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A growing importance has been placed on the recognition and supervision of non-motor features of Parkinson's disease (PD). Depression has been estimated to affect one in three individuals with PD and can lead to worse health outcomes and decreased quality of life. Anxiety, apathy and anhedonia further complicate PD outcomes. In this double-blind, placebo-controlled trial, participants (individuals with mild to moderate PD; n = 24) were randomly assigned to treatment (800 mg/d docosahexaenoic acid (DHA) and 290 mg/d eicosapentaenoic acid, a precursor to DHA) or placebo (an equicaloric amount of corn oil). Treatment duration was 6 months. Treatment had no statistically significant effect on rate of change on either Unified Parkinson's Disease Rating Scale or Hoehn-Yahr Scale score. However, 75% of DHA-treated patients, reduced Hamilton Rating Scale for Depression total score by at least 50%, compared with only 25% into the placebo group. At the end of the six-month study, DHA integration reduced the depressive symptoms.

Background/Aims: Dopamine is an important neurotransmitter involved in the pathophysiology of depression and anhedonia. Dopamine transporters (DAT) may play a crucial role in the pathophysiology of dopaminergic transmission. We investigated the relationship between striatal DAT availability and depression, pointing out possible correlations with anhedonia and treatment outcomes. Methods: Ten depressed patients with anhedonia, 10 depressed patients without anhedonia and 20 healthy controls underwent single photon emission computed tomography using 123I-FP-CIT [123I-N-ω-fluoropropyl-carbomethoxy-3β-(4-iodophenyl)tropane]. Psychometric measures included the Snaith-Hamilton Pleasure Scale and the Hamilton Depression Rating Scale. A further assessment of DAT availability was performed in the 10 patients with marked anhedonia after a 3-month pharmacological treatment. Results: Depressed patients with and without anhedonia showed significantly lower 123I-FP-CIT binding ratios in the bilateral striatum, caudate and putamen. No significant changes were detected after treatment in the 10 patients with marked anhedonia. When considering clinical outcomes, subjects with remission of depression showed a significant reduction of 123I-FP-CIT binding ratios in all regions at baseline, but after treatment no differences were found any longer. Conclusions: We suppose that a hypofunction of the striatal dopaminergic system may be a ‘state' feature of a depressive condition as a whole rather than anhedonia itself. On the other hand, some anhedonic features mainly represent an enduring trait that persists independently of mood state.

Repetitive transcranial magnetic stimulation (rTMS) of human motor cortex can produce long-lasting changes in the excitability of excitatory and inhibitory neuronal networks. The effects of rTMS depend critically on stimulus frequency. The aim of our present study was to compare the effects of different rTMS protocols. We compared the aftereffects of 6 different rTMS protocols [paired associative stimulation at interstimulus intervals of 25 (PAS25) and 10 ms (PAS10); theta burst stimulation delivered as continuous (cTBS) or intermittent delivery pattern (iTBS); 1- and 5-Hz rTMS] on the excitability of stimulated and contralateral motor cortex in 10 healthy subjects. A pronounced increase of cortical excitability, evaluated by measuring the amplitude of motor evoked potentials (MEPs), was produced by iTBS (+56%) and PAS25 (+45%). Five-hertz rTMS did not produce a significant increase of MEPs. A pronounced decrease of cortical excitability was produced by PAS10 (−31%), cTBS (−29%), and 1-Hz rTMS (−20%). Short-interval intracortical inhibition was suppressed by PAS10. Cortical silent period duration was increased by 1-Hz stimulation. No significant effect was observed in the contralateral hemisphere. Head-to-head comparison of the different protocols enabled us to identify the most effective paradigms for modulating the excitatory and inhibitory circuits activated by TMS.

Alzheimer's disease (AD) is a degenerative disorder characterized by a decreased regional cerebral blood flow (CBF). It is most likely that a reduction in CBF could displace a pathway leading to AD genesis, in so far neuron death explains a sustained reduction in the supply of oxygen, glucose, and nutrients. Nevertheless, the concept of secondary CBF deficiency cannot explain the critical stages of early memory loss while, on the other hand, the picture of progressive ischemia due to primary CBF decline sheds light on the course of AD in a most persuasive manner. The concept of primary CBF deficiency is even more strengthened by the lack of correlation between degree of dementia and amount of CBF. Vascular abnormalities, frequently observed to co-occur with AD, might play a critical role in the initiation and aggravation of AD pathology given that the elimination of amyloid-β (Aβ) through a vascular route is an important brain Aβ clearance mechanism and its failure leads to formation of vascular amyloidosis and dense-core plaques. The goal of this review is to provide scientists comprehensive knowledge of the state-of the art influence vascular damage and reduced perfusion have on the final development of AD and to hopefully stimulate more research in this area of neuroscience.

Ketamine is a non-competitive N-methyl-D: -aspartate (NMDA) receptor antagonist which interferes with the action of excitatory amino acids (EAAs) including glutamate and aspartate. The use of ketamine at subanaesthetic doses has increased because of its psychotomimetic properties. However, long-term ketamine abuse may interfere with memory processes and inhibit the induction of long-term potentiation (LTP) in the hippocampus, an effect probably mediated by its NMDA antagonist action. Neurotrophins such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) serve as survival factors for selected populations of central nervous system neurons, including cholinergic and dopaminergic neurons. In addition, neurotrophins, particularly BDNF, may regulate LTP in the hippocampus and influence synaptic plasticity.The purpose of this study was to test the hypothesis that ketamine use in humans is associated with altered serum levels of neurotrophins.We measured by enzyme-linked immunosorbent assay the NGF and BDNF serum levels in two groups of subjects: frequent ketamine users and healthy subjects.Our data show that BDNF serum levels were increased in chronic ketamine users as compared to healthy subjects, while NGF levels were not affected by ketamine use.These findings suggest that chronic ketamine intake is associated with increases in BDNF serum levels in humans. Other studies are needed to explore the pharmacological and molecular mechanism by which ketamine, and/or other NMDA antagonists, may induce modification in the production and utilization of BDNF and alter normal brain function.

