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The purpose of the present study was to detect demographic and clinical factors associated with lifetime suicide attempts in Bipolar Disorder (BD). A total of 1673 bipolar patients from different psychiatric departments were compared according to the lifetime presence of suicide attempts on demographic/clinical variables. Owing to the large number of variables statistically related to the dependent variable (presence of suicide attempts) at the univariate analyses, preliminary multiple logistic regression analyses were realized. A final multivariable logistic regression was then performed, considering the presence of lifetime suicide attempts as the dependent variable and statistically significant demographic/clinical characteristics as independent variables. The final multivariable logistic regression analysis showed that an earlier age at first contact with psychiatric services (odds ratio [OR] = 0.97, p p p p p p

AIM The aim of the present study was to detect factors associated with duration of untreated illness (DUI) in bipolar disorder (BD). METHOD A total of 1575 patients were selected for the purposes of the study. Correlation analyses were performed to analyse the relation between DUI and quantitative variables. The length of DUI was compared between groups defined by qualitative variables through one-way analyses of variance or Kruskal-Wallis's tests according to the distribution of the variable. Linear multivariable regressions were used to find the most parsimonious set of variables independently associated with DUI: to this aim, qualitative variables were inserted with the numeric code of their classes by assuming a proportional effect moving from one class to another. RESULTS An inverse significant correlation between length of DUI and time between visits in euthymic patients was observed (r = -.52, P

Background and aims The primary objective of this study was to investigate the prevalence of at-risk gambling in a large, unselected sample of outpatients attending two community mental health centers, to estimate rates according to the main diagnosis, and to evaluate risk factors for gambling. Methods All patients attending the centers were evaluated with the Canadian Problem Gambling Index and the Mini International Neuropsychiatric Interview. Diagnoses were checked with the treating psychiatrists and after a chart review of the university hospital discharge diagnoses. Results The rate of at-risk gambling in 900 patients was 5.3%. In those who gambled over the last year, 10.1% were at-risk gamblers. The rates in the main diagnostic groups were: 4.7% schizophrenia and related disorders, 4.9% bipolar disorder, 5.6% unipolar depression, and 6.6% cluster B personality disorder. In 52.1% of the cases, at-risk gambling preceded the onset of a major psychiatric disorder. In a linear regression analysis, a family history of gambling disorder, psychiatric comorbidities, drug abuse/dependence, and tobacco smoking were significantly associated with at-risk gambling. Discussion and conclusion The results of this study evidenced a higher rate of at-risk gambling compared to community estimates and call for a careful screening for gambling in the general psychiatric population.

BACKGROUND: Deficits in cortical gray matter (GM) have been found in patients with schizophrenia, with evidence of progression over time. The aim of this study was to determine the role of potential moderators of such changes, in particular of the amount and type of antipsychotic medication intake. METHODS: Longitudinal magnetic resonance imaging studies comparing changes in the volume of cortical GM over time between patients with schizophrenia and healthy control subjects published between January 1, 1983, and March 31, 2014, were analyzed. Hedges’ g was calculated for each study and volume changes from baseline to follow-up were analyzed. Meta-regression statistics were applied to investigate the role of potential moderators of the effect sizes. RESULTS: Eighteen studies involving 1155 patients with schizophrenia and 911 healthy control subjects were included. Over time, patients with schizophrenia showed a significantly higher loss of total cortical GM volume. This was related to cumulative antipsychotic intake during the interval between scans in the whole study sample. Subgroup meta-analyses of studies on patients treated with second-generation antipsychotics and first-generation antipsychotics revealed a different and contrasting moderating role of medication intake on cortical GM changes: more progressive GM loss correlated with higher mean daily antipsychotic intake in patients treated with at least one first-generation antipsychotic and less progressive GM loss with higher mean daily antipsychotic intake in patients treated only with second-generation antipsychotics. CONCLUSIONS: These findings add useful information to the controversial debate on the brain structural effects of antipsychotic medication and may have both clinical relevance and theoretical implications.

