Population Of Schizophrenia Patients Research Articles

The moderating effect of mindfulness on self-defeatist beliefs and negative symptoms in a population of chronic schizophrenia patients in Taiwan

The moderating effect of mindfulness on self-defeatist beliefs and negative symptoms in a population of chronic schizophrenia patients in Taiwan

Conversational metrics, psychopathological dimensions and self-disturbances in patients with schizophrenia.

Difficulties in interpersonal communication, including conversational skill impairments, are core features of schizophrenia. However, very few studies have performed conversation analyses in a clinical population of schizophrenia patients. Here we investigate the conversational patterns of dialogues in schizophrenia patients to assess possible associations with symptom dimensions, subjective self-disturbances and social functioning. Thirty-five schizophrenia patients were administered the Positive and Negative Syndrome Scale (PANSS), the Clinical Language Disorder Rating Scale (CLANG), the Scale for the Assessment of Thought, Language and Communication (TLC), the Examination of Anomalous Self-Experience Scale (EASE), and the Social and Occupational Functioning Assessment Scale (SOFAS). Moreover, participants underwent a recorded semi-structured interview, to extract conversational variables. Conversational data were associated with negative symptoms and social functioning, but not with positive or disorganization symptoms. A significant positive correlation was found between "pause duration" and the EASE item "Spatialization of thought". The present study suggests an association between conversational patterns and negative symptom dimension of schizophrenia. Moreover, our findings evoke a relationship between the natural fluidity of conversation and of the natural unraveling of thoughts.

Toxoplasmosis Is More Frequent in Schizophrenia Patients Than in the General Population in Mexico and Is Not Associated with More Severe Course of Schizophrenia Measured with the Brief Psychiatric Rating Scale.

Toxoplasmosis is a disease, which was discovered in 1908, caused by the intracellular parasite Toxoplasma gondii. T. gondii infects neuronal, glial, and muscle cells, and chronic infections are characterized by the presence of cysts, in the brain and muscle cells, formed by bradyzoites. T. gondii is capable of synthesizing L-DOPA, a precursor of dopamine. Dopamine is a neurotransmitter that is key in the etiology of neuropsychological disorders such as schizophrenia. Previous studies have shown high levels of IgG Toxoplasma antibodies in schizophrenia patients. Many published studies show that the prevalence of toxoplasmosis is higher in schizophrenia patients. In this study, we aimed to identify the prevalence of Toxoplasma infection in patients with schizophrenia and the relationships between, sociodemographic factors and the Brief Psychiatric Rating Scale. A total of 27 schizophrenic patients were included and IgG anti-T. gondii was determined in serum samples by ELISA. The Brief Psychiatric Rating Scale, sociodemographic factors were associated with seropositivity. We found that the prevalence of Toxoplasma antibodies was 51.7%. In the Brief Psychiatric Rating Scale, statistical significant association (p = 0.024) was found in Item 13 which is related to motor retardation, however, the association turned non-significant after of correction for multiple tests or after of analyzed with a logistic regression p = 0.059, odds ratio (OR) = 2.316 with a 95% confidence interval [0.970 to 5.532]. Other association was not found between toxoplasmosis and others factors. The prevalence of toxoplasmosis on our population under study was significantly higher than that reported by general population or other group of Mexican schizophrenia patients.

M10. SERUM AND CLINICAL MARKERS ASSOCIATED WITH MEMBRANE PUFA CONTENT IN A POPULATION OF STABILISED AND TREATED SCHIZOPHRENIA OUTPATIENTS

