Positive And Negative Syndrome Scale Negative Scores Research Articles

Brain-Derived Neurotropic Factor Serum Level and Severity Symptom of Bataknese Male Patients with Schizophrenia in North Sumatera, Indonesia.

BACKGROUND:Schizophrenia is a severe mental disorder that is multi-causative and multi-factor, generally affecting about 1% of the population. The elevation level of brain-derived neurotrophic factor (BDNF) offers several protections from other neurodegenerative processes that occur in schizophrenia since this deficit of neurotrophic factors can contribute to changes in brain structure and function that underlie the schizophrenia psychopathology.AIM:To analyse the correlation between BDNF serum levels and symptom severity by using the Positive and Negative Syndrome Scale (PANSS) instrument in Bataknese male patients with schizophreniaMETHODS:This study was a correlative analytical study with a cross-sectional approach using the Positive and Negative Syndrome Scale (PANSS) instrument to assess symptom severity with 60 subjects of Bataknese male patients with chronic schizophrenia. Moreover, this research was conducted at the Psychiatric Hospital of Prof. Dr M. Ildrem Medan, Indonesia. BDNF serum was analysed with the Quantitative sandwich enzyme immunoassay technique by via Quantikine ELISA Human CXCL8/IL-8 HS. Also, the data analysis was performed through Spearman’s correlative bivariate analytics using SPSS software.RESULTS:A negative correlation between the BDNF serum level and the negative scale PANSS score in men with schizophrenia (r = -0.820, p < 0.001) was found. Moreover, there is a negative correlation between BDNF serum levels and PANSS total scores in men with schizophrenia (r = -0.648, p < 0.001)CONCLUSION:BDNF serum level in Bataknese male patients with schizophrenia has a relationship that affects the severity of symptoms in schizophrenic patients, especially for negative symptoms.

Open Trial of the Addition of Divalproex Sodium for Improving the Symptoms of Batak and Non-Batak Males with Schizophrenia in North Sumatra, Indonesia

Background: Ethnicity is one of many intrinsic factors influencing the drug response and its severity in patients with schizophrenia. In North Sumatera, Indonesia, information is very limited on the effect of divalproex sodium in Batak and non-Batak tribes. Objectives: The study aimed to investigate differences in positive and negative syndrome scale (PANSS) scores between Batak and non-Batak males with schizophrenia receiving risperidone treatment alone or in combination with divalproex sodium. Methods: This open trial experimental study was conducted on 60 Batak and non-Batak male subjects with schizophrenia. The doses of divalproex sodium and risperidone were 1500 mg and 6 mg, respectively. The sample was obtained from Prof. Dr. M. Ildrem Psychiatric Hospital, North Sumatra, Indonesia, in a span of six months from September 2017 to February 2018. The mini international statistical classification of diseases-10 (Mini ICD-10) structured interviews were used for diagnosis. Results: There were no differences between the Batak and Non-Batak groups in the PANSS positive subscale score (P = 0.766), PANSS negative subscale score (P = 0.789), and PANSS total score (P = 0.673) in six weeks of observation. Conclusions: There were no significant differences in the PANSS scores between males with schizophrenia from Batak and non-Batak tribes who received risperidone monotherapy or combined with divalproex sodium.

Elevated serum anti-NMDA receptor antibody levels in first-episode patients with schizophrenia