Objective: This study was designed to explore the efficacy and tolerability of oral paliperidone extended release (ER) in a sample of patients who were switched to flexible doses within the crucial first 5 years after receiving a diagnosis of schizophrenia. Methods: Patients were recruited from 23 countries. Adults with nonacute but symptomatic schizophrenia, previously unsuccessfully treated with other oral antipsychotics, were transitioned to paliperidone ER (3–12 mg/day) and prospectively treated for up to 6 months. The primary efficacy outcome for patients switching for the main reason of lack of efficacy with their previous antipsychotic was at least 20% improvement in Positive and Negative Syndrome Scale (PANSS) total scores. For patients switching for other main reasons, such as lack of tolerability, compliance or ‘other’, the primary outcome was non-inferiority in efficacy compared with the previous oral antipsychotic. Results: For patients switching for the main reason of lack of efficacy, 63.1% achieved an improvement of at least 20% in PANSS total scores from baseline to endpoint. For each reason for switching other than lack of efficacy, efficacy maintenance after switching to paliperidone ER was confirmed. Statistically significant improvement in patient functioning from baseline to endpoint, as assessed by the Personal and Social Performance scale, was observed ( p < 0.0001). Treatment satisfaction with prior antipsychotic treatment at baseline was rated ‘good’ to ‘very good’ by 16.8% of patients, and at endpoint by 66.0% of patients treated with paliperidone ER. Paliperidone ER was generally well tolerated, with frequently reported treatment-emergent adverse events being insomnia, anxiety and somnolence. Conclusions: Flexibly dosed paliperidone ER was associated with clinically relevant symptomatic and functional improvement in recently diagnosed patients with non-acute schizophrenia previously unsuccessfully treated with other oral antipsychotics.

Bipolar disorders (BDs) are prevalent, comorbid and disabling conditions, associated with the highest suicide risk among psychiatric illnesses. In the last few years, new efforts to better characterize the socio-demographic and clinical profiles of BD type I vs II have been documented by several reports, with novel and insightful findings in the field. The present multicenter study aimed to provide a comprehensive and reliable representation of the Italian reality, through the analysis of the largest national sample of bipolar patients collected so far. A total of 1500 patients (BD I n = 963 and BD II n = 537) from different psychiatric departments, participating in the Italian Chapter of the “International Society of Bipolar Disorders” (ISBD), were assessed and divided into two groups on the basis of their diagnostic subtype, and different socio-demographic and clinical variables were compared between the two subgroups. Chi-squared tests for categorical variables and t tests for continuous variables were performed for group comparison. Furthermore, a multivariable logistic regression was performed, considering diagnostic bipolar subtype (type I or II) as dependent variable, and socio-demographic/clinical characteristics as independent variables. BD I vs II patients showed an overall less favorable socio-demographic and clinical profile. In addition, the multivariable logistic regression showed that BD II vs BD I was predicted by the absence of lifetime suicide attempts (OR = 1.58, p = 0.01), a later age of diagnosis (OR = 1.03, p < 0.01), less hypomanic episodes in the last year (OR = 2.29, p < 0.0001) and absence of psycho-educational interventions in the last year (OR = 0.51, p < 0.01). BD I and II patients were found to significantly differ in relation to specific clinical variables, which should be considered within updated diagnostic–therapeutic algorithms.

none 28 no BACKGROUND: The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses. METHOD: A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer-Salovey-Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters. RESULTS: We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (⩾14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI

Summary Schizophrenia is a complex, heterogeneous behavioural and cognitive syndrome whose origins appear to lie in genetic and/or environmental disruption of brain development. Dysfunction of dopaminergic neurotransmission appears to contribute to the genesis of psychotic symptoms but the evidence also points to a more widespread and variable involvement of brain areas and circuits. There is emerging evidence that disturbances of synaptic function might underlie abnormalities of neuronal connectivity possibly involving interneurons, but the precise nature, location and timing of these events is uncertain. Current treatment consists largely in the administration of antipsychotic drugs combined with psychological therapies, social support and rehabilitation, but there is a pressing need for more effective treatments and for services to be delivered more effectively. Progress in understanding the disorder has been great in recent years with advances in genomics, epidemiology and neuroscience, and the opportunities for further scientific advance are great: but so are the challenges.

Genomic studies revealed two main components in the genetic architecture of schizophrenia, one constituted by common variants determining a distributed polygenic effect and one represented by a large number of heterogeneous rare and highly disruptive mutations. These gene modifications often affect neural transmission and different studies proved an involvement of metabotropic glutamate receptors in schizophrenia phenotype. Through the combination of literature information with genomic data from public repositories, we analyzed the current knowledge on the involvement of genetic variations of the human metabotropic glutamate receptors in schizophrenia and related endophenotypes. Despite the analysis did not reveal a definitive connection, different suggestive associations have been identified and in particular a relevant role has emerged for GRM3 in affecting specific schizophrenia endophenotypes. This supports the hypothesis that these receptors are directly involved in schizophrenia disorder.