BackgroundVarious candidate biomarkers have been proposed in schizophrenia to better characterise the several forms of the disorder. Among these candidates, peripheral (e.g. immunological, inflammatory, microbial) and brain (structural and functional) factors have been suggested and could help subtyping schizophrenia. One other potential biomarker, the membrane polyunsaturated fatty acid (PUFA) content, has been described both in peripheral cells and brain membranes of patients. Increased symptom severity along with more severe cognitive impairment were shown to be associated with decrease in the red blood cell (RBC) membrane sphingomyelin and PUFA content. However, little is known regarding the association between this membrane biomarker and serum related ones.The results presented here are preliminary and come from a study examining clinical and cognitive symptoms, RBC total membrane fatty-acid (FA) content, and serum biomarkers in a population of schizophrenia patients.We hypothesised that the sub-group of patients with decreased membrane PUFA content will also exhibit a higher incidence of abnormalities in some other serum biomarkers in comparison with patients with normal membrane PUFA content.MethodsA population of 33 chronic, medicated, and clinically stable patients with schizophrenia gave their informed consent for a study examining in particular their medical, psychiatric, and treatment history. The other measures assessed psychopathology (PANSS, CGI, Calgary scale), functioning and quality of life (GAF, SF36), and cognition (MOCA, MCST). Various biological biomarkers - in particular those related to inflammation, immunity, energy and hormone metabolism - were also examined. The total RBC membrane FA content was also measured using GC-FID (Gas Chromatography–Flame-Ionization Detection).ResultsBased on the standard values of the docosohexaenoic acid (DHA) (expressed as percentage of total fatty acids) in the RBC lipid membrane, a subgroup of 18 patients exhibited an abnormal decrease in DHA content (DHA-), while the remaining 15 individuals had DHA value within the normal range (DHAn). DHA- and DHAn groups were compared using univariate analysis in terms of other clinical and biological associated characteristics.We could also demonstrate a decrease in total membrane PUFAs in the DHA- group (p=0.004). Of interest, serum IL-6 was significantly (p=0.02) increased in the DHA- population. There was also a trend in favour of an increase in serum TNF-alpha in DHA- (mean value 30.5 vs 21 in DHA- and DHAn, respectively). In addition, the DHA- group have had significantly (p=0.03) more hospitalisations since the beginning of the disorder. The duration of untreated psychosis was 4 years vs 1 year in the DHA- vs DHAn groups, respectively. The same applied for the mean duration of hospitalisations (45 vs 34 days in DHA- vs DHAn). These values could not be explained by a longer duration in disease treatment in the 2 subpopulations.DiscussionThe presented data are in accordance with repeated findings showing decreased RBC membrane DHA and total PUFA content in a subgroup of individuals meeting criteria for schizophrenia. The splitting of the studied population into 2 groups numerically comparable as a function of their RBC membrane DHA content was thus justified. Interestingly, patients with lower membrane DHA content also exhibited abnormalities in other known biomarkers described in schizophrenia such as increased inflammation and disease severity. The presented data also show for the first time a biomarker associated with the duration of untreated psychosis. Altogether, these results, despite preliminary, are paving the way towards the identification of schizophrenia subtypes.

Copy number variant syndromes are frequent in schizophrenia: Progressing towards a CNV-schizophrenia model

The genetic underpinnings of schizophrenia (SCZ) remain unclear. SCZ genetic studies thus far have only identified numerous single nucleotide polymorphisms with small effect sizes and a handful of copy number variants (CNVs). This study investigates the prevalence of well-characterized CNV syndromes and candidate CNVs within a cohort of 348 SCZ patients, and explores correlations to their phenotypic findings. There was an enrichment of syndromic CNVs in the cohort, as well as brain-related and immune pathway genes within the detected CNVs. SCZ patients with brain-related CNVs had increased CNV burden, neurodevelopmental features, and types of hallucinations. Based on these results, we propose a CNV-SCZ model wherein specific phenotypic profiles should be prioritized for CNV screening within the SCZ patient population.