Accumulating evidence has shown that N-methyl-D-aspartate (NMDA) glutamate receptors (NMDAR) are implicated in the pathophysiology of neurological and psychiatric disorders, and that patients with NMDAR antibody encephalitis develop psychopathological symptoms. Therefore, we hypothesized that NMDAR antibodies play a key role in the etiology of schizophrenia. In this study, we enrolled 110 first-episode patients with schizophrenia (FEP) and 50 healthy controls (HC). Cognitive function and psychopathology were assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) and Positive and Negative Syndrome Scale (PANSS), respectively. NMDAR antibody levels were measured using enzyme-linked immunosorbent assay. Our results showed that FEP with schizophrenia exhibited cognitive deficits in all domains of the MCCB and had elevated levels of serum anti-NMDAR antibody compared with the healthy controls (9.2 ± 3.5 vs. 7.3 ± 2.9 ng/ml, t = 3.10, p = 0.002). Furthermore, serum antibody levels were positively correlated with PANSS positive, negative and total score, and inversely correlated with performances of verbal learning and memory, working memory, speed of processing and MCCB total score in the patient group. These results indicate that elevated levels of NMDAR antibody may play a role in the pathogenesis of schizophrenia, leading to NMDAR dysfunction, thereby inducing symptoms of psychosis and cognitive impairment. Therefore, NMDAR antibodies may serve as a biomarker and provide a new avenue for treatment of schizophrenia.

24.1 VERBAL COMMUNICATION DISORDERS IN SCHIZOPHRENIA SPECTRUM PATIENTS: SYMPTOM AND SIDE EFFECT

Background: Verbal communication disturbances are a key diagnostic feature of schizophrenia. These disturbances present in different aspects, which can be assessed by looking at form and meaning. However, research on this topic is often confounded by the effects of antipsychotic medication. It therefore remains unclear which aspects of language production are influenced by antipsychotics, and which disturbances can be viewed as true psychotic symptoms. Automated language analysis has recently shown to be a useful tool to characterize verbal communication disturbances in schizophrenia. Methods: The spoken language of 42 healthy controls and 48 patients with a schizophrenia spectrum disorder was recorded using a semi-structured interview designed to elicit spontaneous speech in a natural setting. The audio was analyzed for measures of speed and quantity. For a subset of participants, the transcribed interview was analyzed using a novel Natural Language Processing (NLP) word2vec model to quantify incoherence. For patients, dopamine receptor affinity of their antipsychotic drug was estimated. Symptom severity was assessed by means of the Positive and Negative Syndrome Scale (PANSS). Results: Overall, schizophrenia spectrum patients spoke slower and produced fewer words than the healthy controls. Language measures revealed medium to strong correlations with PANSS negative and general scores. Usage of antipsychotics with strong D2 receptor affinity was found to have the strongest effect on speech. Word2vec trained models were able to differentiate between patients and controls. Conclusions: Automated assessments of aspects of verbal communication show promise in elucidating and quantifying various symptoms. Our results indicate that usage of antipsychotic medication has a marked effect on verbal communication in addition to disturbances that are better interpreted as part of the illness. These medication-effects should be taken into account when analyzing language disturbances in schizophrenia. Word2vec proved to be a useful tool to differentiate between subjects and controls, reflecting disturbances in both meaning and structure in verbal communication. This research illustrates the possibilities in automated assessment of language which can serve as measures of symptom severity, medication effects and open the door to diagnosis and prognosis.

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.

Linking PANSS negative symptom scores with the Clinical Global Impressions Scale: understanding negative symptom scores in schizophrenia

Understanding how rating scale improvement corresponds to a clinical impression in patients with negative symptoms of schizophrenia may help define the clinical relevance of change in this patient population. We conducted post hoc equipercentile linking analyses of Positive and Negative Syndrome Scale (PANSS) outcomes (e.g., PANSS-Factor Score for Negative Symptoms [FSNS]) with Clinical Global Impressions-Improvement (CGI-I) and -Severity (CGI-S) ratings on data from patients treated with cariprazine (n = 227) or risperidone (n = 229) in a clinical study evaluating negative symptoms in schizophrenia. Patients were prospectively selected for persistent, predominant negative symptoms of schizophrenia (PNS), and minimal positive/depressive/extrapyramidal symptoms. Linking results demonstrated that greater improvement on PANSS-derived measures corresponded to clinical impressions of greater improvement, as measured by the CGI-I, and less severe disease states, as measured by the CGI-S. For example, CGI-S scores of 1 (normal), 2, 3, 4, 5, and 6 (severely ill) corresponded to PANSS-FSNS scores of 7, 13, 19, 24, 29, and 35, respectively. Likewise, CGI-I scores of minimally improved, much improved, and very much improved corresponded to a change from baseline in PANSS-FSNS scores of −27%, −49%, and −100%, respectively. These are important findings for the interpretation of the results of trials in patients with persistent negative symptoms.

