PANSS Negative Subscale Scores Research Articles

D-serine and D-amino acid oxidase levels in patients with schizophrenia spectrum disorders in the first episode and 6-month follow-up

BackgroundD-serine and the D-amino acid oxidase (DAO) enzyme, which breaks down d-amino acids, may be involved in the pathophysiology of schizophrenia by affecting the N-methyl-D-aspartate (NMDA) receptor. The exact role of D-serine and DAO, as well as the consequences of increased DAO activity in patients with schizophrenia, remain unclear. We aimed to investigate D-serine and DAO levels in patients with first-episode schizophrenia spectrum disorders before treatment and after six months of treatment. MethodComparisons for the serum levels of D-serine and DAO were made between 81 healthy controls and 89 patients with first-episode schizophrenia spectrum disorders without a history of treatment. Further comparisons were made after 6 months for changes in these levels in the 41 patients in follow-up. The Positive and Negative Syndrome Scale (PANNS), Calgary Scale for Depression in Schizophrenia (CDSS), Montreal Cognitive Assessment Scale (MoCA), Global Assessment Scale (GAS), and Clinical Global Impression Scale (CGI) were used to evaluate the symptom severity and functionality. Secondary results included comparisons related to antipsychotic equivalent doses. ResultsBefore treatment, patients had significantly lower levels of D-serine, DAO, and D-serine/DAO ratio compared to healthy individuals (p < 0.001; p < 0.001; p = 0.004). DAO and D-serine levels of the patients were higher after six months of treatment (p = 0.025; p = 0.001). There was correlation of DAO levels with antipsychotic dosage and with PANSS negative and total subscale scores (rho = 0.421, p = 0.01; rho = 0.280, p = 0.008; rho = 0.371, p = 0.000). No correlation was found between serum D-serine level, DAO level, and the D-serine/DAO ratio with cognitive function. ConclusionsThe results suggest that D-serine and DAO may play a role that is sensitive to treatment effects in schizophrenia spectrum disorders. To gain a more comprehensive understanding of the impact antipsychotic drugs have on NMDA receptor dysfunction, there is a requirement for studies that directly evaluates the activity of the DAO enzyme.

New role of platelets in schizophrenia: predicting drug response

BackgroundElevated platelet count (PLTc) is associated with first-episode schizophrenia and adverse outcomes in individuals with precursory psychosis. However, the impact of antipsychotic medications on PLTc and its association with symptom...

Gender differences in the effect of rtms with the H7-coil on physical and social anhedonia in schizophrenia spectrum disorder; a randomized, sham-controlled trial

IntroductionStudies of differences in the incidence and severity of physical and social anhedonia between women and men diagnosed with schizophrenia spectrum disorder (SSD) are often inconsistent, and gender differences in treatment response have not been well studied. Hormonal factors, such as those related to the menstrual cycle, pregnancy or menopause, as well as social and cultural patterns and roles, may influence treatment response. The incidence of affective or stress-related psychiatric comorbidities may be gender-specific, which could also complicate the treatment of anhedonia and other negative symptoms of SSD. Finally, there is no evidence of sufficient quality on gender differences in the effects of rTMS, but the results are intriguing and point to the need for further research.ObjectivesTo investigate gender differences in the effect of rTMS with the H7-coil on physical and social anhedonia in patients diagnosed with SSD with dominant negative symptoms.MethodsWe conducted a randomized, sham-controlled trial during 2000-2023 in the population of patients diagnosed with SSD with primary negative symptoms defined as PANSS negative symptoms subscale score &gt; 24, and PANSS positive symptoms subscale score &lt; 20. The intervention was HF rTMS H7 coil (Brainsway Ltd. Jerusalem, Israel) once daily for 20 days applied to the prefrontal cortex (mPFC and ACC) at 100% motor threshold with a frequency of 18 Hz, and total of 39600 pulses. The outcomes were Physical and Social Anhedonia Scales (PAS, and SAS). We controlled for the large number of relevant covariates.ResultsWe randomized 49 men and 29 women of similar age. The effect on physical anhedonia was statistically significant in women (b = 9.04; p = 0.016), but not in men (b = 2.87; p = 0.272). The effect on social anhedonia was similar, but the difference was smaller (for men b = 3.71; p = 0.082; for women b = 5.42; p = 0.043). However, the Wald test showed no statistically significant differences between the beta coefficients for women and men.ConclusionsBased on this study, it is not possible to make valid and reliable conclusions about the existence of gender differences in the effects of rTMS treatment of anhedonia with the H7 coil. However, it is possible to claim that the treatment of anhedonia with this protocol is effective in women.Disclosure of InterestNone Declared

A Cross-Sectional Study on Associations Between BDNF, CRP, IL-6 and Clinical Symptoms, Cognitive and Personal Performance in Patients With Paranoid Schizophrenia