To test the efficacy of a training course on the diagnosis and treatment of schizophrenia, tailored for the general practitioner.A course, in a 3-session format, was given to 215 primary care doctors from the city of Brescia and its province, in Italy. All 706 doctors working in primary care were asked to participate. Of these doctors, 30.5% took part in the study. The first session (215 doctors) assessed baseline knowledge of schizophrenia (June 2002), the second (173 doctors) gave formal teaching and assessed post-lesson knowledge (October 2002), and the third (130 doctors) evaluated the retention of knowledge after 8 months (July 2003). The main outcome measures were total number of schizophrenia symptoms identified, total number of antipsychotics identified, and knowledge about antipsychotic-related adverse events.Post-lesson, general practitioners could identify 6.5 more symptoms (p.001) and 4.9 more antipsychotics (p.001). Compared to baseline, 71.5% vs. 15.4% of doctors had a good knowledge of antipsychotic-related adverse events. Although a loss of knowledge was found after the 8-month follow-up, knowledge at the endpoint was significantly higher than at baseline for the 3 main outcome variables (p.001).The teaching course on schizophrenia for general practitioners was effective, and the knowledge gained after teaching was stable across time.

The HLA-SD phenotype distributions of hebephrenic and paranoid schizophrenics, and of the two groups combined, in an Italian population and in a combined group from the Swedish population have been analyzed statistically. There is a significantly decreased frequency of HLA-A10 in all of these. There are some preliminary indications of an increased frequency (a positive association) for some of the other antigens of the HLA-SD series, but there is insufficient data at present for evaluating the significance of these findings. Differences between hebephrenic and paranoid schizophrenics have been detected.

The search for biomarkers of response to antipsychotic medications is hindered by difficulties inherent in the topic or related to persistent methodological difficulties, such as high rates of anticipated discontinuation and consequent distortions in the imputation of missing data. Because early response to antipsychotics represents a sufficiently reliable index of the subsequent treatment response in patients with schizophrenia, we undertook a real-world, genome-wide association study (GWAS) with the aim of identifying genetic predictors of response to risperidone after 2 weeks in 86 patients with schizophrenia. Limited to the associations reaching significance in the GWAS, confirmatory analysis relative to risperidone response over 9 months was also designed involving 97 patients (European only) enroled in the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) genetic substudy. The GWAS revealed a significant association (false discovery rate 0.02) of the single-nucleotide polymorphism rs2133450 inside the GRM7 gene with Emsley's positive domain derived from the positive and negative syndrome scale (PANSS). Patients with the rs2133450 CC genotype presented poorer improvement in the positive domain over 2 weeks, with odds ratios of 12.68 (95% CI, 3.51-45.76) and 6.95 (95% confidence interval (CI), 2.37-20.37) compared with patients with the AA and AC genotypes, respectively. Compared with A homozygotes, rs2133450 C homozygotes enroled in the CATIE-derived confirmatory analysis showed less improvement in Emsley's positive, excited and depression domains, positive and general PANSS subtypes, and total PANSS after 9 months of treatment with risperidone. The original GWAS and the CATIE-derived confirmatory analysis support the proposal that the rs2133450 may have translational relevance as a predictor of response to risperidone.

Inbreeding is a known risk factor for recessive Mendelian diseases and previous studies have suggested that it could also play a role in complex disorders, such as psychiatric diseases. Recent inbreeding results in the presence of long runs of homozygosity (ROHs) along the genome, which are also defined as autozygosity regions. Genetic variants in these regions have two alleles that are identical by descent, thus increasing the odds of bearing rare recessive deleterious mutations due to a homozygous state. A recent study showed a suggestive enrichment of long ROHs in schizophrenic patients, suggesting that recent inbreeding could play a role in the disease. To better understand the impact of autozygosity on schizophrenia risk, we selected, from a cohort of 180 Italian patients, seven subjects with extremely high numbers of large ROHs that were likely due to recent inbreeding and characterized the mutational landscape within their ROHs using Whole Exome Sequencing and, gene set enrichment analysis. We identified a significant overlap (17%; empirical p-value = 0.0171) between genes inside ROHs affected by low frequency functional homozygous variants (107 genes) and the group of most promising candidate genes mutated in schizophrenia. Moreover, in four patients, we identified novel and extremely rare damaging mutations in the genes involved in neurodevelopment (MEGF8) and in GABA/glutamatergic synaptic transmission (GAD1, FMN1, ANO2). These results provide insights into the contribution of rare recessive mutations and inbreeding as risk factors for schizophrenia. ROHs that are likely due to recent inbreeding harbor a combination of predisposing low-frequency variants and extremely rare variants that have a high impact on pivotal biological pathways implicated in the disease. In addition, this study confirms that focusing on patients with high levels of homozygosity could be a useful prioritization strategy for discovering new high-impact mutations in genetically complex disorders.

