Negative Symptoms In Patients Research Articles

What is the Best Latent Structure of Negative Symptoms in Schizophrenia? A Systematic Review

BackgroundDetermining the best latent structure of negative symptoms in schizophrenia could benefit assessment tools, neurobiological research, and targeted interventions. However, no review systematically evaluated studies that assessed and validated latent models of negative symptoms. ObjectiveTo identify and evaluate existing latent structure models in the literature of negative symptoms and to determine the best model. MethodSystematic search of MEDLINE, EMBASE, and Scopus on July 19, 2020, for confirmatory factor analysis models of negative symptoms in patients with schizophrenia. The available evidence was assessed through 2 sets of criteria: (1) study design quality—based on negative symptoms assessment and modeling strategy and (2) psychometric quality and model fit—based on fit indices and factor definition quality. ResultsIn total, 22 studies (n = 17 086) from 9 countries were included. Studies differed greatly regarding symptom scales, setting, and sample size (range = 86–6889). Dimensional models included 2–6 factors (median = 4). Twelve studies evaluated competing models and adopted appropriate instruments to assess the latent structure of negative symptoms. The 5-factor and hierarchical models outperformed unitary, 2-factor, and 3-factor models on all direct comparisons, and most of the analyses derived from the Brief Negative Symptom Scale. Considering the quality criteria proposed, 5-factor and hierarchical models achieved excellent fit in just one study. ConclusionsOur review points out that the 5-factor and hierarchical models represent the best latent structure of negative symptoms, but the immaturity of the relevant current literature may affect the robustness of this conclusion. Future studies should address current limitations regarding psychometric properties and also address biological and clinical validity to refine available models.

Correlation of neurocognitive deficits with positive and negative symptoms in schizophrenia.

Background:Patients with schizophrenia manifests a broad array of cognitive impairments, including impaired performance on measures reflecting attention, information processing, executive functions, memory, and language capabilities.Aim:This study aims to assess neurocognitive deficits and their correlation with positive and negative symptoms in patients with schizophrenia.Materials and Methods:Sample was collected from private clinic of Jabalpur, Bhopal, and Patna. Selection of sample was purposive sampling. The sample size consists of 60 diagnosed cases of schizophrenia on the basis of (International Classification of Diseases-10 [ICD-10] Diagnostic Criteria for Research criteria) and 30 normal controls. Annet's Hand Preference Battery was used to screen handedness and only right-handed male were included in this study. After screening according to inclusion and exclusion criteria, 60 diagnosed (ICD-10 criteria) schizophrenia patients were selected which was further divided into two groups on the basis of positive and negative syndrome scale, i.e. schizophrenia with positive and negative symptoms. Thirty matched normal controls having scores <2 scores on General Health Questionnaire-12 were selected for the study. After filling of sociodemographic details Luria-Nebraska Neuropsychological Battery (LNNB-I) was administered on both schizophrenia group and normal control.Results:Cognitive functions are severely impaired in schizophrenia compared to normal control and within schizophrenia groups negative schizophrenia had poor performance on LNNB-I than positive schizophrenia. Regarding the correlation of neurocognitive deficits, both schizophrenia groups were correlated but negative symptoms of schizophrenia were strongly correlated with neurocognitive deficits.Conclusion:Cognitive functions are severely impaired in schizophrenia as compared to normal control and within schizophrenia groups, negative schizophrenia had poor performance on LNNB-I than positive schizophrenia. Regarding the correlation of neurocognitive deficits, both schizophrenias groups were correlated but negative symptoms of schizophrenia were strongly correlated with neurocognitive deficits.

Resveratrol Adjunct Therapy for Negative Symptoms in Patients With Stable Schizophrenia: A Double-Blind, Randomized Placebo-Controlled Trial.

BackgroundPatients with schizophrenia can generally manifest a broad variety of primary negative symptoms. The current study aimed to assess the efficacy and tolerability of resveratrol add-on therapy in the treatment of negative symptoms in patients with stable schizophrenia.MethodsIn a randomized, double-blind, and placebo-controlled setting, schizophrenia patients were assigned to receive either 200 mg/d resveratrol or matched placebo in addition to a stable dose of risperidone for 8 weeks. Patients were assessed using the positive and negative syndrome scale, the extrapyramidal symptom rating scale, and Hamilton Depression Rating Scale over the trial period. The primary outcome was considered as the change in positive and negative subscale score from baseline to week 8 between the treatment arms.ResultsA total 52 patients completed the trial (26 in each arm). Baseline characteristics of both groups were statistically similar (P > .05). Despite the statistically similar behavior of positive symptoms between the groups across time (Greenhouse-Geisser corrected: F = 1.76, df = 1.88, P = .180), the resveratrol group demonstrated greater improvement in negative, general psychopathology, and total scores (Greenhouse-Geisser corrected: F = 12.25, df = 2.04, P < .001; F = 5.42, df = 1.56, P = .011; F = 7.64, df = 1.48, P = .003). HDRS scores and its changes, ESRS score, and frequency of other complications were not significantly different between resveratrol and placebo groups.ConclusionAdding resveratrol to risperidone can exhibit remarkable efficacy and safety in terms of management of schizophrenia-related negative symptoms.

