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Objective Negative symptoms and cognitive impairment in schizophrenia (SZ) remain unmet treatment needs as they are highly prevalent, associated with poor functional outcomes, and resistant to pharmacologic treatment. The current pilot randomized controlled trial examined the efficacy of an integrated Cognitive-Behavioral Social Skills Training and Compensatory Cognitive Training (CBSST-CCT) intervention compared to Goal-focused Supportive Contact (SC) on negative symptoms and cognitive performance. Methods Fifty-five adults with SZ or schizoaffective disorder with moderate-to-severe negative symptoms were randomized to receive 25 twice-weekly, 1-h manualized group sessions (12.5 weeks total duration) of either CBSST-CCT or SC delivered by master’s level clinicians in five community settings. Assessments of negative symptom severity (primary outcomes) and neuropsychological performance, functional capacity, social skills performance, and self-reported functional ability/everyday functioning, psychiatric symptom severity, and motivation (secondary outcomes) were administered at baseline, mid-treatment, post-treatment, and 6-month follow-up. Results Mixed-effects models using baseline, mid-treatment, and post-treatment data demonstrated significant CBSST-CCT-associated effects on negative symptom severity, as assessed by the Scale for the Assessment of Negative Symptoms (p = .049, r = 0.22), with improvements in diminished motivation driving this effect (p = .037, r = 0.24). The CBSST-CCT group also demonstrated improved verbal learning compared to SC participants (p = .026, r = 0.36). The effects of CBSST-CCT appeared to be durable at 6-month follow-up. Conclusions CBSST-CCT improved negative symptom severity and verbal learning in high-negative-symptom individuals relative to SC. CBSST-CCT warrants larger investigations to examine its efficacy in treating negative symptoms, along with other symptoms, cognition, and, ultimately, real-world functional outcomes. Clinical Trial registration number NCT02170051.

The purpose of this study was to assess and compare neurological soft signs in patients of cannabis use disorder (CUD) with and without co-occurring psychosis in a treatment-seeking sample. Methods: We included 30 right-handed male subjects aged 18-65 years diagnosed with CUD (as per DSM-5) without any co-occurring psychiatric disorder in group I and those with co-occurring non-affective psychosis in group II. Group III consisted of 30 age and sex-matched, right-handed, healthy subjects with no psychiatric or medical conditions. Neurological Evaluation Scale (NES) was applied to measure neurological soft signs across the groups. We also used the Severity of Dependence Scale (in CUD with or without co-occurring non-affective psychosis groups) and Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, Barnes Akathisia Rating Scale, Abnormal Involuntary Movements Scale, and Simpson Angus Scale (in CUD with co-occurring non-affective psychosis group). Results: Our data suggested higher total NES mean scores in CUD with (20.53 ± 13.77) or without co-occurring non-affective psychosis groups (15.93 ± 9.86) as compared to healthy controls (6.20 ± 5.40) (χ2 = 23.12; p < .001). However, there were no differences between cannabis use disorder with or without co-occurring non-affective psychosis groups. The mean of subdomain scores of motor incoordination, sequencing of complex motor tasks, sensory integration, and others was significantly higher in CUD with or without co-occurring non-affective psychosis groups compared to healthy controls. Conclusion: Impairment in neurological soft signs is present in patients with CUD regardless of a co-occurring psychosis. Cannabinoids might be interacting with the brain circuits known to be involved in schizophrenia.

Background Formal 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. Methods 279 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). Results The 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. Conclusions Clustering 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.

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.

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.

Negative symptoms are a core dimension of schizophrenia and other psychoses that account for a large degree of the poor functional outcomes related to these disorders. Newer assessment scales for negative symptoms, such as the Clinical Assessment Interview for Negative Symptoms (CAINS), provide evidence for separate dimensions of motivational and pleasure (MAP) and expression (EXP) dimensions. This study was aimed at extending the analysis of the clinical, functional and cognitive correlates of CAINS dimensions in a sample of patients with psychotic disorders (n = 98) and 50 healthy controls. A psychopathological evaluation was conducted by using the Comprehensive Assessment of Symptoms and History (CASH). To assess the extrapyramidal signs, the UKU scale was used. Community functioning was evaluated by means of real-world and functional attainment measures. Additionally, a full neuropsychological test battery was administered. Pearson correlation and hierarchical multiple linear regression analyses were performed to identify the influencing and predictive factors associated with the CAINS dimensions. The MAP and EXP dimensions showed strong associations with the Scale for the Assessment of Negative Symptoms (SANS) items and were not significantly associated with extra-pyramidal or cognitive deficits. The MAP and EXP CAINS dimensions revealed good predictive validity for real-world functioning and functional attainment measures. These findings suggest that the CAINS scale endorses good convergent validity for the assessment of negative symptoms and is very useful in the prediction of psychosocial functioning. In addition, the CAINS dimensions might provide advantages over old assessment scales on disentangling the complex associations between negative symptoms and cognitive impairment.

Objective: To determine whether changes in serum galectin-3 (gal-3) concentrations in schizophrenia patients have etiopathogenetic importance. Since very little research has assessed the connection between galectins and schizophrenia, we wanted to examine alterations in the inflammatory marker gal-3 in schizophrenia and investigate possible correlations between clinical symptomatology and serum concentrations. Methods: Forty-eight schizophrenia patients and 44 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) were administered to determine symptom severity. Venous blood samples were collected, and serum gal-3 levels were measured. Results: Mean serum gal-3 levels were significantly lower in schizophrenia patients, and there were no significant differences in age or sex with the control group. There was also a significant positive correlation between serum gal-3 concentrations and negative schizophrenia symptoms according to the SANS. Conclusion: The results indicate that gal-3 is decreased in schizophrenia patients, which could contribute to inflammation in the pathogenesis of schizophrenia.

Background and aims: Music therapy is a simple and inexpensive method for the treatment of some psychiatric disorders. The aim of this study was to determine the effect of traditional music on the mental state of hospitalized chronic schizophrenia patients. Methods: In this clinical trial, 30 schizophrenia patients in the intervention group received routine treatment and attended music therapy sessions and 30 patients in the control group received routine treatment alone. Group music therapy sessions with traditional music were conducted 5 times a week for 2 months. Demographic questionnaire and Andreasen’s positive and negative symptoms questionnaires were completed at baseline and after the completion of music therapy sessions. Data analysis was conducted in SPSS version 16.0 using independent and paired t tests. Results: The mean scores of delusion (P=0.001) and bizarre behavior (P=0.036) and the total score of the SAPS (P=0.001) significantly decreased after intervention in the music therapy group. However, in the control group, the differences in the total and individual domain scores of the SAPS were not significant (P>0.05). There was no significant difference between the control and music therapy groups in the total and individual domain scores of the Scale for the Assessment of Negative Symptoms (SANS) before and after the intervention (P>0.05). Additionally, before and after the study, the mean score of avolition in the music therapy group was significantly lower compared to the control group (P=0.03). The mean score of alogia in the music therapy group was significantly lower compared to the control group (P=0.01). Conclusion: Music therapy is effective in improving most of the positive symptoms of schizophrenia and some of its negative aspects, and therefore can be used as a complementary therapy along with drug therapy.