F64. DISRUPTION IN WORKING MEMORY GATING OBSERVED IN SCHIZOPHRENIA

BackgroundWorking memory and cognitive control deficits are hallmarks of schizophrenia. It is not known specifically how gating mechanisms that regulate memory may be disrupted in schizophrenia. Gating mechanisms determine what task-relevant information is selected into working memory while distractors are left out (input gating) and which items stored in working memory are selected for the rule or goal at hand (output gating). The current study investigated whether patients are able to perform the same cognitive control task that is able to dissociate input and output gating processes in a general population, and explored whether schizophrenia patients inappropriately use suboptimal cognitive control strategies (e.g. output gating when input gating can be used).MethodsPatients (n=5) with schizophrenia or schizoaffective disorder were recruited from the Providence VAMC. Participants completed a computer-based cognitive control task. In this task, participants remembered a target item from a sequence of two items in order to select a response. A context (rule) cued which item was relevant to remember, and was presented first in the stimulus sequence (context first) or last (context last). On selective trials, one item in the trial was relevant. On global trials, both items in the trial were relevant.ResultsPatients were able to complete the task with minor modifications to adjust for ability to understand the task rules. Preliminary results of reaction time data suggest that patients were challenged at increased cognitive load. Patients performed poorly on trials where participants could use only an input gating strategy (selective first). Preliminary data also suggest that performance in patients tended to be slightly worse for selective first trials where the distractor was presented before the relevant item (i.e. on trials where input gating would be required to keep the distractor out of working memory).DiscussionThe current study supports the feasibility of using the cognitive control task selected to investigate gating mechanisms in the schizophrenia patient population. Preliminary data suggest disruption in the ability for patients to optimally use gating strategies and handle cognitive load. Future research will seek to reproduce these preliminary results in a larger sample, as well as compare patient performance to an age-matched control population directly. By understanding how gating mechanisms are disrupted in the patient population, we may be able to better develop therapeutic interventions such as cognitive training strategies to treat cognitive dysfunction in schizophrenia patients.

Correlation Between Serum Concentrations of N-Desmethylclozapine and Granulocyte Levels in Patients with Schizophrenia: A Retrospective Observational Study.

Clozapine is restricted to use in patients with treatment-refractory schizophrenia due to the risk of a serious drop in absolute neutrophil granulocyte count (ANC). The formation of reactive, unstable metabolites (adducts) has been suggested as a mechanism of clozapine-induced granulocyte decline. These adducts are not detectable in vivo, but stable clozapine metabolites could potentially be indirect pharmacokinetic measures of adduct formation. The present retrospective observational study investigated the correlation between concentrations of N-desmethylclozapine, the major stable clozapine metabolite, and ANC in a real-life population of clozapine-treated patients. Patients were includedfrom a therapeutic drug monitoring service at the Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway, between March 2005 and December 2015. Information about clozapine and N-desmethylclozapine steady-state trough concentrations, as well as accompanying measurements of ANC, were collected from the laboratory database. Correlations of serum concentrations of N-desmethylclozapine and clozapine (and their respective ratios) with ANC were investigated by linear mixed-model analysis. Overall, 129 patients with 855 measurements of clozapine/N-desmethylclozapine concentrations and ANC (range 0.9-19×109 cells/L, median 4.6) were included. Concentrations of N-desmethylclozapine, but not clozapine, correlated significantly and positively with ANC (estimated model slope 0.0011×109 cells/L/nM; p=0.002), and the N-desmethylclozapine/clozapine ratio also positively correlated with ANC (p=0.040). N-Desmethylclozapine level and ANC significantly correlated in this real-life population of schizophrenia patients. The positive correlation, which was also present for the metabolic ratio, might reflect reduced clozapine availability for the formation of reactive metabolites potentially affecting granulocyte level. However, as our findings were based on ANC mainly within the reference range, this hypothesis should be studied further in clozapine-treated patients with neutropenia or agranulocytosis.

PRM8 - Development of a Systematic Review Search Filter to Identify Medication Adherence Studies

Search filters or hedges are commonly used in systematic reviews to identify studies fulfilling specific criteria. Currently, there are no published filters that focus on identifying studies specific to patients’ medication-taking behavior, i.e. adherence, compliance or persistence. This research aims to develop and validate a medication adherence filter using schizophrenia as a case example. Published literature reviews assessing adherence in schizophrenia were identified from years 2000 to present in the English language, and were used as a reference. A filter search strategy was developed for adherence concepts using the titles of references identified in the reviews. This filter was used to search for medication adherence studies in schizophrenia in MEDLINE and Embase. This process was reiterated until studies included in the reference review articles were captured. 21 published reference review articles were found on schizophrenia and adherence, which cited a total of 180 relevant studies. In the first iteration of the search strategy using the adherence filter, 142 studies were identified, thus capturing 79% of studies included in the reference reviews. After further revision and assessment of the missing articles, the final search filter was able to identify 89% of the reference articles. To our knowledge, this is the most comprehensive filter validation exercise for adherence at this time. The proposed filter was shown to be sensitive in the schizophrenia patient population and may be adapted to other disease areas after further testing.

