Positive And Negative Syndrome Scale General Psychopathology Research Articles

Resilience and recovery style: a retrospective study on associations among personal resources, symptoms, neurocognition, quality of life and psychosocial functioning in psychotic patients.

Background: Personal resources have been identified as important factors in predicting patient healing or symptoms control in schizophrenia. This observational retrospective study aims to explore the influence of resilience and recovery style on the modalities of clinical presentation of the disease, as well as individual functioning and quality of life.Methods: Participants were patients affected by schizophrenia spectrum disorders assessed at different mental health facilities. The rating scales considered are the following: Resilience Scale 10-items (RS); Recovery Style Questionnaire (RSQ); Montreal Cognitive Assessment (MoCA); Schizophrenia Quality of Life Scale (SQLS); Life Skills Profile (LSP); Positive and Negative Syndrome Scale (PANSS).Results: Forty-four patients fulfilled the inclusion criteria. The mean age was 46 years; the average length of the history of the disease at recruitment was 23 years with an average age at first episode of psychosis (FEP) of 23 years. General psychopathology, neurocognition, and integration recovery style can predict psychosocial functioning and explain ~54% of the LSP variance; RS total score and PANSS general psychopathology score can predict and explain ~29% of the LSP variance. A negative association between PANSS general psychopathology and LSP total score supports the need to reduce first the symptomatology, and then successfully apply other types of interventions. A strong positive association between neurocognition and life functioning was detected, showing that deficits in neurocognition have proved to be important predictors of the functional outcome. Integration was also proven to be significantly associated with a good functional outcome. Psychotic symptoms turn out to be a negative predictive factor, whereas resilience can be hypothesized as a protective factor.Conclusions: Resilience and recovery style “integration” can be considered as two complementary predictive resources for a good outcome; this result supports the need to set up personalized treatments, based on the characteristics of the patients.

Obsessive-compulsive symptoms in patients with schizophrenia: Relationships with olanzapine pharmacological parameters, psychopathology, and quality of life

Obsessive-compulsive symptoms (OCS) occur in a substantial portion of schizophrenia patients and have significant impacts on clinical course. This study was intended to investigate the relationships of OCS with pharmacological parameters of olanzapine, psychopathology, and quality of life. Totally 151 schizophrenia patients were recruited, and rated using Yale-Brown Obsessive-Compulsive scale (YBOCS), Positive and Negative Syndrome Scale (PANSS), Montgomery-Åsberg Depression Rating Scale (MADRS), and World Health Organization Questionnaire on Quality of Life: Short Form (WHOQOL-BREF). The concentrations of olanzapine and N-desmethylolanzapine were determined by HPLC. Twenty-five patients (16.6%) revealed the presence of OCS. OCS group had significantly higher olanzapine dose, more numbers of past hospitalizations, higher PANSS total, positive, negative, and general psychopathology scores, and higher MADRS score than those in non-OCS group. The WHOQOL-BREF physical subscale score in schizophrenia patients with OCS was significantly lower. Olanzapine dose, PANSS score, and MADRS score were significantly correlated with YBOCS score. Our findings highlight that OCS is highly prevalent in schizophrenia patients under olanzapine treatment, especially those at high doses. Schizophrenia patients with OCS had higher severity of psychotic and depressive symptoms and poorer quality of life. Clinicians should monitor OCS in patients with schizophrenia receiving olanzapine treatment.

Investigation of Psychological Flexibility in Patients with Schizophrenia

The application of psychotherapies in schizophrenia is becoming increasingly common. Although studies showing the effectiveness of Acceptance and Commitment Therapy (ACT) in patients with schizophrenia based on the psychological flexibility model are increased, there is insufficient information on the mechanisms of action. Our study aims to evaluate the validity of psychological flexibility and the relationship between clinical features in patients with schizophrenia. The study included participants between 18-65 years old, consisted of 110 patients who had been diagnosed with schizophrenia and 110 healthy individuals. Participants in both groups filled Sociodemographic Data Form, Cognitive Fusion Questionnaire(CFQ), Valued Living Questionnaire(VLQ), Self-as-Context Scale(SACS), Freibirg Mindfulness Inventory(FMI) and Acceptance and Action Questionnaire(AAQ-II), in addition, Positive and Negative Syndrome Scale(PANNS) was applied to schizophrenia group by clinicians. The patient and control groups were matched in terms of age, gender, and educational level;. The points in the schizophrenia group AAQ-II and CFQ were higher; and the points of SACS, FMI and VLQ were found lower. Furthermore, the PANNS positive subscale points, SACS, AAQ-II points on the schizophrenia group; PANNS negative subscale points with SACS, VLQ, FMI, AAQ-II points were found associated with each other. PANSS general psychopathology was associated with subscale scores of CCQ, VLQ, FMI and AAQ-II points, PANSS total scores were also associated with SACS, VLQ, FMI, AAQ-II. In this study, it was found that schizophrenia patients were more inflexible than healthy individuals. Our results also imply that psychological flexibility components are related to clinical features of patients. The contribution of the psychological flexibility model to the treatment of schizophrenia patients should be investigated with advanced clinical studies.

