Scale For The Assessment Of Negative Symptoms Research Articles

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.

Atypical Antipsychotics Mediate Dynamics of Intrinsic Brain Activity in Early-Stage Schizophrenia? A Preliminary Study

ObjectiveAbnormalities of static brain activity have been reported in schizophrenia, but it remains to be clarified the temporal variability of intrinsic brain activities in schizophrenia and how atypical antipsychotics affect it. MethodsWe employed a resting-state functional magnetic resonance imaging (rs-fMRI) and a sliding-window analysis of dynamic amplitude of low-frequency fluctuation (dALFF) to evaluate the dynamic brain activities in schizophrenia (SZ) patients before and after 8-week antipsychotic treatment. Twenty-six schizophrenia individuals and 26 matched healthy controls (HC) were included in this study. ResultsCompared with HC, SZ showed stronger dALFF in the right inferior temporal gyrus (ITG.R) at baseline. After medication, the SZ group exhibited reduced dALFF in the right middle occipital gyrus (MOG.R) and increased dALFF in the left superior frontal gyrus (SFG.L), right middle frontal gyrus (MFG.R), and right inferior parietal lobule (IPL.R). Dynamic ALFF in IPL.R was found to significant negative correlate with the Scale for the Assessment of Negative Symptoms (SANS) scores at baseline. ConclusionOur results showed dynamic intrinsic brain activities altered in schizophrenia after short term antipsychotic treatment. The findings of this study support and expand the application of dALFF method in the study of the pathological mechanism in psychosis in the future.

Eye movement characteristics in male patients with deficit and non-deficit schizophrenia and their relationships with psychiatric symptoms and cognitive function

BackgroundThe cognitive impairment pattern of deficit schizophrenia (DS) is centered on an impaired attention function. Previous studies have suggested that the exploratory eye movement (EEM) tests reflect attention deficits in patients with schizophrenia. However, no study has investigated the characteristics of eye movement in DS in the Chinese Han population. This study aimed to investigate the pattern of eye movement characteristics in DS patients and to examine whether eye movement characteristic is associated with serious negative symptoms and cognitive decline in this schizophrenia subtype.MethodsA total of 86 male patients [37 DS and 49 non-deficit schizophrenia (NDS)] and 80 healthy controls (HC) participated in this study. Clinical symptoms were assessed using the Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS). Cognitive function was assessed using the Mattis Dementia Rating Scale (MDRS-2). Eye movement data of subjects were collected using an eye movement tracking analyzer.ResultsThere were significant differences in the overall eye movement data and cognitive test scores among the three groups (all P < 0.001). Both DS and NDS schizophrenia subgroups showed more severe eye movement and cognitive impairment compared with the control group. The number of eye fixations (NEF), total of eye scanning length (TESL), and cognitive function in DS patients were significantly lower than those in NDS patients. The discriminant analysis (D score) was higher than that of the control group (P < 0.001). In the DS group, the inattention factor of SANS was negatively correlated with the attention factor (r = − 0.545, P = 0.001) and structure factor of cognitive (r = − 0.389, P = 0.023), the affective flattening factor of SANS was negatively correlated with TESL (r = − 0.353, P = 0.041) and initiation/retention factor of cognitive (r = − 0.376,P = 0.028). TESL was found to positively correlate with the MDRS-2 total score (r = 0.427, P = 0.012), attention factor (r = 0.354, P = 0.040), and memory factor (r = 0.349, P = 0.043) in the DS group, whereas the mean of eye scanning length (MESL) positively correlated with cognitive impairments in the NDS group. The negative symptoms showed no significant correlation with cognition in the NDS group.ConclusionsTotal of eye scanning length may be a characteristic eye movement symptom in DS patients, which is associated with serious negative symptoms and cognitive impairment in this schizophrenia subtype.

Intermittent theta burst stimulation of cerebellar vermis enhances fronto-cerebellar resting state functional connectivity in schizophrenia with predominant negative symptoms: A randomized controlled trial