BACKGROUND AND PURPOSE: Previous studies have suggested that structural changes do occur in the brain of patients with schizophrenia compared with healthy control participants. However, findings from such studies are inconclusive, probably because of the different methodologic approaches, the clinical heterogeneity of patient samples, and also the fact that patients enrolled were treated with antipsychotic drugs. The aim of this study was to investigate brain GM volumes and intrinsic structural WM changes in first-contact, antipsychotic drug-naive patients with schizophrenia. MATERIALS AND METHODS: A total of 43 first-contact, drug-naive, patients with schizophrenia and 17 age-matched control participants were studied. All participants underwent T1-weighted MR imaging and DTI scans. Voxel-based morphometry and tract-based spatial statistics were used to compare GM volumes and WM DTI metrics between groups. MR imaging measures were correlated with the duration of the untreated psychosis and the clinical positive and negative symptoms. RESULTS: Compared with control participants, patients with schizophrenia showed smaller volumes of the temporal, parietal, and occipital GM, and a pattern of decreased mean diffusivity and increased fractional anisotropy in the brain stem and cerebellum bilaterally, interhemispheric and cortico-cortical connections bilaterally, and right anterior and posterior limb of the internal capsule. In patients, decreased mean diffusivity and increased fractional anisotropy in several brain regions were related to a longer duration of the untreated psychosis and the severity of positive symptoms. CONCLUSIONS: First-contact, drug-naive, patients with schizophrenia present with volumetric and DTI changes, which correlated with their clinical features. This study increases our knowledge on the neural networks involved in the pathophysiologic mechanisms of schizophrenia.

Background Recent studies supported associations between four NMDA-receptor-mediated signalling genes (D-amino acid oxidase, DAO; D-amino acid oxidase activator, DAOA; protein phosphatase 3 catalytic subunit gamma isoform, PPP3CC; dystrobrevin-binding protein 1, DTNBP1) and schizophrenia susceptibility, even though with contrasting results. Methods In an attempt to replicate these findings for the first time in an Italian population, a panel of 32 tagSNPs was analysed in a representative case-control sample involving 879 subjects. Results An association in the allele frequency was observed for the estimated PPP3CC CAG triplotype in the SNP window rs4872499 T/C-rs11780915 A/G-rs13271367 G/A (pcorrect = 0.001). Similarly, the clustered genotype frequencies of the estimated/phased CAG triplotype differed between cases and controls (p = 0.004), with the carriers having a higher frequency in the control population (p = 0.002, odd ratio OR = 0.59, 95% confident interval CI: 0.43-0.82). Following the phenotypic dissection strategy, the analysis of single SNPs evidenced a protective effect in males of rs11780915 and rs13271367 in PPP3CC gene (pcorrect = 0.02, pcorrect = 0.04 respectively). Moreover the estimated/phased GT diplotype (rs2070586A/G-rs3741775G/T) carriers of the DAO gene were more highly represented in female controls (p = 0.017, OR = 0.58, 95% CI: 0.37-0.90), as were the estimated/phased CAG triplotype carriers of the PPP3CC gene in females (p = 0.01, OR = 0.53, 95% CI: 0.32-0.87). In addition, we performed an interaction analysis, and a 66% (p = 0.003, OR = 0.34, 95% CI: 0.17-0.70) lower risk of developing schizophrenia for female (CAG + GT) carriers versus non-CAG or -GT carriers was observed. For DTNBP1, we found a protective effect in males for the rs6459409 (pcorrect = 0.02) and the estimated/phased CT diplotype (rs6459409-rs9476886) carriers (p = 3x10-4 , OR = 0.46, 95% CI: 0.30-0.70). In relation to diagnostic subtypes, the estimated/phased DAO GT diplotype and PPP3CC CAG triplotype female carriers were found to show relative risk ratio (RRR) values of 0.52 and 0.54 lower risk for a paranoid phenotype respectively. Conclusions Although the results are preliminary and needed replication in a larger sample, this study suggests that NMDA receptor-mediated signalling genes (DAO, PPP3CC, DTNBP1) might be involved in schizophrenia pathogenic mechanisms related to gender.

