Scale For The Assessment Of Negative Symptoms Research Articles

The Effectiveness of Augmenting Modafinil to Risperidone or Olanzapine for Treating Negative Symptoms in Schizophrenic Patients: A Randomized Controlled Trail

Background: Recent evidence suggests the potential efficacy of modafinil in addressing specific symptom domains associated with schizophrenia, particularly negative and cognitive symptoms. However, it's important to note that findings in this area have been inconsistent. Objectives: This study was done to assess the impact of modafinil on improving negative symptoms in schizophrenia patients. Methods: In this clinical trial, 40 individuals diagnosed with schizophrenia and referred to Golestan Hospital were selected. Patients received a daily dose of 100 to 200 mg of modafinil in addition to their ongoing antipsychotic treatment with either Risperidone or Olanzapine. In the control group, patients received a placebo along with their prescribed antipsychotic therapy. The duration of the follow-up was 4 weeks. Both the evaluator and the patients were blinded to the administered medication. The Scale for the Assessment of Negative Symptoms (SANS) was utilized to measure negative symptoms before the intervention, and at 2 and 4 weeks following the intervention. Results: The mean age of participants in the intervention and control groups was 34.00 ± 6.60 and 36.90 ± 6.88 years, respectively. Two weeks after the intervention, the average SANS score was lower in the intervention group compared to the placebo group (99.70 ± 10.24 vs. 111.24 ± 7.08, P = 0.04). At 4 weeks post-intervention, the average SANS score in the intervention group was significantly reduced compared to the placebo group (84.39 ± 3.54 vs. 113.79 ± 3.75, P = 0.002). Conclusions: This study suggests that modafinil may be an effective adjunctive therapy for schizophrenia, particularly for treating anhedonia symptoms.

52 Differences in Neuropsychological Test Performance and Symptom Data in Schizophrenia with Co-Occurring Cannabis Use

Objective:Long-term exposure to the psychoactive ingredient in cannabis, delta-9-tetrahydrocanabinol (THC), has been consistently raised as a notable risk factor for schizophrenia. Additionally, cannabis is frequently used as a coping mechanism for individuals diagnosed with schizophrenia. Cannabis use in schizophrenia has been associated with greater severity of psychotic symptoms, non-compliance with medication, and increased relapse rates. Neuropsychological changes have also been implicated in long-term cannabis use and the course of illness of schizophrenia. However, the impact of co-occurring cannabis use in individuals with schizophrenia on cognitive functioning is less thoroughly explored. The purpose of this meta-analysis was to examine whether neuropsychological test performance and symptoms in schizophrenia differ as a function of THC use status. A second aim of this study was to examine whether symptom severity moderates the relationship between THC use and cognitive test performance among people with schizophrenia.Participants and Methods:Peer-reviewed articles comparing schizophrenia with and without cannabis use disorder (SZ SUD+; SZ SUD-) were selected from three scholarly databases; Ovid, Google Scholar, and PubMed. The following search terms were applied to yield studies for inclusion: neuropsychology, cognition, cognitive, THC, cannabis, marijuana, and schizophrenia. 11 articles containing data on psychotic symptoms and neurocognition, with SZ SUD+ and SZ SUD- groups, were included in the final analyses. Six domains of neurocognition were identified across included articles (Processing Speed, Attention, Working Memory, Verbal Learning Memory, and Reasoning and Problem Solving). Positive and negative symptom data was derived from eligible studies consisting of the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), Self-Evaluation of Negative Symptoms (SNS), Brief Psychiatric Rating Scale (BPRS), and Structured Clinical Interview for DSM Disorders (SCID) scores. Meta analysis and meta-regression was conducted using R.Results:No statistically significant differences were observed between SZ SUD+ and SZ SUD-across the cognitive domains of Processing Speed, Attention, Working Memory, Verbal Learning Memory, and Reasoning and Problem Solving. Positive symptom severity was found to moderate the relationship between THC use and processing speed, but not negative symptoms. Positive and negative symptom severity did not significantly moderate the relationship between THC use and the other cognitive domains.Conclusions:Positive symptoms moderated the relationship between cannabis use and processing speed among people with schizophrenia. The reasons for this are unclear, and require further exploration. Additional investigation is warranted to better understand the impact of THC use on other tests of neuropsychological performance and symptoms in schizophrenia.