BackgroundCognitive impairment is among the core dimensions in schizophrenia and is a significant predictor of everyday functioning in people with schizophrenia. Given the enormous burden of schizophrenia, the search for its clinically relevant biomarkers is essential. Researchers have been trying to elucidate factors of cognitive impairment as well as personal performance, but the search is still ongoing. The aim of the study was to search for associations between BDNF, CRP, IL-6 and clinical symptoms, cognitive and personal performance in patients with paranoid schizophrenia.MethodsA total of 86 patients (53.5% women, mean age 31.1 ± 6.5) with paranoid schizophrenia (F20.0; ICD-10) in remission were examined. Clinical and neuropsychological examination included the Positive and Negative Syndrome Scale, Personal and Social Performance Scale, Calgary Depression Scale for Schizophrenia and the Brief Assessment of Cognitive Function in Schizophrenia. IL-6, BDNF, CRP levels were determined in the patients' blood serum.ResultsCognitive impairment was revealed in 79.1% of patients and was more profound in patients with higher number of hospitalizations (p = 0.006). The average BDNF levels were 13.38 ± 15.84 ng/ml, CRP concentration was 2.09 ± 2.54 mg/l, and IL-6 levels were 12.14 ± 5.88 pg/ml. There were no differences in biomarker levels or BACS results in patients that had different antipsychotic therapy or differed in the presence of anticholinergic therapy. CRP levels were higher in patients with longer disease duration, lower age of onset, more impaired personal social performance and processing speed. IL-6 was higher in individuals with lower working memory scores. PANSS negative subscale score negatively correlated and PSP score positively correlated with most cognitive domains. A linear regression established that the first episode vs. multiple episodes of schizophrenia could statistically significantly predict personal and social performance and cognition, including speech fluency and planning, as well as CRP levels.ConclusionsThis study continues the search for biomarkers of schizophrenia and cognitive impairment in schizophrenia to improve the reliability of diagnosing the disorder and find new treatment approaches. The role of the number of psychoses experienced (first episode vs. multiple episodes of schizophrenia) in cognition, personal and social performance and inflammation is shown.

Efficacy and safety of antipsychotic treatments for schizophrenia: A systematic review and network meta-analysis of randomized trials in Japan

BackgroundWe examined the efficacy and safety of using antipsychotic medication for schizophrenia using only randomized trials of antipsychotic for schizophrenia conducted in Japan to avoid the biological and environmental heterogeneities caused by pooling data from various races and ethnicities. MethodsWe searched for eligible studies on Embase, PubMed, and CENTRAL. Primary outcomes were improvement in Positive and Negative Syndrome Scale total score (PANSS−T) and all-cause discontinuation. Other outcomes were improvement in PANSS subscale scores, discontinuation due to adverse events or inefficacy, and the incidence of 16 adverse events. ResultsWe calculated mean difference or risk ratios and 95% credible intervals. We identified 34 RCTs (6798 patients; mean study duration, 9.0 ± 4.24 weeks; proportion of male patients, 53.7%; mean age, 43.3 years). Besides placebo, studies included aripiprazole, asenapine, blonanserin, blonanserin-patch, brexpiprazole, clocapramine (no PANSS data), clozapine (no PANSS data), haloperidol, lurasidone, mosapramine, olanzapine, paliperidone, perospirone, quetiapine, and risperidone. Efficacy and safety profiles differed for antipsychotics used with schizophrenia in Japanese patients. All active treatments other than haloperidol and quetiapine outperformed placebo to improve PANSS−T. Asenapine, olanzapine, paliperidone, and risperidone outperformed placebo for all-cause discontinuation. Asenapine, blonanserin, blonanserin-patch, haloperidol, lurasidone, mosapramine, olanzapine, paliperidone, and risperidone outperformed placebo to improve PANSS positive subscale scores. Aripiprazole, asenapine, blonanserin, blonanserin-patch, brexpiprazole, lurasidone, olanzapine, paliperidone, perospirone, and risperidone outperformed placebo to improve PANSS negative subscale scores. The confidence in evidence of most outcomes was low or very low. ConclusionOur results are similar to those of previous network meta-analysis involving various races and ethnicities.

Negative correlation between PANSS negative subscale score and obesity in a chronic group of patients with schizophrenia, an observational study

Background. Schizophrenia, as a chronic mental disorder with lifelong evolution is associated with low functionality and a high degree of disability. Obesity is an overlapping risk factor that is present in almost half of the patients worldwide and is responsible for increasing the overall mortality by itself or by predisposing to extensive morbidity. Its pathophysiology describes many mechanisms, the central position being occupied by the appetite regulation throughout the lipids and glucose metabolism. It is important to analyze whether the trends of correlation pairs of obesity in schizophrenia in Romanian patients are similar to those described in literature and if they are depicted in smaller groups of patients. Methods. This study paper is an observational cross-sectional study taking into account 110 inpatients with schizophrenia. The study included 110 inpatients diagnosed with schizophrenia admitted in ”Prof. Dr. Alexandru Obregia” Psychiatry Hospital. They were divided into two groups by applying the criterium of BMI with a cut-off point set at 25 and were applied PANSS and GAFs altogether with a structured basic anamnestic interview. Results. The mean age of the patients was 39.15 years in the study group (SG) and 40.95 years in the control group (CG), the sex ratio was similar between the two groups. Regarding previous treatment, 59.3% normal weight patients were priorly medicated and 38.1% of those with BMI&gt;25 received prior treatment. Both groups had a similar mean value of the positive and the general psychopathology subscales, the SG registered a slightly higher mean score on the negative subscale as well as on the total PANSS score. The mean value of Global Assessment of Functioning score was higher for the normal weight group. Discussion. Our findings point out that only PANSS negative subscale score has a negative statistical correlation (p=.005) with obesity in the chronic schizophrenic group we selected. No other statistically significant correlations between sex, age, place of living, education, employment and professional statuses, previous treatment, current antipsychotic medication and obesity were made possible due to reasons such as study design choice or the large number of obese patients related to the entire sample. Conclusion. There is an important number of schizophrenia patients that are overweight or obese. We found no major differences between the two groups on the topic of demographics or clinical variables, resulting in the conclusion that schizophrenia carries an important morbidity load, so that obesity can indiscriminately impact these patients.