Prevalence of neuroleptic-induced movement disorders: an 8-year follow-up study in chronic schizophrenia inpatients

Background: Atypical antipsychotic drug use by schizophrenia patients in Estonia increased from 32% in 2004 to 61% in 2009.Aims: To assess the prevalence of neuroleptic-induced movement disorders in the Estonian institutionalized population of schizophrenia patients twice over a period of eight years, before and after introduction of atypical antipsychotic drugs using DSM-IV criteria.Methods: DSM-IV criteria and specific rating scales were used to evaluate the prevalence of neuroleptic-induced movement disorders among 72 patients who participated in the study in 2009 compared to 99 patients who participated in 2001.Results: Despite increased use of atypical antipsychotics in the study population (up to 30% from 20%), the proportion of movement disorder-free population remained the same over 8 years – 38.9% in 2001 versus 38.4% in 2009. There were significant intra-individual fluctuations. Use of a typical antipsychotic resulted in an almost seven times higher risk of tardive dyskinesia after 8 years. Doses of antipsychotic drugs had no effect on the severity of neuroleptic-induced movement disorders.Conclusions: Unfortunately, in 18% of patients the switch of medication from typical to atypical did not change the overall prevalence of neuroleptic-induced movement disorders in the group. The long-term benefit of atypical antipsychotics requires further research in patients who are treated with antipsychotics for years.

Lack of association between catechol-Omethyltransferase and schizophrenia in a Turkish population

Abstract Objective: Catechol-O-methyltransferase (COMT) is the key molecule in the catabolism of catecholamines like dopamine which is an important molecule in schizophrenia. Due to its function and location COMT gene is a strong candidate gene for schizophrenia. The aim of this study was to investigate the possible associations of 3 COMT single nucleotide polymorphisms (SNPs) and schizophrenia in our population. COMT enzyme activity is regulated by a widely known Val158Met polymorphism (rs4680), along with the variation of the SNPs rs737865 and rs165599. Methods: Val158Met polymorphism (rs4680), the SNPs rs737865 and rs165599 were the targets of this study. The study was performed with 96 patients (66 male and 30 female) and 100 controls (47 male and 53 female) from Malatya region on eastern part of Turkey by using TaqMan genotyping assays. Results: We couldn’t find a significant difference between the schizophrenia patients and normal controls for any of the SNPs that were studied. The genotype frequencies in both the patient and control groups satisfied the Hardy- Weinberg equilibrium. No significant gender differences were observed for the SNPs that were investigated. No significant difference was observed in the allele or genotype frequencies as well. Conclusion: COMT gene doesn’t appear to be a risk factor in this population of schizophrenia patients in Turkey.

Comparative Study of Insight and Medication Adherence in Schizophrenia and Bipolar Disorder.

Insight is defined as the recognition that one has a mental disorder, the ability to identify its symptoms, and cognizance of the need for treatment. Lack of insight into having a mental disorder is found to be associated with a poorer clinical outcome, treatment noncompliance, and a more severe cognitive impairment. Compare the insight and medication adherence in a population of schizophrenia and bipolar disorder patients. We assessed and compared the insight and compliance of 60 patients with schizophrenia (n=30) and bipolar disorder (n=30) recruited in Psychiatry department Sfax, Tunisia. Insight was assessed using the rating scale of consciousness disorder (Q8). Adherence was assessed using the Drug Attitude Inventory [ICD-10]. Patients were mainly young adults, male (70%) and did not live in a couple (61.7%). About half of them (43.3%) had no profession. Insight was low in 15% of patients, intermediate in 53.3%, and good in 31.7% of cases. Bipolar disorder patients displayed better insight into having a mental disorder compared to schizophrenia patients (p=0.04) Good adherence was observed in 64.4% of patients. Factor influencing adherence in both populations was the type of treatment: patients treated with atypical antipsychotics have better compliance (p = 0.005). A good insight was significantly correlated with good adherence (p = 0.000) Our results showed that bipolar disorder patients have better insight compared to schizophrenia patients. So it is necessary; in schizophrenia; to work on awareness of the disorder and the need for treatment to improve adherence.