Efficacy and safety of Transcranial Direct Current Stimulation (tDCS) on cognitive function in chronic schizophrenia with Tardive Dyskinesia (TD): a randomized, double-blind, sham-controlled, clinical trial

ObjectivePrevious studies have shown that transcranial direct current stimulation(tDCS) led to an improvement of cognitive function in patients with schizophrenia, but rare study has explored the effect of tDCS on long-term hospitalized chronic schizophrenia with tardive dyskinesia (TD). The present research explored if cognitive function in patients with long-term hospitalized chronic schizophrenia with TD could be improved through tDCS.MethodsThis study is a randomized, double-blind, sham-controlled clinical trial. Of the 52 patients, 14 dropped out, and 38 completed the experiment. Thirty-eight patients on stable treatment regimens were randomly assigned to receive active tDCS(n = 21) or sham stimulation(n = 17) on weekdays of the first, third, and fifth weeks of treatment. Patients performed the Pattern Recognition Memory (PRM) and the Intra/Extradimensional Set Shift (IED) from the Cambridge Neuropsychological Test Automated Battery (CANTAB) at baseline and the end of week 3, week 5. Clinical symptoms were also measured at the baseline and the fifth week using the Scale for the Assessment of Negative Symptoms (SANS) and the Positive and Negative Syndrome Scale (PANSS). Side effects of tDCS were assessed with an experimenter-administered open-ended questionnaire during the whole experiment.ResultsThere were no significant differences in PRM and IED performance metrics, SANS total score and PANSS total score between active and sham tDCS groups at the end of week 5 (p > 0.05). Furthermore, there was a significant difference in the adverse effects of the tingling sensation between the two groups (p < 0.05), but there was no significant difference in other side effects (p > 0.05).ConclusionAccording to these findings, no evidence supports using anodal stimulation over the left dorsolateral prefrontal cortex to improve cognitive function in patients with long-term hospitalized chronic schizophrenia with TD.

Initial evidence of vowel space reduction in a subset of individuals with schizophrenia.

Acoustic phonetic measures have been found to correlate with negative symptoms of schizophrenia, thus offering a path toward quantitative measurement of such symptoms. These acoustic properties include F1 and F2 measurements (affected by tongue height and tongue forward/back position, respectively), which determine a general "vowel space." Among patients and controls, we consider two phonetic measures of vowel space: average Euclidean distance from a participant's mean F1 and mean F2, and density of vowels around one standard deviation of mean F1 and of F2. Structured and spontaneous speech of 148 participants (70 patients and 78 controls) was recorded and measured acoustically. We examined correlations between the phonetic measures of vowel space and ratings of aprosody obtained using two clinical research measures, the Scale for the Assessment of Negative Symptoms (SANS) and the Clinical Assessment Interview for Negative Symptoms (CAINS). Vowel space measurements were significantly associated with patient/control status, attributed to a cluster of 13 patients whose phonetic values correspond to reduced vowel space as assessed by both phoenetic measures. No correlation was found between phonetic measures and relevant items and averages of ratings on the SANS and CAINS. Reduced vowel space appears to affect only a subset of patients with schizophrenia, potentially those on higher antipsychotic dosages. Acoustic phonetic measures may be more sensitive measures of constricted vowel space than clinical research rating scales of aprosody or monotone speech. Replications are needed before further interpretation of this novel finding, including potential medication effects.

Berberine improves negative symptoms and cognitive function in patients with chronic schizophrenia via anti-inflammatory effect: a randomized clinical trial

BackgroundBased on the neuroinflammation hypothesis in schizophrenia and known anti-inflammatory effects of berberine, the aim of the present study is to investigate the efficacy of berberine in treating negative symptoms and cognitive deficits in adult patients with chronic schizophrenia.MethodsEnrolled participants were randomized to receive berberine or placebo for 3 months. The Scale for the Assessment of Negative Symptoms (SANS), Trail-making Test A (TMT-A), Trail-making Test B (TMT-B), and Hopkins Verbal Learning Test (HVLT) were used to evaluate the negative symptoms and cognitive function at four-time points (baseline, 1st, 2nd, and 3rd month). Serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were used as inflammatory markers. 106 patients with per-protocol were analyzed, 56 in the experimental (berberine) group and 50 in the control (placebo) group.ResultsFrom baseline to month 3, patients receiving berberine demonstrated a decrease in total scores on clinical scales SANS, TMT-A and TMT-B and showed a serum level reduction of IL-1β, IL-6 and TNF-α comparing with patients in the control group (P < 0.05). There were positive correlations between the change of serum IL-1β level and the change of SANS (r = 0.210, P = 0.039), TMT-A (r = 0.522, P < 0.001), and TMT-B (r = 0.811, P < 0.001); between the change of serum IL-6 level and the change of TMT-A (r = 0.562, P < 0.001), and TMT-B (r = 0.664, P < 0.001); between the change of serum TNF-α level and the change of TMT-B (r = 0.472, P < 0.001) after berberine treatment.ConclusionsBerberine is an anti-inflammatory agent that can potentially mitigate the negative symptoms and cognitive deficits in patients with schizophrenia.