Longitudinal study of inflammatory markers and psychopathology in schizophrenia

ObjectiveSchizophrenia is associated with abnormal levels of blood inflammatory markers, which may be correlated with levels of psychopathology. Few previous studies have explored whether baseline inflammatory marker levels predict longitudinal changes in psychopathology. In the present study, we explored this association in a cohort of patients with schizophrenia. MethodWe investigated inflammatory markers and psychopathology after 3, 6, and 12 months of antipsychotic treatment for subjects with baseline and follow-up data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial. Linear regression models, controlling for multiple potential confounding factors, were used to investigate these associations. ResultsThere was a significant decrease in monocyte, ICAM, and adiponectin levels between baseline and 12 months. Higher baseline blood interleukin-6 (IL-6) predicted greater reduction in PANSS total and general subscale scores at 3 and 6 months, and PANSS negative subscale scores at 3 months (β = −0.10 to −0.16, p < 0.05 for each). Higher baseline blood leptin levels predicted greater reduction in PANSS total, negative and general subscale scores at 6 months (β = −0.09 to −0.11, p < 0.05 for each). In post-hoc analyses, associations between baseline IL-6 levels and symptom reduction were strongest in patients treated with either ziprasidone or quetiapine. Changes in blood inflammatory markers were generally not associated with changes in psychopathology. ConclusionsOur findings provide additional support that measuring blood inflammatory markers may be relevant to the clinical care of patients with schizophrenia. Specifically, these markers may help guide selection of antipsychotic treatment towards more personalized medicine approaches for patients with schizophrenia.

Duration of untreated psychosis and response to treatment: an analysis of response in the OPTiMiSE cohort

Some, but not all, studies have found longer duration of untreated psychosis (DUP) to be associated with poor response to treatment and more severe negative symptoms in schizophrenia. The aim of the current analysis was to investigate these parameters in a large cohort of patients in their first psychotic episode. The OPTiMiSE cohort included 446 patients with DUP up to two years, who were administered amisulpride for 4 weeks (Phase I). Patients who did not meet Andreasen remission criteria were randomized to double-blind continuation of amisulpride or olanzapine for 6 additional weeks in a blinded study (Phase II). Analyses showed that shorter DUP was associated with lower baseline CGI scores (p<0.001, r = 0.184), PANSS total (p = 0.025, r = 0.106) and PANSS negative subscale scores (p = 0.023, r = 0.107). Remitters had a significantly shorter mean DUP compared to non-remitters both in Phase I (24.5 weeks ±24.3 vs. 35 weeks ± 32.2, p = 0.01, t=−2.521) and in Phase II (24.3 weeks ± 26.4 vs. 38.3 weeks ± 31.3, p = 0.031, t=−2.194). Logistic regression analyses showed a significant effect of DUP on treatment response both in phase I (p = 0.008) and phase II (p = 0.041). Linear regression analyses found that DUP significantly affects PANSS Total change at the end of phase I (p = 0.028) but not at the end of phase II (p = 0.236). Based on these findings, it is possible to conclude that shorter DUP is associated with better response to treatment, particularly during the first weeks after treatment initiation. These findings highlight the need for early identification of the first psychotic episode.

T56. AN EXPLORATORY ANALYSIS CONVERTING SCORES BETWEEN THE PANSS AND BNSS

BackgroundThe Brief Negative Symptom Scale is a relatively new instrument designed specifically to measure the negative symptoms in schizophrenia. Recently more clinical trials include the BNSS scale as a secondary or exploratory outcome, typically along with the PANSS. In the current analysis we aimed at establishing the equations that would allow conversion between the BNSS scale total score and the PANSS negative subscale and PANSS negative factors score as well as conversion equations between the expressive deficits and avolition/apathy factors of the scales. (Kirkpatrick, 2011; Strauss, 2012)MethodsData from 518 schizophrenia clinical trials subjects with both PANSS and BNSS data available were used. Regression analyses predicting the BNSS total score with the PANSS negative subscale score, and the BNSS total score with the PANSS Negative factor (NFS) score were performed on data from all subjects. Regression analyses predicting the BNSS avolition/apathy factor (items 1, 2, 3, 5, 6, 7, and 8) with the PANSS avolition/apathy factor (items N2, N4 and G16) and the BNSS expressive deficits factor (items 4, 9, 10, 11, 12, and 13)with the expressive deficits factor (items N1, N3, N6, G5, G7, and G13)of the PANSS were performed on a sample of 318 subjects with individual BNSS item scores available. In addition to estimating the equations we as well calculated the Pearson’s correlations between the scales.ResultsThe PANSS and BNSS avolition/apathy factors were highly correlated (r=0.70) as were the expressive deficit factors r=0.83). The following equations predicting the BNSS total score were obtained from regression analyses performed on 2,560 data points:BNSS_total = -11.64 + 2.10*PANSS_negative_subscaleBNSS_total = -9.26 + 2.11*PANSS_NFSThe following equations predicting the BNSS factor scores from the PANSS factor scores were obtained from regression analyses performed on 1,634 data points:BNSS_avolition/apathy = -2.40 + 2.38 * PANSS_avolition/apathyBNSS_expressive_deficit_factor = -4.21 + 1.27 * PANSS_expressive_deficit_factorDiscussionThe BNSS differs from the PANSS negative factor because it addresses all five currently recognized domains of negative symptoms including anhedonia and attempts to differentiate anticipatory from consummatory states. In our analysis we have replicated the strong correlation between the BNSS total score and PANSS negative subscale and newly identified strong correlations between the BNSS total score and NFS as well as strong correlations between the avolotion/apathy and expressive deficit factors of the BNSS and the PANSS scales. (Kirkpatrick, 2011)The provided equations offer a useful tool allowing researchers and clinicians to easily convert the data between the instruments for reasons such as pooling data from multiple trials using one of the instruments, to allow interpretation of results within the context of previously conducted research, etc. but as well offer a framework for risk based monitoring to identify data deviating from the expected relationship and allow for a targeted exploration of the causes for such a disagreement. The data used for analysis included not only subjects with predominantly negative symptoms but as well acutely psychotic subjects as well as subjects in stable conditions allowing therefore to generalize the results across the majority of schizophrenic subjects. This post-hoc analysis is exploratory. We plan to further explore the potential utility of equations addressing the relationships among schizophrenia measures of symptom severity in an iterative manner with larger datasets.