ObjectiveNegative symptoms of schizophrenia are substantially disabling and treatment resistant. Novel treatments like repetitive transcranial magnetic stimulation (TMS) need to be examined for the same using the experimental medicine approach that incorporates tests of mechanism of action in addition to clinical efficacy in trials. MethodsStudy was a double-blind, parallel, randomized, sham-controlled trial recruiting schizophrenia with at least a moderate severity of negative symptoms. Participants were randomized to real or sham intermittent theta burst stimulation (iTBS) under MRI-guided neuro-navigation, targeting the cerebellar vermis area VII-B, at a stimulus intensity of 100% active motor threshold, two sessions/day for five days (total = 6000 pulses). Assessments were conducted at baseline (T0), day-6 (T1) and week-6 (T2) after initiation of intervention. Main outcomes were, a) Scale for the Assessment of Negative Symptoms (SANS) score (T0, T1, T2), b) fronto-cerebellar resting state functional connectivity (RSFC) (T0, T1). ResultsThirty participants were recruited in each arm. Negative symptoms improved in both arms (p < 0.001) but was not significantly different between the two arms (p = 0.602). RSFC significantly increased between the cerebellar vermis and the right inferior frontal gyrus (pcluster-FWER = 0.033), right pallidum (pcluster-FWER = 0.042) and right frontal pole (pcluster-FWER = 0.047) in the real arm with no change in the sham arm. ConclusionCerebellar vermal iTBS engaged a target belonging to the class of cerebello-subcortical-cortical networks, implicated in negative symptoms of schizophrenia. However, this did not translate to a superior clinical efficacy. Future trials should employ enhanced midline cerebellar TMS stimulation parameters for longer durations that can potentiate and translate biological changes into clinical effects.

The clinical relevance of formal thought disorder in the early stages of psychosis: results from the PRONIA study

BackgroundFormal thought disorder (FTD) has been associated with more severe illness courses and functional deficits in patients with psychotic disorders. However, it remains unclear whether the presence of FTD characterises a specific subgroup of patients showing more prominent illness severity, neurocognitive and functional impairments. This study aimed to identify stable and generalizable FTD-subgroups of patients with recent-onset psychosis (ROP) by applying a comprehensive data-driven clustering approach and to test the validity of these subgroups by assessing associations between this FTD-related stratification, social and occupational functioning, and neurocognition.Methods279 patients with ROP were recruited as part of the multi-site European PRONIA study (Personalised Prognostic Tools for Early Psychosis Management; www.pronia.eu). Five FTD-related symptoms (conceptual disorganization, poverty of content of speech, difficulty in abstract thinking, increased latency of response and poverty of speech) were assessed with Positive and Negative Symptom Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS).ResultsThe results with two patient subgroups showing different levels of FTD were the most stable and generalizable clustering solution (predicted clustering strength value = 0.86). FTD-High subgroup had lower scores in social (pfdr < 0.001) and role (pfdr < 0.001) functioning, as well as worse neurocognitive performance in semantic (pfdr < 0.001) and phonological verbal fluency (pfdr < 0.001), short-term verbal memory (pfdr = 0.002) and abstract thinking (pfdr = 0.010), in comparison to FTD-Low group.ConclusionsClustering techniques allowed us to identify patients with more pronounced FTD showing more severe deficits in functioning and neurocognition, thus suggesting that FTD may be a relevant marker of illness severity in the early psychosis pathway.

Galantamine as Adjunctive Treatment for Ameliorating Negative Symptoms of Schizophrenia Patients

Background: Schizophrenia is one of the most serious mental disorders presenting in adolescence. Antipsychotic drugs are the basis of treatment and clinical management of patients with schizophrenia. Despite the efficacy of risperidone as one of the antipsychotic drugs, about two-thirds of patients may experience both positive and negative symptoms during their life. Objectives: We evaluated the efficacy of galantamine as an adjunctive treatment for ameliorating the negative symptoms of schizophrenia patients. Methods: This is a randomized double-blind phase II clinical trial study carried out on schizophrenia patients admitted to a psychiatric department. The patients were randomly divided into two equal groups using the block randomization method. The intervention group received 24 mg galantamine plus 2 - 6 mg risperidone, and controls received 24 mg placebo along with 2 - 6 mg risperidone. Neurological tests included the Scale for the Assessment of Negative Symptoms (SANS) and the Positive and Negative Syndrome Scale (PANSS) at baseline and weeks 2, 4, and 8 after treatment. Results: We studied 28 patients. The mean age of the participants was 44 ± 3.1 and 47 ± 2.7 years in the placebo and intervention groups, respectively. The PANSS score significantly decreased over study time. The intervention group showed significantly greater reduction slopes than the control group (P = 0.034). Alogia (P = 0.0016) and attention (P = 0.0108) reduced more intensely in the intervention group than in the control group. Conclusions: Our findings indicated that galantamine could significantly affect the severity of the symptoms of schizophrenia patients. The findings suggest galantine as an appropriate adjunctive treatment for ameliorating negative symptoms, especially attention and alogia.