Early psychosis intervention services: a work in progress.

Early psychosis intervention services: a work in progress.

Neurological soft signs with respect to type of symptoms in patients with schizophrenia

Introduction Neurological soft signs have been documented to occur in up to 60% of patients with schizophrenia and have been found even in neuroleptic-naive patients. Aims The aims of the study were to illustrate the presence of neurological soft signs among patients with schizophrenia and to show any relationship between neurological soft signs and type of symptoms. Patients and methods One hundred patients with schizophrenia were selected consecutively in a cross-sectional study. The patients were assessed using the Structured Clinical Interview for Diagnostic and statistical manual of mental disorders (DSM) Axis of Disorders, Positive and Negative Syndrome Scale, complete neurological examination, and Cambridge Neurological Inventory for soft sign examinations (primitive reflexes, repetitive movement, sensory integration), and Trail Making Test. Results The main finding in this study indicates that the patients with schizophrenia have neurological impairment. There are positive correlations between soft neurological signs and positive symptoms in paranoid type, other types, and with the total; these indicate that neurological soft signs are more prominent in patients with positive symptoms than in those with negative symptoms. Conclusion Neurological Soft Signs (NSS) occur in a majority of the schizophrenia patient population and are largely distinct from symptomatic and cognitive features of the illness. Neurological signs in patients with schizophrenia are associated with prominent negative symptoms, relatively poor psychosocial performance, and significantly more cognitive impairment.

The effects of cognitive remediation on functional outcomes among people with schizophrenia: A randomised controlled study

Cognitive remediation is an intervention to overcome cognitive deficits through drills and use of strategies. Previous studies have reported positive effects for cognitive remediation on neurocognition, but researchers' allegiance effects are not always adequately controlled. Furthermore, its efficacy amongst the Asian population has not been established. Hence, this study aimed to determine if cognitive remediation would have positive effects on neurocognition and functioning within an English-speaking Asian population, when compared against the effects of a credible and balanced control provided by therapists blinded to the study hypothesis. A total of 70 participants with schizophrenia who attended vocational training or day rehabilitation programmes were randomised to receive a 60-hour programme of either cognitive remediation or physical exercise. Neurocognition and functional outcomes were measured at baseline, upon completion of treatment, 6 months after treatment and 1 year after treatment. Participants who received cognitive remediation had significantly greater improvement in all neurocognitive domains. Furthermore, the cognitive remediation group achieved greater attainment of vocational or independent living skills and better functional outcomes at post-intervention and at the end of the 1-year follow-up. When compared against a credible intervention such as physical exercise, cognitive remediation was able to show significant positive effects on both neurocognition and functional outcomes among the Asian population of schizophrenia patients.

Subjective quality of life and its determinants in a catchment area based population of elderly schizophrenia patients

BackgroundSubjective quality of life (SQOL) is an established outcome measure in schizophrenia. In spite of the substantial proportion of elderly in the total schizophrenia population, evaluation of their SQOL and its determinants has been scarce and findings from epidemiological samples are lacking. MethodsWe assessed SQOL in elderly Dutch patients with schizophrenia or schizoaffective disorder (n=107; mean age 68years), treated within a psychiatric catchment area. Demographic, clinical and social variables were evaluated for their impact on SQOL. ResultsThe mean SQOL score was 4.83, moderately surpassing the midpoint of the SQOL scale. Nearly half of all patients (47.7%) reported an overall favorable SQOL. Of the total variance in SQOL, clinical variables explained 50%, and social variables explained 16%, while demographic factors did not contribute. In multivariable analysis, less self-reported depressive symptoms, worse global neurocognition, and higher observer-based level of social functioning significantly predicted a higher SQOL, explaining 53% of the total variance. ConclusionThe relatively high level of SQOL in this epidemiological sample of elderly patients is in line with what has been reported for both older and younger schizophrenia populations. Depressive symptoms are a robust predictor of SQOL in late life schizophrenia, clearly outweighing psychotic symptoms. This finding has major clinical relevance, as depression is amenable to therapeutic intervention.

