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Aim: Although the precise nature of pathological gambling (PG) is still elusive, currently it is considered an impulse-control disorder that shares several features with substance dependence, such as deficit in self-regulation and impaired impulsivity. The aim of this study was to evaluate the impulsivity of PG patients by means of the Barratt Impulsivity Scale, version 11 (BIS-11), as compared with healthy control subjects, and to explore the possible correlations with gambling severity., Methods: Thirty-five outpatients (all men) with a diagnosis of PG were recruited at their first psychiatric interview in a psychiatric outpatient ward, and compared with a similar group of healthy control subjects. The severity of PG was assessed by means of the South Oaks Gambling Screen (SOGS)., Results: The results showed that the BIS-11 total score, as well as the scores of different factors (motor impulsity and cognitive complexity) and subscales (motor and non-planning impulsivity) were significantly higher in PG patients than in control subjects. In addition, positive correlations were detected between the SOGS and the BIS-11 total scores, and the attention and cognitive instability factor scores, or the attentional and motor impulsivity (rs=0.459, p=.021) subscale scores., Conclusions: These findings support the notion that impulsivity represents a core element of PG linked to the severity of the clinical picture.

Aims: Alterations of plasma amyloid-β (Aβ) peptides have been related to a high risk for cognitive impairment and dementia. The present study aimed to measure plasma Aβ peptides (Aβ40, Aβ42) and the Aβ40/Aβ42 ratio in a sample of drug-resistant bipolar depressed patients, as well as to explore the possible correlation between biological parameters and clinical changes along an electroconvulsive therapy (ECT) course., Methods: Aβ40 and Aβ42 were measured by means of an ELISA assay in 25 drug-resistant bipolar depressed patients before (T0) and 1 week after (T1) the end of ECT. The patients were clinically evaluated by means of the Hamilton Rating Scale for Depression, 21-item (HRSD-21), the Mini-Mental State Examination, and the Clinical Global Impressions-Severity of Illness Scale., Results: Plasma Aβ levels and the Aβ40/Aβ42 ratio were similar at T0 and T1. The Aβ40/Aβ42 ratio correlated positively with the HRSD total score at both T0 and T1. At T0, a negative correlation was found between the Aβ40/Aβ42 ratio and the improvement of depressive and cognitive symptoms. Moreover, remitters (n = 9; HRSD ≤10) showed a significantly lower Aβ40/Aβ42 ratio at T0 than nonremitters., Conclusion: The present data suggest that a low Aβ40/Aβ42 ratio might characterize a subgroup of depressed patients who respond to ECT, while higher values of this parameter seem to be typical of more severe cases of patients with cognitive impairment., (Copyright © 2013 S. Karger AG, Basel.)

Trazodone is a triazolopyridine derivative that belongs to the class of serotonin receptor antagonists and reuptake inhibitors (SARIs). The drug is approved and marketed in several countries worldwide for the treatment of major depressive disorder (MDD) in adult patients. In clinical studies, trazodone has demonstrated comparable antidepressant activity to other drug classes, including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline (norepinephrine) reuptake inhibitors (SNRIs). Moreover, the SARI action of trazodone may overcome the tolerability issues that are often associated with second-generation antidepressants such as SSRIs (i.e. insomnia, anxiety and sexual dysfunction). Recent focus has been placed on the development of a new prolonged-release once-a-day formulation of trazodone (TzCOAD), which may provide improved tolerability over the conventional immediate-release formulation of trazodone. Clinical studies have led to the recent approval in the USA of TzCOAD (as Oleptro™; Angelini Labopharm LLC, Princeton, NJ, USA), which may see resurgence of interest in the drug for the management of patients with MDD. Although trazodone is approved for the treatment of depression, evidence supports the use of low-dose trazodone as an off-label hypnotic for the treatment of sleep disorders in patients with MDD. The most common adverse effects reported with trazodone are drowsiness (somnolence/sedation), headache, dizziness and dry mouth. Other events reported, albeit with low incidence, include orthostatic hypotension (particularly in elderly patients or those with heart disease), minimal anticholinergic activity, corrected QT interval prolongation and torsade de pointes, cardiac arrhythmias, and rare occurrences of priapism and suicidal ideation. Overall, trazodone is an effective and well tolerated antidepressant (SARI) with an important role in the current treatment of MDD both as monotherapy and as part of a combination strategy. Trazodone is effective in controlling a wide range of symptoms of depression, while avoiding the negative effects on sleep seen with SSRI antidepressants. The recently approved prolonged-release formulation should provide further optimization of this antidepressant and may be useful for enabling an appropriate therapeutic dose to be administered with improved patient compliance.