Development of a Scoring Guide for the Positive and Negative Syndrome Scale(PANSS) Abstract Thinking Subscale

Background: The Positive and Negative Syndrome Scale (PANSS) is a widely used instrument for symptom severity assessment in schizophrenia. Its Abstract Thinking item (N5) was developed for the assessment of thought disorder. This item currently lacks examples of correct and incorrect responses to similarities and proverb items. Different raters may judge these items as correct or incorrect based on their own level of abstraction, cultural background, and familiarity with possible responses. Precision in scoring is especially important, when the instrument is used to evaluate changes in schizophrenia symptoms over time and with treatment. This study proposes a new method of scoring the N5 subscale. Objectives: The aim of the present study was to develop a new scoring guide for the PANSS N5 Similarities and Proverbs scale and to assess inter-rater reliability using the newly developed scoring guide. Method: The authors analysed responses to PANSS questions of subjects who completed a double blind, randomized, placebo controlled clinical trial of oral naltrexone for treatment of alcohol use disorders in schizophrenia. Results: Of the 90 subjects, 45 had schizophrenia and 45 had schizoaffective disorder. 95% of subjects had alcohol dependence, 5% had alcohol abuse. Subjects consumed a median of 21 standard drinks per week at study entry. Participants had low to moderate PANSS Positive, Negative, and General Psychopathology scores. 434 different responses to similarities and 748 different responses to proverbs were sorted independently by two psychologists using a newly developed scoring guide for N5. The guide sorted responses into 4 categories, from correct to marginal, to concrete, to incorrect; examples of almost each type of responses were provided in the guide. Inter-rater reliability for scoring all Similarities responses was 93%, Weighed Cohen Kappa 0.83, p< .001; for scoring all Proverbs was 87%, Weighted Cohen Kappa 0.62, p<.001. Conclusion: Strong inter-rater reliability was achieved using a newly-developed scoring guide for Similarities and Proverbs of PANSS. The Guide could be used to improve accuracy of scoring PANSS N5.

Sex difference in association of symptoms and white matter deficits in first-episode and drug-naive schizophrenia

Accumulating evidence shows that disruption of white matter (WM) may be involved in the pathophysiology of schizophrenia, even at the onset of psychosis. However, very few studies have explored sex difference in its association with psychopathology in schizophrenia. This study aims to compare sex differences in clinical features and WM abnormalities in first-episode and drug-naive (FEDN) schizophrenia among Han Chinese inpatients. The WM fractional anisotropy (FA) values of the whole-brain were determined using voxel-based diffusion tensor imaging (DTI) in 39 (16 males and 23 females) FEDN patients with schizophrenia and 30 healthy controls (13 males and 17 females) matched for gender, age, and education. Patient psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS).Our results showed that compared with the controls, the patients showed widespread areas of lower FA, including corpus callosum, brainstem, internal capsule, cingulate, and cerebellum (all adjusted p < 0.01). Further, male patients showed lower FA values in left cingulate (F = 4.92, p = 0.033), but higher scores on the PANSS total, positive, and general psychopathology subscale scores (all p < 0.01) than female patients. Multivariate regression analysis showed that for male patients, FA values in right corpus callosum were positively associated with the PANSS total (beta = 0.785, t = 3.76, p = 0.002) and the negative symptom scores (beta = 0.494, t = 2.20, p = 0.044), while for female patients, FA values in left cingulate were negatively associated with the PANSS positive symptom score (beta = −0.717, t = −2.25, p = 0.041). Our findings indicate sex difference in white matter disconnectivity and its association with psychopathological symptoms in an early course of schizophrenia onset.