Is there a Relationship Between Caffeine Intake and Smoking and Positive and Negative Symptom Severity in Schizophrenia?

It has been reported that caffeine intake and smoking are more frequent in patients with schizophrenia than the general population. However, the cause of high caffeine and smoking and its correlation with positive and negative symptoms is unclear. Therefore, the aim of the present study is to evaluate the correlation between daily caffeine intake and smoking and the severity of positive and negative symptoms in patients with schizophrenia. This study included 177 participants, 89 of whom were healthy controls and 88 patients with schizophrenia. Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS) scales were applied to the patients with schizophrenia to measure the severity of positive and negative symptoms of the disease. The amounts of caffeine and tobacco consumption were significantly higher in the patients group than healthy controls (p=0.001 and p<0.001, respectively). There was no significant correlations between daily caffeine consumption and SAPS or SANS scores in patients with schizophrenia. There was a significant positive relationship between SAPS-delusions score and tobacco consumption. Our study is the first study in the literature that examines the relationship between caffeine and cigarette intake and SANS and SAPS scales in patients with schizophrenia. Although caffeine intake is higher in patients with schizophrenia than healthy controls, this study is valuable as it shows that it is not associated with symptom severity. In addition, although it is known that smoking is high in patients with schizophrenia, this study showed a positive relationship between SAPS-delusion scores and tobacco consumption.

Using support vector machine to explore the difference of function connection between deficit and non-deficit schizophrenia based on gray matter volume.

Schizophrenia can be divided into deficient schizophrenia (DS) and non-deficient schizophrenia (NDS) according to the presence of primary and persistent negative symptoms. So far, there are few studies that have explored the differences in functional connectivity (FC) between the different subtypes based on the region of interest (ROI) from GMV (Gray matter volume), especially since the characteristics of brain networks are still unknown. This study aimed to investigate the alterations of functional connectivity between DS and NDS based on the ROI obtained by machine learning algorithms and differential GMV. Then, the relationships between the alterations and the clinical symptoms were analyzed. In addition, the thalamic functional connection imbalance in the two groups was further explored. A total of 16 DS, 31 NDS, and 38 health controls (HC) underwent resting-state fMRI scans, patient group will further be evaluated by clinical scales including the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), and the Scale for the Assessment of Positive Symptoms (SAPS). Based on GMV image data, a support vector machine (SVM) is used to classify DS and NDS. Brain regions with high weight in the classification were used as seed points in whole-brain FC analysis and thalamic FC imbalance analysis. Finally, partial correlation analysis explored the relationships between altered FC and clinical scale in the two subtypes. The relatively high classification accuracy is obtained based on the SVM. Compared to HC, the FC increased between the right inferior parietal lobule (IPL.R) bilateral thalamus, and lingual gyrus, and between the right inferior temporal gyrus (ITG.R) and the Salience Network (SN) in NDS. The FC between the right thalamus (THA.R) and Visual network (VN), between ITG.R and right superior occipital gyrus in the DS group was higher than that in HC. Furthermore, compared with NDS, the FC between the ITG.R and the left superior and middle frontal gyrus decreased in the DS group. The thalamic FC imbalance, which is characterized by frontotemporal-THA.R hypoconnectivity and sensory motor network (SMN)-THA.R hyperconnectivity was found in both subtypes. The FC value of THA.R and SMN was negatively correlated with the SANS score in the DS group but positively correlated with the SAPS score in the NDS group. Using an SVM classification method and based on an ROI from GMV, we highlighted the difference in functional connectivity between DS and NDS from the local to the brain network, which provides new information for exploring the neural physiopathology of the two subtypes of schizophrenic.

Using dimensionality-reduction techniques to understand the organization of psychotic symptoms in persistent psychotic illness and first episode psychosis

Psychotic disorders are highly heterogeneous. Understanding relationships between symptoms will be relevant to their underlying pathophysiology. We apply dimensionality-reduction methods across two unique samples to characterize the patterns of symptom organization. We analyzed publicly-available data from 153 participants diagnosed with schizophrenia or schizoaffective disorder (fBIRN Data Repository and the Consortium for Neuropsychiatric Phenomics), as well as 636 first-episode psychosis (FEP) participants from the Prevention and Early Intervention Program for Psychosis (PEPP-Montreal). In all participants, the Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS) were collected. Multidimensional scaling (MDS) combined with cluster analysis was applied to SAPS and SANS scores across these two groups of participants. MDS revealed relationships between items of SAPS and SANS. Our application of cluster analysis to these results identified: 1 cluster of disorganization symptoms, 2 clusters of hallucinations/delusions, and 2 SANS clusters (asocial and apathy, speech and affect). Those reality distortion items which were furthest from auditory hallucinations had very weak to no relationship with hallucination severity. Despite being at an earlier stage of illness, symptoms in FEP presentations were similarly organized. While hallucinations and delusions commonly co-occur, we found that their specific themes and content sometimes travel together and sometimes do not. This has important implications, not only for treatment, but also for research—particularly efforts to understand the neurocomputational and pathophysiological mechanism underlying delusions and hallucinations.