Objectives: A “disconnectivity model” of schizophrenia has been proposed, but it is still unclear if white matter abnormalities are associated with gray matter changes and if they may be the anatomic substrate of cognitive impairment, which is a core symptom of the disorder. The first objective was to detect if white matter microstructure alterations in schizophrenia are associated with or independent of gray matter change, using an optimized method for white matter (Tract-Based Spatial Statistics) and gray matter analyses (whole-brain voxel-wise approach). The second objective was to identify the neuropsychological correlates of white matter abnormalities in the schizophrenic group, using a comprehensive neuropsychological battery. Methods: In this case-control study 43 schizophrenic patients and 43 healthy volunteers were consecutively enrolled and matched for age and gender. Results: Fractional anisotropy reduction was found in 6 fronto-temporal clusters (corrected p-valuesb0.05)inschizophrenicgroupincomparisonwithhealthyvolunteers,and3clustersshowed fractional anisotropy increase (corrected p-values b0.05). Two of the clusters showing reduced fractional anisotropy were associated with reduced gray matter density in neuroanatomically-related regions in schizophrenic subjects (p-values ranging from 0.001 to 0.026). Executive, constructionalpraxis, and working memory deficits were significant predictors of fractional anisotropy reduction in 4 clusters in the schizophrenic group (p-values ranging from b0.0001 to 0.0017). Conclusions: Ourdatasupportthedisconnectivityhypothesisinschizophrenia,enlighteningalink between reduced fronto-temporal connectivity and “frontal” cognitive deficits. Reduced gray matterdensitymaybeinvolvedprimarilyinthepathogenesisofsomeofthesedisconnectedareas.

"Punding" is a stereotypical motor behavior characterized by an intense fascination with repetitive handling and examining of objects. Since its first description in amphetamine and cocaine addicts, data on punding has only derived from studies performed in patients with Parkinson's disease (PD). Punding is classifiable as the most severe form of Repetitive Reward-Seeking Behaviours (RRSB) syndromes. The aim of this study was to investigate the occurrence and phenomelogy of RRSB acutely induced by cocaine in order to determine the prevalence, severity and distinctive features discriminating "punders" from "non-punders". A consecutive sample of 50 cocaine addicts received a clinical psychiatric interview. RRSB diagnosis and severity were assessed using a modified version of a previous published questionnaire designed to identify punding in patients with PD. In the present series, 38% of the cocaine addicts met the proposed diagnostic criteria for a RRSB and 8% were considered punders. Subjects with vs. without RRSB did not differ in terms of sex ratio, age, education, occupation, predisposing habits, duration of cocaine use, hours of sleep, comorbid psychiatric disorders, and concomitant use of other drugs. These results and the observation that in the majority of cases RRSB started soon after first drug intake, strongly suggest that an underlying unknown predisposition led to the development of these behaviors. In conclusion, RRSB and punding is much more common than has been described previously and the resultant social disability is often overlooked.

Premenstrual dysphoric disorder (PMDD) is a complex clinical syndrome that is notoriously difficult to treat. The purpose of the present study was to provide preliminary data on the effectiveness of duloxetine in PMDD.Fifty-five women with PMDD were treated with a 60 mg/day dosage of duloxetine for two menstrual cycles. Responses were assessed at first and second treatment cycle.Outcome measures included a visual analogue scale, the Zung Self-rating Scale for Depression, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale and the Clinical Global Impressions Scale.Fifty patients completed the trial. All had significant improvement of depression and anxiety and response, defined as a 50% decrease in daily symptom scores, occurred in 39 (78%) patients. The effects of active treatment were marked by the first active cycle of menstruation.Duloxetine 60 mg/day was effective in reducing PMDD symptoms and generally well tolerated. Limitations of the study were open-label design and lack of placebo control. However, the results appeared to be strong and consistent across measures. Adverse events (nausea, insomnia, poor appetite) were low. Further studies are needed to confirm these results.

Chronic cocaine and heroin users display a variety of central nervous system (CNS) dysfunctions including impaired attention, learning, memory, reaction time, cognitive flexibility, impulse control and selective processing. These findings suggest that these drugs may alter normal brain functions and possibly cause neurotoxicity. Neurotrophins are a class of proteins that serve as survival factors for CNS neurons. In particular, nerve growth factor (NGF) plays an important role in the survival and function of cholinergic neurons while brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity and in the maintenance of midbrain dopaminergic and cholinergic neurons. In the present study, we measured by enzyme-linked immunosorbent assay (ELISA) the NGF and BDNF levels in serum of three groups of subjects: heroin-dependent patients, cocaine-dependent patients and healthy volunteers. Our goal was to identify possible change in serum neurotrophins in heroin and cocaine users. BDNF was decreased in heroin users whereas NGF was decreased in both heroin and cocaine users. These findings indicate that NGF and BDNF may play a role in the neurotoxicity and addiction induced by these drugs. In view of the neurotrophin hypothesis of schizophrenia the data also suggest that reduced level of neurotrophins may increase the risk of developing psychosis in drug users.

Objective To investigate if different interneuronal circuits in human motor cortex mediate inhibition through different subtypes of the gamma-aminobutyric acid A receptor (GABAAR). Methods Two distinct forms of motor cortical inhibition were measured in 10 healthy subjects by established transcranial magnetic stimulation (TMS) protocols: short interval intracortical inhibition (SICI) and short latency afferent inhibition (SAI). Their modification by a single oral dose of three different positive GABAAR modulators (20 mg of diazepam, 2.5 mg of lorazepam and 10 mg of zolpidem) with different affinity profiles at the various α-subunit bearing subtypes of the GABAAR (diazepam: non-selective, lorazepam: unknown, zolpidem: 10-fold higher affinity to α1- than α2- or α3-subunit bearing GABAARs, no affinity to α5-subunits) was tested in a randomized crossover design. In addition, the sedative drug effects were recorded by a visual analogue scale. Results Diazepam and lorazepam increased SICI, whereas zolpidem did not change SICI. In contrast, diazepam had no effect on SAI, whereas lorazepam and zolpidem decreased SAI. The sedative effects were not different between drugs. Conclusions The dissociating patterns of drug modification of SICI versus SAI strongly suggest that different GABAAR subtypes are involved in SICI and SAI. Significance We provide evidence, for the first time, for a dissociation of effects of diazepam and zolpidem on SAI and confirm the previously reported differential effect of zolpidem and of diazepam and lorazepam on SICI. The differential effects of the three benzodiazepines on SAI and SICI suggest that neuronal circuits in human motor cortex that mediate inhibition through different GABAAR subtypes can be segregated by TMS.