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.

The role of weight gain in explaining the effects of antipsychotic drugs on positive and negative symptoms: An analysis of the CATIE schizophrenia trial

Second-generation antipsychotics are associated with moderate benefits in terms of improved schizophrenia symptoms, but also with higher rates of side-effects such as excessive weight gain (WG); a consensus on their efficacy has not been reached. To date, no study has evaluated the interplay of treatments and side-effects in a single framework, which is a critical step to clarify the role of side-effects in explaining the efficacy of these antipsychotics. We used recent methods for mediation and interaction to clarify the role of WG in explaining the effects of second-generation drugs on schizophrenia symptoms. We used data from 1460 participants in the CATIE trial, assigned to either perphenazine (first-generation comparison drug), olanzapine, quetiapine, risperidone, or ziprasidone. The primary outcome was an individual's score on the Positive and Negative Syndrome Scale (PANSS) for symptoms of schizophrenia after 9 months, separately evaluated as positive (PANSS+), negative (PANSS−), and total PANSS score. WG after 6 months was investigated as a potential mediator and effect modifier. Results showed that, by limiting WG, patients would benefit of a considerably better improvement in terms of PANSS symptoms. In the scenario of weight change being controlled between −2% and 1% for all participants, patients assigned to olanzapine would experience the highest significant improvements in both PANSS+ (−2.66 points; 95% CI: −4.98, −0.35), PANSS− (−1.59; 95% CI: −4.31, 1.14), and total PANSS (−6.11; 95% CI: −13.13, 0.92). In conclusion, occurrence of excessive WG hampers the potentially beneficial effects of second-generation antipsychotics, thus suggesting future directions for treatment and interventions.

Prolactin and Thyroid Stimulating Hormone (TSH) Levels and Sexual Dysfunction in Patients with Schizophrenia Treated with Conventional Antipsychotic Medication: A Cross-Sectional Study.

BackgroundThis study aimed to investigate the relationship between serum profiles of prolactin and thyroid stimulating hormone (TSH) and sexual dysfunction in patients with schizophrenia treated with conventional antipsychotic medication.Material/MethodsA hospital-based cross-sectional study included 118 patients, age range 18–57 years (55 men, 63 women), with a confirmed diagnosis of schizophrenia. All patients were stable after antipsychotic treatment. Serum levels of hormones, including prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), progesterone, testosterone, thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3) and free thyroxine (FT4), were detected in venous blood. The Positive and Negative Syndrome Scale (PANSS) score was used to measure symptom severity of patients with schizophrenia. The Mandarin Chinese version of the Arizona Sexual Experience Scale (ASEX), a 5-item scale, was used to measure sexual function.ResultsThere were 66 patients (55.9%) who had hyperprolactinemia, the prevalence of hyperprolactinemia was markedly higher in the sexual dysfunction group than the non-sexual dysfunction group (91.8% vs. 17.5%) (P<0.001). Mean prolactin levels were significantly increased in patients with sexual dysfunction compared with the patients without sexual dysfunction (P<0.001), with a higher incidence in female patients. Subclinical hypothyroidism and hyperprolactinemia were found to be independently associated with sexual dysfunction, and an increased PANSS negative score was an independent risk factor for the development of sexual dysfunction.ConclusionsThe incidence of sexual dysfunction was significantly increased in patients with schizophrenia. Hyperprolactinemia and subclinical hypothyroidism were associated with sexual dysfunction, especially in female patients.

