease, PD) we developed a comparative non-radioactive RT-PCR assay to detect the mRNA levels of the peripheral benzodiazepine receptor, the 5alpha-reductase type 1 and 3alpha-hydroxysteroid-oxidoreductase type 1 and 2 in lymphocytes obtained from PD patients. The results were compared with that obtained from simultaneous quantification of progesterone, 5alpha-dihydroprogesterone and 3alpha,5alpha-tetrahydroprogesterone in the plasma and cerebro-spinal fluid of the same individuals using a gas chromatography mass spectrometry (GC/MS) technique. We found a significant decrease of the rate-limiting enzyme 5alpha-R1 along with a significant decrease in plasma and CSF of the 3alpha,5alpha-tetrahydroprogesterone and of the 5alpha-dihydroprogesterone. Comparative RT-PCR assay, along with complimentary techniques (i.e. GC/MS), has the sensitivity, selectivity and dynamic range to allow specific and reliable quantization of the enzymes involved in the neurosteroids pathway and represent a valuable tool to assess their expression in human neuropsychiatric conditions.
    Journal of Neuroscience Methods 07/2006; 153(2):290-8. · 2.11 Impact Factor
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    ABSTRACT: Concentrations of 3alpha-reduced neuroactive steroids are altered in depression and normalize after antidepressant pharmacotherapy with selective serotonin re-uptake inhibitors (SSRIs). We investigated the impact of mirtazapine on the activity of a key neurosteroidogenic enzyme, the 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD), and on the levels of neuroactive steroids in relation to clinical response. A total of 23 drug-free in-patients suffering from a major depressive episode (DSM-IV criteria) underwent 5-week treatment with mirtazapine (45 mg/day). Plasma samples were taken weekly at 0800 and quantified for neuroactive steroids by means of combined gas chromatography/mass spectrometry analysis. Enzyme activity was determined by assessment of steroid conversion rates. Irrespective of clinical outcome, there were significant increases in 3alpha,5alpha-tetrahydroprogesterone, 3alpha,5beta-tetrahydroprogesterone, 5alpha-dihydroprogesterone, and 5beta-dihydroprogesterone after mirtazapine treatment, whereas 3beta,5alpha-tetrahydroprogesterone levels were significantly decreased. In vitro investigations demonstrated a dose-dependent inhibitory effect of mirtazapine on the activity of the microsomal 3alpha-HSD in the oxidative direction (conversion of 3alpha,5alpha-tetrahydroprogesterone to 5alpha-dihydroprogesterone). Mirtazapine affects neuroactive steroid composition similarly as do SSRIs. The inhibition of the oxidative pathway catalyzed by the microsomal 3alpha-HSD is compatible with an enhanced formation of 3alpha-reduced neuroactive steroids. However, the changes in neuroactive steroid concentrations more likely reflect direct pharmacological effects of this antidepressant rather than clinical improvement in general.
    Molecular Psychiatry 04/2006; 11(3):261-72. · 15.15 Impact Factor
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    ABSTRACT: Certain neuroactive steroids modulate ligand-gated ion channels via non-genomic mechanisms. Especially 3alpha-reduced pregnane steroids are potent positive allosteric modulators of the GABA type A-receptor. During major depression there is a dysequilibrium of 3alpha-reduced neuroactive steroids, which is corrected by clinically effective pharmacological treatment. To investigate whether these alterations are a general principle of successful antidepressant treatment we studied the impact of non-pharmacological treatment options on neuroactive steroid concentrations during major depression. Neither partial sleep deprivation, transcranial magnetic stimulation nor electroconvulsive therapy affected neuroactive steroid levels irrespectively of the response to these treatments. These studies suggest that the changes in neuroactive steroids observed after antidepressant pharmacotherapy more likely reflect distinct pharmacological properties of antidepressants rather than the clinical response. In patients with panic disorder changes in neuroactive steroid composition have been observed opposite of those seen in depression. These changes may represent counterregulatory mechanisms against the occurrence of spontaneous panic attacks. However, during experimental panic induction with either cholecystokinin-tetrapeptide or sodium lactate there was a pronounced decline in the concentrations of 3alpha-reduced neuroactive steroids in patients with panic disorder, which might result in a decreased GABAergic tone. In contrast, no changes in neuroactive steroid concentrations could be observed in healthy controls with the exception of 3alpha, 5alpha-tetrahydrodeoxycorticosterone, allotetrahydrodeoxycorticosterone. The modulation of GABA type A-receptors by neuroactive steroids might contribute to the pathophysiology of depression and anxiety disorders and might offer new targets for the development of novel anxiolytic compounds.