T226. CLINICAL PREDICTORS OF FUNCTIONAL CAPACITY IN TREATMENT RESISTANT SCHIZOPHRENIA PATIENTS: COMPARISON WITH RESPONDER PATIENTS, ROLE OF NEGATIVE SYMPTOMS, PROBLEM SOLVING DYSFUNCTIONS, AND NEUROLOGICAL SOFT SIGNS

BackgroundTreatment Resistant Schizophrenia (TRS) patients show more severe impairments in community functioning compared to Antipsychotic Responder Schizophrenia (ARS) patients. The scope of this work was to assess whether TRS patients suffer from more severe alterations in functional capacity, i.e. the baseline potential of a patient to function in the community, and whether factors affecting functional capacity differ between TRS and ARS patients.Methods60 out of 182 eligible patients were included. A multistep diagnostic procedure to separate TRS from ARS was then used. Patients were administered a range of assessment tools including (but not limited to): the PANSS; cognitive performances tests; the Specific Level of Functioning (SLOF); the Neurological Evaluation Scale (NES); the UCSD Performance-Based Skills Assessment (UPSA) extended version. Univariate and multivariate statistics were performed. Significance was set at p<.05.ResultsAfter controlling for covariates, no significant differences in both total and subscales UPSA scores were found between TRS and ARS patients. However, TRS patients constantly scored lower than ARS patients.Stepwise regression was used to determine predictors of UPSA score. The first group encompassed clinical variables. In the whole sample, the final significant model, F(2,57)=18.848, p<.0005, adjusted R2=.37, included: PANSS negative subscale score and NES score. In TRS patients, the final significant model, F(3,24)=16.552, p<.0005, adjusted R2=.63, included PANSS negative scale score, education years, and NES score. In ARS patients, no significant models were found.The second group included cognitive performance variables. In the whole sample, the final significant model, F(2,57)=7.64, p=.001, adjusted R2=.18, included Problem Solving and Verbal Memory. In TRS patients, the final significant model included Problem Solving and VisuoSpatial Memory. In ARS patients, the final significant model included Verbal Memory only.The third group included psychosocial variables. In the whole sample, the final significant model, F(1,58)=18.82, p<.0005, adjusted R2=.23, included SLOF Area5 score only. In TRS patients the final significant model included SLOF Area1 score only, while in ARS patients, no significant models were found.By hierarchical multiple regressions, NES score was found to be predictive of the highest UPSA score variance ratio among schizophrenia patients. The addition of PANSS Negative scale score and Problem Solving (in this order) led to a statistically significant increase in R2. No further models were found to add significant increase in R2. In TRS patients, PANSS Negative scale score was the variable that explained the most variance in UPSA score. The addition of Problem Solving and education years (in this order) led to a statistically significant increase in R2. No further models were found to add significant increase in R2, although NES score showed a trend toward significance.At last, we performed a path analysis to evaluate the type (direct or indirect) and the direction of relationships among these variables and UPSA score. The only variables that were in direct relationship with UPSA score were PANSS Negative Scale score and Problem Solving. SLOF Area5 was in indirect relationship with UPSA score by PANSS Negative Scale score, while NES score relationship with UPSA score was mediated by Problem Solving.DiscussionOur study demonstrated that negative symptoms, altered cognitive performances, and more severe neurological soft signs were the major factors influencing functional capacity in schizophrenia patients. These factors were more relevant in TRS than in ARS patients.