Assessing negative symptoms in schizophrenia: Validity of the clinical assessment interview for negative symptoms in Singapore

This study aimed to examine the validity of the Clinical Assessment Interview for Negative Symptoms (CAINS) in Singapore. 274 participants with schizophrenia were assessed on the CAINS, Scale for the Assessment of Negative Symptoms (SANS), Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia (CDSS), Social and Occupational Functioning Assessment Scale (SOFAS) and the Simpson-Angus Extrapyramidal Side Effects Scale (SES). Factor analyses were conducted and Cronbach's coefficient alpha was calculated. Spearman's correlation coefficient was used to assess correlations. The 2-factor model of the CAINS failed to fit our data. Exploratory factor analysis of a randomly selected split-half of the sample yielded four factors: motivation-pleasure (MAP) social, MAP vocational, MAP recreational and expression (EXP), accounting for 73.94% of the total variance. Confirmatory factor analysis on the remaining sample supported this factor structure. Cronbach's alpha for the CAINS was 0.770. Significant correlations were observed between the CAINS total and the SANS total and PANSS negative subscale scores. Good divergent validity was shown by insignificant correlations with PANSS positive subscale score and CDSS total score. The MAP social and recreational factor scores had moderate correlations with the SANS anhedonia-asociality subscale scores, whereas the MAP vocational factor had the highest correlation with the avolition-apathy subscale of the SANS. EXP factor score correlated strongly with the SANS affective flattening and alogia subscales scores. In conclusion, the CAINS has good psychometric properties and can be used by clinicians to assess negative symptoms in individuals with schizophrenia in the local population.

Latent Iron Deficiency as a Marker of Negative Symptoms in Patients with First-Episode Schizophrenia Spectrum Disorder.

Iron deficiency may alter dopaminergic transmission in the brain. This study investigated whether iron metabolism is associated with negative symptoms in patients with first-episode psychosis. The study enrolled 121 patients with first-episode schizophrenia spectrum disorder, whose duration of treatment was 2 months or less. Negative symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) and Clinician-Rated Dimensions of Psychosis Symptom Severity (Dimensional) scale of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Prominent negative symptoms were defined as moderate or severe negative symptoms on the Dimensional scale of the DSM-5. Iron deficiency was defined as a serum ferritin ≤ 20 ng/mL. Patients with iron deficiency were significantly more likely to have prominent negative symptoms (45.2 vs. 22.2%; p = 0.014) and a higher PANSS negative symptoms score (p = 0.046) than those with normal ferritin levels. Patients with prominent negative symptoms had significantly lower ferritin levels (p = 0.025). The significance of these results remained after controlling for the duration of illness and other confounding variables. Our finding of an independent association between iron deficiency and negative symptoms in patients at the very early stage of illness implies that iron dysregulation has an effect on negative symptoms in patients with schizophrenia. The possibility of therapeutic intervention with iron should be further investigated.

Comparison of the efficacy and safety of 4 and 2 mg/day brexpiprazole for acute schizophrenia: a meta-analysis of double-blind, randomized placebo-controlled trials.