Background: Mitochondria play a key role in the production of the cell energy. The final product of this process is adenosine triphosphate (ATP), used as a source of chemical energy. Besides this major role, mithocondria have been shown to be involved in other functions, such as signaling, cellular differentiation, cell death, as well as the control of the cell cycle and cell growth. The aim of this paper is to highlight the relationships between psychiatric disorders, especially schizophrenia, bipolar disorder (BD), autism, attention deficit-hyperactivity disorder (ADHD) and Alzheimer's dementia., Results: The review of the available literature indicate that different mitochondrial dysfunctions may accompany and/or be part of the clinical picture of some neuropsychiatric disorders., Conclusions: Different data would indicate that mitochondrial dysfunctions may be involved in the pathophysiology of different neuropsychiatric disorders, given their key role in the cell energy metabolism. Moreover, they would greatly contribute to the process of neural apoptosis that should be at the basis of neurodegenerative disorders, such as schizophrenia, Alzheimer's dementia and the most severe forms of BD. In addition, data are available that mithocondrial abnormalities are present also in developmental disorders, such as autism and ADHD, although the studies aiming at elucidating the role of mithocondria in the onset and pathophysiology of all these conditions should be considered preliminary. In any case, taken together, these scattered findings would suggest novel drugs targeting protecting mitochondria from oxidative stress.

Unlabelled: A(2A) adenosine receptors are considered an excellent target for drug development in several neurological and psychiatric disorders. It is noteworthy that the responses evoked by A(2A) adenosine receptors are regulated by D(2) dopamine receptor ligands. These two receptors are co-expressed at the level of the basal ganglia and interact to form functional heterodimers. In this context, possible changes in A(2A) adenosine receptor functional responses caused by the chronic blockade/activation of D(2) dopamine receptors should be considered to optimise the therapeutic effectiveness of dopaminergic agents and to reduce any possible side effects. In the present paper, we investigated the regulation of A(2A) adenosine receptors induced by antipsychotic drugs, commonly acting as D(2) dopamine receptor antagonists, in a cellular model co-expressing both A(2A) and D(2) receptors. Our data suggest that the treatment of cells with the classical antipsychotic haloperidol increased both the affinity and responsiveness of the A(2A) receptor and also affected the degree of A(2A)-D(2) receptor heterodimerisation. In contrast, an atypical antipsychotic, clozapine, had no effect on A(2A) adenosine receptor parameters, suggesting that the two classes of drugs have different effects on adenosine-dopamine receptor interaction. Modifications to A(2A) adenosine receptors may play a significant role in determining cerebral adenosine effects during the chronic administration of antipsychotics in psychiatric diseases and may account for the efficacy of A(2A) adenosine receptor ligands in pathologies associated with dopaminergic system dysfunction., Electronic Supplementary Material: The online version of this article (doi:10.1007/s11302-010-9201-z) contains supplementary material, which is available to authorized users.