F241. DEVELOPMENT AND VALIDATION OF THE SOCIAL FUNCTIONING ASSESSMENT SCALE (SFAS) FOR PEOPLE WITH SCHIZOPHRENIA IN TURKEY

BackgroundSocial functioning is generally defined as having profound and qualitative interpersonal relations, and meeting the expectations and defined roles in society. Determining the level of the social functioning is important especially for people with schizophrenia that proceed with disabilities. Main dimensions of the social functioning are 1) Self-care, 2) Independent living, 3) Interpersonal relationships (family, friends, neighbors, etc.), 4) Leisure time and recreation, and 5) Occupational activities like school or job. The purpose of this study was to develop a culturally-sensitive, user-friendly scale that could assess the social functioning of the people with schizophrenia.MethodsAfter examining the studies assessed social functioning in people with mental illnesses, an original 50-item scale was formed. Habits of 425 people living in the community was examined with this form so as identifying the prevalence and frequency of behavior patterns related with social functioning in Turkish community. Regarding the findings of that study, 28-item scale was formed that assess the social functioning of the patients. New form was given to 25 patients, and items which was difficult to comprehend were reevaluated and the scale was finalized as Social Functioning Assessment Scale. One hundred and thirty outpatients with schizophrenia or schizoaffective disorder were given a sociodemographic form, Social Functioning Assessment Scale (SFAS), Clinical Global Impression-Severity (CGI-S), and Global Assessment of Functioning (GAF). At the same time, Social Functioning Scale (SFS) and SFAS was given to the relatives of the patients who live together. For reliability analyses; internal consistency coefficient, item-total correlation, and split-half reliability was assessed. For validity analyses; explanatory factor analysis, and convergent validity were examined via Spearman correlation.ResultsThe data from 104 patients with schizophrenia and 26 with schizoaffective disorder whose 75% were males, 69% were single, mean age was 37, the level of education was 10 years was examined. The average onset of the illness was 23 years, and the duration of illness was 14 years. Cronbach’s alpha coefficient for SFAS total score was .83, and for factors were between .69 and .77. Split-half reliability coefficient of SFAS was .73. There was a satisfactory correlation between SFAS filled by patients and by relatives (r=.60, p<0.001). For factor analysis, Kaiser-Meyer-Olkin value was .78, and Barlett test was significant (p<0.001). In explanatory factor analysis, SFAS was found to be compose of three factors (self-care, interpersonal relationships and recreation, independent living) and that they can explain 45% of the total variance. Nine items were omitted because of having lower factor value than .40. Self-care factor had 7-item, interpersonal relationships and recreation factor had 7 items and independent living factor had 4 items. Occupational life could not get in any of factors; however, since it was very important for social functioning, it was added to the scale as fourth factor.SFAS total score was correlated with PANSS negative subscale (r=-.35, p<0,001), PANSS-total (r=-.29, p<0,001), CGI-S (r=-.33, p<0,001), GAF (r=.28, p<0,001) and SFS total score (r=.52, p<0,001).DiscussionRegarding the findings of the study, SFAS was considered a culturally-sensitive, easy-to-use, and valid instrument that objectively assesses the social functioning of the patients with schizophrenia in Turkey.

S57. TREATMENT SATISFACTION IN ACUTE PHASE PSYCHOSIS: COMPARISON BETWEEN ANTIPSYCHOTIC NAïVE AND PREVIOUSLY MEDICATED PATIENTS

BackgroundPatient satisfaction is a complex phenomenon, and relations between patient satisfaction, symptom load, insight, side effects and depression have been shown in patients treated for psychosis. However, few studies on patient satisfaction in psychosis discriminate between persons previously treated with antipsychotic drugs and those who are antipsychotic drug naïve.Our aim was to test whether predictors for treatment satisfaction differ between previously medicated with antipsychotics (PM) and those who were antipsychotic naïve (AN) at admission.MethodsIn total 226 consecutive patients were included when admitted to hospital due to symptoms of active psychosis (≥4 on in one or more items of PANSS positive subscale), and were candidates for oral antipsychotic medication. At baseline PANSS, CDSS and Clinical Global Impression- Severity of Illness scale (CGI-S) were conducted. A total of 104 patients were assessed at discharge or follow up after a maximum of 11 weeks (mean 28.5 days, SD 14.1). In addition to the baseline assessments, patient satisfaction was assessed by the UKU Consumer Satisfaction Rating scale and the UKU Side Effect Rating Scale. For statistics structural equation modelling was performed to test multi sample growth models.ResultsPatients assessed at baseline were found to be statistically similar to those also assessed at discharge/follow-up, with the exception of a slightly higher PANSS negative subscale score in those assessed at baseline only (independent samples t-test: p = 0.023, mean difference 2.3, 95% confidence interval of the mean difference 0.3–4.3).There was a general improvement in function between baseline and follow-up, reflected in the CGI-S score reduction from 5.17 (SD .619) to 3.70 (SD 1.09) and symptom reduction in PANSS positive: mean change - 6.68 (SD 5.00).For PM patients (N =55), satisfaction was predicted by level of insight (b = - 2.21, β = - 0.42, p = 0.000), and positive symptom reduction (b = -0.56, β = -0.39, p = 0.012). The most satisfied patients had high level of insight at baseline, and the steepest decline in positive symptoms.For AN patients (N =49), satisfaction was predicted by level and change of insight (respectively: b= - 2.21, β = - 0.46, p = 0.000; b = - 1.53, β = - 0.32, p = 0.032), change in depression (b = -0.37, β = -0.26, p = 0.025), and side effects (b = -0.15, β = -0.30, p = 0.033). The most satisfied patients had high level of insight at baseline, most improvement in insight, the steepest decline in the CDSS score, and the lowest level of side effects.DiscussionThe consecutive inclusions of patients make these finding relevant and generalizable to everyday practice in similar clinical settings.Our findings suggest that reducing positive symptoms and side effects are important, but not solely sufficient to enhance patient satisfaction, and that differences exist among drug naïve and previously medicated patients. Improving insight and reducing depression are key processes to enhance satisfaction, particularly for antipsychotic naïve patients. Being drug naïve may be considered a proxy for First Episode Psychosis (FEP). Symptoms of depression seem to be particularly prevalent in FEP patients (1), and might dominate the experienced distress relative to symptoms of psychosis in these patients. Furthermore, FEP patients are more sensitive to the side effects of antipsychotic drugs. Another key target for improving satisfaction is to keep antipsychotic drug treatment at the lowest effective doses, as most side effects are dose-related.