Background Negative symptoms are key features of psychosis-spectrum disorders linked to psychosis development and functional impairments. This study investigated the predictive strength of negative symptoms domains on multiple aspects of real-life functional outcome in individuals at clinical high-risk (CHR) for psychosis. Methods A total of 146 UHR individuals were enrolled in a randomized, clinical trial (RCT), with this being analyses secondary to the RCT. The participants were assessed at baseline with the Scale for the Assessment of Negative Symptoms (SANS) encompassing the four domains of affect, alogia, avolition, and anhedonia. Functioning measures, encompassing overall-, social-, and role functioning, self-report social functioning, and quality of life, were obtained at 12-month follow-up. Regression analyses elucidated on the relationship between the four negative symptom domains and functional outcomes. Results Anhedonia and avolition were the aspects of negative symptoms most predictive of real-life functioning at 12-month follow-up explaining 7–20% of the variance on the outcome measures. Alogia was predictive of social functioning. These findings were maintained when controlling for the effect of neurocognition, antipsychotic medication, and depressive symptoms. Discussion Our findings show experiential negative symptoms to predict multiple areas of real-life functioning and quality of life, while expressive negative symptoms exert a modest influence on the functional prognosis of CHR individuals. Experiential negative symptoms may therefore constitute an important treatment target in intervention approaches aimed at enhancing the functional outcome of CHR individuals.

Background: Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment strategy for negative symptoms. However, the evidence for its efficacy is mixed, with contradictory results between studies due to lack of consensus about the optimal stimulation parameters. Aim: The present study was planned to assess the safety and efficacy of 20-Hz rTMS over left dorsolateral prefrontal cortex (Lt-DLPFC) with more robust stimulation parameters for adjunctive treatment of negative symptoms in patients with schizophrenia. Materials and Methods: Thirty patients with negative symptoms of schizophrenia (Positive and Negative Syndrome Scale [PANSS] negative subscore ≥15) were randomized to receive a 4-week treatment with either real-rTMS (n = 15) or sham-rTMS (n = 15). The study outcomes were assessed at baseline, after 5th and 20th rTMS sessions with PANSS, Scale for the Assessment of Negative Symptoms (SANS), Calgary Depression Scale for Schizophrenia, Clinical Global Impressions-Severity of illness scale, and rTMS side-effect checklist. Results: There was significantly greater reduction in negative symptoms assessed by SANS score in the real rTMS group, compared with the sham rTMS group. There was no significant difference in the rate of side-effects reported between the two groups. The rTMS treatment was well-tolerated by all the patients, except one seizure episode reported in the active group. Conclusion: The high-frequency rTMS protocol was safe and well-tolerated, provided patients prone to developing seizure were excluded by baseline electroencephalography prior to starting of the treatment. The 20-Hz rTMS over Lt-DLPFC with more robust stimulation parameters (100% motor threshold and 40,000 pulses) might be an effective augmentation strategy for the treatment of negative symptoms in schizophrenia.

We explored differences in performance on the Synthetic House–Tree–Person Test between people with mainly positive symptoms and those with mainly negative symptoms of schizophrenia and, further, aimed to provide a basis for the diagnosis of schizophrenia symptom type. Participants were 58 people receiving treatment for schizophrenia, and we asked them to complete the Scale for the Assessment of Positive Symptoms, the Scale for the Assessment of Negative Symptoms, and the Synthetic House–Tree–Person Test. There were significant differences in results on the Synthetic House–Tree–Person Test between the group with positive symptoms, the group with a mix of positive and negative symptoms, and the group with negative symptoms. There were 12 features of participants' drawings, such as big hands, which were correlated with hallucinations and delusions in positive symptoms, and 9 features, such as trees in a landscape, which were correlated with avolition and anhedonia in negative symptoms. Our study results suggest differences in performance on the Synthetic House–Tree–Person Test between these different symptom subtypes of schizophrenia; hence, the features that appear in drawings made during the test may contribute to the diagnosis of symptoms of people with schizophrenia.

Background The 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. Methods A 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. Results There were significant differences in the overall eye movement data and cognitive test scores among the three groups (all P P 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. Conclusions Total 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.

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.

BackgroundThere is a large variability in the recovery trajectory and outcome of first episode of psychosis [FEP] patients. To date, individuals’ outcome trajectories at early stage of illness and potential risk factors associated with a poor outcome trajectory are largely unknown. This study aims to apply three separate predictors (positive symptoms, negative symptoms, and soft neurological signs) to identify homogeneous function outcome trajectories in patients with FEP using objective data-driven methods, and to explore the potential risk /protective factors associated with each trajectory.MethodsA total of 369 first episode patients (93% antipsychotic naive) were included in the baseline assessments and followed-up at 4-8 weeks, 6 months, and 1 year. K means cluster modelling for longitudinal data (kml3d) was used to identify distinct, homogeneous clusters of functional outcome trajectories. Patients with at least 3 assessments were included in the trajectory analyses (N=129). The Scale for the Assessment of Negative Symptoms (SANS), Scale for the Assessment of Positive Symptoms (SAPS), and Neurological examination abnormalities (NEA) were used as predictors against Global Assessment of Functioning Scale (GAF).ResultsIn each of the three predictor models, four distinct functional outcome trajectories emerged: “Poor”, “Intermediate”, “Good” and “Catch-up”. Individuals with male gender; ethnic minority status; low premorbid adjustment; low executive function/IQ, low SES, personality disorder, substance use history may be risk factors for poor recovery.ConclusionsFunctioning recovery in individuals with FEP is heterogeneous, although distinct recovery profiles are apparent. Data-driven trajectory analysis can facilitate better characterization of individual longitudinal patterns of functioning recovery.

There is no reliable and valid psychometric measure in Bangladesh to assist mental health and relevant professionals to assess the presence and severity of symptoms of schizophrenic patient...

The aim of the study was to investigate the moderating roles of the current self-reported psychological maladjustment and gender in the relationship between perceived parental rejection in childhood and negative symptoms of schizophrenia patients. The study sample consisted of 52 outpatients (20 females and 32 males between the ages of 19 and 61), diagnosed with schizophrenia at Ankara University and Ege University Faculty of Medicine Department of Psychiatry in Turkey. Participants' negative symptoms, recollections of parental rejection, and psychological maladjustment were assessed by Scale for the Assessment of Negative Symptoms, Adult Parental Acceptance-Rejection Questionnaire, and Personality Assessment Questionnaire, respectively. The findings revealed that negative symptoms were not directly linked to maternal and paternal rejection. However, negative symptoms significantly associated with psychological maladjustment. Three-way interaction (moderated moderation) analyses showed that the effects of perceived maternal and paternal rejection in childhood on negative symptoms were significantly moderated by the current self-reported psychological maladjustment for female patients with schizophrenia, but not for males. The study highlighted the importance of applying trauma or attachment-focused interventions and a gender-specific psychiatric treatment in schizophrenia.