Predictors of therapeutic response in schizophrenia – preliminary results

IntroductionSchizophrenia is a heterogenous disease and there is wide variation in the therapeutic response in patients, with some being good responders and others - severely disabled and defined as treatment resistant.ObjectivesTo identify specific socio-demographic and clinical characteristics as prognostic factors for therapeutic response in the search of course prognosis and disease outcome.MethodsThe study has naturalistic, non-interventional design and includes one-year prospective follow-up. Schizophrenic patients are being evaluated in three time points – at admission (T1), by discharge (T2), and one year after the hospitalization (T3). Psychopathology is evaluated by the Positive and Negative Syndrome Scale (PANSS), as well as negative symptoms – by the Scale for the Assessment of Negative Symptoms (SANS), aggression by the Modified Overt Aggression Scale (MOAS) and functioning by the GlobalAssessment of Functioning (GAF). Statistical analyses are performed using Descriptive methods, Student’s t-test, Wilcoxon Signed Ranks Test, as well as multiple regression. An ethical approval of the study has been obtained.ResultsThe sample consists of 108 patients with mean age of 39 (SD±12.7) and 89.8 % (N=97) of them were prospectively assessed after one year. All symptom dimensions in the 5 -factor model – positive, negative, disorganized, manic, and depressive, measured by PANSS, as well as negative symptoms (objectified by SANS) and aggression (objectified by MOAS) are significantly lower after inpatient treatment. There is an improvement in functioning one year after admission (z=-8.01, p&lt;.001), although both negative symptoms (z=-2,45, p=0.015) and aggressive behavior (z=-4.260, p&lt;.001) are significantly higher one year after discharge. From the multiple regression, at T1, involuntary admission is a significant predictor for higher aggression and lower functioning (p&lt;.001). The duration of hospitalization is longer with lower compliance (p=.022) and the treatment with atypical antipsychotics decreases the hospital stay (p=.021). One year after admission, employment serves as a positive predictive factor as it decreases the psychopathology (p=.001), negative symptoms (p&lt;.001), and improves the functioning (p&lt;.001). Good compliance is a predictor for lower psychopathology (p=.015), less aggression and higher functioning (p&lt;.001).ConclusionsThe inpatient treatment is efficacious in terms of psychopathology, aggression and is linked to better functioning. The naturalistic design shows depletion of the positive effects of treatment in terms of negative symptoms and aggression probably due to incomplete medication compliance, which is a bad prognostic factor for functioning. This implies the need of continuous psychosocial services and better psychoeducation after discharge.Disclosure of InterestNone Declared

Longitudinal changes of cognitive function and its relationship with subdomains of negative symptoms in patients with adult-onset first-episode schizophrenia: A 4-year follow up study

BackgroundsThis study explores the longitudinal changes and trajectories of cognitive functions in patients with adult-onset first-episode schizophrenia (FES) over four years and their relationships with the baseline subdomains of negative symptoms. MethodsA total of 177 patients of age 25–55 with FES were recruited. Baseline demographics, clinical, social and cognitive functions were assessed. Diminished expression and diminished motivation of negative symptoms were assessed with Scale for the Assessment of Negative Symptoms (SANS). Patients had yearly follow-up of cognitive function assessments over four years. Latent class growth analysis (LCGA) and mixed linear regression model were used to explore the longitudinal changes of cognitive functions and the effect of baseline negative symptoms on the longitudinal cognitive function changes. Relationships of baseline negative symptoms subdomains and cognitive functions were also explored. ResultsTwo trajectories of cognitive functions were identified. Longitudinal improvements were found in most cognitive functions apart from the logical memory. One trajectory of patients had significant deterioration of logical memory while the other group had significant improvement. Baseline diminished expression was associated with baseline and longitudinal changes of processing speed and verbal fluency while diminished motivation was associated with baseline and longitudinal changes of processing speed. ConclusionsAdult-onset FES patients had a homogeneous longitudinal improvement in most cognitive functions but not for logical memory suggesting the unique nature of verbal memory. The distinct relationship between baseline subdomains of negative symptoms with baseline and longitudinal cognitive functions suggesting the presence of differential overlapping etiology between negative symptom subdomains and cognitive functions.

Validity and Reliability Study of Turkish Version of Clinical Assessment Interview for Negative Symptoms (CAINS).