F233. NEGATIVE SYMPTOMS ARE INDEPENDENT MODERATOR FACTORS OF TREATMENT RESISTANT SCHIZOPHRENIA EFFECTS ON MULTIPLE CLINICAL, PSYCHOPATHOLOGICAL, COGNITIVE AND PSYCHOSOCIAL VARIABLES

BackgroundNegative symptoms (NSs) are more severe in Treatment Resistant Schizophrenia (TRS) than Antipsychotic Responder Schizophrenia (ARS) patients. NSs are predictors of outcomes of neurological soft signs and functional capacity in TRS but not in ARS patients. The scope of this work is to clarify whether NSs effects are integral to or independent from the TRS diagnosis in our sample of patients.Methods70 out of 206 eligible putative TRS and ARS patients were included (enrollment still ongoing). Patients were tested by the Neurological Evaluation Scale (NES); the CGI-S; the PANSS; the Heinrichs’ Quality of Life Scale (QLS); the UCSD Performance-Based Skills Assessment (UPSA); the Personal and Social Performance (PSP) scale and Specific Level of Functioning (SLOF). Patients were subdivided in NSHigh (severe NSs) and NSLow (mild NSs) based on ROC curve-derived cut-off.ResultsAt the Student’s t test, NSHigh had significantly lower scores than NSLow patients on: Verbal Fluency; QLS score; PSP score; UPSA Financial, Communication, and Family Skills; UPSA total score; all SLOF areas (except Area4). NSHigh patients had significantly higher scores than NSLow patients on CGI-S; PANSS Positive and General Psychopathology Subscale scores; and NES score.Distribution of NS patients was significantly different between TRS/ARS diagnostic groups, as NSHigh patients were significantly more frequent in the TRS group (Pearson chi square: □1=5.51, p=.001). Notably, mean PANSS Negative Subscale scores were significantly higher in TRS compared to ARS patients (Student’s t: F1,58=2.84, p=.006).Since multiple variables found to be significantly different in NSHigh vs. NSLow patients were also significantly different between TRS and ARS patients, the question arises whether the significant differences found between diagnostic groups may depend on the higher percentage of patients with more severe NSs in the TRS group. Therefore, a two-way ANOVA was carried out with dichotomous NS and Diagnosis variables as the independent variables. Outcomes on multiple clinical variables were significantly different among groups. A NS*Diagnosis interaction effect was found for NES score (F1,58=4.32, p=.042, Visuospatial Memory, UPSA Transportation skills, and SLOF Area1. In all these cases, NSHigh/TRS patients performed significantly worse than the other patient groups; in the case of NES score, NSHigh/TRS patients score significantly higher than the other groups. Independent effect of either NSs or Diagnosis were also found for multiple variables, suggesting that NSs and Diagnosis may interact but their effects are not completely overlapping. To have a more deepen comprehension of NS effects on diagnosis, we carried out a moderator regression analysis and an ANCOVA analysis that further confirmed the finding that NSs’ mediate Diagnosis effects on a number of clinical outcomes.Given that NSs largely affect clinical variables, we asked which distinct symptom may exert the greater impact on each of these variables. Therefore, we carried out a including the seven PANSS Negative Subscale items as the independent variables. The items that explained the highest variance in clinical variables were mostly Stereotyped Thinking (N7), Passive Social Withdrawal (N4), and Difficulty in Thinking (N5).DiscussionThese data suggest that NSs are both independent determinants and moderators of TRS/ARS diagnosis effect on multiple psychopathology, cognitive, and psychosocial factors. More impaired functions attributed to non-response to antipsychotics may depend on more severe NSs. However, only a subset of NSs appears to exert this action, possibly related to the multidimensional construct of these symptoms.

Correlations between the affective response and aggressiveness level at patients with psychotic disorders

Schizophrenia is a mental disorder in which positive symptoms (hallucinations, delusions, conceptual disorganization and behavioral), negative symptoms, cognitive dysfunction and improper emotional responses are considered cardinal symptoms. Hostility and aggression are common in major psychiatric disorders such as schizophrenia, schizoaffective disorder and bipolar affective disorders, aggressive behavior constituting a diagnostic criterion for certain personality disorders: antisocial disorder and borderline disorder. Emotional expressiveness may cause malfunctioning, verbal and physical aggression. Material and method: The preliminary study was conducted on a total of 26 patients diagnosed with schizophrenia and schizoaffective disorder according to DSM-V operational criteria (2013) and ICD 10 (1992). In the study group were predominantly male, urban areas, the average age being 37 years old; most patients had secondary education. We applied: scale PANSS with subscales PANSS positive PANSS negative and PANSS general scale YMRS, HAM-D, HAM-A and questionnaire aggression Bush &amp; Perri (1992) with four subscales (physical aggression and verbal, anger, hostility). The objective of this study was to establish correlations between the level of aggression and emotional response PANSS negative subscale scores determined by, YMRS, HAM-D, HAM-A. Results and discussions: Applying regression methods multiline and correlations between variables were revealed significant positive relationships between YMRS scale values, namely (a) total score of aggression questionnaire (r = .428, p = .029, (b) Physical Aggression Factor ( r = .593, p = .001), and (c) factor Anger (r = .418, p = .034). The items of the scale PANSS negative subscale correlated significantly negative with the Anger factor in the aggression questionnaire (r = - 0.440, p = .024). Conclusions: Aggression and anger are positively correlated with manic symptoms and negative with affective flattening, apathy. In conclusion, physical aggression can be predicted by YMRS score or PANSS negative score.