Obesity, altered oxidative stress, and clinical correlates in chronic schizophrenia patients

Antipsychotic pharmacotherapy is strongly obesogenic and is associated with increased oxidative stress in patients with schizophrenia. However, whether these changes reflect psychopathology, antipsychotic efficacy, or some other factor is not known. Our study aims to investigate the degree of oxidative stress in different BMI categories and to identify clinical symptomatology that may be paired with increased oxidative stress in a schizophrenia population. To this end, we performed a cross-sectional study and recruited 89 long-term inpatients with schizophrenia and collected the following variables: plasma malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), routine biochemical analysis, and psychopathology through the Positive and Negative Syndrome Scale (PANSS). The results indicate that the levels of the lipid peroxidation product, MDA, were significantly higher in the high BMI group than the low (normal) BMI group. As expected, high BMI was associated with an atherogenic lipid profile; however, it was also associated with fewer psychopathological symptoms. Multiple regression analysis found that MDA levels, the PANSS general psychopathology subscore, and triglyceride levels (all p < 0.05) were independent contributors to the BMI in patients. These results suggested that oxidative stress may play an important role in antipsychotic-induced weight gain. Further investigations using the longitudinal design in first-episode schizophrenia patients are needed to explore the beneficial effect of antioxidants on the abnormal lipid metabolism mediated by antipsychotic treatment.

Mapping the Positive and Negative Syndrome Scale scores to EQ-5D-5L and SF-6D utility scores in patients with schizophrenia

ObjectiveThe current study aims to map the Positive and Negative Syndrome Scale (PANSS) onto the five-level EuroQol five-dimensional (EQ-5D-5L) and Short Form six-dimensional (SF-6D) utility scores for patients with schizophrenia.MethodsA total of 239 participants with schizophrenia spectrum disorder were recruited from a tertiary psychiatric hospital in Singapore. Ordinary least squares (OLS), censored least absolute deviations and Tobit regression methods were employed to estimate utility scores from the EQ-5D-5L and SF-6D. Model selection of the 18 regression models (three regression methods × six model specifications) was primarily determined by the smallest mean absolute error and mean square error, and the largest R2 and adjusted R2.ResultsThe mean age of the sample was 39.7 years (SD = 10.3). The mean EQ-5D-5L and SF-6D utility scores were 0.81 and 0.68, respectively. The EQ-5D-5L utility scores were best predicted by the OLS regression model consisting of three PANSS subscales, i.e. positive, negative and general psychopathology symptoms, and covariates including age and gender. The SF-6D was best predicted by OLS regression model consisting of five PANSS subscales, i.e. positive, negative, excitement, depression and cognitive subscales.ConclusionThe current study provides important evidence to clinicians and researchers on mapping algorithms for converting PANSS scores into utility scores that can be easily applicable for cost–utility analysis when EQ-5D-5L and SF-6D data are not available for patients with schizophrenia spectrum disorder in Singapore.

Disease Severity in Treatment Resistant Schizophrenia Patients Is Mainly Affected by Negative Symptoms, Which Mediate the Effects of Cognitive Dysfunctions and Neurological Soft Signs.

This post-hoc study was aimed at assessing whether disease severity was higher in a sample of Treatment Resistant Schizophrenia patients (TRS) compared to schizophrenia patients responsive to antipsychotics (non-TRS). Determinants of disease severity were also investigated in these groups. Eligible patients were screened by standardized diagnostic algorithm to categorize them as TRS or non-TRS. All patients underwent the following assessments: CGI-S; PANSS; DAI; NES; a battery of cognitive tests. Socio-demographic and clinical variables were also recorded. TRS patients exhibited significantly higher disease severity and psychotic symptoms, either as PANSS total score or subscales' scores. A preliminary correlation analysis ruled out clinical and cognitive variables not associated with disease severity in the two groups. Hierarchical linear regression showed that negative symptoms were the clinical variable explaining the highest part of variation in disease severity in TRS, while in non-TRS patients PANSS-General Psychopathology was the variable explaining the highest variation. Mediation analysis showed that negative symptoms mediate the effects of verbal fluency dysfunctions and high-level neurological soft signs (NSS) on TRS' disease severity. These results show that determinants of disease severity sharply differ in TRS and non-TRS patients, and let hypothesize that TRS may stem from cognitive disfunctions and putatively neurodevelopmental aberrations.