BackgroundCognitive dysfunction has been demonstrated in patients with schizophrenia, and this may affect patients’ functional outcome. The improvement of such dysfunction by means of cognitive remediation interventions has become a relevant target in the care of schizophrenia.ObjectiveTo assess the effectiveness of the cognitive subprograms of Integrated Psychological Therapy (IPT) on symptomatological, neuropsychological and functional outcome variables and to analyze the relationships between cognitive and functional outcome changes in schizophrenia.MethodsThirty-two patients with schizophrenia were assigned to cognitive remediation (IPT-cog) or usual rehabilitative interventions in a naturalistic setting of care. Clinical, neuropsychological and functional outcome variables were assessed at baseline and after 24 weeks of treatment.ResultsThe IPT-cog group improved significantly more than the comparison group with respect to psychopathological and functional outcome variables. Moreover, only the IPT-cog group improved significantly in the neuropsychological domains of verbal and working memory, with specific significant correlations between neurocognitive performance and functional outcome changes.ConclusionsThe results of the study confirm the effectiveness of the cognitive remediation component of IPT in schizophrenia, and indicate that some of the changes in functional outcome may be mediated by improvement in specific cognitive domains.

Cognitive deficits are a core feature of schizophrenia and the need for a simple and reliable method for assessment of cognitive functions in schizophrenia is well recognized. The Schizophrenia Cognition Rating Scale (SCoRS) has proved to be a valid measure of neurocognitive performance and to correlate with the psychosocial functioning of schizophrenic patients. Aim of the present study was to investigate the correlations among global ratings of the Italian version of the SCoRS and measures of cognitive performance, symptoms severity and psychosocial functioning in schizophrenic subjects. We intended also to test the SCoRS sensitiviity to change over time, in relation also to changes of the above mentioned clinical, neurocognitive and outcome parameters. Forty-eight patients with schizophrenia (29 males, 19 female; mean age 39.1 years) were assessed at baseline and after three months of usual outpatient treatment according to the Italian community assertive treatment program, with the following instruments:1)SCoRS;2)comprehensive neuropsychological battery;3)the Positive And Negative Syndrome Scale and the Clinical Global Impression;4)the Global Assessment of Functioning, the Health of the Nation Outcome Scale, the Camberwell Assessment of Needs scale.At baseline, SCoRS global ratings significantly correlated with the composite scores of cognitive performance, with positive, negative and total PANSS scores and with all measures of psychosocial functioning. Conversely, SCoRS global ratings did not change significantly over the 3-month follow up and the changes from baseline did not significantly correlate with the changes of neurocognitive, clinical and functional assessments over the same time period.

The aim of the present investigation was to characterize the EEG power spectrum in two samples of young schizophrenics, with and without LVE, as compared with a group of age-homogeneous normal controls. Further, the frequency of the peak in the alpha frequency band was compared in the two patient samples

Objective: This study investigated the level of knowledge about schizophrenia of primary care doctors working in the city of Brescia, Italy, and variables associated with better information. Method: The study design was devised after 2 joint meetings with leading figures of the Italian College of General Practitioners. A cross-sectional evaluation of 215 general practitioners was performed (June 2002). A random subgroup was selected to participate in a 4-month retest session in order to evaluate the reliability of the schedule (October 2002). The setting was the local health unit of Brescia, which involves 706 primary care doctors working in the city and its province. Of these, 30.5% took part in the study. A structured self-report questionnaire (SAKS) was devised for this study. General practitioners were also asked to rate videotaped cases of 5 patients with different DSM-IV diagnoses. The main outcome measures were the scores from subscales measuring knowledge of schizophrenia symptoms and signs, knowledge of antipsychotics and their adverse events, and correct diagnoses of 5 videotaped cases. Results: Primary care doctors identified positive (79.0%), negative (72.6%) and general (72.1%) symptoms of schizophrenia (p < .001). Of the 5 cases on videotape, they correctly rated a mean of 3.1 cases. The mean percentage of anti-psychotics correctly identified was 34.1% (older) and 51.2% (novel) (p < .001). Better answers were given by doctors who knew the diagnostic criteria, had read books on psychiatry, and had attended previous courses. Conclusion: More teaching on the diagnosis of schizophrenia and clinical psychopharmacology should be given to general practitioners.