Psychometric properties and diagnostic criteria of Scale for the assessment of negative symptoms (SANS) in schizophrenia

The Scale for the assessment of negative symptoms (SANS) is one of the most widely used clinical assessment tools for negative symptoms.Thepurposeof this study was psychometric analysis and modification of the SANS with the definition of criteria for assessing the severity of negative symptoms in the dynamics of therapy in patients with schizophrenia.Materialandmethods:The study involved 157 patients with a diagnosis of schizophrenia, the age range of participants ranged from 18 to 59 years. Psychometric analysis was done on the base of the Rush measurement with the definition of criteria for assessing the severity of negative symptoms based on the index of minimum detectable changes for 95% probability (Minimum detectable change95%— MDC95%).Results:Five SANS diagnostic items with low construct validity were identified. The technique was modified by excluding these invalid items. SANS was modified by eliminating of 5 invalid items. The modified version of SANS demonstrated high reliability (reliability index = 0.97) and discriminativeness (the ability to differentiate 12 metric levels of severity of negative symptoms). Factor analysis revealed the heterogeneity of the metric structure of the technique: points in the first group reflect the impoverishment of speech and emotional manifestations, points in the second group reflect the decrease of the patient’s involvement in various activities and restriction of social interaction. Thus, the two-dimensional structure of the SANS scale (“expression” factor and “motivation” factor) is fully consistent with the modern concept of negative symptoms, which allows to consider the total SANS score as an indicator of the severity of the negative syndrome construct. In the course of the metric analysis, the criteria for assessing the severity of negative symptoms in the dynamics of the therapy were determined.Conclusion:The modified version of SANS has adequate psychometric characteristics. The diagnostic criteria are suitable for use in clinical practice and research.

Lowered serum cesium levels in schizophrenia: association with immune-inflammatory biomarkers and cognitive impairments.

Objectives:A previous study has shown that schizophrenia (SCZ) is accompanied by lowered levels of trace/metal elements, including cesium. However, it is not clear whether changes in cesium, rubidium, and rhenium are associated with activated immune-inflammatory pathways, cognitive impairments, and the symptomatology of SCZ.Methods:This study measured cesium, rubidium, and rhenium, cognitive impairments (using the Brief Assessment of Cognition in Schizophrenia [BACS]), and the levels of cytokines/chemokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and eotaxin (CCL11) in 120 patients with SCZ and 54 healthy controls. Severity of illness was assessed using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the Fibromyalgia and Chronic Fatigue Syndrome Rating (FF) Scale, and the Hamilton Depression Rating Scale (HAM-D).Results:Serum cesium was significantly lower in patients with SCZ as compared with controls. Further, serum cesium was significantly and inversely associated with CCL11 and TNF-α, but not IL-1β, in patients with SCZ; significant inverse associations were also noted between serum cesium levels and BPRS, FF, HAM-D, and SANS scores. Finally, cesium was positively correlated with neurocognitive probe results including the Tower of London, Symbol Coding, Controlled Word Association, Category Instances, Digit Sequencing Task, and List Learning tests.Conclusion:The results suggest that lowered serum cesium levels may play a role in the pathophysiology of SCZ, contributing to specific symptom domains including negative, depressive and fatigue symptoms, neurocognitive impairments (spatial working, episodic, and semantic memory and executive functions), and neuroimmune pathways.

Digit ratio as an endophenotype in a schizophrenia population.

BackgroundSchizophrenia is a debilitating mental health condition affecting the lives of many South Africans. The origins of the heterogeneity in the presentation of the illness remain uncertain.AimThis cross-sectional study performed a retrospective data analysis to determine the usefulness of digit ratio as an endophenotype in a South African schizophrenia population.SettingA large genetic study in a South African schizophrenia population recruited patients from services in the Western and Eastern Cape.MethodsComplete clinical histories were captured for participants, including sets of images of the face and extremities. Software was utilised to measure the lengths of participants’ digits from said images and digit ratios (2D:4D) were calculated. Descriptive analyses were performed on the ratios and statistical differences in digit ratio means were calculated between groups characterised by sex, age of onset and the presence vs absence of positive symptoms. Linear modelling was utilised to assess for correlates between 2D:4D and positive and negative symptom severity using scores obtained from the Positive and Negative Syndrome Scale (PANSS) and Scale for the Assessment of Negative Symptoms (SANS).Results2D:4D in male participants did not significantly differ from female participants as in healthy populations. 2D:4D did not significantly correlate with the severity of positive or negative symptoms and 2D:4D means between groups did not significantly relate to age of onset.Conclusion2D:4D appears to be a possible endophenotype in schizophrenia in this population. 2D:4D, however, may not be as readily identifiable as certain minor physical anomalies and neurological soft signs significantly associated with schizophrenia in this population.