This study aims to translate and investigate the validity and reliability of the Turkish version of the Clinical Assessment Interview for Negative Symptoms (CAINS), which has additional features compared to other scales in assessing negative symptoms in patients with schizophrenia. The Turkish version of CAINS was constructed upon an initial translation to Turkish, and an English back translation of the scale was later conducted. The patients diagnosed with schizophrenia (n=79) according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria were administered the Turkish version of CAINS, the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS), the Scale for the Assessment of Positive Symptoms (SAPS), the Calgary Depression Scale for Schizophrenia (CDSS), the Clinical Global Impression Scale (CGI), the Global Assessment of Functioning Scale (GAF) and the Simpson-Angus Extrapyramidal Side Effects Assessment Scale (SAS). In addition, two interviewers assessed the video recordings of 11 patients for reliability analysis. Inter-rater reliability was found to be high (intraclass correlation coefficient (ICC): 0.831). Exploratory and confirmatory factor analyses indicated that Cronbach's alpha was 0.956 for the full scale, and the two-dimensional structure explained the scale better. In convergent validity analyses, CAINS overall scores correlated significantly with the SANS total score (r=0,932) and PANSS negative score (r=0,902). In discriminant validity analyses, CAINS overall scores markedly correlated with the SAPS total (r=0,615), PANSS positive (r=0,497) and PANSS general psychopathology (r=0,737) scores. Additionally, when CGI and GAF scores were considered covariant, the significant correlation of CAINS total scores with the SANS total and PANSS negative scores continued; however, the correlation with PANSS positive score was prominently reduced, and the correlation with PANSS general psychopathology disappeared. The Turkish version of the CAINS appears to be a valid and reliable tool with strong psychometric properties in a sample consisting of patients with schizophrenia.

Evidence of innate immune dysfunction in first-episode psychosis patients with accompanying mood disorder

BackgroundInflammation and increases in inflammatory cytokines are common findings in psychiatric disorders such as schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). Meta-analyses of studies that measured circulating cytokines have provided evidence of innate inflammation across all three disorders, with some overlap of inflammatory cytokines such as IL-6 and TNF-α. However, differences across disorders were also identified, including increased IL-4 in BD that suggest different immune mechanisms may be involved depending on the type of disorder present.MethodsWe sought to identify if the presence or absence of an affective disorder in first-episode psychotic (FEP) patients was associated with variations in cytokine production after stimulation of peripheral blood mononuclear cells (PBMC). 98 participants were recruited and grouped into healthy controls (n = 45) and first-episode psychosis patients (n = 53). Psychosis patients were further grouped by presence (AFF; n = 22) or lack (NON; n = 31) of an affective disorder. We cultured isolated PBMC from all participants for 48 h at 37 °C under four separate conditions; (1) culture media alone for baseline, or the following three stimulatory conditions: (2) 25 ng/mL lipopolysaccharide (LPS), (3) 10 ng/mL phytohemagglutinin (PHA), and (4) 125 ng/ml α-CD3 plus 250 ng/ml α-CD28. Supernatants collected at 48 h were analyzed using multiplex Luminex assay to identify differences in cytokine and chemokine production. Results from these assays were then correlated to patient clinical assessments for positive and negative symptoms common to psychotic disorders.ResultsWe found that PBMC from affective FEP patients produced higher concentrations of cytokines associated with both innate and adaptive immunity after stimulation than non-affective FEP patients and healthy controls. More specifically, the AFF PBMC produced increased tumor necrosis fctor (TNF)-α, interleukin (IL)-1β, IL-6, and others associated with innate inflammation. PBMC from AFF also produced increased IL-4, IL-17, interferon (IFN)γ, and other cytokines associated with adaptive immune activation, depending on stimulation. Additionally, inflammatory cytokines that differed at rest and after LPS stimulation correlated with Scale for the Assessment of Negative Symptoms (SANS) scores.ConclusionsOur findings suggest that immune dysfunction in affective psychosis may differ from that of primary psychotic disorders, and inflammation may be associated with increased negative symptoms. These findings could be helpful in determining clinical diagnosis after first psychotic episode.