PurposeThe purpose of this study was to compare the efficacy and safety of brexpiprazole 4 mg/day (B4) and 2 mg/day (B2) for treating acute schizophrenia.Patients and methodsWe performed three categorical meta-analyses (B4 vs placebo, B2 vs placebo, and B4 vs B2) of double-blind, randomized placebo-controlled trials (DBRCTs) that reported improvements in the Positive and Negative Syndrome Scale (PANSS) scores, response rate, Clinical Global Impression–Improvement and Severity (CGI-I and CGI-S) scores, discontinuation rate, and incidence of individual adverse events.ResultsWe identified three DBRCTs with 1,444 patients. Both B4 and B2 were superior to placebo for PANSS total score (B4: standardized mean difference [SMD] =−0.30, 95% CI =−0.43, −0.17; B2: SMD =−0.30, 95% CI =−0.46, −0.13), PANSS negative score, response rate, CGI-S score, and CGI-I score. B2, but not B4, was superior to placebo for the PANSS positive score. However, there was considerable heterogeneity in the meta-analysis for B4’s PANSS positive score, which disappeared after excluding a 2018 Japanese study from the meta-analysis that included more patients on a high-dose antipsychotic prior to their participation. A meta-analysis that excluded the data from the abovementioned patients showed B4 to be superior to the placebo in terms of the PANSS positive score (SMD =−0.22, 95% CI =−0.40, −0.03). B2, but not B4, was associated with a lower incidence of all-cause discontinuation compared with placebo. Both B4 and B2 were superior to placebo for discontinuation due to adverse events and schizophrenia, but both were associated with a higher incidence of weight gain compared with placebo. B4 was also associated with a higher risk of extrapyramidal symptoms than B2.ConclusionBoth B4 and B2 benefitted patients with schizophrenia, particularly those who were not previously on high-dose antipsychotics. Both the regimens were well-tolerated, but carried a risk of weight gain and extrapyramidal symptoms, although the latter risk was higher for B4 than B2.

Health-related quality of life associated with different symptoms in women and in men who suffer from schizophrenia

Health-related quality of life (HRQoL) in patients with schizophrenia is related to the severity of psychiatric symptoms. The objective of this study is to analyze whether the symptoms that influence HRQoL are similar in women and men. Data were part of the Pattern study, an international observational investigation which collected data from 1379 outpatients with schizophrenia. Patients were evaluated with the Mini International Neuropsychiatric Inventory, the Clinical Global Impression-Schizophrenia, and the Positive and Negative Syndrome Scale (PANSS), and reported their quality of life using the Schizophrenia Quality of Life Scale (SQLS), the Short Form-36 (SF-36), and the EuroQol-5 Dimension (EQ-5D). Men reported higher HRQoL on all scales. PANSS total score was 80.6 (SD 23.6) for women and 77.9 (SD 22.1) for men. In women, a higher PANSS negative score and a higher PANSS affective score were associated with a lower SQLS score. In men, a higher PANSS positive score and a higher PANSS affective score were associated with a lower SQLS score. The same pattern appeared with EQ-VAS and EQ-5D tariff. In women, greater age and higher PANSS affective score were associated with a lower SF-36 mental component score. In men, higher PANSS affective, positive, and cognitive scores were associated with a lower SF-36 mental component score. This study shows that HRQoL is influenced by different psychiatric symptoms in women and men. This may have significant implications when deciding the main treatment target in patients with schizophrenia.ClinicalTrials.gov Identifier: https://clinicaltrials.gov/ct2/show/NCT01634542.

Relationship between social and cognitive functions in people with schizophrenia.

PurposeThe purpose of the present study was to examine clinical factors related to social function in people with schizophrenia.Patients and methodsThe participants were 55 stabilized outpatients with schizophrenia. Their mean age was 39.36 (SD =10.65) years. Social function was assessed using the Quality of Life Scale (QLS). Cognitive function was evaluated with the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia, and the Drug-Induced Extrapyramidal Symptoms Scale.ResultsNeither the MCCB cognitive domain score nor composite score was correlated with the QLS scores. However, of the 10 MCCB subtests, the Trail Making Test Part A and the Brief Assessment of Cognition in Schizophrenia-Symbol Coding (BACS-SC) scores were positively correlated with the QLS scores. Among clinical variables, especially the PANSS negative syndrome scale score had a strong negative correlation with the QLS scores. Stepwise regression analyses showed that the PANSS negative syndrome scale score was an independent predictor of the QLS scores, and although the BACS-SC score predicted the QLS common objects and activities subscale score, the association was not so strong compared to the PANSS negative syndrome scale score.ConclusionThese results indicate that speed of processing evaluated by BACS-SC could predict some aspect of social function but negative symptoms have a much stronger impact on global social function in people with schizophrenia.