Intermittent theta burst stimulation for negative symptoms of schizophrenia\u2014A double-blind, sham-controlled pilot study

Optimal noninvasive brain stimulation parameters for the treatment of negative symptoms of schizophrenia remain unclear. Here, we aimed to investigate the clinical and biological effects of intermittent theta burst transcranial magnetic stimulation (iTBS) in patients with treatment-resistant negative symptoms of schizophrenia (NCT00875498). In a randomized sham-controlled 2-arm study, 22 patients with schizophrenia and treatment-resistant negative symptoms received 20 sessions of either active (n = 12) or sham (n = 10) iTBS. Sessions were delivered twice a day on 10 consecutive working days. Negative symptom severity was assessed 5 times using the Scale for the Assessment of Negative Symptoms (SANS): before iTBS, after iTBS, and 1, 3, and 6 months after iTBS. As a secondary objective, we explored the acute effects of iTBS on functional connectivity of the left dorsolateral prefrontal cortex (DLPFC) using seed-based resting-state functional connectivity MRI (rsFC fMRI) images acquired before and after iTBS. Active iTBS over the left DLPFC significantly decreased negative symptoms severity compared to sham iTBS (F(3,60) = 3.321, p = 0.026). Post hoc analyses revealed that the difference between groups was significant 6 months after the end of stimulation sessions. Neuroimaging revealed an increase in rsFC between the left DLPFC and a brain region encompassing the right lateral occipital cortex and right angular gyrus and a right midbrain region that may encompass dopamine neuron cell bodies. Thus, iTBS over the left DLPFC can alleviate negative symptoms of schizophrenia. The effect might be driven by significant modulation of dopamine transmission.

High mobility group box-1 levels in schizophrenia: Potential biomarker of remission phase.

Background: Schizophrenia is a chronic mental disorder, characterized byacute exacerbation and remission phases. Immune system has a role in the pathophysiology of schizophrenia. High mobility group box-1 (HMGB-1) is a macrophage secreted protein activating immune cells to produce cytokines. The aim of this study was to evaluate HMGB-1 levels among patients with schizophrenia both in acute exacerbation and remission phases. Methods: Consecutive schizophrenia patients in acute exacerbation and remission phases were enrolled and compared with each other and with age-sex matched healthy subjects. Patients were assessed with the Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms (SANS), Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression Scale (CGI). Results: Mean HMGB-1 levels were not significantly different in acute exacerbation phase versus remission phase schizophrenia patients (2.139±0.564 g/L vs. 2.326± 0.471 g/L, p=0.335) and both were individually higher than the control group (1.791±0.444 g/L, p=0.05 for acute exacerbation vs control, p=0.002 for remission vs control). In remission phase schizophrenic patients, HMGB-1 levels were positively correlated with Scale For The Assessment of Positive Symptoms (r=0.447, p=0.015) and BPRS (r=0.397, p=0.033) scores and HMGB-1 levels were independently associated with BPRS. Conclusions: Serum HMGB-1 levels were shown to be increased in patients with schizophrenia patients irrespective of phase, there were no differences between patients in acute exacerbation and remission phase in terms of biomarker and HMGB-1 levels were related to symptom severity according to psychiatric scales among patients in remission phase of schizophrenia.

Neural mapping of anhedonia across psychiatric diagnoses: A transdiagnostic neuroimaging analysis

Anhedonia has been associated with abnormal reward-related striatal dopamine functioning in patients with different psychiatric disorders. Here, we tested whether anhedonia expression mapped onto striatal volume across several psychiatric diagnoses.T1-weighted images from 313 participants including 89 healthy controls (HC), 22 patients with opioid use disorder (OUD), 50 patients with major depressive disorder (MDD), 45 patients with borderline personality disorder (BPD), 49 patients with first-episode psychosis (FEP), 43 patients with cocaine use disorder (CUD) and 15 patients with schizophrenia (SZ) were included. Anhedonia was assessed with subscores of the Beck Depression Inventory (BDI) and/or the Scale for the Assessment of Negative Symptoms (SANS). Voxel-based morphometry (VBM) was conducted for identifying dimensional symptom-structure associations using region of interest (ROI, dorsal and ventral striatum) and whole-brain analyses, as well as for group comparisons of striatal volume.ROI analyses revealed significant negative relationships between putamen volume and BDI and SANS anhedonia scores across OUD, MDD, BPD, CUD and SZ patients (n = 175) and MDD, FEP and SZ patients (n = 114), respectively. Whole-brain VBM analyses confirmed these associations and further showed negative relationships between anhedonia severity and volume of the bilateral cerebellum. There were group differences in right accumbens volume, which however were not related to anhedonia expression across the different diagnoses.Our findings indicate volumetric abnormalities in the putamen and cerebellum as a common neural substrate of anhedonia severity that cut across psychiatric entities.