Background: Childhood traumatic events and functional abnormalities of the hypothalamus-pituitary-adrenal (HPA) axis have been widely reported in psychiatric patients, although neither is specific for any diagnosis. Among the limited number of studies that have evaluated these topics, none has adopted a trans-diagnostic approach. The aim of the present research is to explore the relationship between childhood stressors, HPA axis function and psychiatric symptoms, independent of the diagnosis., Method: A total of 93 moderate to severely ill psychiatric out-patients of Florence and Pisa University Psychiatric Units and 33 healthy control subjects were recruited. The assessment consisted of salivary cortisol pre- and post-low dose (0.5 mg) Dexamethasone, early and recent life events, 121 psychiatric symptoms independent of diagnosis, SCID, BPRS., Results: In total, 33.5% of patients were Dexamethasone Suppression Test (DST) non-suppressors, compared with 6.1% of controls (p=0.001). Among patients, non-suppression was associated with particular symptoms (i.e. depressive and psychotic), but not to any specific diagnosis. Early stressful life events were significantly associated with higher salivary cortisol levels, with DST non-suppression and with approximately the same subset of symptoms. A recent stressful event seemed to be associated to the HPA response only in those subjects who were exposed to early traumata., Conclusions: Our report suggests a relationship between life stress, HPA axis and psychopathology. A cluster of specific psychiatric symptoms seems to be stress related. Moreover, it seems that an abnormal HPA response is possibly triggered by an excessive pressure in vulnerable individuals.

The present study explored the possible relationship between romantic attachment and jealousy in 100 healthy subjects. The romantic attachment and jealousy were evaluated by means of, respectively, the "Experiences in Close Relationships" questionnaire (ECR), and the "Questionario della Gelosia" (QUEGE). The ECR anxiety scale was related to all QUEGE dimensions, while the ECR avoidance scale to three. Individuals with the preoccupied attachment style showed higher scores than secure subjects on the obsessionality, interpersonal sensitivity and fear of loss dimensions. Fearful-avoidant individuals had higher score than secure subjects on the fear of loss dimension only, while dismissing individuals had lower scores on the self-esteem dimension.These findings suggest that romantic attachment and jealousy are intertwined.

Trazodone is an antidepressant which behaves as a selective 5-HT(2) antagonist and 5-HT reuptake inhibitor. The lack of information on its effects in vivo prompted us to evaluate alpha(2)-adrenoceptors by means of the specific binding of [(3)H]-rauwolscine, and the 5-HT transporter (SERT) by means of the binding of [(3)H]-paroxetine ([(3)H]-Par), in platelets of depressed patients, before and after one month of treatment with trazodone (75-300 mg/day). Twenty-five outpatients of both sexes with a diagnosis of major depression, as assessed by the Structured Clinical Interview for DSM IV, were included in the study. Depressive symptoms were evaluated by means of the Hamilton Rating Scale for Depression: the total score (mean +/- SD) was 20 +/- 6 at baseline (t(0)) and 7 +/- 4 after one month of treatment (t(1)). Platelet membranes, [(3)H]- rauwolscine and [(3)H]-Par bindings were carried out according to standardized protocols. The results showed that the B(max) values of [(3)H]-Par were statistically lower at t(1) than at t(0) (733 +/- 30 vs 1471 +/- 99, P < 0.001), while the K(d) and the [(3)H]-rauwolscine binding parameters remained unchanged. The findings of this study suggest that in vivo trazodone modifies the number of the SERT proteins and that, perhaps, most of its antidepressant properties are related to this activity.

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.

The aim of our study was to investigate and compare the dopamine (DA) transporter (DAT) in resting lymphocytes of 20 psychotic patients and 20 healthy control subjects, by means of both the binding parameters (Bmax and Kd) of 3H-WIN 35,428, and the reuptake parameters (Vmax and Km) of 3H-DA. The results showed that both the Bmax of 3H-WIN 35,428 binding and the Vmax of 3H-DA reuptake of the patients were significantly lower than those of healthy subjects, while the Kd or Km did not show any change. These findings, while indicating a reduced density of the lymphocyte DAT proteins, provide further support of the role of DA in psychoses and suggest that DA alterations may not be limited to brain structures.