Amisulpride augmentation therapy improves cognitive performance and psychopathology in clozapine-resistant treatment-refractory schizophrenia: a 12-week randomized, double-blind, placebo-controlled trial

BackgroundAlthough clozapine is an effective option for treatment-resistant schizophrenia (TRS), there are still 1/3 to 1/2 of TRS patients who do not respond to clozapine. The main purpose of this randomized, double-blind, placebo-controlled trial was to explore the amisulpride augmentation efficacy on the psychopathological symptoms and cognitive function of clozapine-resistant treatment-refractory schizophrenia (CTRS) patients.MethodsA total of 80 patients were recruited and randomly assigned to receive initial clozapine plus amisulpride (amisulpride group) or clozapine plus placebo (placebo group). Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Clinical Global Impression (CGI) scale scores, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Treatment Emergent Symptom Scale (TESS), laboratory measurements, and electrocardiograms (ECG) were performed at baseline, at week 6, and week 12.ResultsCompared with the placebo group, amisulpride group had a lower PANSS total score, positive subscore, and general psychopathology subscore at week 6 and week 12 (PBonferroni < 0.01). Furthermore, compared with the placebo group, the amisulpride group showed an improved RBANS language score at week 12 (PBonferroni < 0.001). Amisulpride group had a higher treatment response rate (P = 0.04), lower scores of CGI severity and CGI efficacy at week 6 and week 12 than placebo group (PBonferroni < 0.05). There were no differences between the groups in body mass index (BMI), corrected QT (QTc) intervals, and laboratory measurements. This study demonstrates that amisulpride augmentation therapy can safely improve the psychiatric symptoms and cognitive performance of CTRS patients.ConclusionThis study indicates that amisulpride augmentation therapy has important clinical significance for treating CTRS to improve clinical symptoms and cognitive function with tolerability and safety.Trial registration Clinicaltrials.gov identifier- NCT03652974. Registered August 31, 2018, https://clinicaltrials.gov/ct2/show/NCT03652974

Delayed improvements in visual memory task performance among chronic schizophrenia patients after high-frequency repetitive transcranial magnetic stimulation.

BACKGROUNDCognitive impairments are core characteristics of schizophrenia, but are largely resistant to current treatments. Several recent studies have shown that high-frequency repetitive transcranial magnetic stimulation (rTMS) of the left dor-solateral prefrontal cortex (DLPFC) can reduce negative symptoms and improve certain cognitive deficits in schizophrenia patients. However, results are inconsistent across studies.AIMTo examine if high-frequency rTMS of the DLPFC can improve visual memory deficits in patients with schizophrenia.METHODSForty-seven chronic schizophrenia patients with severe negative symptoms on stable treatment regimens were randomly assigned to receive active rTMS to the DLPFC (n = 25) or sham stimulation (n = 22) on weekdays for four consecutive weeks. Patients performed the pattern recognition memory (PRM) task from the Cambridge Neuropsychological Test Automated Battery at baseline, at the end of rTMS treatment (week 4), and 4 wk after rTMS treatment (week 8). Clinical symptoms were also measured at these same time points using the Scale for the Assessment of Negative Symptoms (SANS) and the Positive and Negative Syndrome Scale (PANSS).RESULTSThere were no significant differences in PRM performance metrics, SANS total score, SANS subscores, PANSS total score, and PANSS subscores between active and sham rTMS groups at the end of the 4-wk treatment period, but PRM performance metrics (percent correct and number correct) and changes in these metrics from baseline were significantly greater in the active rTMS group at week 8 compared to the sham group (all P < 0.05). Active rTMS treatment also significantly reduced SANS score at week 8 compared to sham treatment. Moreover, the improvement in visual memory was correlated with the reduction in negative symptoms at week 8. In contrast, there were no between-group differences in PANSS total score and subscale scores at either week 4 or week 8 (all P > 0.05).CONCLUSIONHigh-frequency transcranial magnetic stimulation improves visual memory and reduces negative symptoms in schizophrenia, but these effects are delayed, potentially due to the requirement for extensive neuroplastic changes within DLPFC networks.

Increased NLRP3 inflammasome expression in peripheral blood mononuclear cells of patients with schizophrenia: a case-control study

Objective This study aimed to evaluate the gene expression of the P2X purinoceptor 7 (P2X7R)- nod-like receptor pyrin domain-containing protein 3 (NLRP3) signal pathway in peripheral blood mononuclear cells (PBMCs) between schizophrenia (SCZ) patients and healthy controls (HC) to reveal its relationship with clinical variables. Methods Thirty-two SCZ patients and 41 healthy controls were included in this study. The Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS), The Global Assessment of Functioning (GAF) scale and the Functioning Assessment Short Test (FAST) scales were applied. P2X7R, NLRP3, IL-1β and IL-18 gene expression levels were evaluated by real-time polymerase chain reaction in PBMCs. Results NLRP3, P2RX7, IL-1β and IL-18 expression levels were significantly higher in PBMCs of SCZ patients than in HC subjects. Negative correlations were found between NLRP3 gene expression levels and GAF and FAST scales scores. There was a negative correlation between IL-18 expression levels and the GAF and FAST scales scores and a positive correlation with the SAPS scale scores. Conclusions Systemic inflammation is implicated in SCZ pathogenesis, according to our findings, which suggest that the NLRP3 pathway may be involved. The NLRP3 inflammasome may serve as a biomarker for SCZ, and its pharmacological regulation may be a promising treatment approach. Key points We hypothesised that the NLRP3 pathway may contribute to the etiopathogenesis of schizophrenia. NLRP3, IL-1β and IL-18 mRNA levels were higher in patients with schizophrenia compared to healthy controls. Negative correlations were found between NLRP3 gene expression levels and GAF and FAST scales scores. There was a negative correlation between IL-18 expression levels and the GAF and FAST scales scores. The SAPS scale scores and IL-18 expression levels had a positive correlation. Given all these findings, it can be stated that NLRP3 inflammasome may play a role in the pathogenesis and symptoms of schizophrenia.