This report presents data from the extension phase of a 6-month trial that evaluated the efficacy of risperidone long-acting injectable (RLAI) in stable psychotic patients requiring a treatment change. Patients continued to receive RLAI every 2 weeks for a maximum of 12 months from study entry. Symptoms were assessed using the PANSS after 1, 3, 6, 9 and 12 months of treatment (or treatment endpoint). Remission of severity criteria were defined as ≤3 points in all PANSS items suggested by the Remission in Schizophrenia Working Group. 715 patients (63% male) entered the extension phase and 508 completed the 12-month study. The mean PANSS total score at Day 0 was 74.9±22.7. This was significantly reduced after 1 month (67.7 ±22.3, p≤0.001), with continued improvements over the 12 months of the study until treatment endpoint (59.7±21.9). Significant improvements from Day 0 to endpoint were also seen in the scores for all PANSS subscales and symptom factors. The proportion of patients who met the PANSS severity criteria for remission increased from 29% at Day 0 to 60% at endpoint, and the proportion of patients who met these criteria for ≤ 6 months increased from 24% at Month 6 to 45% at endpoint. Treatment with RLAI for up to 12 months provided significant and sustained improvements in symptom control in patients with schizophrenia. These improvements may help patients to achieve and remain in remission.

Findings from Arnone et al ’s[1][1] systematic review and meta-analysis of magnetic resonance imaging (MRI) studies suggest that patients with bipolar disorder are characterised, in comparison with healthy controls, by significant reductions of whole-brain and prefrontal lobe volumes and by

Structured group psychoeducation for bipolar patients: a study of effectiveness in Italy V. Candini, C. Buizza, G. de Girolamo, C. Ferrari, M.T. Caldera, R. Ermentini, G. Nobili, R. Pioli, M. Sabaudo, E. Sacchetti, F. M. Saviotti, G. Seggioli, A. Zanini IRCCS St. John of God Fatebenefratelli, Brescia, Italy MHD of Desenzano del Garda, Desenzano del Garda, Italy MHD of Brescia, Brescia, Italy University of Brescia, Brescia, Italy

Background Recent reviews of evidence-based guidelines for the clinical management of Bipolar Disorders (BD) have recommended that “all patients with BD should be offered group or individual psychoeducation” to prevent relapse, improve treatment adherence, quality of life and functioning. The present study aimed at evaluating the psychoeducation in routine mental health. Methods One hundred and two outpatients were recruited from two Italian DMHs. Inclusion criteria were a lifetime diagnosis of BD type I or II assessed by SCID-I, being euthymic for at least 3 months. Exclusion criteria were a DSM-IV Axis I comorbidity, mental retardation (IQ Results Data show that the number of patients hospitalized during the 1-year follow-up, the mean number of hospitalizations per patient and the mean number of days in hospital were significantly lower for psychoeducated patients. Conclusion Our study supports the view that group psychoeducation is an efficacious intervention to prevent patients’ hospitalization and decrease hospital days in pharmacologically treated patients with bipolar disorder, also in routine clinical settings. The results seem to confirm that the psychoeducation promotes an improvement in the course of illness, avoiding acute phases, and producing a greater stabilization of the disease and consequently an improvement in quality of life in people with BD.

ObjectiveTo explore tolerability and treatment response in adult patients with recently diagnosed (5 years) schizophrenia treated with flexible doses of paliperidone ER.MethodsInternational prospective open-label 6-month study. Endpoints were the Positive and Negative Syndrome Scale (PANSS), patient functioning and treatment-emergent adverse events (TEAEs).ResultsOf 713 recently diagnosed patients, most were male (60.9%), mean age was 33.6 ± 11.2 years and mean time since diagnosis was 2.3 ± 1.7 years. Chronic patients (n = 1003) were predominantly male (59.2%) with a mean age of 43.8 ± 11.4 and mean time since diagnosis of 15.6 ± 9.2 years. 70.4% and 71.7% of patients completed the study, respectively. Mean mode doses of paliperidone ER were similar between recently diagnosed and chronic patients (7.0 ± 2.9 mg/day and 7.2 ± 2.9 mg/day). 63.1% of recently diagnosed and 60.8% of chronic patients switching due to lack of efficacy with their previous antipsychotic had a >20% improvement in PANSS total score at endpoint, and improvement with other switching reasons was consistently numerically higher in recently diagnosed patients. The rate of patients with mild or no functional impairment increased from 17.7% to 39.8% in recently diagnosed and from 14.4% to 32.9% in chronic patients. TEAEs reported in >5% were insomnia (10.7% and 8.1%), anxiety (8.6% and 6.0%) and somnolence (5.8% and 3.4%), respectively.ConclusionThese data suggest that both recently diagnosed and chronic patients previously unsuccessfully treated with other oral antipsychotics may benefit from paliperidone ER, with a tendency for recently diagnosed patients showing some higher treatment response in psychotic symptoms and patient functioning.