Different data show that circulating lymphocytes possess functional serotonin and dopamine transporters (SERT and DAT, respectively). This papers aims to review most of the available literature on this topic, while highlighting the possible role of SERT and DAT, as well as that of their substrates including antidepressants on the immune system.

Background: 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., Method: BDNF plasma levels were evaluated in 30 inpatients suffering from major depression, according to DSM-IV criteria, by means of a commonly employed ELISA method. The clinical characteristics were assessed by the Hamilton Rating Scale for Depression (HRSD) and the Clinical Global Impression Scale., Results: BDNF plasma levels were significantly lower in the patients with the severest illness compared with the others, and the same was true for patients with dissociative symptoms, severe sleep disturbance and recurrent depression. A significant and negative correlation was observed between the biological parameter and the retardation factor score of the HRSD., Conclusion: These findings suggest that low BDNF levels are related to both recurrence and severity of depression, as well as to symptoms typical of dysfunctions of the hypothalamic-pituitary-adrenal axis., (Copyright © 2010 S. Karger AG, Basel.)

The controversial and limited data on the distribution of dopamine (DA) receptors of type 4 (D(4)) in the human brain prompted us to explore their density and pharmacological characteristics in the prefrontal cortex, striatum and hippocampus, through a series of binding assays. Brain samples were taken during autopsy from seven subjects. Tissue homogenates were incubated with increasing concentration of [(3)H]-YM-09151-2, a D(2)-like receptor antagonist, and L-745,870 and/or sulpiride to define the non-specific binding, while PPAP was used to block sigma receptors. The results showed a low density of D(4) receptors in the hippocampus only, with a preponderance of D(2)/D(3) and sigma receptors in the prefrontal cortex and striatum. In conclusion, these findings underline that it is possible to label D(4) receptors by means of [(3)H]-YM-09151-2, provided that D(2), D(3) and sigma receptors are blocked.

Aims: ABCB1 is a transmembrane transporter that is expressed in excretory organs (kidneys and liver), in intestine mucosa and on the blood-brain barrier. Because of the particular distribution of the protein, the activity of ABCB1 may significantly affect drug pharmacokinetics during absorption and distribution. Of note, several SNPs of ABCB1 are known and many of them affect transporter activity and/or expression. In this view, changes in the pharmacokinetics of drugs that are ABCB1 substrates could be clinically relevant and the evaluation of ABCB1 SNPs should deserve particular attention. Therefore, the aim of the present study was to investigate the possible association between ABCB1 polymorphisms and clozapine plasma levels in psychotic patients., Materials & Methods: c.1236C>T (exon 12), c.2677G>T (exon 21) and c.3435C>T (exon 26) SNPs of ABCB1 were evaluated by PCR techniques, while plasma levels of clozapine and norclozapine were measured by HPLC in 40 men (aged, 47.6 +/- 16.6 years, median: 42 years) and 20 women (aged 40.7 +/- 11.4 years, median: 38 years) 1 month after the start of clozapine administration., Results: A total of three SNPs were in Hardy-Weinberg equilibrium, with a calculated frequency of the wild-type alleles of 0.54, 0.55 and 0.45 for SNPs on exons 12, 21 and 26, respectively. Patients with c.3435CC or c.2677GG genotypes had significantly lower dose-normalized clozapine levels than those who were heterozygous or TT carriers. More interestingly, c.3435CC patients (15 subjects) needed significantly higher daily doses of clozapine (246 +/- 142 mg/day) compared with the remaining 24 CT and 21 TT patients (140 +/- 90 mg/day) in order to achieve the same clinical benefit., Conclusion: c.3435CC patients require higher clozapine doses to achieve the same plasma concentrations as CT or TT patients, and ABCB1 genotyping should be considered as a novel strategy that should improve drug use.