Kaiming Zhuo,1 Yingying Tang,1,2 Zhenhua Song,1 Yingchan Wang,1 Junjie Wang,2 Zhenying Qian,2 Hui Li,2 Qiong Xiang,1 Tianyi Chen,1,3 Zhilei Yang,1,4 Yifeng Xu,1,5 Xiaoduo Fan,6 Jijun Wang,1–2,5 Dengtang Liu1,51First-episode Schizophrenia and Early Psychosis Program, Division of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of EEG and Imaging, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Shanghai Hong Kou Mental Health Center, Shanghai, People’s Republic of China; 4Shanghai Jia Ding Mental Health Center, Division of Psychotic Disorders, Shanghai, People’s Republic of China; 5Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 6Psychotic Disorders Program, UMass Memorial Medical Center, University of Massachusetts Medical School, Worcester, MA, USAPurpose: Effective treatment options for negative symptoms and cognitive impairment in patients with schizophrenia are still to be developed. The present study was to examine potential benefits of repetitive transcranial magnetic stimulation (rTMS) to improve negative symptoms and cognition in this patient population.Methods: The study was a 4-week, randomized, double-blind sham-controlled trial. Patients with schizophrenia were treated with adjunctive 20-Hz rTMS for 4 weeks or sham condition to the left dorsolateral prefrontal cortex (DLPFC). Negative symptoms were measured using the Scale for the Assessment of Negative Symptoms (SANS) and the Positive and Negative symptom scale (PANSS) negative subscale at baseline and week 4. Cognitive function was measured using the MATRICS Consensus Cognitive Battery (MCCB) at the same two time points. In addition, possible moderators for rTMS treatment efficacy were explored.Results: Sixty patients (33 in the treatment group, 27 in the sham group) completed the study. There was a significant decrease in negative symptoms after 4-week rTMS treatment as measured by the SANS total score and the PANSS negative symptom subscale score. However, there was no significant improvement in cognition with rTMS treatment. Stepwise multiple linear regression analysis suggested that the baseline severity of positive symptoms may predict poorer improvement in negative symptoms at week 4.Conclusion: Twenty-Hz rTMS stimulation over left DLPFC as an adjunctive treatment might be beneficial in improving negative symptoms of schizophrenia. Future studies with a longer treatment duration and a larger sample size are needed.Clinical trial ID:NCT01940939.Keywords: schizophrenia, negative symptoms, cognitive impairment, repetitive transcranial magnetic stimulation, rTMS, MCCB

WOS: 000468758600003, PubMed: 31132838, Objective The aim of this study was to investigate the rates childhood traumatic experiences (CTEs) of schizophrenia patients and to examine relationship between childhood traumatic experiences, dissociation and psychotic symptoms. Methods One hundred schizophrenia patients who had 5 or 5 points below in Clinical Global Impression-Severity (CGI-S) and who were not in active psychotic episode and 50 healthy siblings who grew up in the same environment with the patients were included to the study. Structured Clinical Interview for DSM IV, Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, Dissociative Experiences Scale (DES), CGI-S, Global Assessment of Functioning Scale and Childhood Trauma Questionnaire (CTQ-28) applied to the patients. Results Childhood abuse subscales and DES scores were statistically higher in the patient group (p

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. Published version

BackgroundMotivational deficits in people with schizophrenia (PSZ) are associated with an inability to integrate the magnitude and probability of previous outcomes. The mechanisms that underlie probability-magnitude integration deficits, however, are poorly understood. We hypothesized that increased reliance on “value-less” stimulus-response associations, in lieu of expected value (EV)-based learning, could drive probability-magnitude integration deficits in PSZ with motivational deficits.MethodsHealthy volunteers (n= 38) and PSZ (n=49) completed a reinforcement learning paradigm consisting of four stimulus pairs. Reward magnitude (3/2/1/0 points) and probability (90%/80%/20%/10%) together determined each stimulus’ EV. Following a learning phase, new and familiar stimulus pairings were presented. Participants were asked to select stimuli with the highest reward value.ResultsPSZ with high motivational deficits made increasingly less optimal choices as the difference in reward value (probability*magnitude) between two competing stimuli increased. Using a previously-validated computational hybrid model, PSZ relied less on EV (“Q-learning”) and more on stimulus-response learning (“actor-critic”), which correlated with SANS motivational deficit severity. PSZ specifically failed to represent reward magnitude, consistent with model demonstrations showing that response tendencies in the actor-critic were preferentially driven by reward probability. ConclusionsProbability-magnitude deficits in PSZ with motivational deficits arise from underutilization of EV in favor of reliance on value-less stimulus-response associations. Consistent with previous work and confirmed by our computational hybrid framework, probability-magnitude integration deficits were driven specifically by a failure to represent reward magnitude. This work reconfirms the importance of decreased Q-learning/increased actor-critic-type learning as an explanatory framework for a range of EV deficits in PSZ.

Background: Auditory hallucinations may persist in a subset of chronic psychotic patients in spite of treatment. It is important to understand the personal meaning and significance of voices in these patients. In spite of its relevance, only a limited literature is available. Aim: This exploratory study aimed to assess the beliefs regarding voices in treatment-seeking patients with chronic schizophrenia having persistent auditory verbal hallucinations (AVHs) and assess their relation to the severity of psychosis. Materials and Methods: We recruited thirty adult patients with chronic schizophrenia as per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition with both lifetime and current significant AVHs (≥50% days/month). Co-occurring psychiatric disorders were ruled out using the Mini International Neuropsychiatric Interview-7.0.0. Patients were assessed using a semi-structured proforma, Beliefs about Voices Questionnaire-Revised (BAVQ-R), Psychotic Symptom Rating Scale (PSYRATS), Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms (SANS), and Clinical Global Impression-Schizophrenia (CGI-SCH)-severity. Results: The median age of the patients was 32 years (interquartile range [IQR]: 23.8–40.5). The median duration of illness and treatment was 7 years (IQR: 3.4–15.0) and 3 years (IQR: 1.9–10.5), respectively. Higher BAVQ-R scores were found on “malevolence,” “omnipotence,” and “emotional and behavioral resistance.” These beliefs had a significant positive correlation with PSYRATS hallucination subscale, but not with the severity of psychosis (SAPS, SANS, and CGI-SCH). The sample had lower scores for “benevolence” and “engagement” subscales of BAV-Q. Conclusion: Overall, the study sample believed AVH to be more malicious and omnipotent rather than benevolent, and resisted the voices, engaging only minimally with them. These beliefs were not related to the severity of psychosis, but were related to the severity of hallucinations. Assessing the beliefs regarding AVH in larger, diverse samples may help to plan behavioral interventions.