Prevalence and Clinical Correlates of and Cognitive Function at the Time of Suicide Attempts in First-Episode and Drug-Naive Patients With Schizophrenia.

It is well established that patients with chronic schizophrenia have a substantially higher rate of attempted and completed suicide than the general population. However, the actual prevalence of suicide attempts at first-episode psychosis is relatively unknown. Previous studies showed that suicidal schizophrenia patients demonstrate higher cognitive function than nonsuicidal patients, though with inconsistent results. The aims of the study were to examine the prevalence of suicide attempts and the association of this prevalence with demographic and clinical variables and cognitive function in Chinese first-episode, drug-naive (FEDN) schizophrenia patients using a cross-sectional and case-control design. A total of 357 FEDN inpatients meeting DSM-IV criteria for schizophrenia and 380 healthy controls were enrolled and completed a detailed in-house questionnaire. The suicide attempt data were collected from medical records and interviews with the patients and their family members. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was administered to measure cognition in the 28 patients with and 95 patients without a history of suicide attempt and 151 healthy controls. Also, patients were rated on the Positive and Negative Syndrome Scale (PANSS). This study was conducted from June 2013 to December 2015. A suicide attempt rate of 12.0% was found in inpatients with first-episode schizophrenia. The attempters were more likely to smoke (34.4% vs 17.9%; χ² = 5.49, P = .019) and had lower severity of negative symptoms (F₁,₃₅₄ = 4.12, P = .043) as compared to FEDN patients without a suicide attempt. All 5 RBANS subscales (all P < .001) except for the Visuospatial/Constructional index (P > .05) showed significantly lower cognitive performance for FEDN patients than for healthy controls. Among the FEDN patients, the suicide attempters performed better than nonattempters on attention (F₁,₁₂₁ = 5.12, P = .025), with an effect size of 0.49. The following variables were independently associated with suicide attempt as shown by multivariate regression analysis: PANSS negative symptom subscale score (Wald χ²₁ = 7.90 P = .005; adjusted OR = 0.807, 95% CI, 0.696-0.936) and Attention (Wald χ²₁ = 4.69, P = .03; adjusted OR = 0.957, 95% CI, 0.918-0.997). FEDN patients with schizophrenia attempt suicide more often than the general population. The suicidal patients were more likely to smoke, had lower severity of negative symptoms, and showed better attention than nonsuicidal patients.

Citicoline (CDP-choline) add-on therapy to risperidone for treatment of negative symptoms in patients with stable schizophrenia: A double-blind, randomized placebo-controlled trial.

We aimed to evaluate the efficacy and tolerability of citicoline add-on therapy in treatment of negative symptoms in patients with stable schizophrenia. In a double-blind and placebo-controlled study, patients with stable schizophrenia (DSM-5) were randomized to receive either 2,500mg/day citicoline or placebo in addition to risperidone for 8weeks. The patients were assessed using the positive and negative syndrome scale (PANSS), the extrapyramidal symptom rating scale (ESRS), and Hamilton depression rating scale (HDRS). The primary outcome was the difference in PANSS negative subscale score reduction from baseline to week 8 between the citicoline and the placebo groups. Sixty-six individuals (out of 73 enrolled) completed the trial. The citicoline group demonstrated significantly greater improvement in negative scores, F(1.840, 118.360)=8.383, p=.001, as well as general psychopathology, F(1.219, 78.012)=6.636, p=.008; change in general psychopathology did not remain significant after adjustment, and total PANSS scores, F(1.633, 104.487)=15.400, p<.001, compared with the placebo. HDRS scores and its changes, ESRS score, and frequency of other side effects were not significantly different between the two groups. Citicoline add-on therapy to risperidone can effectively improve the primary negative symptoms of patients with schizophrenia.