A pilot choral intervention in individuals with schizophrenia-spectrum conditions; Singing away loneliness.

Social disconnection is associated with poor outcome and long-term disability in individuals with schizophrenia-spectrum conditions (SCZ) but social isolation is not typically a target for treatment. Singing together has long been shown to promote unique group cohesion and improve sense of well-being across the lifespan. Accordingly, we devised a novel choral intervention to examine the potential efficacy of this low-burden social intervention strategy designed to reduce loneliness in SCZ. Seventeen SCZ participated in a weekly, 1-hr choir group for 8 weeks. At pre- and post-intervention, we examined symptoms, loneliness, stress, and face recognition. Choral intervention led to significant reductions in scores for loneliness, the Brief Psychiatric Rating Scale (BPRS) and the Beck Depression Inventory-II (BDI-II). No significant changes were observed in scores for the Scale for the Assessment of Negative Symptoms (SANS), the Scale for the Assessment of Positive Symptoms (SAPS), face recognition, or the Perceived Stress Scale (PSS). Diminished loneliness was inversely correlated with the number of sessions attended. Participants judged the choir intervention to be acceptable and enjoyable. Reduced loneliness and symptom improvement after 8 weeks of intervention in SCZ suggest that choral intervention presents an enjoyable and low-burden opportunity to collaborate in a group setting for isolated individuals and thus may serve as a beneficial adjunct in a multi-arm intervention strategy for alleviating symptom distress and loneliness.

Study of Negative Symptoms among 100 Schizophrenic Patients

Introduction: Schizophrenia is a clinical syndrome of variable but profoundly disruptive, psychopathology that involves cognition, emotion, perception and other aspects of behavior. The expression of these manifestations varies across patients and over time, but the effect of the illness is always severe and usually long lasting. The disorder usually begins before age 25, persists throughout life, and affects persons of all social classes. Both patients and their families often suffer from poor care and social ostracism because of widespread ignorance about the disorder. Schizophrenia is equally prevalent in men and women. Objective: To find out the pattern and frequency of negative symptoms in Schizophrenic patients. Materials and Methods: This descriptive cross-sectional study was conducted from 1st June to 31st December 2014 among 100 schizophrenic patients. For demographic assessment every patient was interviewed by a semi-structured questionnaire, after taking informed consent. Scale for the Assessment of Negative Symptoms (SANS) was used to interview the Schizophrenic patient. The scale is internationally well accepted research instrument for assessing negative symptoms in Schizophrenic patient. The study was conducted in Combined Military Hospital (CMH), Dhaka, National Institute of Mental Health (NIMH), Dhaka and Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka. Sampling size was 100 where Schizophrenia was diagnosed by psychiatrists. Results: The age group of the patients was from 18 years to 59 years with mean age 27.3 years (SD ±11.0), most of the patients were below the age of 30 years. Eighty six (86%) out of one hundred patients were found to have negative symptom. Most of the patient were male, literate, Muslim and came from a middle class family background. Onset of the disease was mostly insidious in nature. Conclusion: Schizophrenia is a major psychiatric disorder. Both the patient and their families suffer a lot by schizophrenia and its consequences. So improving the management of negative symptoms may reduce the overall burden of schizophrenic patients and their caregivers. JAFMC Bangladesh. Vol 17, No 1 (June) 2021: 22-25

Reduced learning bias towards the reward context in medication-naive first-episode schizophrenia patients