Background: Negative symptoms are frequent in patients with schizophrenia and are associated with marked impairments in social functioning. The efficacy of drug-based treatments and psychological interventions on primary negative symptoms remains limited. The Positive Emotions Programme for Schizophrenia (PEPS) is designed to improve pleasure and motivation in schizophrenia patients by targeting emotion regulation and cognitive skills relevant to apathy and anhedonia. The main hypothesis of this study is that patients who attend 8 one-hour sessions of PEPS and treatment as usual (TAU) will have lower total apathy-avolition and anhedonia-asociality composite scores on the Scale for the Assessment of Negative Symptoms (SANS) than patients who attend only TAU. Methods: Eighty participants diagnosed with schizophrenia or schizoaffective disorder were randomized to receive either TAU or PEPS + TAU. The participants were assessed by independent evaluators before randomization (T0), in a post-test after 8 weeks of treatment (T1) and at a 6-month follow-up (T2). Results: The post-test results and 6-month follow-up assessments according to an intention-to-treat analysis showed that the apathy and anhedonia composite scores on the SANS indicated statistically greater clinical improvements in PEPS participants than in non-PEPS participants. In the post-test, anhedonia but not apathy was significantly improved, thus favouring the PEPS condition. These results were sustained at the 6-month follow-up. Conclusions: PEPS is an effective intervention to reduce anhedonia in schizophrenia. PEPS is a short, easy-to-use, group-based, freely available intervention that is easy to implement in a variety of environments (ClinicalTrials.gov ID: NCT02593058).

Stable phase schizophrenia is characterized by altered patterning in tryptophan catabolites (TRYCATs) and memory impairments, which are associated with PHEMN (psychosis, hostility, excitation, mannerism and negative) and DAPS (depression, anxiety and physio-somatic) symptoms. This study was carried out to examine the association between TRYCAT patterning, memory impairments, psychopathological features and health-related quality of life (HR-QoL) in schizophrenia. The World Health Organization (WHO) QoL instrument-Abbreviated version (WHO-QoL-BREF), IgA/IgM responses to TRYCATs, cognitive tests, Scale for the Assessment of Negative Symptoms (SANS), Hamilton and Depression (HAMD) and Anxiety (HAMA) Rating Scales and the Fibromyalgia and Chronic Fatigue Syndrome Rating Scale (FF) were measured in 80 schizophrenia patients and 40 controls. Neural Network analysis shows that the total HR-Qol score is best predicted by (in descending order) HAMA, FF, HAMD, and psychosis. Partial least Squares (PLS) analysis shows that 56.7% of the variance in the WHO-QoL scores is explained by PHEMN / DAPS symptoms, while 64.3% of the variance in those symptoms is explained by TRYCAT patterning and episodic/semantic memory impairments. IgA responses to picolinic acid, xanthurenic acid and 3-hydroxy-kynurenine (all negatively) and anthranilic acid (positively) have highly significant indirect effects on WHO-QoL scores, which are completely mediated by cognitive impairments and PHEMN / DAPS symptoms. The results show that lowered HR-Qol in schizophrenia is strongly associated with noxious TRYCATs and that these effects are mediated by impairments in episodic / semantic memory and schizophrenia phenomenology, especially physio-somatic and anxiety symptoms. Mucosal activation of the TRYCAT pathway combined with a deficit in natural IgM isotype antibodies to TRYCATs determine cognitive impairments and DAPS/PHEMN symptoms, which together determine to a large extent lowered HR-QoL in schizophrenia.

Immunological abnormalities are increasingly reported in people with schizophrenia, but no clear functional biomarkers associated with genetic correlates of the disease have been found. Regulatory T cells (Tregs) are key immunoregulatory cells involved in the control of inflammatory processes and their functions are directly related to the human leucocyte antigen (HLA) gene, which has been implicated in schizophrenia genetic studies. However, there is a lack of studies reporting Treg status in people with schizophrenia. In the current study, the proportion of circulating Tregs was examined using flow cytometry in 26 medicated participants with schizophrenia and 17 healthy controls. Psychiatric symptoms and cognitive function were evaluated using the Scale for the Assessment of Negative Symptoms, the Brief Psychiatric Rating Scale, and the MATRICS Consensus Cognitive Battery. The proportion of Tregs was found to be significantly greater in the schizophrenia group compared to healthy controls. No differences were observed in total lymphocyte counts or CD3(+) and CD4 (+) T cells, confirming a specific effect for Tregs. Elevated Tregs in schizophrenia correlated with fewer negative symptoms, a core domain of the illness. These results suggest that Tregs may contribute to improved negative symptoms in schizophrenia, possibly by counteracting on-going inflammatory processes.

It has been suggested that the relationship between cognitive function and functional outcome in schizophrenia is mediated by clinical symptoms, while functional outcome is assessed by the Quality of Life Scale (QLS) and the Global Assessment of Functioning (GAF) Scale. To determine the outcome assessed by QLS and GAF, we established a bagging ensemble framework with a feature selection algorithm resulting from the analysis of factors such as 3 clinical symptom scales and 11 cognitive function scores of 302 patients with schizophrenia in the Taiwanese population. We compared our bagging ensemble framework with other state-of-the-art algorithms such as multilayer feedforward neural networks, support vector machine, linear regression, and random forests. The analysis revealed that the bagging ensemble model with feature selection performed best among predictive models in predicting the QLS functional outcome by using 20-item Scale for the Assessment of Negative Symptoms (SANS20) and 17-item Hamilton Depression Rating Scale (HAMD17). Moreover, to predict the GAF outcome, the bagging ensemble model with feature selection performed best among predictive models by using SANS20 and the Positive and Negative Syndrome Scale-Positive (PANSS-Positive) subscale. The study indicates that there are synergistic effects between negative (SANS20) and depressive (HAMD17) symptoms as well as between negative and positive (PANSS-Positive) symptoms in influencing functional outcome of schizophrenia using the bagging ensemble framework with feature selection.

Background: Schizophrenia 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. Aim: This cross-sectional study performed a retrospective data analysis to determine the usefulness of digit ratio as an endophenotype in a South African schizophrenia population. Setting: A large genetic study in a South African schizophrenia population recruited patients from services in the Western and Eastern Cape. Methods: Complete 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). Results: 2D: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. Conclusion: 2D: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.&nbsp

Highlights • Anhedonia is present in many different psychiatric disorders. • Anhedonia has been associated with abnormal reward-related striatal dopamine functioning. • This study tested whether transdiagnostic anhedonia expression mapped onto striatal volume. • Our findings suggest volumetric abnormalities in the putamen and cerebellum as a common neural substrate of anhedonia severity that cut across psychiatric entities., 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.

Objective:There is ongoing debate regarding the relationship between clinical symptoms and cognition in schizophrenia spectrum disorders (SSD). The present study aimed to explore the potential relationships between symptoms, with an emphasis on negative symptoms, and social and non-social cognition.Method:Hierarchical cluster analysis with k-means optimisation was conducted to characterise clinical subgroups using the Scale for the Assessment of Negative Symptoms and Scale for the Assessment of Positive Symptoms in n = 130 SSD participants. Emergent clusters were compared on the MATRICS Consensus Cognitive Battery, which measures non-social cognition and emotion management as well as demographic and clinical variables. Spearman’s correlations were then used to investigate potential relationships between specific negative symptoms and emotion management and non-social cognition.Results:Four distinct clinical subgroups were identified: 1. high hallucinations, 2. mixed symptoms, 3. high negative symptoms, and 4. relatively asymptomatic. The high negative symptom subgroup was found to have significantly poorer emotion management than the high hallucination and relatively asymptomatic subgroups. No further differences between subgroups were observed. Correlation analyses revealed avolition-apathy and anhedonia-asociality were negatively correlated with emotion management, but not non-social cognition. Affective flattening and alogia were not associated with either emotion management or non-social cognition.Conclusions:The present study identified associations between negative symptoms and emotion management within social cognition, but no domains of non-social cognition. This relationship may be specific to motivation, anhedonia and apathy, but not expressive deficits. This suggests that targeted interventions for social cognition may also result in parallel improvement in some specific negative symptoms.