Progressive Grey Matter Volume Changes in Patients with Schizophrenia over 6 Weeks of Antipsychotic Treatment and Their Relationship to Clinical Improvement

Cross-sectional and longitudinal studies have identified widespread and progressive grey matter volume (GMV) reductions in schizophrenia, especially in the frontal lobe. In this study, we found a progressive GMV decrease in the rostral medial frontal cortex (rMFC, including the anterior cingulate cortex) in the patient group during a 6-week follow-up of 40 patients with schizophrenia and 31 healthy controls well-matched for age, gender, and education. The higher baseline GMV in the rMFC predicted better improvement in the positive score on the Positive and Negative Syndrome Scale (PANSS), and this might be related to the improved reality-monitoring. Besides, a higher baseline GMV in the posterior rMFC predicted better remission of general symptoms, and a lesser GMV reduction in this region was correlated with better remission of negative symptoms, probably associated with ameliorated self-referential processing and social cognition. Besides, a shorter disease course and higher educational level contributed to better improvement in the general psychopathological PANSS score, and a family history was negatively associated with improvement of the negative and total PANSS scores. These phenomena might be important for understanding the neuropathological mechanisms underlying the symptoms of schizophrenia and for making clinical decisions.

The effect of transcranial direct current stimulation on psychotic symptoms of schizophrenia is associated with oxy-hemoglobin concentrations in the brain as measured by near-infrared spectroscopy: A pilot study

Transcranial direct current stimulation (tDCS) has been shown to be effective in treating some of the symptoms of schizophrenia. In the current study, we sought to determine whether oxy-hemoglobin ([oxy-Hb]), measured by near-infrared spectroscopy (NIRS), is associated with effects of transcranial direct current stimulation (tDCS) on psychotic symptoms of schizophrenia. Twenty-six patients underwent tDCS (2 mA × 20 min) two times per day for five consecutive days. The anodal electrode was placed over the left dorsolateral prefrontal cortex while the cathodal electrode was placed over the right supraorbital region. One month after the last administration of tDCS, positive, but not negative symptoms, evaluated by the Positive and Negative Syndrome Scale (PANSS), were significantly improved. At baseline, regional [oxy-Hb] concentrations in the brain were measured by a 52-channel NIRS instrument. Significant negative correlation was demonstrated between [oxy-Hb] concentrations of left temporoparietal regions throughout verbal fluency tasks vs. changes of PANSS Positive and Negative subscale scores. This is the first study to demonstrate the correlation between the response of neural activity to cognitive tasks at baseline and the ability of tDCS to improve positive and negative psychotic symptoms. Our observations suggest that NIRS provides a marker to predict the response to treatment with tDCS in schizophrenia.

Minocycline adjunctive treatment to risperidone for negative symptoms in schizophrenia: Association with pro-inflammatory cytokine levels

BackgroundWe attempted to replicate the efficacy of minocycline, a second-generation tetracycline, as adjunctive therapy for the negative symptoms of schizophrenia, and to investigate its association with pro-inflammatory cytokine levels. MethodsSeventy-five schizophrenia patients with negative symptoms entered a 3-month, double blind, randomized, placebo-controlled clinical trial. Subjects were assigned low dose (100 mg per day) or high dose minocycline (200 mg per day) or placebo combined with risperidone. The outcomes used the Scale for the Assessment of Negative Symptoms (SANS) and the Positive and Negative Syndrome Scale (PANSS)-negative subscale. We assessed three pro-inflammatory cytokines in serum: interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor–α (TNF-α). ResultsSubjects receiving high dose minocycline not only had greater improvements on the SANS total scores and PANSS negative subscale scores (P < 0.01), but also had greater reductions in IL-1β and IL-6 serum levels (P < 0.01) when compared with those receiving low dose minocycline or placebo. The improvement in negative symptoms with minocycline was significantly correlated with the reduction of IL-1β and IL-6 serum levels (P < 0.05). ConclusionsSchizophrenia patients showed a significant improvement in negative symptoms with the addition of minocycline to risperidone. Reducing pro-inflammatory cytokines may play an important role in the potential mechanism for efficacy.