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.

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.

Although the main biological hypothesis on the pathophysiology of obsessive-compulsive disorder (OCD) is centered on the serotonin system, indications are available that other neurotransmitters, and even second messengers, particularly the cyclic adenosine monophosphate (cAMP) signaling, may be involved, though effective data are few. Therefore, the aim of the present study was to evaluate and compare the basal and isoprenaline (ISO)-stimulated velocity of adenylate-cyclase (AC) in human platelet membranes of patients with OCD and healthy control subjects. The results showed that the basal and ISO-stimulated AC activity, as well as the dose-response curves of ISO by using agonist concentrations ranging between 0.1 nM and 10 muM, were not different in the two groups. However, OCD patients showed lower EC(50) and higher E(max) values than healthy subjects. These findings suggest the presence of supersensitive beta-adrenergic receptors in platelets of OCD patients.

During the transduction of extracellular signals within the cell, the stimulation of specific G protein-coupled receptors (GPCRs) can modulate adenylyl or guanylyl cyclase, phospholipase C activity and ion channels, which regulate second-messengers. These, in turn, trigger several biochemical cascades, including Ca(2+) release, activation of protein kinases and gene expression. Significant changes of monoamine GPCR activity may occur in patients suffering from mood disorders and the majority of antidepressants exert part of their effects through GPCR-mediated systems. The main signal transduction pathways activated by metabotropic receptors in the brain and their possible involvement in the pathophysiology of mood disorders will be reviewed herein with a special focus on the horizons opened by this approach in terms of innovative therapeutic strategies.

Introduction: The high percentage (between 40% and 60%) of resistance to first-line drugs, such as clomipramine or selective serotonin reuptake inhibitors, is a major problem in the pharmacologic management of obsessive-compulsive disorder (OCD). In these cases, different strategies have been employed with controversial outcomes. The meager information available on the association of two serotonergic drugs prompted us to explore the possible effectiveness and tolerability of citalopram+clomipramine in resistant OCD patients., Methods: Twenty outpatients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of OCD, who had failed to respond to at least two trials with a selective serotonin reuptake inhibitor and were currently taking clomipramine at different doses, were administered citalopram at a maximum dose of 60 mg/day. The clinical assessment was carried out at baseline (t0) and at the 4th (t1), 12th (t2), 24th (t3), 36th (t4), and 48th (t5) week by means of the Yale-Brown Obsessive Compulsive Scale, Hamilton Rating Scale for Depression, Clinical Global Impression scale, and the Dosage Record and Treatment Emergent Symptom Scale. The response was defined as a 35% decrease of the Yale-Brown Obsessive-Compulsive Scale total score., Results: The results showed that approximately 50% of the patients improved significantly after 1 month of this regimen and after 1 year of treatment., Conclusion: This study, although carried out in a small sample and in an open fashion, represents one of the few experiences with the association of two serotonergic compounds in resistant OCD and confirms its potential usefulness and good tolerability profile. Controlled research on this association in OCD is recommended.

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.

The paucity of information on the presence of the dopamine transporter (DAT) in blood cells, prompted us to explore it in human resting lymphocytes by means of the binding of 3H-WIN 35,428, a compound which is currently considered the most selective ligand for labelling this protein, and by means of the specific reuptake of 3H-dopamine (3H-DA). Lymphocytes were obtained by 15 healthy subjects. The results showed the presence of a specific and saturable binding of 3H-WIN 35,428, which labelled one site only. A specific 3H-DA reuptake was also measured. The pharmacological characterization of both binding and reuptake was overlapping. These findings would indicate that human resting lymphocytes carry the DAT, whose functions in periphery are still unknown.