The aim of this paper was to evaluate the efficacy of risperidone long-acting injectable (RLAI) for reducing negative symptoms of schizophrenia in patients with predominantly negative symptoms at baseline. A subanalysis was performed on data from the 6-month, open-label Switch to Risperidone Microspheres trial. Patients with Positive and Negative Syndrome Scale (PANSS) negative subscale score ≥21, which was higher than their PANSS positive subscale score, were included in this subanalysis. Improvement in negative symptoms was measured by assessing change in the PANSS negative subscale and a negative factor score. Additional outcome variables included measures in general functioning, quality of life and patient satisfaction. A total of 842 patients were eligible for inclusion in this subanalysis. Six months of treatment was completed by 631 (74.9%) patients. Forty-three (5.1%) patients discontinued treatment due to an adverse event. Negative symptoms were significantly reduced by 6.1 ± 6.3 points for the PANSS negative score and 6.1 ± 6.4 points for the negative factor score ( P < 0.0001 for both). Significant improvements were also noted for total PANSS and other PANSS subscale scores, general functioning, quality of life and patient satisfaction ( P < 0.0001). The most common treatment-emergent adverse events (>5%) were: anxiety (6.8% of patients), exacerbation of disease (6.2%) and insomnia (5.7%). Overall, RLAI was well tolerated and associated with significant reductions in movement disorder severity. The treatment resulted in a significant improvement in negative symptom severity and was well tolerated in patients with predominantly negative symptoms, who switched from a stable antipsychotic regimen.

Smooth pursuit eye movements (SPEM) were examined in 67 schizophrenic patients and 101 control subjects. Our study confirms that eye tracking in schizophrenic patients is impaired compared to that in controls. The similar pattern of distribution of SPEM abnormalities in Italian patients as in ethnically different populations strengthens the hypothesis that these abnormalities may be a biological marker for schizophrenia. We also examined the relationship between SPEM abnormalities and the ventricle-brain ratio (VBR), which is also considered useful for differentiating schizophrenic subgroups. Our preliminary results indicate that there is an inverse correlation between abnormal SPEM performance and ventricular enlargement, suggesting that these abnormalities mark distinct subgroups of patients.

SummaryA group of 33 schizophrenic patients were typed for HLA-SD antigens and their qualitative clinical responses to chlorpromazine therapy determined. A highly significant positive correlation was found between response to chlorpromazine and HLA-A1 positive, while HLA-A2 positive subjects showed a significant negative correlation to chlorpromazine treatment.In a second group of 17 patients the clinical responses to chlorpromazine were evaluated quantitatively, by WPRS, in HLA-A1 positive and HLA-A1 negative patients. There were no pre-treatment differences in the scores. After treatment the scores of positive patients were significantly lower, indicating that they responded to a greater degree.Since the frequency of HLA-A1 in hebephrenic patients is higher than that in other schizophrenics this may explain our earlier finding that hebephrenics, as a group, respond better to chlorpromazine than do other schizophrenics.

HLA phenotype distribution was investigated in 91 affective patients. Significant increases over those of the control population were found in HLA-A 29 and in Bw 22 frequencies, while A 10 and A 30 were decreased. No significant difference was shown between the two clinical subgroups (41 unipolar patients and 50 bipolar ones). On comparing our data with those from other authors, Bw 16 was significantly increased. However, a high degree of heterogeneity was also shown for this antigen. Of some interest is the finding that relapsed and non-relapsed patients during long-term lithium therapy display diverging HLA phenotype distributions, with B 5 increased among the non-relapsed subjects.