Serum levels of TNF-alpha in patients with chronic schizophrenia during treatment augmentation with sarcosine (results of the PULSAR study)

Sarcosine, glycine transporter inhibitor, increases glycine levels around NMDA receptor, improving primary negative symptoms of schizophrenia. The aim of our study was to find a potential relationship between initial TNF-alpha level, its changes and schizophrenia symptoms severity, resulting from adding sarcosine to a stable antipsychotic treatment. Sixty subjects with stable schizophrenia were randomized to receive either 2 g of sarcosine or placebo and completed a 6-month, double blind, placebo-controlled study. Three patients on sarcosine and one taking placebo did not complete TNF-alpha tests, planned at the beginning, after 6 weeks and after 6 months. For clinical assessments we used PANSS and CDSS scales. No changes in TNF-alpha serum concentrations in both groups at any time-points was noted. The sarcosine group achieved significant improvement in negative symptoms, general psychopathology and total PANSS score group, however without any significant correlations between TNF-alpha levels and PANSS scores in all assessments. Positive correlations between TNF-alpha levels and CDSS score were found in the placebo group and total study group. Initial TNF-alpha concentrations cannot be used as a predictor of the improvement resulting from adding sarcosine. Sarcosine does not significantly affect TNF-alpha levels. TNF-alpha may be involved in mechanisms related to depressive symptomatology in schizophrenia.

COMT Val 108/158 Met polymorphism and treatment response to aripiprazole in patients with acute schizophrenia.

IntroductionThe COMT Val 108/158 Met polymorphism (rs4680) may affect treatment response to antipsychotics, as well as metabolism and dynamics of neurotransmitters during the treatment of schizophrenia. We investigated the effects of the COMT Val 108/158 Met polymorphism on treatment response to aripiprazole and plasma monoamine metabolite levels in patients with acute schizophrenia.Materials and methodsForty patients with schizophrenia were treated with aripiprazole for 6 weeks. We measured Positive and Negative Syndrome Scale (PANSS) and plasma levels of homovanillic acid (HVA) and plasma MHPG (3-methoxy-4-hydroxyphenethyleneglycol) at baseline and endpoint. The COMT Val 108/158 Met polymorphism was genotyped with the polymerase chain reaction and restriction fragment length polymorphism.ResultsThere were significant genotype–time interactions on PANSS total and general psychopathology scores, with Met/Met genotype showing greater improvement. The response rate to aripiprazole did not differ between COMT Val 108/158 Met genotype groups. We found a significant time effect on plasma MHPG levels, but no time effect on plasma HVA levels or time–genotype interactions in the plasma levels of HVA and MHPG. Although the responder rate did not differ among the 3 genotype groups.ConclusionOur results suggest that individuals with the Met/Met genotype had greater improvement in PANSS score after the treatment with aripiprazole. On the other hand, the Val 108/158 Met polymorphism may not induce changes in plasma levels of monoamine metabolites during aripiprazole treatment. Because of the small sample size, further studies are needed to confirm and to extend our results.

Effect of postoperative systemic antipsychotic therapy on psychiatric recurrence in patients with meningiomas

A number of patients with meningiomas and psychiatric disorders will suffer psychiatric symptom recurrence following tumorectomies. The present study reported a retrospective analysis regarding 42 cases of patients with meningiomas using complete clinical follow-up data from June 2005 to June 2013. The patients were divided into the systemic antipsychotic (SP) group (n=20) following 6months of postoperative SP therapy and the none-SP (NSP) group (n=22), who did not receive postoperative antipsychotic treatment. Patients were assessed using the Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) at the time points of prior to surgery, immediately following surgery, and 6 months, 12 months and 3 years following surgery. The effective rate, recurrence rate, rehospitalization rate and survival analysis were calculated. The BPRS score and PANSS scores (including PANSS positive, PANSS negative, PANSS general psychopathology and PANSS overall) in the SP group at 6 months, 12 months and 3 years following surgery were significantly decreased compared with the NSP group (P<0.05). The effective rate was 95, 90 and 90% at 6 months, 12 months and 3 years, respectively, in the SP group, whilst it was 68.2, 63.6 and 59%, respectively, in the NSP group, which was statistically significant (χ2=4.89, χ2=4.01 and χ2=5.12; P<0.05). The recurrence rate of the SP group was 0, 5 and 10% at 6 months, 12 months and 3 years, respectively, whilst in the NSP group it was 22.7, 31.8 and 54.5%, respectively, which was statistically significant (χ2=5.16, χ2=4.89 and χ2=9.34; P<0.05). The rehospitalization rate of the SP group was 0, 0 and 5% at 6 months, 12 months and 3 years, respectively, whilst in the NSP group it was 13.6, 22.7 and 36.4%, respectively, and the data at 12 months and 3 years was statistically significant (χ2=5.16 and χ2=6.12; P<0.05). Kaplan-Meier survival analysis indicated that the accumulative survival rates of recurrence and rehospitalization in the SP group were improved compared with the NSP group. The log-rank of recurrence was χ2=9.369 (P=0.002) and the log-rank of rehospitalization was χ2=6.330 (P=0.012). In conclusion, postoperative SP therapy is of great importance to the consolidation of mental symptoms in patients with meningiomas and psychiatric symptoms, and it may significantly reduce the recurrence and rehospitalization rates.