In a cross-comparison study, the Cloninger's Temperament and Character Inventory (TCI) personality profile was administered to 28 probable pathological gamblers (PPGs), 32 nonpathological gamblers (non-PGs), and 65 controls. As a screening device, the validated Italian version of the South Oak Gambling Screen was administered to all subjects. Novelty Seeking (NS) values were higher in PPGs in comparison with both non-PGs (p.05) and controls (p.001). PPGs showed lower Self-Directedness (SD) and Cooperativeness (CO) values with respect to both non-PGs (p.05 and p = .001, respectively) and controls (p.001 and p = .001, respectively). The subsamples of PPGs reporting either a current substance misuse condition or a parental involvement in gambling/substance misuse showed higher NS (p = .01) and lower CO (p = .005) values than the remaining PPGs. A duration of problem gambling in excess of 20 years was associated with lower (p = .001) CO values. Specific temperamental (NS) and character (SD; CO) dimensions differentiated PPGs from both non-PGs and controls; assessment of personality profile with the TCI may identify at-risk social gamblers.

Inhibition is of fundamental importance to regulate activity in cortical circuits. Inhibition is mediated through a diversity of different interneurones and γ-aminobutyric acid A receptor (GABAAR) subtypes. Here we employed paired-pulse transcranial magnetic stimulation (TMS) to measure short interval intracortical inhibition (SICI), a GABAAR-mediated inhibition in human motor cortex, to address the question of which GABAAR subtype is responsible for this form of inhibition. It has been shown that classical benzodiazepines (diazepam and lorazepam) have a non-selective affinity profile at different α-subunit-bearing subtypes of the GABAAR while zolpidem has a 10-fold greater affinity to the α1-subunit-bearing GABAAR compared with those bearing the α2- or α3-subunit. We found that, in seven healthy subjects, a single oral dose of 20 mg of diazepam or 2.5 mg of lorazepam significantly increased SICI, whereas 10 mg of zolpidem did not change SICI. This dissociation occurred despite equal sedation by all three drugs, an α1-subunit GABAAR-mediated effect. The findings strongly suggest that SICI is not mediated by the α1-subunit-bearing subtype of the GABAAR but by those bearing either the α2- or α3-subunit. This study represents an attempt by means of TMS to identify GABAAR subtype-specific action at the systems level of human cortex, a highly relevant issue because the different α-subunit-bearing subtypes of the GABAAR are differently involved in benzodiazepine-mediated effects such as sedation, amnesia or anxiolysis, in developmental cortical plasticity, and in neurological disorders such as epilepsy.

A day hospital setting may provide a good management for suicidal patients. Of 70 subjects admitted for a suicide attempt to the "A. Gemelli" Hospital in Rome, eight (11.4%) dropped out, 62 (88.5%) completed the study, and 15 (24.19%) showed suicidal ideation within 1 year. No patients completed suicide.

Keywords: itching, nodules, pregabalin, prurigoSUMMARYWhat is known and objective: Prurigo nodularis (PN) is achronic skin condition that is difficult to treat. Pregabalin isone of the possible treatments for PN but its safety and effi-cacy are not well defined. We aimed to assess the efficacy ofpregabalin in patients with PN.Methods: Thirty patients (10 men, 20 women; mean age51.6 ± 9.39 years) were treated with pregabalin (75 mg/day) for3 months. Efficacy was classified as (i) successful (disappear-ance of the pruritus and reduction of nodules); (ii) slightimprovement/reduction of the nodules, that is, number and/orflattening, no disappearance of itching; or (iii) unsuccessful.Results: Twenty-three patients (76%) responded successfullyafter 3 months of treatment. There was a statistically signifi-cant difference between visual analogue scale scores beforeand after 1 month treatment period (8AE15 ± 2AE04 and 1AE5±1AE12,respectively; P

Although the pathophysiology of gambling is unknown, an involvement of midbrain dopaminergic pathway has been hypothesized. In this study, the association between brain-derived neurotrophic factor (BDNF) and pathological gambling was investigated. We measured BDNF serum levels in (1) video players (n = 10); (2) card players (n = 9); (3) mixed players (n = 21; both video and card players) and (4) age-matched controls (n = 18). Mixed players had increased BDNF serum levels as compared to controls and higher South Oaks Gambling Screen score as compared to card or video players. Thus, the data demonstrate that patients affected by severe pathological gambling show enhanced BDNF serum levels.

It has been proposed that deficits in the production and the utilization of brain-derived neurotrophic factor (BDNF) may contribute to the pathogenesis of schizophrenia. At the same time, electroconvulsive shock, an experimental model of electroconvulsive therapy (ECT), has been shown to induce an increase of BDNF protein in brains of animal models. These findings suggest that one putative mechanism of action of ECT is the regulation of BDNF and/or related neurotrophins. In this case report, a 54-year-old man with severe treatment-resistant schizophrenic symptoms was treated with ECT. To evaluate the effect of ECT on BDNF serum levels, we collected a blood sample before each ECT session. During the course of ECT treatment, the paranoid and hallucinatory symptoms gradually improved, whereas BDNF levels increased over time. In addition, there was a general improvement of its positive and negative schizophrenic symptoms and depressive state. In conclusion, this case report further validates the therapeutic efficacy of ECT in schizophrenic patients with inadequate or poor response to traditional treatments. Moreover, ECT therapeutic effect is associated with an increase in BDNF serum levels. Further studies are needed to characterize the relationship between BDNF and ECT in schizophrenic patients.

