Negative symptom severity at discharge from an index hospitalization and subsequent use of psychiatric care resources: A retrospective 1-year follow-up study on 450 patients with schizophrenia spectrum disorders.

Negative symptoms of schizophrenia have a great impact on patients' functioning and are among the most important contributors to subject's disability. However, few studies have assessed the role of type and severity of symptomatology of schizophrenia on the psychiatric care resource utilization. We investigated if the clinical profile of patients at discharge from an index hospitalization might be associated with a different use of psychiatric care resources in the subsequent 1-year period in a large population of patients with schizophrenia spectrum disorders. Clinical records of 450 patients with schizophrenia spectrum disorders admitted in an acute psychiatric inpatient service and subsequently followed in the outpatient services of the same Department were reviewed. Patients with more severe negative symptoms at discharge from hospital showed a higher number and duration of hospitalizations in the 1-year follow-up, as well as a higher number of rehabilitative residential admissions than patients with milder severity of negative symptoms. The same was true for patients with predominant negative symptoms. A global resource utilization index indicated a higher use of psychiatric resources in patients with higher severity of negative symptoms. In conclusion, showing moderate to severe negative symptoms versus positive symptoms at discharge from a hospitalization for an acute exacerbation of schizophrenia spectrum disorder does predict a higher use of psychiatric care resources. This underlines the importance of relieving negative symptoms even in the acute phase of treatment and the need to develop more effective treatments for this symptom dimension.

The GRM7 gene, early response to risperidone, and schizophrenia: a genome-wide association study and a confirmatory pharmacogenetic analysis.

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.

Social cognition in people with schizophrenia: a cluster-analytic approach.

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 <10), but not in simple sarcasm. Moreover, functioning, neurocognition, disorganization and SC had a linear relationship across the three clusters, while positive symptoms were significantly lower in patients with unimpaired SC as compared with patients with impaired and very impaired SC. On the other hand, negative symptoms were highest in patients with impaired levels of SC. CONCLUSIONS: If replicated, the identification of such subtypes in clinical practice may help in tailoring rehabilitation efforts to the person's strengths to gain more benefit to the person.

Patterns of brain structural changes in first-contact, antipsychotic drug-naive patients with schizophrenia.

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-naïve patients with schizophrenia. MATERIALS AND METHODS: A total of 43 first-contact, drug-naïve, 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-naïve, 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.

Progressive loss of cortical gray matter in schizophrenia: a meta-analysis and meta-regression of longitudinal MRI studies.

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.

Psychopathologic, neuropsychological and functional outcome measures during cognitive rehabilitation in schizophrenia: a prospective controlled study in a real-world setting.

BACKGROUND: Cognitive 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. OBJECTIVE: To 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. METHODS: Thirty-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. RESULTS: The 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. CONCLUSIONS: The 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.

Neuroanatomy of vulnerability to psychosis: a voxel-based meta-analysis.

BACKGROUND: Individual structural imaging studies in the pre-psychotic phases deliver contrasting findings and are unable to definitively characterize the neuroanatomical correlates of an increased liability to psychosis and to predict transition to psychosis. METHOD: Ninenteen voxel-based morphometry (VBM) studies of subjects at enhanced risk for psychosis and healthy controls were included in an activation likelihood estimation (ALE) meta-analysis. RESULTS: The overall sample consisted of 701 controls and 896 high risk subjects. Subjects at high risk for psychosis showed reduced gray matter (GM) volume as compared to controls in the right superior temporal gyrus, left precuneus, left medial frontal gyrus, right middle frontal gyrus, bilateral parahippocampal/hippocampal regions and bilateral anterior cingulate. High risk subjects who later developed a psychotic episode showed baseline GM volume reductions in the right inferior frontal gyrus and in the right superior temporal gyrus. CONCLUSIONS: GM volume reductions in temporo-parietal, bilateral prefrontal and limbic cortex are neuroanatomical correlates of an enhanced vulnerability to psychosis. Baseline GM reductions in superior temporal and inferior frontal areas are associated with later transition to psychosis.

Long-acting risperidone improves negative symptoms in stable psychotic patients.

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 > or = 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

Long-term remission in schizophrenia and related psychoses with long-acting risperidone: results obtained in an open-label study with an observation period of 18 months.

OBJECTIVE: To monitor long-term symptomatic tolerability and remission in patients with stable but suboptimally treated psychoses after switching to risperidone long-acting injectable (RLAI). METHOD: This subgroup analysis of the Switch to Risperidone Microspheres (StoRMi) open-label trial followed up patients with psychoses who were converted to RLAI for a period of 18 months or until RLAI became commercially available in their country of residence. It included patients from seven European countries. Dosage adjustments were performed as clinically necessary. The efficacy endpoint was achieving and maintaining remission, defined as absent to mild core schizophrenia symptoms for > or = 6 months. A schizophrenia assessment was also completed and patients were monitored for the development of adverse events (AEs). Discontinuation rates were calculated based on Kaplan-Meier estimates where patients switching to commercial RLAI were used as censored observations. RESULTS: A total of 529 patients were followed for up to 18 months. At 18 months, the discontinuation rate was 55.7% based on Kaplan-Meier estimates. The median time to discontinuation was 15.7 months (95% CI (14.0; 17.5)). RLAI was generally well tolerated with most AEs mild-to-moderate in severity. 13% of patients discontinued treatment because of an AE. Body weight of patients increased by a mean A+/- SD of 1.0 A+/- 6.1 kg from treatment initiation to endpoint (p = 0.0001). Glucose-related AEs occurred in four patients (0.8%). Among those patients not meeting severity remission criteria at baseline, 44.8% were in remission at endpoint. Among those patients meeting severity criteria for remission at baseline, 84.2% were in remission at endpoint. A total of 93.7% of the patients who achieved or maintained remission at 6 months were in remission at endpoint. CONCLUSIONS: RLAI is safe during long-term treatment up to 18 months in adults requiring antipsychotics. Conversion to RLAI resulted in improved symptom control. Most patients achieved and maintained a sustained remission (> or = 6 months) after conversion to RLAI.