    Neuroscience 02/2006; 138(3):1041-8. · 3.12 Impact Factor
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    ABSTRACT: Certain neuroactive steroids modulate ligand-gated ion channels via non-genomic mechanisms. Especially 3alpha-reduced pregnane steroids are potent positive allosteric modulators of the gamma-aminobutyric acid type A (GABA(A)) receptor. During major depression, there is a disequilibrium of 3alpha-reduced neuroactive steroids, which is corrected by clinically effective pharmacological treatment. To investigate whether these alterations are a general principle of successful antidepressant treatment, we studied the impact of nonpharmacological treatment options on neuroactive steroid concentrations during major depression. Neither partial sleep deprivation, transcranial magnetic stimulation, nor electroconvulsive therapy affected neuroactive steroid levels irrespectively of the response to these treatments. These studies suggest that the changes in neuroactive steroid concentrations observed after antidepressant pharmacotherapy more likely reflect distinct pharmacological properties of antidepressants rather than the clinical response. In patients with panic disorder, changes in neuroactive steroid composition have been observed opposite to those seen in depression. However, during experimentally induced panic induction either with cholecystokinine-tetrapeptide or sodium lactate, there was a pronounced decline in the concentrations of 3alpha-reduced neuroactive steroids in patients with panic disorder, which might result in a decreased GABAergic tone. In contrast, no changes in neuroactive steroid concentrations could be observed in healthy controls with the exception of 3alpha,5alpha-tetrahydrodeoxycorticosterone. The modulation of GABA(A) receptors by neuroactive steroids might contribute to the pathophysiology of depression and anxiety disorders and might offer new targets for the development of novel anxiolytic compounds.
    Neuroendocrinology 02/2006; 84(4):244-54. · 3.54 Impact Factor
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    ABSTRACT: There is evidence that both cerebrospinal fluid (CSF) and plasma concentrations of 3alpha-reduced neuroactive steroids are decreased in major depressive disorder. Successful antidepressant pharmacotherapy, for example, with selective serotonin reuptake inhibitors (SSRIs), over several weeks is accompanied by an increase in CSF and plasma concentrations of these neuroactive steroids. However, no such increase has been observed during nonpharmacological treatments such as partial sleep deprivation or repetitive transcranial magnetic stimulation. In order to investigate whether concentration changes in neuroactive steroids are an important component of clinically effective antidepressant treatment, we examined plasma concentrations of the neuroactive steroids 3alpha,5alpha-tetrahydroprogesterone, 3alpha,5beta-tetrahydroprogesterone, 3beta,5alpha-tetrahydroprogesterone, and their precursors progesterone, 5alpha-dihydroprogesterone, and 5beta-dihydroprogesterone in 31 pharmacotherapy-resistant depressed in-patients before and after unilateral electroconvulsive therapy (ECT) as a monotherapy over 4 weeks. Samples were quantified for neuroactive steroids by means of a highly sensitive and specific combined gas chromatography/mass spectrometry analysis. In all, 51.6% of the patients were treatment responders. There was no influence of ECT on the plasma concentrations of any neuroactive steroid studied. Moreover, neuroactive steroid levels did not differ between treatment responders and nonresponders. Our study shows that changes in neuroactive steroid plasma levels are not a mandatory factor for successful antidepressant treatment by ECT. Thus, the previously observed changes in plasma concentrations of neuroactive steroids following treatment with antidepressants such as SSRIs more likely reflect distinct pharmacological properties of these compounds rather than clinical improvement.
    Neuropsychopharmacology 07/2005; 30(6):1181-6. · 8.68 Impact Factor
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    ABSTRACT: Dehydroepiandrosterone has been recently recognized as neuroactive steroid with several vital neurophysiological activities on membrane receptors, such as N-methyl-d-aspartate, and gamma-aminobutyric acid receptors and on genomic androgen receptors. DHEA does also have an antiglucocorticoid effect. So far, the relevance of this neuroactive steroid to psychiatric disorders is not well known. In this study, plasma levels of DHEA were determined with a highly sensitive and specific gas-chromatography/mass-spectrometry method in 23 outpatients suffering from Diagnostic and Statistical Manual of Mental Disorders-IV schizophrenia compared with 23 healthy control subjects matched for age and sex. Plasma levels of DHEA were found to be strongly elevated in the group of schizophrenic patients (mean+/-SD=90.9+/-61.4 nmol/l) compared to that of control subjects (mean+/-SD=24.0+/-17.9 nmol/l) and the difference was highly significant (t=5.018, df=44, p<0.0001). This statistically significant difference was also found when we divided the groups of schizophrenics and controls in subgroups of males (t=4.536, df=24, p=0.0001) and females (t=2.777, df=18, p=0.0124). These results suggest that DHEA may have some role in the pathophysiology of schizophrenia due to its complex mechanism of action in the brain involving genomic and non-genomic components. Therefore, its study may provide further understanding of the pathophysiology of psychoses and open new avenues for their treatment.