The recreational drug 'ecstasy'[3,4-methylenedioxymethamphetamine (MDMA)] exerts a potent action on central serotonergic and dopaminergic neurons. These neurons utilize neurotrophins for their survival and function. In order to explore MDMA effects on neurotrophins, we measured by enzyme-linked immunosorbent assay the serum levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in 'ecstasy-addicted', 'ecstasy-addicted with signs of psychosis' and 'healthy' subjects. We found that BDNF serum levels were significantly increased in both groups of 'ecstasy-addicted' as compared with 'healthy subjects', supporting the hypothesis that BDNF is involved in MDMA action.

Antiphospholipid syndrome is a disorder characterised by recurrent venous or arterial thrombosis and/or foetal losses associated with typical laboratory abnormalities. The initial manifestation of anthiphospholipid syndrome can involve many organ systems either singly or in combination. We describe the case of a 62 year old female showing schizophrenia-like symptoms in which further evaluations allowed us to diagnose the antiphospolipid syndrome.

Study Objectives: To evaluate sleep modifi cations induced by chronic benzodiazepine (BDZ) abuse. Methods: Cohort study, comparison of sleep measures between BDZs abusers and controls. Drug Addiction Unit (Institute of Psychiatry) and Unit of Sleep Disorders (Institute of Neurology) of the Catholic University in Rome. Six outpatients affected by chronic BDZ abuse were enrolled, (4 men, 2 women, mean age 53.3 ± 14.8, range: 34-70 years); 55 healthy controls were also enrolled (23 men, 32 women, mean age 54.2 ± 13.0, range: 27-76 years). All patients underwent clinical evaluation, psychometric measures, ambulatory polysomnography, scoring of sleep macrostructure and microstructure (power spectral fastfrequency EEG arousal, cyclic alternating pattern [CAP]), and heart rate variability. Results: BDZ abusers had relevant modifi cation of sleep macrostructure and a marked reduction of fast-frequency EEG arousal in NREM (patients: 6.6 ± 3.7 events/h, controls 13.7 ± 4.9 events/h, U-test: 294, p = 0.002) and REM (patients: 8.4 ± 2.4 events/h, controls 13.3 ± 5.1 events/h, U-test: 264, p = 0.016), and of CAP rate (patients: 15.0 ± 8.6%, controls: 51.2% ± 12.1%, U-test: 325, p < 0.001). Discussion: BDZ abusers have reduction of arousals associated with increased number of nocturnal awakenings and severe impairment of sleep architecture. The effect of chronic BDZ abuse on sleep may be described as a severe impairment of arousal dynamics; the result is the inability to modulate levels of vigilance.

The diagnosis of bipolar disorder (BD) is predominantly clinical. Some authors have suggested that BD is underdiagnosed and that many patients, particularly those with major depressive disorder, actually have BD. Some studies have suggested that BD is wrongly diagnosed, probably because of the idea of a "bipolar spectrum." To address this potential overdiagnosis, clinicians should carefully and systematically assess whether symptoms are included in diagnostic criteria and include the individual context of the patient.

The aims of the study were: (1) to study possible associations between temperament, personality dimensions, and psychopathological variables in a clinical sample of euthymic patients with bipolar disorder (BD) and cyclothymia; and (2) to assess how Cloninger's temperament and personality dimensions were associated with affective temperaments. Participants, consisting of 60 patients with BD (type I or II) and cyclothymia in the euthymic phase, completed Akiskal's Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire (TEMPS-A), and Cloninger's Temperament and Character Inventory-revised version (TCI-R). The diagnostic groups differed in past hospitalization, for age at onset of the disorder, and on two affective temperaments: the TEMPS-A Hyperthymia, and the TEMPS-A Irritability. There were six significant associations between affective temperaments and Cloninger's personality dimensions, ranging from 0.26 to 0.54. The measures of Akiskal and of Cloninger tap common behavioral features in patients with bipolar disorder and cyclothymia, yet the differences indicate that the two measures are not redundant. BD and cyclothymic patients differed significantly in temperament and personality, differences that may have important implications for treatment.

BACKGROUND: Mixed mood states, even in their sub-threshold forms, may significantly affect the course and outcome of bipolar disorder (BD). AIM: To compare two samples of BD patients presenting a major depressive episode and a sub-threshold mixed state in terms of global functioning, clinical outcome, social adjustment and quality of life during a 1-year follow-up. METHODS: The sample was composed by 90 subjects (Group 1, D) clinically diagnosed with a major depressive episode and 41 patients (Group 2, Mx) for a sub-threshold mixed state. All patients were administered with a pharmacological treatment and evaluated for depressive, anxious and manic symptoms by common rating scales. Further evaluations included a global assessment of severity and functioning, social adjustment and quality of life. All evaluations were performed at baseline and after 1, 3, 6 and 12 months of treatment. RESULTS: The two groups were no different for baseline as well as improvement in global severity and functioning. Though clearly different for symptoms severity, the amount of change of depressive and anxiety symptoms was also no different. Manic symptoms showed instead a trend to persist over time in group 2, whereas a slight increase of manic symptoms was observed in group 1, especially after 6 months of treatment. Moreover, in group 1, some manic symptoms were also detected at the Young Mania Rating Scale (n = 24, 26.6%). Finally, improvement in quality of life and social adjustment was similar in the two groups, though a small trend toward a faster improvement in social adjustment in group 1. CONCLUSIONS: Sub-threshold mixed states have a substantial impact on global functioning, social adjustment and subjective well-being, similarly to that of acute phases, or at least major depression. In particular, mixed features, even in their sub-threshold forms, tend to be persistent over time. Finally, manic symptoms may be still often underestimated in depressive episodes, even in patients for BD.