Background Despite adequate antipsychotic treatment, most people with schizophrenia continue to exhibit persistent positive and negative symptoms and cognitive impairments. The current study was designed to examine the efficacy and safety of adjunctive anti-inflammatory combination therapy for these illness manifestations. Methods Thirty-nine people with either Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, schizophrenia or schizoaffective disorder were entered into a 12-week double-blind, 2-arm, triple-dummy, placebo-controlled, randomized clinical trial: 19 were randomized to anti-inflammatory combination therapy and 20 were randomized to placebo. The Brief Psychiatric Rating Scale positive symptom item total score was used to assess positive symptom change, the Scale for the Assessment of Negative Symptoms total score was used to assess negative symptom change, the Calgary Depression Scale total score was used to assess depressive symptom change, and the MATRICS Consensus Cognitive Battery was used to assess neuropsychological test performance. Results There was a significant time effect for Brief Psychiatric Rating Scale positive symptom item score (t226 = -2.66, P = 0.008), but the treatment (t54=1.52, P = 0.13) and treatment × time (t223 = 0.47, P = 0.64) effects were not significant. There were no significant time (t144 = 0.53, P = 0.72), treatment (t58=0.48, P = 0.63), or treatment × time (t143 = -0.20, P = 0.84) effects for the Scale for the Assessment of Negative Symptoms total score; or for any of the other symptom measures. There were no significant group differences in the change in the MATRICS Consensus Cognitive Battery composite score over the course of the study (F1,26=2.20, P = 0.15). Conclusions The study results suggest that there is no significant benefit of combined anti-inflammatory treatment for persistent positive symptoms or negative symptoms or cognitive impairments (clinicaltrials.gov trial number: NCT01514682).

Formal thought disorder (FTD) refers to abnormal speech patterns that can be characterized by deficiencies in thought organization and direction. The present study aimed to assess the factor structure of FTD and to examine its relationship with cognition and clinical features at first admission in patients with first-episode schizophrenia. We also examined the course of FTD during the twelve months after first admission. We assessed FTD using the alogia items of the Scale for the Assessment of Negative Symptoms and FTD items of the Scale for the Assessment of Positive Symptoms in 160 drug-naive patients. A three-factor structure as a disorganization factor, poverty factor, and verbosity factor were found in principal component analysis. The poverty factor was correlated negatively with executive functions, attention, and global cognition. The poverty factor was also correlated with global functioning. Admission FTD factor scores were not related to global functioning and work/study status at one year. The positive-FTD score decreased from admission to the third month, but no change occurred from the third to the twelfth month. The negative-FTD score did not differ throughout the follow-up. Our findings showed that FTD had three factors. Each factor had a different relationship with cognition and functioning.

Background: Deficiencies in membrane polyunsaturated fatty acids (PUFA) such as omega-3 (n-3) fatty acids are thought to contribute to the pathophysiological processes underlying psychotic disorders. Emerging evidence suggests that the levels of PUFA are related to clinical symptoms but significant heterogeneity exists between studies. Here, we investigated associations of membrane PUFA with clinical symptoms and functioning in a large sample of individuals at ultra-high risk (UHR) for psychosis. Methods: A total of 285 participants of the NEURAPRO clinical trial were investigated for erythrocyte PUFA levels, including the n-3 index, n-6/n-3 PUFA ratio, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). Severity of general psychopathology [Brief Psychiatric Rating Scale (BPRS)], psychotic symptoms (BPRS psychosis subscale), negative symptoms [Scale for the Assessment of Negative Symptoms (SANS)], manic symptoms [Young Mania Rating Scale (YMRS)], depressive symptoms [Montgomery Asberg Depression Rating Scale (MADRS)], and functioning [Social and Occupational Functioning Scale (SOFAS), Global Functioning Social (GF-S) and Role (GF-R) scales] were assessed concurrently. Partial correlation taking into account the effects of gender, age, and smoking was used to examine the relationship between PUFAs and symptoms severity. Results: The n-3 index negatively correlated with the severity of general psychopathology, psychotic symptoms, depressive symptoms, and manic symptoms. The n-6/n-3 PUFA ratio positively correlated with severity of psychotic and depressive symptoms. The n-3 PUFA DHA negatively correlated with the severity of general psychopathology, positive, manic, and depressive symptoms. EPA negatively correlated with manic symptoms. Nervonic acid, an n-9 monounsaturated fatty acid, positively correlated with general psychopathology, positive and negative symptoms, depressive symptoms, and manic symptoms. The long-chain saturated fatty acid tetracosanoic acid positively correlated with general psychopathology, positive, manic, and depressive symptoms. Conclusions: Partially consistent with a previous study, psychotic symptoms, depressive symptoms, and symptoms of mania were associated with several classes of FAs in the present study. These findings support the relevance of membrane fatty acids for the onset of psychotic symptoms and indicate that FAs should be further evaluated as biomarkers in the UHR for psychosis group. Clinical Trial Registration: ANZCTR, identifier: 12608000475347.

Objective The nature of associations between recent cannabis use and negative symptoms, positive symptoms, and neurocognitive deficits remains unclear. In a relatively large sample of well-characterized patients with first-episode psychosis, we hypothesized that, compared to first-episode patients without cannabis use in the three months prior to first hospitalization, those having used cannabis would have lesser negative symptoms, greater positive symptoms, and no differences in cognitive functioning. Dose-response relationships were also examined. Methods Between 2008 and 2013, 247 first-episode psychosis patients were assessed during their hospitalization at one of six participating inpatient psychiatric units. Measures included the Longitudinal Substance Use Recall for 12 Weeks instrument, the Scale for the Assessment of Negative Symptoms, the Scale for the Assessment of Positive Symptoms, and the MATRICS Consensus Cognitive Battery (MCCB). Results Anhedonia-asociality was significantly lower among those using cannabis in the past three months (10.7±4.6 v. 12.1±4.4, p=.023). Delusions were more severe among those having used cannabis (19.3±8.4 v. 15.9±9.1, p=.005), as was bizarre behavior (p=.01). There were no significant differences between those using and not using cannabis across nine MCCB measures. Correlations between the “dose” of cannabis and all of these measures were not significant. Conclusions Compared to those without cannabis use, those who use cannabis in recent months have lesser anhedonia-asociality, greater delusion and bizarre behavior severity, and no significant differences in neurocognition. Such characterizations could shed light on subgroups of individuals with first-episode psychosis, as well as risk factors for cannabis use in the early course of these disorders.