Plasma levels of β-endorphin (β-EP), β-lipotropin (β-LPH) and ACTH were assayed in 15 chronic schizophrenics, nine patients with primary affective disorders (PAD) and seven patients with secondary affective disorders (SAD). Patients received no therapy for 10 days prior to study. All subjects were studied once; eight schizophrenics were studied again after 10 days of Haloperidol therapy, at a dose of 0.1 mg/kg body weight. β-LPH levels were significantly higher in the schizophrenics without hallucinations and in the PAD and SAD patients in comparison to the controls; β-EP levels were higher in the schizophrenics and SAD patients compared to the controls; and ACTH concentrations were significantly lower in the SAD than in the PAD patients. Haloperidol therapy failed to induce significant changes in β-LPH, β-EP or ACTH plasma levels. Statistical evaluation by multiple linear regression confirmed the significant positive correlations among β-LPH, β-EP and ACTH in the controls, schizophrenics with hallucinations, and PAD and SAD patients, while inverse correlations between β-LPH and the other two peptides were found in the schizophrenics without hallucinations. The same analysis revealed that, while in the PAD patients equimolar amounts of the three peptides occurred, the SAD patients were characterized by ACTH/β-LPH and ACTH/β-EP molar ratios of 0.5. Although these results are preliminary, they seem to indicate that β-LPH, β-EP and ACTH secretion patterns in chronic schizophrenia, PAD and SAD may help in revealing specific groups of patients with different biochemical substrates.

Alpha EEG reactivity was assessed in a carefully diagnosed sample of 84 schizophrenic and schizophrenic spectrum disorder patients, both under resting conditions (eyes closed and eyes open) and during two spatial-geometric cognitive tasks. The influence of the subject's demographic (sex and age), clinical (diagnostic subtypes, disease course, CT scan characteristics) and neurophysiological (hemispheric recording and different cognitive tasks) characteristics on alpha peak reactivity was analyzed by means of multivariate analysis of variance. The results indicated a significant effect of type of illness on alpha EEG reactivity, patients with a diagnosis of undifferentiated and disorganized schizophrenia having the lowest alpha reactivity levels. None of the other variables considered had any contributing effect. The results are discussed in terms of orienting responses and hemispheric CNS organization in functional psychoses. OI scarone, silvio/0000-0001-7187-3747 ZS 0 Z8 1 ZR 1 Alpha EEG reactivity was assessed in a carefully diagnosed sample of 84 schizophrenic and schizophrenic spectrum disorder patients, both under resting conditions (eyes closed and eyes open) and during two spatial-geometric cognitive tasks. The influence of the subject's demographic (sex and age), clinical (diagnostic subtypes, disease course, CT scan characteristics) and neurophysiological (hemispheric recording and different cognitive tasks) characteristics on alpha peak reactivity was analyzed by means of multivariate analysis of variance. The results indicated a significant effect of type of illness on alpha EEG reactivity, patients with a diagnosis of undifferentiated and disorganized schizophrenia having the lowest alpha reactivity levels. None of the other variables considered had any contributing effect. The results are discussed in terms of orienting responses and hemispheric CNS organization in functional psychoses.

Cortical gray matter deficits have been found in patients with schizophrenia, with evidence of progression over time. The aim of this study was to determine the extent of progressive cortical gray matter volume changes over time in schizophrenia, their site and time of occurrence, and the role of potential moderators of brain changes. English language articles published between 1 January 1983 and 31 March 2012 in the MEDLINE and EMBASE databases were searched. Longitudinal magnetic resonance imaging studies comparing changes in cortical gray matter volume over time between patients with schizophrenia and healthy controls were included. Hedges g was calculated for each study. Analyses were performed using fixed- and random-effects models. A subgroup analysis was run to explore the pattern of brain changes in patients with first-episode schizophrenia. A meta-regression statistic was adopted to investigate the role of potential moderators of the effect sizes (ESs). A total of 19 studies, analyzing 813 patients with schizophrenia and 718 healthy controls, were included. Over time, patients with schizophrenia showed a significantly higher volume loss of total cortical gray matter, left superior temporal gyrus (STG), left anterior STG, left Heschl gyrus, left planum temporale and posterior STG bilaterally. Meta-analysis of first-episode schizophrenic patients showed a more significant pattern of progressive loss of whole cerebral gray matter volume involving the frontal, temporal and parietal lobes, and left Heschl gyrus compared with healthy controls. Clinical, pharmacologic and neuroradiological variables were found to be significant moderators of brain volume changes in patients with schizophrenia. The meta-analysis demonstrates that progressive cortical gray matter changes in schizophrenia occur with regional and temporal specificity. The underlying pathological process appears to be especially active in the first stages of the disease, affects the left hemisphere and the superior temporal structures more and is at least partly moderated by the type of pharmacological treatment received.