Objective In this open, prospective study we aimed to investigate the efficacy, medical safety and practicability of pregabalin in outpatient detoxification of alcohol-dependent patients with mild-to-moderate alcohol withdrawal syndrome (AWS). Craving reduction, improvement of psychiatric symptoms and quality of life were the secondary endpoints. Methods Forty alcohol dependent patients (DSM-IV) were detoxified receiving 200–450 mg of pregabalin. Withdrawal (Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar)) and craving (Visual Analogue Scale (VAS); Obsessive and Compulsive Drinking Scale (OCDS)) rating scales were applied; psychiatric symptoms and quality of life were evaluated using the Symptom Check List-90 Revised (SCL-90-R) and the QL-Index, respectively. Relapsed and abstinent patients in the post-detoxification evaluation have been compared. Results Alcohol withdrawal symptoms and craving for alcohol resulted significantly reduced (p

Brain-derived neurotrophic factor (BDNF) gene variants may potentially influence behaviour. In order to test this hypothesis, we investigated the relationship between BDNF Val66Met polymorphism and aggressive behaviour in a population of schizophrenic patients. Our results showed that increased number of BDNF Met alleles was associated with increased aggressive behaviour.

Behavioural addictions (BAs) can be understood as disorders characterized by repetitive occurrence of impulsive and uncontrolled behaviours. Very few studies have investigated their association with mood disorders. The present study was undertaken to determine the prevalence of the main behavioural addictions in a sample of bipolar outpatients in euthymic phase or stabilised by medications and to investigate the role of impulsivity and temperamental and character dimensions.One-hundred-fifty-eight Bipolar Disorder (BD) (DSM-IV) outpatients were assessed with tests designed to screen the main behavioural addictions: pathological gambling (SOGS), compulsive shopping (CBS), sexual (SAST), Internet (IAD), work (WART) and physical exercise (EAI) addictions. TCI-R and BIS-11 were administered to investigate impulsivity and personality dimensions mainly associated with BAs. The clinical sample has been compared with 200 matched healthy control subjects.In bipolar patients, 33% presented at least one BA respect to the 13% of controls. Significantly higher scores at the scales for pathological gambling (p.001), compulsive buying (p.05), sexual (p.001) and work addictions (p.05) have been found. Self-Directness (p=.007) and Cooperativeness (p=.014) scores were significantly lower while impulsivity level was significantly higher (p=.007) in bipolar patients with BA than those without BA.To our knowledge, this is the first study investigating the prevalence of behavioural addictions in BD showing a significant association of these disorders. BAs are more frequent in bipolar patients than in healthy controls and are related to higher impulsivity levels and character immaturity.

Pregabalin (PRE) acts as a presynaptic inhibitor of the release of excessive levels of excitatory neurotransmitters by selectively binding to the α2-δ subunit of voltage-gated calcium channels. In this randomised, double-blind comparison trial with naltrexone (NAL), we aimed to investigate the efficacy of PRE on alcohol drinking indices. Craving reduction and improvement of psychiatric symptoms were the secondary endpoints. Seventy-one alcohol-dependent subjects were detoxified and subsequently randomised into two groups, receiving 50 mg of NAL or 150—450 mg of PRE. Craving (VAS; OCDS), withdrawal (CIWA-Ar) and psychiatric symptoms (SCL-90-R) rating scales were applied. Alcohol drinking indices and craving scores were not significantly different between groups. Compared with NAL, PRE resulted in greater improvement of specific symptoms in the areas of anxiety, hostility and psychoticism, and survival function (duration of abstinence from alcohol). PRE also resulted in better outcome in patients reporting a comorbid psychiatric disorder. Results from this study globally place PRE within the same range of efficacy as that of NAL. The mechanism involved in the efficacy of PRE in relapse prevention could be less related to alcohol craving and more associated with the treatment of the comorbid psychiatric symptomatology.

It is well documented that psychostimulants may alter neuronal function and neurotransmission in the brain. Although the mechanism of psychostimulants is still unknown, it is known that these substances increase extracellular level of several neurotransmitters including dopamine (DA), serotonin, and norepinephrine by competing with monoamine transporters and can induce physical tolerance and dependence. In addition to this, recent findings also suggest that psychostimulants may damage brain neurons through mechanisms that are still under investigation. In the recent years, it has been demonstrated that almost all psychostimulants are able to affect a class of proteins, called neurotrophins, in the peripheral and central nervous system (CNS). Neurotrophins, such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), have relevant action on neurons involved in psychostimulant action, such as DA and serotonergic neurons, and can play dual roles: first, in neuronal survival and death, and, second, in activity-dependent plasticity. In this review, we will focalize on the effects of psychostimulants on this class of proteins, which may be implicated, at least in part, in the mechanism of the psychostimulant-induced neurotoxicity. Moreover, since altered neurotrophins may participate in the pathogenesis of psychiatric disorders and psychiatric disorders are common in drug users, one plausible hypothesis is that psychostimulants can cause psychosis through interfering with neurotrophins synthesis and utilization by CNS neurons.

Alzheimer's disease (AD) leads to a dramatic decline in cognitive abilities and memory. A more modest disruption of memory often occurs in normal aging and the same circuits that are devastated through degeneration in AD are vulnerable to sub-lethal age-related changes that alter synaptic transmission. There are numerous indications that aberrant plasticity is critically involved in Alzheimer's. Is ageing itself the major risk factor for AD? Is AD an acceleration of normal ageing? We assume that the ability of the brain is to modify its own structural organization and functioning which is liable to become impaired in ageing until it becomes dramatically impaired in Alzheimer's. Moreover, ageing can compromise the conversion of dietary alpha-linolenic acid (ALA) to docosahexaenoic acid (DHA). DHA regulates synaptogenesis and affects the synaptic structure, and synapse density is reduced in ageing. DHA and newly identified DHA-derived messenger, neuroprotecting D1 (NPD1), protect synapses and decrease the number of activated microglia in the hippocampal system. Delaying AD onset by a few years would reduce the number of the cases of dementia in the community. DHA (and NPD1?) and aspirin induce brain-derived neurotrophic factor (BDNF) protein expression and this protein has a crucial role in neuronal survival. The authors--in view of the increased neuroinflammatory reaction frequently observed during normal brain ageing--suggest the long-term use of "fatty aspirin", an association of DHA and/or NPD1 and aspirin (or nitroaspirin), to postpone, or prevent, the structural neurodegeneration of the brain.