In the last few decades, there has been a long debate on the existence of agoraphobia (AG) without a history of panic attacks (PAs). In the present study, the problem of the relationships between AG and PAs is addressed trough a reevaluation of the cases who had been diagnosed with AG in the community survey of Sesto Fiorentino. Forty-one of the 75 subjects who met the criterion of AG in the Sesto Fiorentino Study were reinterviewed by experienced clinical psychiatrists. The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and the Composite International Diagnostic Interview were used to make the diagnoses. The Mobility Inventory for Agoraphobia (MIA) and a specific adjunctive question, "why do/did you avoid?", were used to compare AG subjects with or without PD. Of the 41 subjects with a lifetime history of AG, 12 cases had original diagnosis of AG without PAs and the remaining 29 had PD with AG. After the reassessment, in 10 cases, the criteria for the diagnosis of AG without PAs were confirmed, totaling a lifetime prevalence of 0.4% (confidence interval, 0.2-0.8). Agoraphobia subjects with and without PAs were comparable as regard to sex, age, age of onset, duration of illness, family history for anxiety or mood disorders, MIA scores, number, and type of situations avoided. Thus, AG seems to exist also in absence of a history of PAs, and the one-way relationship between the occurrence of PAs and a following development of AG, postulated by DSM-IV, should be reconsidered for the future classifications.

Background: Pathological gambling (PG) is an impulse control disorder characterized by persistent and maladaptive gambling behaviors with disruptive consequences for familial, occupational and social functions. The pathophysiology of PG is still unclear, but it is hypothesized that it might include environmental factors coupled with a genetic vulnerability and dysfunctions of different neurotransmitters and selected brain areas. Our study aimed to evaluate a group of patients suffering from PG by means of some neuropsychological tests in order to explore the brain areas related to the disorder., Methods: Twenty outpatients (15 men, 5 women), with a diagnosis of PG according to DSM-IV criteria, were included in the study and evaluated with a battery of neuropsychological tests: the Wisconsin Card Sorting Test (WCST), the Wechsler Memory Scale revised (WMS-R) and the Verbal Associative Fluency Test (FAS). The results obtained in the patients were compared with normative values of matched healthy control subjects., Results: The PG patients showed alterations at the WCST only, in particular they had a great difficulty in finding alternative methods of problem-solving and showed a decrease, rather than an increase, in efficiency, as they progressed through the consecutive phases of the test. The mean scores of the other tests were within the normal range., Conclusion: Our findings showed that patients affected by PG, in spite of normal intellectual, linguistic and visual-spatial abilities, had abnormalities emerging from the WCST, in particular they could not learn from their mistakes and look for alternative solutions. Our results would seem to confirm an altered functioning of the prefrontal areas which might provoke a sort of cognitive "rigidity" that might predispose to the development of impulsive and/or compulsive behaviors, such as those typical of PG.

Oxytocin (OT) is a neurohypophysial hormone synthesized in the paraventricular and supraoptic nuclei of the hypothalamus. Although OT-like substances have been identified in all vertebrates, OT has been found only in mammals where it plays a major role in the onset and maintaining of behaviors which are typical of these animals, such as labour and lactation. Recently, several data have suggested the involvement of OT in the formation of infant attachment, maternal behavior, pair bonding and, more generally, in linking social signals with cognition, behaviors and reward. The aim of this paper was to review critically the role of OT in the regulation of different physiological functions and complex behaviors, as well as its possible involvement in the pathophysiology of some neuropsychiatric disorders. MEDLINE and PubMed (1972-2007) databases were searched for English language articles by using the following keywords: oxytocin, physiology, cognitive functions, attachment, psychopathology, psychiatric disorders. Papers were examined that addressed the following aspects of the OT system: synthesis and localization, receptors, physiology: In addition, latest findings showing abnormalities of OT and OT system in several neuropsychiatric disorders, including autism, obsessive-compulsive disorder, eating disorders, addiction, schizophrenia, post-traumatic stress disorder and Prader-Willy syndrome, will be also discussed together with the possible clinical use of OT or its analogues and/or antagonists.