Os instrumentos Scale for the Assessment of Negative Symptoms (SANS) e a Scale for the Assessment of Positive Symptoms (SAPS) objetivam avaliar sintomas negativos e positivos, respectivamente, em pessoas com sintomas psic?ticos. A SANS avalia sintomas negativos, como embotamento afetivo, alogia, avoli??o/apatia, anedonia e aten??o. A SAPS avalia sintomas positivos, como alucina??es, del?rios, comportamento e pensamento desorganizado. Objetivos: Esta tese teve como principal objetivo traduzir, adaptar culturalmente e verificar evid?ncias de validade de conte?do das escalas Scale for the Assessment of Negative Symptoms e Scale for the Assessment of Positive Symptoms para o portugu?s brasileiro. Para responder a esse objetivo foram elaborados tr?s artigos, um deles te?rico e dois emp?ricos. O artigo te?rico teve como objetivo investigar sistematicamente a literatura sobre a utiliza??o das escalas SANS e SAPS. O segundo artigo teve como principal objetivo traduzir e adaptar culturalmente a escala SANS para o portugu?s brasileiro e obter evid?ncias de validade baseadas no conte?do. O terceiro artigo teve como principal objetivo traduzir e adaptar culturalmente a escala SAPS para o portugu?s brasileiro e obter evid?ncias de validade baseadas no conte?do. M?todos: No artigo te?rico, foi constru?da uma revis?o sistem?tica, utilizando-se das recomenda??es da Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A busca de artigos foi realizada por dois ju?zes, nas bases de dados PsycARTICLES, Web of Science, Medline e Scopus. Ap?s aplica??o dos crit?rios de inclus?o/exclus?o, foram recuperados e analisados 31 artigos. Nos artigos emp?ricos, o m?todo foi organizado em duas etapas: 1) Tradu??o e adapta??o do instrumento; e 2) C?lculo do ?ndice de Validade de Conte?do (ICV). Participaram da segunda etapa da pesquisa 11 profissionais com ampla experi?ncia na ?rea de sa?de mental. Resultados: O primeiro estudo encontrou que a maioria dos artigos utilizou as escalas para avaliar a intensidade de sintomas positivos e negativos, correlacionando os escores da SANS e da SAPS com outras vari?veis, bem como para verificar o efeito de interven??es medicamentosas e n?o medicamentosas. No que tange a qualidade dos artigos, observou-se que apenas uma pequena parcela dos artigos foi publicada em peri?dicos com alto fator de impacto e apenas sete artigos utilizaram procedimentos de randomiza??o. O segundo estudo de tradu??o e adapta??o da SANS encontrou n?veis de concord?ncia acima de 81%. Referente aos ?ndices de validade de conte?do todos os t?picos apresentaram escores entre 0,64 e 1,00, indicando n?veis adequados. Os achados do estudo de tradu??o e adapta??o da SAPS apontam que 30 dos seus itens obtiveram ICV = 1,00, 4 obtiveram ICV = 0,82 e apenas 1 obteve ICV = 0,64. Referente aos n?veis de concord?ncia, os resultados tamb?m foram acima de 81%. Conclus?o: Pode-se concluir que os instrumentos SANS e SAPS s?o ferramentas aplic?veis e adequadas para avalia??o de sintomatologia positiva e negativa em diversos contextos. Os resultados mostraram que as escalas SANS e SAPS est?o adequadas para uso na popula??o brasileira, pois apresentaram alto grau de concord?ncia entre os avaliadores, e bons ?ndices de validade de conte?do. Sugerem-se novos estudos que verifiquem outras evid?ncias de validade desses instrumentos. Scale for the Assessment of Negative Symptoms (SANS) and Scale for the Assessment of Positive Symptoms (SAPS) aim to evaluate negative and positive symptoms, respectively, in people with psychotic symptoms. The SANS evaluates negative symptoms such as affective blunting, alogia, avolition-apathy, anhedonia and attention. The SAPS evaluate positive symptoms, such as hallucinations, delusions, behavior and disorganized thinking. Objectives: The main objective of this thesis was to translate, culturally adapt and verify evidence of content validity of the Scale for the Assessment of Negative Symptoms and Scale for the Assessment of Positive Symptoms scales into Brazilian Portuguese. To answer this objective, three articles were elaborated, one theoretical and two empirical. The theoretical article aimed to systematically investigate the literature on the use of the SANS and SAPS. The second article aimed to translate and culturally adapt the SANS to Brazilian Portuguese and obtain evidence of validity based on the content. The third article aimed to translate and culturally adapt the SAPS into Brazilian Portuguese and obtain evidence of validity based on the content. Methods: In the theoretical article, a systematic review was built, using the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA). The search for articles was carried out by two judges in the PsycARTICLES, Web of Science, Medline and Scopus databases. After applying the inclusion / exclusion criteria, 31 articles were retrieved and analyzed. In the empirical articles, the method was organized in two stages: 1) Translation and adaptation of the instrument; and 2) Calculation of the Content Validity Index (ICV). Eleven professionals with extensive experience in the mental health field participated in the second stage of the research. Results: The first study found that most articles used the scales to assess the intensity of positive and negative symptoms, correlating the SANS and SAPS scores with other variables, as well as to verify the effect of drug and non-drug interventions. Regarding the quality of the articles, it was observed that only a small portion of the articles was published in journals with a high impact factor and only seven articles used randomization procedures. The findings of the SAPS translation and adaptation study show that 30 of its items obtained ICV = 1.00, 4 obtained ICV = 0.82 and only 1 obtained ICV = 0.64. Regarding the levels of agreement, the results were also above 81%. Conclusions: It can be concluded that the SANS and SAPS instruments are applicable and appropriate tools for evaluating positive and negative symptoms in different contexts. The results showed that the SANS and SAPS scales are suitable for use in the Brazilian population, as they showed a high degree of agreement between the evaluators, and good content validity indexes. Further studies are suggested to verify other evidence of the validity of these instruments. Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES

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.

Non-invasive transcranial brain stimulation therapies, such as transcranial direct current stimulation, have been found to improve negative symptoms in schizophrenia. Another new technique is transcranial alternating current stimulation (tACS). Here we report a series of three patient treated with twice-daily 10min prefrontal 40Hz tACS stimulation over ten days. Patients showed an improvement in the Positive and Negative Syndrome Scale, Scale for the Assessment of Negative Symptoms, and subjective well-being. Furthermore, there was an improvement in the Trail Making Test and word fluency. ytACS merits further investigation in the treatment of schizophrenia symptoms.

Objective This study aimed to investigate whether aberrant tendency of noncurrent emotion was present in individuals at ultra-high risk (UHR) for psychosis and to explore its associations with various clinical profiles. Methods Fifty-seven individuals at UHR and 49 normal controls were enrolled. The tendency of experiencing noncurrent emotion was assessed using various noncurrent emotional self-reported formats, including trait [Neuroticism and Extraversion of the Eysenck Personality Questionnaire], hypothetical (Chapman’s Revised Physical and Social Anhedonia Scales), and retrospective [Anhedonia-Asociality Subscale of the Scale for the Assessment of Negative Symptoms (SANS)] measures. Self-related beliefs (Self-Perception Scale), clinical positive and negative symptoms (SA Positive Symptoms and SANS), psychosocial function (Global Functioning Scale: Role Function and Global Functioning Scale: Social Function) were also examined. Results Subjects at UHR for psychosis reported more trait unpleasant and less trait pleasant emotions, more hypothetical physical and social anhedonia, and more retrospective anhedonia than normal controls. In UHR, self-perception was correlated to trait unpleasant emotion and hypothetical physical and social anhedonia. Negative symptoms in UHR were associated with hypothetical physical anhedonia and retrospective anhedonia. Global social functioning was related to trait pleasant emotion, hypothetical physical and social anhedonia, and retrospective anhedonia. Neurocognitive function, positive symptoms, and global role functioning were not related with any noncurrent emotional experience measures in UHR. Conclusion These findings suggest that the aberrant tendency of noncurrent emotional experience may be present at the ‘putative’ prodromal phase and are grossly associated with self-related beliefs and psychosocial functioning but not neurocognitive functioning.