F238. COMPETENCE-PERFORMANCE DISCREPANCY IN SOCIAL FUNCTIONING IN PATIENTS WITH SCHIZOPHRENIA: THE IMPACT OF SOCIAL ANXIETY

BackgroundSocial functioning deficits are of critical importance in patients with schizophrenia, because they affect the long-term outcomes and quality of life (QOL) of the patients. Two aspects of social functioning, namely, competence (ability to perform skilled activities, that is, what one can do) and performance (actual performance of skilled activities, that is, what one actually does) are considered to have a significant influence on how well the patients can live independently in the community. Although the two aspects are usually thought to go hand in hand, discrepancy between the two is often observed in patients with schizophrenia in clinical practice. Some patients are not able to function in the community to the best of their ability; some patients appear to get along everyday living better than they would be expected to. The aim of the present study was to identify factors influencing the occurrence of such discrepancy of social functioning in patients with schizophrenia.MethodsA total of 205 stable outpatients with schizophrenia aged 40 years old or under were recruited at the Toho University Omori Medical Center, Tokyo. Of the 205 patients, 100 were male (48.8%) and 105 (51.2%) were female. The mean age of the participants was 29.3 years and the mean estimated premorbid IQ was 100.8. The mean age at disease onset was 22.0 years old, and the mean duration of illness at the start of the study was 6.7 years. The social functioning, psychiatric symptoms, social anxiety, cognitive function, and QOL of the participants were assessed. The patients were divided into 4 groups by the cutoff points for competence and performance calculated using a comprehensive dataset of the Social Functioning Scale (SFS) obtained from multiple facilities.ResultsThe subjects were divided according to their level of competence and performance as follows: good competence and good performance (CP) group, 108 (52.7%) patients; good competence but poor performance (Cp) group, 40 (19.5%) patients; poor competence but good performance (cP) group, 13 (6.3%) patients; poor competence and poor performance (cp) group, 44 (21.5%) patients. Among the 4 groups, the objects of particular interest in this study were the differences between CP and Cp groups and between the cP and cp groups. One-way ANOVA revealed significant differences among the groups in the scores on the Positive and Negative Syndrome Scale (PANSS), Liebowitz Social Anxiety Scale (LSAS), Global Assessment of Functioning Scale (GAF), World Health Organization-Quality of Life 26 (WHOQOL26), and Social Functioning Scale (SFS). Post-hoc comparisons revealed that the PANSS negative symptoms and general psychopathology scores, GAF score, WHOQOL26 score, and SFS total score were significantly worse in the Cp group than in the CP group, and that the LSAS score, GAF score, WHOQOL26 score, and SFS total score were significantly better in the cP group than in the cp group.DiscussionIn patients who are capable of living well in the community but do not perform well, negative symptoms may be involved in this discrepancy of social functioning. Patients who are able to maintain themselves well despite their poor social competence appear to have milder social anxiety symptoms as compared to patients who are neither competent nor capable of performing well in terms of social functioning in the community. Suitable and personalized approaches based on the patients’ profile of dysfunction would seem to be indispensable for the recovery of such patients.

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.

F58. COMMUNITY-BASED MULTI-SITE RANDOMIZED CONTROLLED TRIAL OF BEHAVIORAL ACTIVATION FOR NEGATIVE SYMPTOMS OF INDIVIDUALS WITH CHRONIC SCHIZOPHRENIA