Background/aims: The aim of this study was to investigate the serotonin transporter (SERT), by means of the 3H-paroxetine ([3H]-Par) binding to platelet membranes, in patients affected by pathological gambling (PG), as compared with a similar group of healthy control subjects., Methods: Seventeen PG patients were selected amongst those who were drug-free and at the first psychiatric interview in a Department of Addiction. The diagnosis was assessed according to DSM-IV criteria and PG severity was measured by means of the South Oaks Gambling Screen. The platelet [3H]-Par binding was carried out according to a standardized method. The binding parameters, the maximum binding capacity (B(max)) and the dissociation constant (K(d)), were obtained by means of the Scatchard analysis., Results: The B(max) values of PG patients were significantly lower than that of healthy subjects, while the K(d) values were not different in the two groups. No significant effect of age, sex or psychiatric comorbidity on B(max) or K(d) was observed; there were also no correlations between clinical and biological variables., Conclusions: PG patients showed a dysfunction at the level of the platelet SERT that would suggest the involvement of the 5-HT system in this condition., (2008 S. Karger AG, Basel.)

Introduction: Romantic attachment is the establishment of a relationship with a partner and is strongly influenced by the individual's attachment style. While several studies have shown that attachment style may contribute to the development of psychopathology, less information is available for romantic attachment. The aim of the present study was to compare romantic attachment styles among patients with different mood and anxiety disorders and control subjects., Method: The study sample included a total of 126 outpatients, 62 of whom were affected by bipolar disorders, 22 by major depressive disorder (MDD), 27 by panic disorder, 15 by obsessive-compulsive disorder, and 126 healthy control subjects. Romantic attachment was assessed by means of the Italian version of the "Experiences in Close Relationships" (ECR) questionnaire., Results: The results showed that the secure attachment style was more frequent in the control group, while the preoccupied style prevailed among the patients, with no difference among the diagnostic categories. The scores of the ECR anxiety and avoidance scales were significantly higher in the patients than in the control subjects. A trend toward higher ECR anxiety scale scores in women with panic disorder was detected, with the opposite being true for MDD., Conclusion: Our findings indicate that patients with different psychiatric disorders would be characterized by higher scores on both the ECR anxiety and the avoidance scales, as well as by the preoccupied style of attachment. In addition, women with panic disorder and MDD seem to be characterized by, respectively, higher and lower scores of the ECR anxiety scale than men.

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.

Background: Rabbit syndrome is a movement disorder that is associated with long-term exposure to neuroleptic medications. Of particular interest and importance is the risk of rabbit syndrome with exposure to the newer atypical antipsychotics. Our recent experience with such a case brought to light the importance of exploring this risk., Methods: MEDLINE and PubMed (1972-2006) databases were searched for English language articles using the keywords rabbit syndrome, tardive dyskinesia, antipsychotic, extrapyramidal symptoms and side effects. A recent case study is used to expand upon the literature available on newer antipsychotics and rabbit syndrome., Results: We reviewed papers that addressed the following aspects of rabbit syndrome 1) the clinical manifestations 2) prevalence and risk factors, 3) etiopathogenesis 4) older antipsychotics and rabbit syndrome 5) newer antipsychotics, 6) treatment options. Moreover, we report a case of RS in a 50 year old white female, diagnosed with bipolar I disorder, that, after the discontinuation of risperidone, developed involuntary movements of the mouth that were fine, rhythmic and rapid, along the vertical axis, and without involvement of the tongue. After the re-introduction of risperidone, the symptoms decreased in a few hours and disappeared after 3 days., Conclusion: Eleven cases of rabbit syndrome have been documented since the implementation of newer antipsychotics. Future research is needed to better understand the etiopathogenesis of rabbit syndrome in psychiatric populations treated with the atypical antipsychotics. Understanding the differences and similarities of rabbit syndrome and tardive dyskinesia is crucial to the creation of a successful treatment paradigm.