The idea of the infinite has its origins in the very beginnings of western philosophy and was developed significantly by modern philosophers such as Galileo and Leibniz. Freud discovered the Unconscious which does not respect the laws of classical logic, flouting its fundamental principle of non-contradiction. This opened the way to a new epistemology in which classical logic coexists with an aberrant logic of infinite affects. Matte Blanco reorganized this Freudian revolution in logic and introduced the concept of bi-logic, which is an intermingling of symmetric and Aristotelic logics. The authors explore some epistemological and clinical aspects of the functioning of the deep unconscious where the emergence of infinity threatens to overwhelm the containing function of thought, connecting this topic to some of Bion's propositions. They then suggest that bodily experiences can be considered a prime source of the logic of turmoil, and link a psychoanalytic consideration of the infinite to the mind-body relation. Emotional catastrophe is seen both as a defect-a breakdown of the unfolding function which translates unconscious material into conscious experience-and as the consequence of affective bodily pressures. These pressures function in turn as symmetrizing or infinitizing operators. Two clinical vignettes are presented to exemplify the hypotheses.

Pregabalin is a new anxiolytic that selectively binds to the alpha2-delta subunit of voltage-gated calcium channels, inhibiting release of excessive levels of excitatory neurotransmitters. In this open-label trial we aimed to investigate the efficacy of pregabalin on alcoholism indices in detoxified alcohol-dependent subjects. Reduction of cravings, psychiatric symptom improvements, and the evaluation of safety parameters were the secondary endpoints.Thirty-one alcohol-dependent patients were consecutively recruited and screened for the study. Twenty detoxified patients received pregabalin starting at 50 mg/day (orally) in the first week, gradually increasing to a flexible dose of 150-450 mg/day. Subjects were assessed at the beginning of the treatment, and after 2, 8 and 16 weeks. Craving (visual analogue scale, Obsessive and Compulsive Drinking Scale [OCDS]) and withdrawal (Clinical Institute Withdrawal Assessment for Alcohol [CIWA-Ar]) rating scales were applied; psychiatric symptoms were evaluated through the Symptom Check List-90-Revised (SCL-90-R).Out of the twenty patients who received the study drug, 15 completed the study procedures: 10 remained totally alcohol-free for the duration of the study, five relapsed. An additional four patients dropped out during the study, and one stopped taking medication due to adverse events. A significant progressive reduction of both craving and withdrawal symptomatology were observed. Safety parameters did not show any significant variation during treatment.Pregabalin shows promise as a treatment for alcohol dependence. Although limited by a low number of participants and by the open design, this is the first study concerning the efficacy and safety of pregabalin in current alcoholics. In these patients pregabalin was effective and well tolerated. Additional research is needed to explore the clinical relevance of these findings.

Objective The purpose of the present study was to assess a group of patients with fibromyalgia (FM) and control subjects using the personality questionnaire proposed by Cloninger and to determine possible changes in the Italian version of the Temperament and Character Inventory—Revised patterns of patients with FM after therapy with serotoninergic antidepressants (selective serotonin reuptake inhibitors [SSRIs]). Methods Sixty patients with FM filled out the Temperament and Character Inventory—Revised and Beck Depression Inventory before and after 6-month therapy with SSRIs (escitalopram 10 mg, fluoxetine 20 mg, or paroxetine 20 mg). A total of 80 age-, sex-, and education level-matched healthy subjects were selected as a control group. Results Both in the pretreatment and posttreatment period, patients were found to have higher harm avoidance and lower self-directedness scores than healthy controls. In addition, harm avoidance and self-directedness were state and trait dependent. Conclusions Depressive symptoms in patients with FM can be significantly decreased by treatment with SSRIs. A careful clinical assessment and study of personality profile is needed to identify patients with FM who may benefit from antidepressant pharmacologic therapy and specific psychotherapeutic interventions.

Chronic cannabis use produces effects within the central nervous system (CNS) which include deficits in learning and attention tasks and decreased brain volume. Neurotrophins, in particular nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), are proteins that serve as survival factors for CNS neurons. Deficits in the production and utilization of these proteins can lead to CNS dysfunctions including those associated with cannabis abuse. In this study we measured by enzyme-linked immunosorbent assay (ELISA) the NGF and BDNF serum levels in two groups of subjects: cannabis-dependent patients and healthy subjects. We found that NGF serum levels were significantly reduced in cannabis abusers as compared to healthy subjects. These findings indicate that NGF may have a role in the central action of cannabis and potentially in the neurotoxicity induced by this drug. These data also suggest that chronic cannabis consumption may be a risk factor for developing psychosis among drug users.

Anhedonia, or the inability to experience pleasure, may be regarded either as a temperamental trait or as a state symptom of negative schizophrenia or melancholic depression. In substance use disorders, anhedonia was linked to hypoactivity of the dopaminergic mesolimbic system during protracted withdrawal. The authors investigated the influence of recent clinical and social-environmental factors on the hedonic capability and related psychopathology in a sample of 70 patients manifesting substance dependence (alcohol, opiates, multiple drugs) without severe comorbidity. Three symptom scales covering anhedonia (Snaith-Hamilton Pleasure Scale, SHAPS; Scale for the Assessment of Negative Symptoms, SANS; Bech-Rafaelsen Melancholia Scale, BRMES) were administered together with the European adaptation of the Addiction Severity Index (EuropASI). The composite scores from the seven areas of the EuropASI were introduced as independent factors in a stepwise regression analysis having symptom scores of anhedonia as dependent variables. Overall, the EuropASI composites do not explain the variability of the scores of anhedonia. Only in few cases, the regression models show a weak predictive capacity for medical status, alcohol use, and drug use composite scores, with R-square values ranging from 10 to 22%. Even if the study's limitations are noted, anhedonia appears as a psychopathological entity independent from other clinical and psychosocial features of treated addicts.