BackgroundReinforcement learning has been proposed to contribute to the development of amotivation in individuals with schizophrenia (SZ). Accumulating evidence suggests dysfunctional learning in individuals with SZ in Go/NoGo learning and expected value representation. However, previous findings might have been confounded by the effects of antipsychotic exposure. Moreover, reinforcement learning also rely on the learning context. Few studies have examined the learning performance in reward and loss-avoidance context separately in medication-naïve individuals with first-episode SZ. This study aimed to explore the behaviour profile of reinforcement learning performance in medication-naïve individuals with first-episode SZ, including the contextual performance, the Go/NoGo learning and the expected value representation performance.MethodsTwenty-nine medication-naïve individuals with first-episode SZ and 40 healthy controls (HCs) who have no significant difference in age and gender, completed the Gain and Loss Avoidance Task, a reinforcement learning task involving stimulus pairs presented in both the reward and loss-avoidance context. We assessed the group difference in accuracy in the reward and loss-avoidance context, the Go/NoGo learning and the expected value representation. The correlations between learning performance and the negative symptom severity were examined.ResultsIndividuals with SZ showed significantly lower accuracy when learning under the reward than the loss-avoidance context as compared to HCs. The accuracies under the reward context (90%win- 10%win) in the Acquisition phase was significantly and negatively correlated with the Scale for the Assessment of Negative Symptoms (SANS) avolition scores in individuals with SZ. On the other hand, individuals with SZ showed spared ability of Go/NoGo learning and expected value representation.ConclusionsDespite our small sample size and relatively modest findings, our results suggest possible reduced learning bias towards reward context among medication-naïve individuals with first-episode SZ. The reward learning performance was correlated with amotivation symptoms. This finding may facilitate our understanding of the underlying mechanism of negative symptoms. Reinforcement learning performance under the reward context may be important to better predict and prevent the development of schizophrenia patients’ negative symptom, especially amotivation.

Rationale and study design of a trial to assess rTMS add-on value for the amelioration of negative symptoms of schizophrenia (RADOVAN)

BackgroundSchizophrenia is a severe and often difficult to treat psychiatric illness. In many patients, negative symptoms dominate the clinical picture. Meta-analysis has suggested moderate, but significant effects of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on these symptoms. For treatment of depression a much shorter protocol - intermittent theta burst stimulation (iTBS) - has shown to be non-inferior to conventional high-frequency rTMS. This randomized, sham-controlled, rater-blinded clinical trial assesses the effects of conventional HF-rTMS as well as of iTBS of the left dorsolateral prefrontal cortex in comparison with sham. MethodsThe study will be conducted at two psychiatric university hospitals in Germany and at two in the Czech Republic. Assuming an effect size of 0.64 to be detected with a power of 80%, the calculated sample size is 90 patients. Primary outcome will be the difference in the Scale for the Assessment of Negative Symptoms (SANS) score between each active arm and the sham arm at end of treatment.In addition, the trial investigates effects on depressive symptoms, cognitive performance and cigarette smoking. Recording magnetic resonance imaging (MRI) and electroencephalography (EEG) data will serve to assess whether treatment success can be predicted by neural markers and is related to specific neurobiological changes. DiscussionThis is a clinical trial directly comparing 10 Hz-rTMS and iTBS in a sham-controlled manner in treating negative symptoms of schizophrenia. If successful, this would present an interesting treatment option for a chronic and severe condition that can be applied at most psychiatric hospitals and only takes up a few minutes per day. Trial registration numberThis trial has been registered at clinicaltrials.gov, Identifier: NCT04318977. Data disseminationResults from the trial shall be published in peer-reviewed journals and presented at meetings and conferences.

Distinctively lower DISC1 mRNA levels in patients with schizophrenia, especially in those with higher positive, negative, and depressive symptoms

BackgroundThe issue of genetic influence on schizophrenia has received considerable attention. The DISC1 gene has been shown in several studies to play a role in the pathophysiology of schizophrenia. However, the relationship between DISC1 mRNA expression vs. schizophrenia and its clinical symptoms is uncertain. MethodsFifty-six subjects (32 patients with schizophrenia and 24 healthy controls) were enrolled. Peripheral blood was obtained from all subjects to exam the DISC1 mRNA expression. Schizophrenia patients were evaluated with Hamilton Rating Scale for Depression (HAMD), Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS) and Scale for the Assessment of Negative Symptoms (SANS) scales. Healthy subjects were assessed with HAMD scale. ResultsPatients with schizophrenia had significantly lower levels of the DISC1 mRNA expression than the healthy control (P = 0.002). We also found that lower DISC1 mRNA levels in schizophrenia patients were associated with higher degree of depression in HAMD (P = 0.037), severer positive symptoms in PANSS (P = 0.032) and more negative symptoms in SANS (P = 0.038). ConclusionThe results showed that schizophrenia patients had lower levels of DISC1 mRNA than healthy individuals, and that the schizophrenia patients with lower DISC1 mRNA levels were more likely to manifest more marked symptoms, including positive, negative, and depressive symptoms. The findings suggest that lower DISC1 expression may be related with the pathogenesis and phenotypes of schizophrenia. Future studies are needed to replicate the results and to further establish its potential role in clinical application of early diagnosis and outcome follow-up.