BackgroundAs existing treatments for negative symptoms in schizophrenia have limited empirical support, development of effective treatments for negative symptoms in schizophrenia is in urgent need. Behavioral activation (BA), which is an evidence-based treatment for depression, is a promising candidate treatment for negative symptoms as it proved its feasibility and preliminary efficacy in non-randomized controlled trial for community dwelling individuals with chronic schizophrenia (Choi et al., 2015; Mairs et al., 2011). The primary purpose of the current study was to investigate whether BA would improve negative symptoms as compared with treatment as usual (TAU) for community dwelling individuals with chronic schizophrenia in a multi-site randomized controlled trial. In addition, we explored whether BA would improve other psychiatric symptoms, quality of life and neuro-cognitive functioning.MethodsFor multi-site trials, mental health professionals were trained with BA manual (Choi et al., 2015) and their fidelity was checked by the authors. BA was delivered in a group format once a week for 10 weeks. Participants aged 18 years or older were recruited from community mental health centers and day hospitals in Seoul and Gyeonggi-do area. A total of seventy-two patients with negative symptoms of schizophrenia were randomly assigned into either BA+TAU or TAU. As a primary outcome, negative symptoms were measured using clinical interviews (e.g., BNSS, CAINS, PANSS negative symptoms factor) and self-report questionnaires (i.e., MAP-SR) before and after the 10-week treatments. The secondary outcome measures included other psychiatric symptoms, quality of life, and neuro-cognitive assessment.ResultsBA was well accepted by community dwelling individuals with chronic schizophrenia (drop-out rates of BA+TAU and TAU, 10% and 14%, respectively). Intention-to-treat analyses indicated that compared to TAU condition, BA+TAU group showed greater improvement in negative symptoms, as measured by CAINS, BNSS, and PANSS negative symptom factor (Time*Group interaction effects, F=7.476, p<.01 for CAINS total; F=5.663, p<.05 for BNSS total; F=6.092, p<.05 for PANSS negative symptoms factor). In addition, the results indicated group differences in favor of BA+TAU on the PANSS general psychopathology factor and the Quality of Life, but not neurocognitive functioning (Time*Group interaction effects, F=5.660, p<.05 for PANSS general psychopathology factor; F=7.541, p<.01 for QOL total).DiscussionThe results of the current study demonstrate the feasibility and the efficacy of BA+TAU for negative symptoms of community dwelling individuals with chronic schizophrenia as compared to TAU when delivered by BA trained mental health professionals. Thus, it is speculated that BA is an effective adjunct psychosocial approach to usual comprehensive psychiatric rehabilitation for negative symptoms. Since the current study is ongoing and follow-up data will be available by the time of presentation at SIRS 2018, it will be examined whether benefits of BA would be maintained 3 months after the termination of 10-week BA treatment.

Early-onset psychosis: What is the diagnostic outcome?

Background and objectivesSchizophrenia and bipolar disorder may show overlapping symptom profiles especially in early-onset cases. The aim of this study was to establish a final diagnosis, examine possible similarities and differences in symptom presentations, and overall functioning of patients with early-onset psychotic episode. MethodsAdolescents, presenting with at least one psychotic symptom, who were clinically followed up for at least 6 months, constituted our sample. Psychiatric diagnoses were established by using Schedule for Affective Disorders and Schizophrenia for School Aged Children Present-Lifetime Version (K-SADS-PL), psychotic symptoms were assessed by Positive and Negative Syndrome Scale (PANSS), and level of functioning was determined by Children's Global Assessment Scale (CGAS). ResultsOf 51 patients, 55% received a diagnosis of Psychotic Disorder (PD) and 45% a Mood Disorder (MD). Besides a major overlap in symptom presentation, there were significant differences in distribution. Hallucinations, disorganized speech, and withdrawal/isolation were encountered significantly more in the PD group, whereas hyperactivity, increased speech, and aggression were significantly more frequent in the MD group. PANSS positive, negative, and general psychopathology scores were significantly higher in the PD group. The difference was more pronounced in terms of PANSS negative scores. Overall functioning was similar in two groups. ConclusionsAdolescents with early-onset psychotic episodes present with a combination of psychotic and mood related symptoms. Initial assessments may have the risk of misdiagnosis. During follow-up, clinicians should not underestimate the possibility of a mood disorder with psychotic features, whereas negative psychotic symptoms may have a discriminative value in favor of psychotic disorders.

P.1.017 - New link between inflammation and schizophrenia: IgG with nuclease activity