A scale of autonomy for patients with schizophrenia – new instrument for clinical assessment of the level of independency: Description and validation

IntroductionToday the scales for measurement of functional status and life satisfaction (GAF, PSP, EQ-5D, SQLS) gain more importance in assessing schizophrenic patients. Autonomy of living is to the great extent the basis of patient well-being. Each of these scales has the criteria, testing ability for independent life, but none of it tests autonomy as a separate object.ObjectiveDevelopment of a new scale.AimsDescription and validation of a scale for evaluation of autonomy of living in schizophrenic patients.MethodsForty patients diagnosed with schizophrenia according to ICD−10 (F 20.хх), 13 males and 27 females, aged 49.8 ± 9, disease duration is 22 ± 8.6 years. New scale and PANSS, CGI-S, NSA, BACS, GAF, PSP was administered.ResultsThe scale comprises five points (activity, intentional behavior, range of social interaction, specificity of interaction with the doctor (medical conventionality) and autonomy), and total score. The internal consistency of the scale was high – cronbach's alpha 0.83. The construct validity with GAF and PSP was moderate (R varied from 0.36 to 0.55). The total score of the new scale correlated with the PANSS negative subscale score (R = −0.51), with CGI-S score (R = −0.57), and with the BACS total score (R = −0.57).ConclusionThe scale of autonomy corresponds to the major psycho-diagnostic requirements: internal consistency, construct and discriminative validities. It can be considered a new instrument for assessing the integrative target of treatment and rehabilitation of patients with schizophrenia.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Scales for assessment of depression in schizophrenia: Factor analysis of calgary depression rating scale and hamilton depression rating scale

This study aimed to evaluate the factor structure of Calgary depression rating scale (CDSS) and Hamilton Depression Rating Scale (HDRS) among patients with schizophrenia in acute and remission phase of illness by using exploratory factor analysis. For this, 267 patients with schizophrenia were assessed on CDSS and HDRS. Exploratory factor analysis of CDSS yielded 2 factor models for the whole sample, patients in clinical remission and patients not in clinical remission phase of schizophrenia. Factor analysis of HDRS yielded 3 factor models; however, there was significant difference in the factor structure between those in clinical remission and those not in clinical remission phase of schizophrenia. CDSS total score did not correlate with PANSS positive and negative subscale scores. In contrast, HDRS total score correlated positively with PANSS positive subscale score, PANSS negative subscale score and PANSS general psychopathology subscale score. To conclude, present study suggests while CDSS items separate out into 2 factors, which are stable across different stages of illness, whereas HDRS factor structure appears to be less stable across different stages of illness. Correlation analysis suggests that rating on HDRS may be affected by positive and negative symptoms of schizophrenia, whereas CDSS do not correlate with positive and negative symptoms of schizophrenia.

EFFECTS OF FOLIC ACID AND VITAMIN B12 SUPPLEMENTATION ON NEGATIVE SYMPTOMS AND RELATED MRI INDICES

We examined the efficacy and safety of using antipsychotic medication for schizophrenia using only randomized trials of antipsychotic for schizophrenia conducted in Japan to avoid the biological and environmental heterogeneities caused by pooling data from various races and ethnicities.We searched for eligible studies on Embase, PubMed, and CENTRAL. Primary outcomes were improvement in Positive and Negative Syndrome Scale total score (PANSS−T) and all-cause discontinuation. Other outcomes were improvement in PANSS subscale scores, discontinuation due to adverse events or inefficacy, and the incidence of 16 adverse events.We calculated mean difference or risk ratios and 95% credible intervals. We identified 34 RCTs (6798 patients; mean study duration, 9.0 ± 4.24 weeks; proportion of male patients, 53.7%; mean age, 43.3 years). Besides placebo, studies included aripiprazole, asenapine, blonanserin, blonanserin-patch, brexpiprazole, clocapramine (no PANSS data), clozapine (no PANSS data), haloperidol, lurasidone, mosapramine, olanzapine, paliperidone, perospirone, quetiapine, and risperidone. Efficacy and safety profiles differed for antipsychotics used with schizophrenia in Japanese patients. All active treatments other than haloperidol and quetiapine outperformed placebo to improve PANSS−T. Asenapine, olanzapine, paliperidone, and risperidone outperformed placebo for all-cause discontinuation. Asenapine, blonanserin, blonanserin-patch, haloperidol, lurasidone, mosapramine, olanzapine, paliperidone, and risperidone outperformed placebo to improve PANSS positive subscale scores. Aripiprazole, asenapine, blonanserin, blonanserin-patch, brexpiprazole, lurasidone, olanzapine, paliperidone, perospirone, and risperidone outperformed placebo to improve PANSS negative subscale scores. The confidence in evidence of most outcomes was low or very low.Our results are similar to those of previous network meta-analysis involving various races and ethnicities.