Increased level of serum cytokines, chemokines and adipokines in patients with schizophrenia is associated with disease and metabolic syndrome

At present there are strong indications of a shared vulnerability factor for schizophrenia (SZ), diabetes and the metabolic syndrome (metS). In this study we focus on an aberrantly activated monocyte/macrophage system as the shared factor. We measured in SZ patients (n=144), the serum levels of monocyte/macrophage cytokines/chemokines/adipokines CCL2, CCL4, IL-1β, TNF-α, IL-6, PTX3, leptin, adiponectin, PAI-1, OPG and ICAM-1 and compared these levels to healthy controls (HC) (n=138). Using multivariate analysis, we studied the effect of the presence of the disease SZ, the components of the metS including BMI, the levels of lipids (HDL cholesterol and triglycerides (TG)), diabetes (hyperglycemia) and the use of antipsychotic medication, on the serum levels of these immune compounds. We found all measured immune compounds with the exception of PAI-1 and OPG to be elevated in the SZ patient population. Multivariate analysis showed that elevations were linked to gender (ICAM-1, leptin, TNF-α and adiponectin), an increased BMI (leptin, adiponectin), hyperglycemia/diabetes (CCL4, and OPG), reduced HDL-cholesterol or increased levels of TG (adiponectin and PTX3) or the metS (CCL2, leptin and adiponectin). IL-1β and IL-6 were the only immune compounds raised in the serum of patients not affected by any of the included factors. Although many of the immune compounds were found linked to (components of) the metS, the most dominant linkage was found with the disease schizophrenia, confirming earlier reports on increased monocyte/macrophage activation as a key component for understanding the pathogenesis of schizophrenia.

Clozapine is gold standard, but questions remain

In their recent publication, Frogley and colleagues have reviewed the evidence indicating that clozapine treatment reduces aggressive behaviour in patients with schizophrenia, and perhaps with other disorders as well (Frogley et al. 2012). Although randomized controlled trials testing this anti-aggressive effect are relatively scarce, the evidence based on many studies supports it. There is general agreement on the superiority of clozapine's anti-aggressive effect in schizophrenia, as reflected for example in published expert consensus guidelines (Kane et al. 2003, p. 38) and in standard textbooks (Volavka et al. 2012). However, there are issues that are not quite as clear. Failure to respond to clozapine is one of these issues. In the general population of schizophrenia patients with treatment-resistant illness, only about 50% of patients respond to clozapine (Lieberman et al. 1994). The proportion of responders to clozapine in the treatment of aggression in schizophrenia has not been reliably established, but it is clear that not all patients will respond. The data published by Krakowski et al. (2006) probably represent the most robust support for the anti-aggressive superiority of clozapine over other antipsychotics in schizophrenia. The statistical analyses used in that paper (Krakowski et al. 2006) were not designed to define the outcome in dichotomous terms (response vs. non-response). However, the published interquartile ranges strongly suggest that non-responders to clozapine were present. Similar variability of response to clozapine was observed in other studies. The causes of this variability of response are not well understood. In a follow-up paper, Krakowski & Czobor (2012) demonstrated that the superiority of clozapine was probably not due to its effect on executive functioning. The variability of response is therefore apparently attributable to other factors than cognitive performance. One reason for this variability is that aggressive behaviour in schizophrenia is …

Poster #9 REPEATED FORCED SWIMMING REDUCES GLUTAMATE UPTAKE IN HIPPOCAMPAL SLICES AND AFFECTS DIFFERENTLY THE RATS BEHAVIOR IN TWO MODELS RELATED TO COGNITIVE SYMPTOMS OF SCHIZOPHRENIA: NOVEL OBJECT RECOGNITION AND PRE-PULSE IHNIBITION

performance observed at the 0.32 mg/kg dose of Ketamine did not differ significantly from the saline control condition. However, the higher doses of Ketamine did. With increasing dosage, the monkey made more errors on the trial type in which schizophrenia patients tend to make more errors. This trial type requires intact context processing to perform correctly. Discussion: The current study demonstrates that Ketamine is able to replicate in a monkey the behavioral performance pattern on the DPX task seen in schizophrenia patients performing the AX-CPT and the DPX task. The monkey tended to make more errors on the trial type that requires intact context processing to perform indicating a drug induced context processing deficit. The results of this study, pending replication, lay the groundwork for establishing a non-primate model to better study and characterize the context processing deficit seen in the schizophrenia patient population.