Introduction Schizophrenia is known to be associated with the disorganization of neurotransmission processes in the brain as well as immunological disturbances [1]. Inflammation in the perinatal period can lead to a violation of synaptic plasticity and pruning of synapses in the adulthood [2]. Also, microRNAs play an important role in neuronal development. The microRNA expression profiles in the circulation and brain are altered in schizophrenia. It is shown that a change in the levels of microRNAs in the blood serum or brain leads to a violation of behavior [3]. We have shown that the formation of catalytic antibodies (abzymes) is one of the signs of immune system pathology. Catalytic antibodies hydrolyzing DNA were detected in the serum of patients with schizophrenia [4]. We assume that antibodies hydrolyzing the circulating regulatory nucleic acids can play a role in schizophrenia pathogenesis. Objectives To investigate a) microRNA-hydrolyzing activity of IgG antibodies from the serum of patients with schizophrenia; b) correlation of the microRNA-hydrolyzing activity level with clinical features of the disease; c) the cytotoxicity of isolated IgG on the human neuroblastoma cell culture IMR-32. Materials and Methods In our study, 35 patients with a verified diagnosis of simple or paranoid schizophrenia and 20 healthy donors were included. The average age in the group of patients was 35.8±8.9 years, duration of disease – 9.1±5.4 years. Electrophoretically and immunologically homogeneous IgGs were obtained by affinity chromatography of the serum proteins under conditions removing non-specifically bound proteins. The microRNA-hydrolyzing activity of IgG was detected by the level of hydrolysis of two neuro-specific fluorescently labeled microRNAs (miR-137 and miR-219a-2-3p). The products of the hydrolysis were analyzed by PAGE under denaturing conditions using laser scanner. Cytotoxicity of antibodies on human neuroblastoma cell culture IMR-32 was studied using MTT-test. Statistical analysis was carried out using the Pearson’s correlation in the Statistica 10 software. Results We have shown for the first time that IgG from all schizophrenia patients possesses microRNA-hydrolyzing activity. Using strict criteria, we proved that the observed activity is an intrinsic property of IgGs in schizophrenia. Interestingly, the microRNA-hydrolyzing activity level on miR-137 is strongly negatively correlated with the disease duration (R=–0.879). The activity decreased with increasing duration of the disease. Also, the level of RNase activity on miR-219a-2-3p was positively correlated with the values of the General Psychopathology PANSS scale and the PANSS Total score (R>0.8). It was shown that the RNase activity is metal-dependent. The kinetic parameters of nuclease reactions catalyzed by IgG were significantly lower than that for native enzymes. Besides, we detected the major hydrolysis sites of two neuro-specific microRNAs. Also, we show that IgG from schizophrenia patients with nuclease activity reduced the survival rate neuroblastoma IMR-32 cell culture by 10-28%. Conclusion We propose that immunological disorders can play an important role in schizophrenia, especially in the prodromal period. The environment and genetic predisposition can lead to inflammation and the formation of antibodies hydrolyzing the microRNAs. These antibodies can contribute to changes in the level of circulating microRNAs and schizophrenia development.

Efficacy and Tolerability of Clozapine versus Quetiapine in Treatment-resistant Schizophrenia.

Objectives:To compare the efficacy and tolerability of clozapine and quetiapine in patients with treatment-resistant schizophrenia (TRS).Patients and Methods:In this prospective, randomized, open label study of 14 weeks, 53 patients with schizophrenia diagnosed as per ICD-10 and fulfilling the modified version of Conley and Kelly's criteria of TRS were randomly assigned to receive clozapine or quetiapine as per a computer-generated random table. After 2-weeks of dose-titration phase, doses were fixed at minimum therapeutic dose and subsequently adjusted according to the clinical improvement. All patients received dosage of respective drug in therapeutic range. 13 patients were lost to follow up. Treatment efficacy and side effects were evaluated with standardized rating scales.Results:Clozapine group (reduction in total score: mean=14.45, SD=10.39) had significantly greater reductions (P=0.004; CI=3.541-17.059) in the Positive and Negative Syndrome Scale (PANSS) total score, PANSS positive subscale and PANSS general psychopathology subscale at 14 weeks in comparison to the quetiapine group (reduction in total score: mean=4.15, SD=10.71). Significant reduction in PANSS negative subscale was seen with both drugs but no significant difference was present between the two drugs. At 14 weeks, 30% patients in clozapine group and 15% patients in quetiapine group showed response. Clozapine led to significantly greater side effects (P< 0.001, CI=2.241-6.059) on Glassgow Antipsychotic Side-effect Scale (GASS) than quetiapine.Conclusions:Clozapine was found to be more efficacious than quetiapine in patients with TRS but was associated with greater side effects. Both the drugs were found to be equally effective in reducing the negative symptoms.