Background Amisulpride was introduced into China in 2010 as a second-generation atypical antipsychotic, while olanzapine has been on the market since 1999 as one of the leading treatments for schizophrenia in China. Since more Chinese patients are gaining access to amisulpride, the study aims to compare the efficacy, safety, and costs between amisulpride and olanzapine for schizophrenia treatment in China. Methods PubMed, Embase, the Cochrane library, China National Knowledge Infrastructure (CNKI) and WanFang database were systematically searched for randomized controlled trials (RCTs) up to July 2018. The Cochrane Risk of Bias tool was utilized to assess the quality of included studies. A meta-analysis was performed to compare the efficacy and safety of amisulpride and olanzapine, followed by a cost-minimization analysis using local drug and medical costs reported in China. Results Twenty RCTs with 2000 patients were included in the systematic review. There were no significant differences between amisulpride and olanzapine on efficacy measures based on scores from the Positive and Negative Syndrome Scale, the Scale for the Assessment of Negative Symptoms, the Brief Psychiatric Rating Scale and the Clinical Global Impressions-Severity or Improvement. For safety outcomes, amisulpride was associated with lower fasting blood glucose and less abnormal liver functions as well as significantly lower risks of weight gain, constipation, and somnolence; olanzapine was associated with significantly lower risks of insomnia and lactation/amenorrhea/sexual hormone disorder. No significant differences were found in risks of extrapyramidal symptoms (EPS), tremor, akathisia, abnormal corrected QT interval. Cost-minimization analysis showed that amisulpride was likely to be a cost-saving alternative in China, with potential savings of 1358 Chinese Yuan (CNY) per patient for a three-month schizophrenia treatment compared with olanzapine. Conclusion As the first meta-analysis and cost-minimization analysis comparing the efficacy, safety and cost of amisulpride and olanzapine within a Chinese setting, the study suggests that amisulpride may be an effective, well-tolerated, and cost-saving antipsychotic drug alternative in China.

Objective This study examined the effect of adjunctive minocycline on psychopathology and possibly relevant biomarkers in patients with schizophrenia. Method In a 16-week randomized, double-blind, placebo-controlled study, subjects received either minocycline (200 mg per day) or placebo. Psychopathology was assessed using the Scale for the Assessment of Negative Symptoms (SANS) and the Positive and Negative Syndrome Scale (PANSS) at baseline and week 16. Plasma levels of tumor necrosis factor α (TNFα), interleukin-1 β (IL-1β) and nitric oxide metabolites were assessed at both time points. Results Fifty-five patients completed the study (27 in the minocycline group, 28 in the placebo group). The minocycline group had significant decreases in the SANS total sore, the PANSS total score and the PANSS negative symptoms score at week 16 compared to the placebo group. In addition, the minocycline group had a significant decrease in plasma levels of nitric oxide metabolites, but no significant difference in changes in plasma levels of IL-1β or TNF-α, compared to the placebo group at week 16. Further, the more decrease in plasma levels of nitric oxide metabolites was associated with less improvement in negative symptoms. Conclusion The beneficial effect of adjunctive minocycline treatment on negative symptoms might be through mechanisms other than the nitric oxide pathway. The implications for future studies were discussed.

Despite their theoretical rationale, nicotinic alpha-7 acetylcholine (nα(7)) receptor agonists, have largely failed to demonstrate efficacy in placebo-controlled trials in schizophrenia. AVL-3288 is a nα(7) positive allosteric modulator (PAM), which is only active in the presence of the endogenous ligand (acetylcholine), and thus theoretically less likely to cause receptor desensitization. We evaluated the efficacy of AVL-3288 in a Phase 1b, randomized, double-blind, placebo-controlled, triple cross-over study. Twenty-four non-smoking, medicated, outpatients with schizophrenia or schizoaffective disorder and a Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) ≥62 were randomized. Each subject received 5 days of AVL-3288 (10, 30 mg) and placebo across three separate treatment weeks. The primary outcome measure was the RBANS total scale score, with auditory P50 evoked potential suppression the key target engagement biomarker. Secondary outcome measures include task-based fMRI (RISE task), mismatch negativity, the Scale for the Assessment of Negative Symptoms of Schizophrenia (SANS) and the Brief Psychiatric Rating Scale (BPRS). Twenty-four subjects were randomized and treated without any clinically significant treatment emergent adverse effects. Baseline RBANS (82 ± 17) and BPRS (41 ± 13) scores were consistent with moderate impairment. Primary outcomes were negative, with non-significant worsening for both active groups vs. placebo in the P50 and minimal between group changes on the RBANS. In conclusion, the results did not indicate efficacy of the compound, consistent with most prior results for the nα(7) target.

Objective To compare the relation symptom severity and testosterone levels, and DHEA-S and cortisol in premenopausal women with schizophrenia and an age- and sex-matched control group. Methods Thirty-two women with schizophrenia and 32 age- and sex-matched healthy controls were included in the study. All participants were aged between 20 and 45 years, and their previous treatments were olanzapine (n=14) and quetiapine (n=18). Symptom severity was assessed using the Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS). A chemiluminescence immunoassay was used to investigate hormone profiles of the two groups, which were then compared and analyzed. The relation between the hormone levels and SANS and SAPS scores of the study group and controls was examined. Results There were statistically significantly higher levels of serum DHEA-S (p=0.002) in the study group than in the control group. No statistically significant difference was determined between the groups regarding serum testosterone and cortisol levels. A positive correlation was determined between the study groups' SANS scores and DHEA-S levels (p=0.012, r=0.440). Conclusion DHEA-S might be a potential biologic marker for schizophrenia because there is evidence of an association between DHEA-S and the pathophysiology of schizophrenia. However, further research with greater patient numbers is required to verify these findings.