A framework on surface-based connectivity quantification for the human brain

Quantifying the connectivity between arbitrary surface patches in the human brain cortex can be used in studies on brain function and to characterize clinical diseases involving abnormal connectivity. Cortical regions of human brain in their natural forms can be represented in surface formats. In this paper, we present a framework to quantify connectivity using cortical surface segmentation and labeling from structural magnetic resonance images, tractography from diffusion tensor images, and nonlinear inter-subject registration. For a single subject, the connectivity intensity of any point on the cortical surface is set to unity if the point is connected and zero if it is not connected. The connectivity proportion is defined as the ratio of the total connected surface area to the total area of the surface patch. By nonlinearly registering the connectivity data of a group of normal controls into a template space, a population connectivity metric can be defined as either the average connectivity intensity of a cortical point or the average connectivity proportion of a cortical region. In the template space, a connectivity profile and a connectivity histogram of an arbitrary cortical region of interest can then be derived from these connectivity quantification values. Results from the application of these quantification metrics to a population of schizophrenia patients and normal controls are presented, revealing connectivity signatures of specified cortical regions and detecting connectivity abnormalities.

Cost Effectiveness of Long-Acting Risperidone in Sweden

In Sweden, risperidone long-acting injectable (RLAI) is generally used in a population of schizophrenia patients who are at a high risk of being non-compliant. However, RLAI might also be suitable for use in the general schizophrenia population. To analyse the clinical and economic effects of RLAI in the Swedish treatment practice using a discrete-event simulation (DES) model. Treatment outcomes and direct costs were analysed for both the high-risk non-compliant patient population and the general schizophrenia population. An existing DES model was adapted to simulate the treatment of schizophrenia in Sweden. Model inputs were based on literature research and supplemented with expert opinion. In the high-risk non-compliant schizophrenia population, RLAI was compared with haloperidol LAI. The analysis was built upon differences in symptom reduction, time between relapses, compliance and adverse effect profile between the two drugs. Main outcomes were the predicted incremental (discounted) costs (€) and effects (QALYs). In the general schizophrenia population, RLAI was compared with oral olanzapine. This analysis was built upon differences in compliance and adverse effects between the drugs. Multivariate probabilistic sensitivity analyses (PSA) were carried out to assess the sensitivity of the results of the two analyses. In the high-risk non-compliant patient population, RLAI was predicted to generate 0.103 QALYs per patient over 3 years while realizing cost savings of €5013 (year 2007 values) compared with haloperidol LAI. The main driver of the cost effectiveness of RLAI was the difference in Positive and Negative Syndrome Scale (PANSS) reduction between the two drugs, followed by the difference in adverse effects. The PSA showed that, in this setting, RLAI had a probability of 100% of being cost effective at a willingness-to-pay (WTP) threshold of €43,300 per QALY gained, compared with haloperidol LAI. The probability that RLAI combines additional effectiveness with cost savings compared with haloperidol LAI was estimated at 94%. When analysing RLAI in the general schizophrenia population, it was predicted to generate 0.043 QALYs and save €239 per patient over 5 years compared with olanzapine. Compliance was the main driver of the cost effectiveness of RLAI in this scenario. In the PSA it was shown that RLAI had a probability of 78% of being cost effective at a WTP threshold of €43,300 per QALY gained, compared with olanzapine. The estimated probability that RLAI combines additional effectiveness with cost savings was 50% and the probability that RLAI is less effective and more costly than olanzapine was negligible (0.2%). Treatment with RLAI is suggested to result in improved QALYs combined with cost savings compared with haloperidol LAI among the Swedish, high-risk non-compliant schizophrenia patient population. In the general schizophrenia population, RLAI also resulted in positive incremental QALYs and cost savings, when compared with olanzapine. However, the estimates used in the model for compliance and symptom reduction need further validation through naturalistic-based studies with reasonable follow-up to more definitely establish the real-life differences between RLAI and the comparators in the considered patient populations and to further reduce the uncertainty of these parameters.