Association of schizophrenia onset age and white matter integrity with treatment effect of D-cycloserine: a randomized placebo-controlled double-blind crossover study

BackgroundIt has been reported that drugs which promote the N-Methyl-D-aspartate-type glutamate receptor function by stimulating the glycine modulatory site in the receptor improve negative symptoms and cognitive dysfunction in schizophrenia patients being treated with antipsychotic drugs.MethodsWe performed a placebo-controlled double-blind crossover study involving 41 schizophrenia patients in which D-cycloserine 50 mg/day was added-on, and the influence of the onset age and association with white matter integrity on MR diffusion tensor imaging were investigated for the first time. The patients were evaluated using the Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Brief Assessment of Cognition in Schizophrenia (BACS), and other scales.ResultsD-cycloserine did not improve positive or negative symptoms or cognitive dysfunction in schizophrenia. The investigation in consideration of the onset age suggests that D-cycloserine may aggravate negative symptoms of early-onset schizophrenia. The better treatment effect of D-cycloserine on BACS was observed when the white matter integrity of the sagittal stratum/ cingulum/fornix stria terminalis/genu of corpus callosum/external capsule was higher, and the better treatment effect on PANSS general psychopathology (PANSS-G) was observed when the white matter integrity of the splenium of corpus callosum was higher. In contrast, the better treatment effect of D-cycloserine on PANSS-G and SANS-IV were observed when the white matter integrity of the posterior thalamic radiation (left) was lower.ConclusionIt was suggested that response to D-cycloserine is influenced by the onset age and white matter integrity.Trial registrationUMIN Clinical Trials Registry (number UMIN000000468). Registered 18 August 2006

Effects of adjunctive fluvoxamine on metabolic parameters and psychopathology in clozapine-treated patients with schizophrenia: A 12-week, randomized, double-blind, placebo-controlled study

ObjectiveNumerous studies have demonstrated that fluvoxamine has considerable pharmacokinetic and pharmacodynamic interactions with clozapine. We conducted a 12-week, randomized, double-blind, placebo-controlled study to evaluate the effects of fluvoxamine on metabolic parameters and psychopathology in clozapine-treated patients with schizophrenia. MethodsWe recruited 85 patients who received a DSM-IV diagnosis of schizophrenia. Eligible patients were randomized to receive fluvoxamine 50mg/day plus clozapine 100mg/day or clozapine 300mg/day. We studied metabolic parameters, psychopathology, and drug levels at baseline and 4, 8, and 12weeks after the intervention. Plasma levels of clozapine, norclozapine, clozapine N-oxide, and fluvoxamine were determined using high-performance liquid chromatography with ultraviolet detection. ResultsNo significant difference was observed in baseline characteristics between the two groups. Clozapine–fluvoxamine combined treatment significantly attenuated the increments in body weight, insulin resistance, and levels of insulin, glucose, and triglycerides compared with clozapine monotherapy. Both groups exhibited significant improvements in their Positive and Negative Syndrome Scale (PANSS) total and negative scores. The combined treatment group showed significant reduction in the PANSS general psychopathology scores compared with the monotherapy group. No difference was observed in the plasma clozapine level between the two groups. The monotherapy group showed higher levels of norclozapine and clozapine N-oxide than the combined group. ConclusionsCompared with clozapine monotherapy, treatment with adjunctive fluvoxamine with clozapine for 12weeks can alleviate body weight gain and metabolic abnormalities in patients with schizophrenia, without sacrificing the clinical effect. Clinicians should interpret these findings cautiously considering the short duration of this study.The study was registered at www.clinicaltrials.gov (NCT01401491).

Prevalence, demographic and clinical features of comorbid depressive symptoms in drug naïve patients with schizophrenia presenting with first episode psychosis

Depressive symptoms are common in first episode schizophrenia. However, the prevalence and its associations of comorbid depressive symptoms with clinical variables are less well characterized in Chinese Han patients with schizophrenia. In this cross-sectional study, we recruited 240 first-episode and drug naïve (FEDN) inpatients with schizophrenia. All patients were rated on the 17-item Hamilton Depression Rating Scale (HAMD-17) to measure depressive symptoms, and also on the Positive and Negative Syndrome Scale (PANSS) for psychopathology. Our results showed that 131 patients had a total score of 8 or more points on HAMD-17, making the prevalence of comorbid depressive symptoms 54.6%. Fewer women (48.1%, 62 of 129) than men (62.2%, 69 of 111) had comorbid depressive symptoms. Compared to those patients without depressive symptoms, those with depressive symptoms showed higher PANSS total, general psychopathology, cognitive factor and negative symptom scores (all p<0.05). Further stepwise multiple logistic regression analysis indicated that the PANSS general psychopathology, the PANSS total score and gender (all p<0.05) remained significantly associated with depressive symptoms. In addition, correlation analysis showed significant correlations between HAMD total score and the following parameters: the PANSS general psychopathology, total score, and cognitive factor (Bonferroni corrected p's<0.05). Our results suggest that depressive symptoms occur with high prevalence in FEND schizophrenia in a Chinese Han population, and show association with general psychopathology, as well as with cognitive impairment.