Background In Alzheimer's disease (AD), the common symptom is loss of memory. Learning and memory are associated with amoeboid movements of synaptic endings. Docosahexaenoic acid (DHA) is a major lipid constituent of synaptic end sites. Minor changes in the fluidity of phospholipidic membranes have a dramatic impact on the function of synapses, where membrane fluidity may influence the neurotransmitter receptor activity. Method Studies pertaining to the role of DHA as a neuroprotective agent was reviewed. Results Here we will show a conceptual framework for the role of DHA in the prevention of AD. The DHA content has been shown to be decreased in the brain and plasma of patients affected by AD. Aspirin triggers the generation of DHA-derived mediators that are themselves neuroprotective. Conclusion Adequate dietary intakes of the neuroprotective DHA (and aspirin?) may slow down the progression of AD. An essential reserve of synapses from early development is needed.

Objective Oxidative stress has been suggested as a contributor of Alzheimer disease (AD) neurodegeneration, particularly in those patients with late-onset AD (LOAD). Therefore, the authors studied the effect of glutathione S -transferase (GST) P1-M1-T1 gene polymorphisms and their interactions with the apolipoprotein E (ApoE) ɛ4 allelic variant on the three-year longitudinal course of AD. Methods Global cognitive level as measured by the Mini-Mental State Exam, basic activities of daily living (BADLs) as measured by the Physical Self-Maintenance Scale, and behavior as measured by the Neuropsychiatric Inventory, were assessed at baseline and after 1, 2, and 3 years in a sample of 99 LOAD patients. These subjects were drug naive and had undergone the first clinical examination for the diagnosis of AD. Results A multiple regression analysis indicated that the presence of ApoE ɛ 4 allelic variant or GSTT1 null phenotype predicted the faster age at onset of the illness (F = 5.76, df=2, 96, p=0.0043). Carriers of GSTP1 *C allelic variant had a faster decline in cognitive functions (repeated measures analysis of variance [ANOVA]: F=4.00, df=3, 285, p=0.008) and in BADLs (repeated measures ANOVA: F=5.27, df=3, 285, p=0.001). This faster decline was independent from ApoE ɛ 4 allele possession. No effect of GST P1-M1-T1 polymorphisms was found on behavioral symptom severity. Conclusion These data are in line with the hypotheses that oxidative damage is a prominent feature in the clinical progression and the age at onset of LOAD.

Background Awareness may lack in some stroke patients who are not capable of evaluating the nature and severity of illness. Thus, unawareness may have different forms such as anosognosia, neglect, and alexithymia or unawareness of emotions. In this study we investigated the relationship among anosognosia, neglect, alexithymia, and cognition. Methods Fifty consecutive right stroke inpatients were approached within the first 3 months from the acute event. Anosognosia was measured with the Bisiach scale, alexithymia with the TAS-20 scale and neglect with line crossing, letter cancellation, figure and shape copying, and line bisection tests. A neuropsychological test battery was used to measure different areas of cognition. Results despite the strong comorbidity rate among the different forms of unawareness, there are patients who suffer from pure forms of these types of lack of awareness. A multivariate logistic regression model evidenced that presence of neglect (OR = 10.3; 95% CI = 1.4–76.3; p = 0.023) and more difficulty in describing feelings (TAS-20 F2 subscore; OR = 1.3; 95% CI = 1.1–1.7; p = 0.014) were the only predictors of anosognosia. In addition, anosognosics with alexithymia performed worst in a frontal task such as the verbal fluency task (p = 0.042) and in the verbal span forward task (p = 0.026) than pure anosognosics. Conclusions Anosognosia for motor impairment is strictly associated with a specific form of unawareness of emotions. Future studies have to clarify if frontal cognitive impairment previously described in anosognosics is a manifestation of unawareness of emotions or anosognosia for motor impairment. Copyright © 2007 John Wiley & Sons, Ltd.

The neurobiology of suicidality in schizophrenia is largely unknown. We therefore assessed gray and white matter volumes associated with past suicidality and current self-aggression in schizophrenia. Fifty-five outpatients with schizophrenia (n=55) and healthy controls (n=55), matched for age, gender and handedness, were recruited. Ten patients had a life-time history of one or more suicide attempts. Current self-aggression was assessed using the Modified Overt Aggression Scale. High resolution structural magnetic resonance images were analyzed by voxel-based morphometry. We found significantly larger inferior frontal white matter volumes bilaterally in patients with a previous suicide attempt as compared with those patients without a history of suicidality. No other significant white or gray matter volume differences were observed. White matter volume in these regions did not differ between healthy controls and those patients without a previous suicide attempt. Furthermore, among patients, the level of current self-aggression showed a significant positive correlation with white matter volume in the same regions. Inferior frontal white matter alterations in fronto-temporo-limbic circuits may be associated with suicidality and self-aggression in schizophrenia.

Oxcarbazepine (OXC) is a keto-congener of carbamazepine, which has fewer side effects and drug interactions. However, the efficacy of OXC in treating bipolar disorder is not as well established as that of carbamazepine. This article is a systematic literature review of all studies regarding OXC and bipolar disorders, with particular attention to papers published in the last 6 years. Using the terms 'oxcarbazepine and bipolar disorder', 'oxcarbazepine and mania' or 'oxcarbazepine and bipolar depression', a computer-aided search of MEDLINE for the years 2000-2006 has been conducted. Since its introduction as an antiepileptic drug in early 2000, clinical research regarding the potential role of OXC in the treatment of bipolar disorder remains limited. There is a lack of double-blind, placebo-controlled studies. Studies recently published have small samples of patients, with insufficient follow-up periods and other methodological weaknesses. The efficacy of OXC in bipolar disorder has not been widely studied. Some authors recommend using OXC as monotherapy or as add-on therapy in refractory mania, although results are not conclusive. It is unknown whether OXC has efficacy in the maintenance treatment of bipolar disorder. OXC can be particularly useful as an add-on treatment in bipolar disorder patients for whom previous treatments have failed, or in patients who have difficulty tolerating adequate dosages of standard approved treatments.