A six month randomized controlled trial of long acting injectable risperidone 50 and 100 mg in treatment resistant schizophrenia

It has been suggested that atypical antipsychotic drugs (A-APDs) other than clozapine may be effective to improve positive symptoms in some patients with treatment resistant schizophrenia (TRS), if both the dose is higher, and the duration of the trial longer, than those which have been ineffective in non-TRS (NTRS) patients. This hypothesis was tested with long acting injectable risperidone (Risperdal Consta®, RLAI). One hundred sixty TRS patients selected for persistent moderate–severe delusions or hallucinations, or both, were randomized to RLAI, 50 or 100mg biweekly, in a six month, outpatient, double-blind, multicenter trial. We hypothesized that RLAI, 100mg, would be more effective than RLAI, 50mg. However, both doses produced clinically significant and equivalent improvement in PANSS Total, Positive, and Negative subscale scores, as well as key cognitive, global and functional measures, with increasing response during the course of the study, confirming the value of longer clinical trial duration for patients with TRS, but not superiority of the higher dose. The overall response rate was comparable to that previously reported for clozapine and high dose olanzapine, another A-APD, in TRS. Both doses of RLAI were equally well tolerated, producing minimal extrapyramidal side effects and few drop outs. Plasma levels of the active moiety, risperidone+9-hydroxyrisperidone, during treatment with RLAI 100mg, were comparable to those for 6–8mg/day oral risperidone, which have not been effective in TRS. Further study of RLAI, ≥50–100mg biweekly, should compare it with clozapine and oral risperidone in TRS, with duration of treatment ≥six months.

1598 – Suicidal behaviour and affective comorbidity in delusional disorder: effectiveness of paliperidone palmitate long acting injection (PPILD)

Introduction Suicide is one of the leading causes of premature death among people with psychotic disorders. However, little is known about treating suicide in delusional disorder. Objectives To investigate effectiveness of PPLAI in delusional disorder (DD) patients. Aims To compare effectiveness of PPLAI vs,other atypical antipsychotics (OAA) in psychopathology and suicidality. Methods Prospective observational study including 45 DD outpatients (DSM-IV-RT) attended at the Department of Psychiatry (Hospital Clinic- BCN) from 2008 to 2012 and followed up for 6 months. Demographic and clinical variables were recorded. Hamilton Rating Scale for Depression-17 (HRSD-17), PANSS for psychopathology, Personal and Social Performance Scale (PSP) and Columbia Suicide Severity Rating Scale (C-SSRS) were assessed at baseline and after 6 months. The sample was divided into four groups according to which treatment they received: oral risperidone, Risperidone Long Acting Injection (RLAI), OAA and PPLAI. For comparisons, Kruskal-Wallis and Chi-square tests were used. Results Eighty-two per cent were women. Mean age (SD) at onset: 46.9(11.8) years. 6 patients received oral risperidone, 23 OAA, 7 RLAI and 9 were treated with PPLAI. No statistically significant differences were found regarding demographic features, motives leading for consultation, depressive comorbidity and antidepressant prescription. After 6 months, patients treated with PPLAI presented lower frequency of ideation (0% vs.11.1%;p=0.027) and suicidal behaviour (0% vs.2.2%;p=NS). The group receiving PPILD presented a significant increase in functionality (PSP) (p=0.046) and an improvement in PANSS negative subscale scores (p=0.017). Conclusions Patients receiving PPLAI showed a decrease in suicidality, an improvement in psychotic symptoms and functionality.

Nicotinic acetylcholine receptor expression on B-lymphoblasts of healthy versus schizophrenic subjects stratified for smoking: [3H]-nicotine binding is decreased in schizophrenia and correlates with negative symptoms

Heavy smoking and schizophrenia are diversely associated with nicotinic acetylcholine receptor expression, as was shown for brain and lymphocytes. Most studies so far have not systematically differentiated between schizophrenia smokers and non-smokers and were confined either to in vivo or post-mortem study approaches. In order to avoid variable in vivo influences or post-mortem bias, we used stably transformed B-lymphoblast cultures derived from healthy and schizophrenia subjects stratified for smoking versus non-smoking in order to differentiate these clinical conditions with regard to nicotinic acetylcholine receptor expression and regulation. Receptor quantities were measured using [(3)H]-nicotine and [(3)H]-epibatidine binding. At baseline, [(3)H]-nicotine binding was not statistically different between healthy smokers and never-smokers (1.59 ± 0.73 vs. 1.26 ± 0.91 fmol/10(6) cells), while it was reduced in schizophrenia smokers compared to healthy smokers (1.05 ± 0.69 fmol vs. 1.44 ± 0.84/10(6) cells, P = 0.01). In schizophrenia, baseline [(3)H]-nicotine correlated inversely with higher PANSS negative subscale scores. After long-term nicotine incubation (1 μM), [3H]-nicotine binding increased in the group of schizophrenia smokers only (from 1.05 ± 0.69 to 1.54 ± 0.77 fmol/106 cells, P = 0.013), while [(3)H]-epibatidine binding decreased in this group (4.52 ± 1.52 to 3.82 ± 1.38 fmol/10(6) cells, P = 0.038). Our data are in further support of a decrease of nicotinic acetylcholine receptor expression in schizophrenia linked to negative psychotic symptoms, which may be counter-regulated by nicotine exposure.