    Journal of Psychiatric Research 06/2005; 39(3):267-73. · 4.09 Impact Factor
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    ABSTRACT: Because it has been suggested that agents acting on the gamma-aminobutyric acid-A (GABA(A)) receptor complex, such as the neuroactive steroid 3!#!alpha;,5alpha-tetrahydroprogesterone (3alpha,5alpha-THP), may be biologic modulators of aggression, we aimed to measure 3alpha,5alpha-THP plasma concentrations in subjects with schizophrenia in order to investigate a possible relation with aggressive and hostile behaviour. Eight outpatients with schizophrenia diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), were included. Aggression and hostility were assessed using the Modified Overt Aggression Scale and the paranoid/belligerence symptom cluster of the Positive and Negative Syndrome Scale. Plasma samples were obtained 1 hour before psychometric assessment and were quantified for 3alpha,5alpha-THP using a highly sensitive and specific combined analysis by gas chromatography-mass spectrometry. Increased aggressiveness and hostility were associated with increased 3alpha,5alpha-THP plasma levels (Pearson r = 0.72, p = 0.043 and Pearson r = 0.72, p = 0.041, respectively). These preliminary results suggest that the neuroactive steroid 3alpha,5alpha-THP may affect aggression and hostility in humans.
    Journal of psychiatry & neuroscience: JPN 02/2005; 30(1):49-52. · 6.24 Impact Factor
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    ABSTRACT: 3alpha-reduced neuroactive steroids such as 3alpha, 5alpha-tetrahydroprogesterone (3alpha, 5alpha-THP) and 3alpha, 5alpha-tetrahydrodeoxycorticosterone (3alpha, 5alpha-THDOC) are potent positive allosteric modulators of gamma-aminobutyric acid type A (GABAA) receptors and display pronounced anxiolytic activity in animal models. Experimental panic induction with cholecystokinin-tetrapeptide (CCK-4) and sodium lactate is accompanied by a decrease in 3alpha, 5alpha-THP concentrations in patients with panic disorder, but not in healthy controls. However, no data are available on 3alpha, 5alpha-THDOC concentrations during experimental panic induction. Therefore, we quantified 3alpha, 5alpha-THDOC concentrations in 10 healthy volunteers (nine men, one woman) before and after panic induction with CCK-4 by means of a highly sensitive and specific gas chromatography/mass spectrometry analysis. CCK-4 elicited a strong panic response as assessed by the Acute Panic Inventory. This was accompanied by an increase in 3alpha, 5alpha-THDOC, ACTH and cortisol concentrations. This increase in 3alpha, 5alpha-THDOC might be a consequence of hypothalamic-pituitary-adrenal (HPA) axis activation following CCK-4-induced panic, and might contribute to the termination of the anxiety/stress response following challenge with CCK-4 through enhancement of GABAA receptor function.
    Neuropsychopharmacology 02/2005; 30(1):192-5. · 8.68 Impact Factor
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    ABSTRACT: Evidence from preclinical and clinical studies indicates that concentrations of neuroactive steroids are altered in depression and normalize after antidepressant pharmacotherapy. However, data on the impact of sleep deprivation on concentrations of neuroactive steroids are not available. Therefore, 29 drug-free patients (12 men, 17 women) with major depression according to DSM-IV criteria were treated with partial sleep deprivation (PSD). Response to PSD was defined as a reduction of at least 30% according to the 6-item version of the Hamilton Depression Scale (6-HAMD). Plasma samples were taken the day before and the day after PSD (day 0 and 1) and after one night of recovery sleep (day 2) at 8:00 am. Samples were quantified for neuroactive steroids by means of a highly sensitive and specific combined gas chromatography/mass spectrometry analysis. PSD did not influence concentrations of neuroactive steroids in either PSD responders (n = 20) or nonresponders (n = 9). However, nonresponders showed significantly higher concentrations of 3alpha,5alpha-tetrahydroprogesterone, 3alpha,5beta-tetrahydroprogesterone, and dehydroepiandrosterone before or after PSD compared to responders. In contrast to antidepressant drugs which correct the dysequilibrium of neuroactive steroids in major depression within several weeks, PSD does not affect the concentrations of neuroactive steroids in either responders or nonresponders.
    Annals of the New York Academy of Sciences 01/2005; 1032:216-23. · 4.38 Impact Factor

Publication Stats

2k Citations
258.04 Total Impact Points

Institutions

  • 2000–2011
    • Foundation Santa Lucia
      Roma, Latium, Italy
  • 2002–2010
    • Ludwig-Maximilian-University of Munich
      • Department of Psychiatry
      München, Bavaria, Germany
  • 1996–2010
    • University of Rome Tor Vergata
      Roma, Latium, Italy
  • 1997–2003
    • Max Planck Institute of Psychiatry
      München, Bavaria, Germany
  • 1994
    • Georgetown University
      • Department of Medicine
      Washington, D. C., DC, United States
  • 1993
    • Mayo Foundation for Medical Education and Research
      Rochester, Michigan, United States
  • 1992–1993
    • The Neurosciences Institute
      La Jolla, California, United States
    • University of Padova
      Padua, Veneto, Italy