High-density EEG during sleep represents a powerful new tool to reveal potential abnormalities in rhythm-generating mechanisms while avoiding confounding factors associated with waking activities. As a first step in this direction, the authors employed high-density EEG to explore whether sleep rhythms differ between schizophrenia subjects, healthy individuals, and a psychiatric control group with a history of depression.Healthy comparison subjects (N=17), medicated schizophrenia patients (N=18), and subjects with a history of depression (N=15) were recruited. Subjects were recorded during the first sleep episode of the night with a 256-electrode high-density EEG. Recordings were analyzed for changes in EEG power spectra, power topography, and sleep-specific cortical oscillations.The authors found that the schizophrenia group had a significant reduction in centroparietal EEG power, from 13.75 to 15.00 Hz, in relation to both the comparison and depression groups. No significant difference in EEG power between the comparison and depression groups was identified. The authors also found a decrease in sleep spindle number, amplitude, duration, and integrated spindle activity in schizophrenia patients. Furthermore, integrated spindle activity had an effect size corresponding to 93.0% or 90.2% separation of the schizophrenia from the comparison or depression group.Sleep spindles are generated by the thalamic reticular nucleus in conjunction with specific thalamic nuclei and are modulated by corticothalamic and thalamocortical connections. The deficit in sleep spindles in schizophrenia subjects may reflect dysfunction in thalamic-reticular and thalamocortical mechanisms and could represent a biological marker of illness.

Despite the high prevalence of depressive disorders in cancer patients and elderly people, the topic of depression in elderly cancer patients still remains unexplored. This emerges from a systematic review of the literature conducted to investigate issues of depression, diagnosis, pathogenesis, treatment and their complex neuroimmunobiological interactions. Indeed, it becomes apparent that depression in elderly patients with cancer may have a peculiar phenomenology. In addition, the moderate rate of major depressive disorder and the high rate of minor depressive disorder are accompanied by subthreshold forms of depression that are at risk to be underrecognized and untreated. Immune dysfunction may represent a common pathogenic ground of depression, cancer and aging. This may have important implications for treatment. In the near future, we need to develop validated mood disorder diagnoses and verify antidepressant treatment efficacy for elderly cancer patients with depression in order to improve their clinical outcome and quality of life.

Apolipoprotein E (ApoE) ε4 allele represents a well known vascular risk factor for developing Alzheimer disease (AD) and differences in ApoE genotypes may explain a part of the variability in AD phenotypes. In fact, ApoE ε4 allele possession seems to be associated with a more precocious age of onset, greater episodic memory impairment, and psychotic symptoms. The first question we discuss regards the role of ApoE ε4 on cognitive progression of AD. In fact, while a general agreement exists about the role played by ApoE ε4 on the precocious onset of AD, cognitive decline has been differently associated with ApoE ε4 allele possession in AD patients in a continuum of faster decline, no effect, and slower decline. An attemptable interpretation is that the biological processes leading to the onset of AD are different from those involved in determining its clinical course. The second question regards the possible relationship between the presence of the degenerative pathological hallmarks of the disease in specific cerebral areas and different cognitive or behavioural symptoms. In fact, there is evidence that degenerative pathology in hippocampal formation and frontal cortex reflects the progression of cognitive deficits in brain aging and AD and that hypometabolism in right frontal lobe and greater frontal neuropsychological deficits occur in AD patients with psychosis in comparison to those without. The third question regards, specifically, the relationship between ApoE ε4 variant and behavioural symptoms. In fact, there is evidence supporting the link between being carriers of ApoE ε4 allele and severity of delusions, mostly at the early stage of the illness. In an interpretative challenge, we suggest that the link between being carriers of ApoE ε4 allele and suffering from delusions in AD may be explained by frontal lobe dysfunctions. Finally, we hypothesize that the most precocious onset of AD illness, described in carriers of ApoE ε4 allelic variant, may also be related to the precocious onset of psychotic symptoms, which produces caregiver and patient distress and requires immediate assessment and treatment.

IntroductionThis issue of the Journal of Public Health presents articlesrelating to different fields in public health research, fromthe organization of humanitarian aid action to the preven-tion of infectious diseases, the diffusion of problematicbehaviors, and the management of chronic conditions. Mostof the contributors underline the importance of the diffusionof knowledge and information among the general popula-tion for the primary prevention of diseases, and the role ofcommunication and patient education in the management ofchronic conditions.Human behavior can in fact influence the spread ofinfectious diseases, and it is based on the individuals’knowledge as well as on the information received aboutsuch conditions (Funk et al. 2010). In turn, a correctevaluation of the benefits obtained from immunization, andof the risks and the adverse effects related to the vaccineswould facilitate a wider diffusion of vaccinations (Baejens2010). Some of the papers in this issue are in line with theafore-mentioned hypotheses: Al-lela et al., who developed aquestionnaire on knowledge, attitude and practice aboutimmunization among Iraqi parents, suggest that parentswho have adequate information on this field also have apositive attitude and practices towards immunization;Kamal et al. assessed the knowledge, attitude and practicetowards the pandemic H1N1 influenza virus among El-MiniaUniversity students in Egypt, and maintain that adequateacquaintance with the problem is associated with a betterwillingness to comply with preventive measures; Naing andTan focused on the knowledge of pandemic influenza A andon the willingness to be vaccinated among a sample of 264medical students in Kuala Lumpur, Malaysia, and underlinethenecessitytostrengthenevidence-basedhealtheducationinorder to help people adopting effective preventive behaviorsand vaccination.One of the main factors contributing to the spread ofbacterial resistance is the misuse of antibiotics. Educationalprograms for both health professionals and the generalpopulation are strongly needed: reducing misconceptionsabout the utility of antibiotics in minor ailments andimprovingthegeneralpublicawarenessoftheriskscorrelatedwiththeirimproperusewouldbeakeycomponentonpoliticsaimed to control the diffusion of antibiotic resistance(Grigoryan et al. 2010). Two studies focus respectively onthe topic of the diffusion of antibiotic-resistant bacteria andon the knowledge of MRSA in both medical students and thegeneral population: Sathiamoorthi et al. describe the preva-lence of multidrug-resistant Salmonella enterica typhi andparatyphi among 368 human cases of typhoid and paraty-phoid fever from the Tiruchirappalli district in India, whileDe Giusti et al. report a survey conducted on a sample ofstudents attending an Italian Faculty of Medicine and ontheir cohabitants, focusing on their knowledge on MRSA, its