Direct transition to long-acting risperidone--analysis of long-term efficacy.

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 < or =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< or =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 < or = 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.

Quetiapine, clozapine, and olanzapine in the treatment of tardive dyskinesia induced by first-generation antipsychotics: a 124-week case report.

Our report of a patient with severe tardive dyskinesia (TD) who has been exposed to both typical antipsychotic and clozapine, olanzapine and quetiapine during a 124-week follow-up period supports the possible beneficial effect of atypical antipsychotics on pre-existing symptoms of TD. Persistently high AIMS scores during all the periods of treatment with typical antipsychotics contrast strongly with the drop in scores that occurs in strict chronological sequence after switching to both clozapine (45%), olanzapine (27.8%) and quetiapine (85%). Since the reversal to haloperidol from the three atypical agents was systemically associated with a return to high AIMS scores, it seems likely that the improvement noted with clozapine, olanzapine and quetiapine represents a temporary symptomatic effect rather than a sustained resolution of the disorder. The olanzapine-clozapine-quetiapine rank order of increasing effectiveness against TD symptoms suggests that this property, although shared by the atypical antipsychotics, is to some degree drug-specific. Patient- and/or drug-dependent mechanisms may be involved in this gradient of effect.

Depressive disorders and personality variables in HIV positive and negative intravenous drug-users.

BACKGROUND: Only a few reports investigated the prevalence of depression in intravenous drug-users with HIV infection, including both asymptomatic and symptomatic subjects. In the same group, the association of depression and personality diagnoses was also poorly researched. METHODS: A consecutive sample of intravenous drug-users was collected from patients admitted to an infectious disease clinic, another random sample was taken from out-patients attending a methadone maintenance treatment program. Subjects were first screened with the Hospital Anxiety and Depression Scale, and then all positive subjects were evaluated with the Composite International Diagnostic Interview. Depression was diagnosed according to DSM-IIIR. In-patients were also given a structured personality inventory (Karolinska Psychodynamic Profile). RESULTS: HIV-positive patients had a high rate of depression (major depression 36.2%, dysthymic disorder 7.1%) when compared to HIV-negatives (15.7 and 3.9%, respectively). In-patients had the highest rate of depression, irrespective of HIV clinical staging. A personality disorder was diagnosed in 36% of the sample, but these subjects were no more significantly depressed. LIMITATIONS: Poor detection of depression by the admitting physician may have led to selective hospitalization of patients with both HIV and mood disorder. The composition of the sample may also be biased by the help-seeking behavior of HIV patients who are also depressed. CONCLUSION: Physicians treating AIDS patients should be alerted to the high rate of depression in clinical HIV illness, in order to identify and properly treat depression.

Cytokine profiles in drug-naive schizophrenic patients.

A large body of evidence concerning immunological abnormalities in schizophrenic patients seems to suggest a role of the immune system in the multifactorial pathogenesis of schizophrenia. We investigated the production of various cytokines [interleukin (IL)-2, IL-4, IL-10, interferon (INF)-gamma] in drug-free (n=26) and drug-naive (n=7) schizophrenic patients and in healthy controls (n=33). Production of IL-2 and INF-gamma was significantly higher (respectively P=0.021 and P=0.001) in patients than in controls. These findings provide further evidence that immunological abnormalities are present in some schizophrenic patients.

H(2) antagonist nizatidine may control olanzapine-associated weight gain in schizophrenic patients.

BACKGROUND: Olanzapine is temporally associated, in a number of patients with schizophrenia, with weight gain. H(2) antagonists, like nizatidine, have been shown to control appetite in overweight patients. METHODS: A patient with olanzapine temporally associated weight gain was treated with nizatidine as "add-on" therapy. RESULTS: Nizatidine treatment was associated with good control and subsequent reduction of weight after 4 to 5 weeks of therapy in a patient with repetitive episodes of weight gain during olanzapine treatment. Olanzapine was otherwise well tolerated and effective in controlling psychopathology. CONCLUSIONS: H(2) antagonist treatment with olanzapine may be a valid medical strategy in preventing and/or reducing weight gain in patients with schizophrenia. Controlled studies are recommended to confirm this observation.

Variables associated with the hospitalization of psychiatric emergencies evaluated in the community.

We investigated hospitalization factors in acutely ill patients visited by psychiatrists at home. A series of 100 consecutive calls for psychiatric emergencies of a community mental health centre were investigated with a structured evaluation of psychiatric symptoms and aggressiveness (IEF, GAS, and VSAS). First order interactions were tested, and selected variables were tested with logistic regression analysis. Admission was significantly associated with GAS scores (low scores were found in 92.6% of admitted patients vs. 43.8% of patients not admitted), paranoid delusions (66.7 vs. 39.7%), and lack of social support (70.4 vs. 30.1%). Multivariate analysis confirmed a significant independent effect only for low GAS score and lack of social support. The study replicated some findings from research on hospitalization in emergency wards, while other factors, such as 'diagnosis' and 'suicide risk', were not significant.