Objawy negatywne schizofrenii są poważnym problemem diagnostycznym i terapeutycznym w psychiatrii. Stanowią istotną przyczynę zaburzającą stan zdrowia, funkcjonowanie społeczne i jakość życia pacjentów, a leczenie tych objawów jest bardzo trudne. W pracy przedstawiono rozwój koncepcji schizofrenii, ze szczególnym uwzględnieniem problematyki objawów negatywnych. Omówiono modele objawów pozytywnych i negatywnych schizofrenii, jakie przedstawili w latach 1980-tych Timothy Crow i Nancy Andreasen. Zaprezentowano koncepcję Williama Carpentera dotyczącą tzw. zespołu deficytowego, a także kryteria podziału objawów negatywnych na pierwotne i wtórne. Opisano aktualne poglądy na patogenezę objawów negatywnych z uwzględnieniem badań neuroobrazowych, zaburzeń neuroprzekaźnictwa, deficytów neuropsychologicznych oraz badań genetycznych, immunologicznych i epidemiologicznych. Oddzielny podrozdział poświęcono narzędziom diagnostycznym służącym rozpoznawaniu oraz ocenie nasilenia objawów negatywnych. Narzędzia te, ze względu na chronologię ich wprowadzenia można podzielić na skale I i II generacji. Do pierwszej należą skale Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms (SANS), Positive and Negative Syndrome Scale (PANSS), Schedule for the Deficit Syndrome (SDS) i Proxy for Deficit Syndrome. Do drugiej generacji należą, powstałe w następstwie rekomendacji grupy amerykańskich ekspertów w 2006 roku, skale kliniczne Brief Negative Syndrome Scale (BNSS) i Clinical Assessment Interview for Negative Symptoms (CAINS) oraz skale samooceny: Motivation and Pleasure Scale- Self Report (MAP-SR) i Self-assessment of Negative Symptoms (SNS). Szczegółowo omówiono skalę BNSS oraz skalę samooceny SNS, których polskie wersje zostały opracowane w Klinice Psychiatrii Dorosłych UM w Poznaniu.

Nicola Poloni, Daniele Zizolfi, Marta Ielmini, Roberto Pagani, Ivano Caselli, Marcello Diurni, Anna Milano, Camilla Callegari Department of Medicine and Surgery, Division of Psychiatry, University of Insubria, Varese, Italy Objective: Resilience is a multidimensional process of adaptation aimed to overcome stressful or traumatic life experiences; only in the last few years it has been considered as a personal resource in psychosis and schizophrenia. This study aimed to assess the relationship between intrapersonal and interpersonal resilience factors and schizophrenia, particularly whether and how resilience can improve the course of psychotic illness. Patients and methods: In this observational study, all patients recruited had to fulfill the following inclusion criteria: diagnosis of schizophrenia spectrum disorder (Diagnostic and Statistical Manual of Mental Disorders-5); aged between 18 and 65 years; provided written informed consent; to be clinically stable (Clinical Global Impression Scale

WOS: 000452309400002, OBJECTIVE: The aim of the study was to examine the efficacy of electroconvulsive therapy (ECT) combined with antipsychotic (AP) medication on symptom profile in patients with a diagnosis of schizophrenia who had received acute psychiatric inpatient treatment. METHODS: In this prospective study, patients were evaluated for inclusion in the study who were diagnosed with schizophrenia according to DSM-IV diagnostic criteria and were to receive ECT. The patients were evaluated using the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms (SANS), and Clinical Global Impression - Improvement (CGI-I) sub-scale before the first session ECT, once following every two subsequent sessions and after the final session. RESULTS: The patients showed significant improvements in BPRS scores at each evaluation compared with their scores at baseline, and a significant clinical improvement was found on the CGI-I sub-scale at the end of treatment. Across all SAPS sub-scores, significant decreases were found, and the symptoms related to hallucinations and positive formal thought disorder showed the most rapid response to treatment. Across all SANS sub-scores, significant decreases were found, and affective flattening or blunting symptoms responded most rapidly to treatment. CONCLUSION: One of the most important findings in the present study of hospitalized patients with acute schizophrenia was the good response to treatment, which provided significant improvements in both positive and negative symptoms. The most rapid response to treatment was found for hallucinations, positive formal thought disorder, and affective flattening or blunting symptoms. The most important limitation of our study may be the small number of cases. In future, well-standardized studies using a double-blinded, comparative, prospective design and including a sufficient number of patients are needed.

Although patients with schizophrenia exhibit impaired suppression of the P50 event-related brain potential in response to the second of two identical auditory stimuli during a paired-stimulus paradigm, uncertainty remains over whether this deficit in inhibitory gating of auditory sensory processes has relevance for patients' clinical symptoms or cognitive performance. The authors examined associations between P50 suppression deficits and several core features of schizophrenia to address this gap.P50 was recorded from 52 patients with schizophrenia and 41 healthy comparison subjects during a standard auditory paired-stimulus task. Clinical symptoms were assessed with the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms. The MATRICS Consensus Cognitive Battery was utilized to measure cognitive performance in a subsample of 39 patients. Correlation and regression analyses were conducted to examine P50 suppression in relation to clinical symptom and cognitive performance measures.Schizophrenia patients demonstrated a deficit in P50 suppression when compared with healthy subjects, replicating prior research. Within the patient sample, impaired P50 suppression covaried reliably with greater difficulties in attention, poorer working memory, and reduced processing speed.Impaired suppression of auditory stimuli was associated with core pathological features of schizophrenia, increasing confidence that P50 inhibitory processing can inform the development of interventions that target cognitive impairments in this chronic and debilitating mental illness.

Objective To analyse the relationship between burden of illness and coping strategies and the demographic variables of caregivers, and the demographic and clinical variables of people diagnosed with schizophrenia. Methods Multicentre correlational cross-sectional study including 70 people diagnosed with schizophrenia, or a schizoaffective disorder, and 70 primary informal caregivers. They were evaluated using the Zarit Caregiver Burden Interview, Family Coping Strategies Questionnaire, Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, and the brief Disability Assessment Scale. Results Burden of illness positively associated with patient impairment in occupational and social functioning, and negatively with education level. Avoidance, coercion and positive communication were positively associated with impairment in occupational and social functioning of patients. Social interest and friendships showed a positive association with the education level of caregivers. Spiritual assistance negatively correlated with impairment in social functioning and patient age, and resignation was negatively associated with length of the disorder and patient education level. Conclusions Burden and dysfunctional coping strategies, such as avoidance and coercion, are associated with functional impairment of the patient. These findings suggest the need to provide support to caregivers, adjusted to the functional level of the patient, in order to prevent burden of care.

Schizophrenia is a debilitating disease that affects approximately 1% of the population. Negative symptoms are among the major determinants of the functional impairment and a significant proportion of patients with negative symptoms will continue to experience these symptoms despite antipsychotic medications. There are promising results in the application of brain stimulation, particularly transcranial direct current stimulation (tDCS), for the reduction of negative symptoms of schizophrenia. However, findings are still controversial. This is a selective review of the literature published between 2011 and 2017 on use of tDCS in treatment of negative symptoms of schizophrenia. We included only randomized controlled trials where schizophrenia and negative symptoms were assessed using any psychometrically validated scale (eg, Positive and Negative Symptoms Scale or Scale for the Assessment of Negative Symptoms). Studies of participants with neurological conditions were excluded, as were those that did not report any symptom outcome variables. Only 5 studies are included. Three studies showed a decrease of negative symptoms. The other studies did not show any therapeutic effects of tDCS in the severity of positive and negative symptoms compared to controls. Our findings suggest that negative symptoms in schizophrenia can be treated with tDCS over the dorsolateral prefrontal cortex, but results are affected by several factors, such as the electrode montage, the concomitant medication, the homogeneity of the sample, the intensity of the tDCS treatment. Further randomized, double-blinded, sham-controlled studies in large samples are still needed to establish the effectiveness of the tDCS in the treatment of negative symptoms in schizophrenia, but there is the potential for tDCS to become a useful complementary treatment option in this population.