S228. TOWARD EARLY DETECTION OF TREATMENT RESISTANT SCHIZOPHRENIA: PREDICTIVE INFORMATION ON NON-RESPONSE TO ANTIPSYCHOTICS BY EVALUATION OF A FEW CLINICAL FACTORS: A STUDY BY ROC CURVE ANALYSIS AND CONFIRMATORY MULTIVARIATE ANALYSIS

BackgroundTreatment Resistant Schizophrenia (TRS) is associated to poor prognosis and highly disabling course. Early detection of the condition is crucial to rapidly provide targeted interventions. The aim of this study was to evaluate whether it may be possible to distinguish TRS from Antipsychotic Responder Schizophrenia (ARS) patients on the basis of a limited number of measurable clinical factors.Methods60 out of 182 eligible patients were included. A multistep diagnostic procedure to separate TRS from ARS was then used. Clinical parameters were recorded. Rating scales were administered, including: the Neurological Evaluation Scale (NES); the Positive and Negative Syndrome Scale (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).We used the Receiver Operating Characteristic (ROC) curves analysis to distinguish between TRS and ARS. Confirmatory logistic regression and discriminant analysis were additionally used.ResultsAmong clinical and demographic parameters, AUCs were significant for previous hospitalizations (AUC=.71; p=.004; SE= .068); antipsychotic dose (AUC=.73; p=.002; SE=.66); duration of illness (AUC=.67; p=.02; SE=.71) and NES score (AUC=.77; p<.0005; SE=.062). Moreover, significant AUCs were found for PANSS Negative subscale score (AUC=.68; p=.013; SE=.068); PANSS total score (AUC=.64; p=.05; SE=.071); QLS score (AUC=.73; p=.003; SE=.067); PSP score (AUC=.69; p=.012; SE=.68); all SLOF areas (AUC ranging from .76 to .68, p<.05), with the exclusion of Area4. A trend toward significance was found for Problem Solving (AUC=.63; p=.08). Among the whole significant variables, the highest specificity for diagnosis was found for NES score and previous hospitalizations (75% and 78.1%, respectively); the highest sensitivity for NES score (71.4%). Accordingly, Odds Ratio of being categorized as TRS were larger for NES score <21.5 (7.5), QLS score <57 (5.49), previous hospitalizations >1.45 and SLOF Area5 <43.5 (4.76 both).Multivariate analysis supported results of ROC curve analysis. Stepwise logistic regression showed that the following variables were significant predictors of TRS/ARS status: previous hospitalizations, NES score, and antipsychotic dose among clinical variables (χ(3)=27.25, p<.0005, Nagelkerke R2=.48); PANSS Negative subscale score among psychopathology variables (χ(1)=7.75, p=.005, Nagelkerke R2=.16); QLS score among quality of life variables (χ(1)=7.91, p=.005, Nagelkerke R2=.16); SLOF Area2 among social functioning variables (χ(1)=18.05, p<.0005, Nagelkerke R2=.34).The descriptive discriminant analysis function was significant for clinical variables, χ(6)=23.84, p=.001. The most relevant discriminator variables in this group were NES score, antipsychotic doses, and previous hospitalizations. Discriminant function was also significant for SLOF variables χ(6)=17.67, p=.007, with Area1 and Area3 scores ensuring the highest discriminative power. Discriminant function was only weakly significant for psychopathology and for quality of life variables (PANSS Negative subscale score and QLS score showed the highest discriminative power, respectively).DiscussionTherefore, the evaluation of a few clinical factors may give solid and predictive information about patient potential to be responsive or non-responsive to antipsychotics. A patient exhibiting a combination of 2 or more lifetime hospitalizations; high NSS; high negative symptoms; low quality of life and psychosocial functioning has low possibility (less than approximately 20%, according to our data) to be responsive to antipsychotic agents.