Systematic review: the relationship between sleep spindle activity with cognitive functions, positive and negative symptoms in psychosis

BackgroundSleep disturbances are associated with worse cognitive and psychotic symptoms in individuals with schizophrenia. Growing literature reveals sleep spindle deficits in schizophrenia may be an endophenotype reflecting a dysfunctional thalamo-thalamic reticular nucleus-cortical circuit. Since thalamic functions link to cognitive, positive and negative symptoms, it is possible that sleep spindle activity is associated with these symptoms. The primary objectives of this systematic review were to assess the associations of sleep spindle activity in psychotic patients with 1) cognitive functions; and 2) positive and negative symptom severity. A secondary objective was to examine which spindle parameter would be the most consistent parameter correlating with cognitive functions, and positive and negative symptoms. MethodObservational studies reporting an association between sleep spindle activity and cognitive functions, positive and negative symptoms in patients with psychotic disorders were considered eligible. We developed a comprehensive electronic search strategy to identify peer-reviewed studies in Pubmed, Embase, PsycINFO and CINAHL covering all dates up to the search date in May 2020 with no language restriction. The references of published articles were hand-searched for additional materials. The authors of published articles were contacted for newer or unpublished data. Risk of bias was assessed by Appraisal of Cross-sectional Studies (AXIS). ResultsA total 11 cross-sectional studies (n = 255) with low-to-moderate quality, were selected for the systematic review. 8 of them addressed the association between sleep spindle activity and cognitive functions (n = 193), of which 6 studies reported positive correlations (r only reported in 4 studies, from 0.45 to 0.75). Out of multiple cognitive domains, we have only found attention/cognitive processing speed to have a more consistent positive association with sleep spindle activity. On the other hand, 8 studies investigated the relationship between sleep spindle and positive/negative symptom severity (n = 190), but findings were inconsistent. Spindle density is the most consistent parameter correlating with cognitive functions, while the best spindle parameter for correlating with positive and negative symptom severity cannot be identified due to mixed results. DiscussionThis systematic review confirms the linkage between sleep spindle activity and cognitive functions. However, included studies had small sample sizes, with high risks of sampling and response bias. Moreover, confounders were often not controlled. The heterogeneous report of spindle parameters and use of cognitive assessment tools rendered meta-analysis infeasible. It is necessary to examine the longitudinal change of sleep spindle activity with the course of illness, as well as the effect of sleep spindle enhancing agents on cognitive function.

DISABILITY AND EXECUTIVE FUNCTIONS IN SCHIZOPHENIA: A CROSSSECTIONAL STUDY. (RELATION BETWEEN DISABILITY AND POSITIVE, NEGATIVE SYMPTOMS)

The aim of the study was to see if there is any association between disability, positive- negative symptoms in patients of schizophrenia.&#x0D; Study had a crossectional design with purposive sampling in 50 patients with schizophrenia. Subjects were assessed using sociodemographic and clinical data sheet, PANSS, IDEAS (disability) .&#x0D; The result of the study revealed a significant association was seen between IDEAS and WCST variables in patients of schizophrenia. A significant association was also seen between PANSS (positive and negative score) with IDEAS and WCST variables (disability and executive functions being more strongly associated with negative symptoms). On correlation analysis of socio-demographic and clinical data with IDEAS and WCST variables, a significant correlation (positive) of age and duration of illness was seen with IDEAS.&#x0D; Executive functions and negative symptoms are crucial for functional outcome and independent living and are important target for intervention in order to reduce disability and improve quality of life in patients suffering from Schizophrenia.&#x0D; Keywords: Schizophrenia, Disability, Positive–negative symptoms, Executive functions.

Validation of a European Spanish-version of the Self-Evaluation of Negative Symptoms (SNS) in patients with schizophrenia.

Negative symptoms can be grouped into five domains: apathy/avolition, anhedonia, asociality, alogia, and affective flattening. There are few validate self-rated measures that assess these five dimensions. Therefore, this study aimed to validate the Self-Evaluation of Negative Symptoms (SNS) in Spanish patients with schizophrenia. Cross-sectional, validation study in 104 outpatients with schizophrenia evaluated using the Spanish version of the following scales: Clinical Assessment Interview for Negative Symptoms (CAINS), Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale for Schizophrenia (CGI-SCH), Personal and Social Performance (PSP), Motivation and Pleasure Scale - Self-Report (MAP-SR), 36-item Short-Form Health Survey (SF-36) and the Self-Evaluation of Negative Symptoms (SNS). Internal consistency (Cronbach's alpha) was 0.915. Convergent validity: The Pearson correlation coefficient between MAP-SR and SNS Total scores was 0.660 (p<0.001). For PANSS-N, the correlation was 0.437 (p<0.005) and with the CAINS-Total was 0.478 (p<0.005). Divergent validity: The Pearson correlation coefficient between SNS and PSP was r=-0.372 (p≤0.001), and with SF-36 Physical and Mental Summary Component scores were r=-0.213 (p=0.066) and r=-0.144 (p=0.219), respectively. Discriminant validity: SNS Total scores were significantly statistically different according to the severity of the negative symptomatology rated by the CGI-SCH negative scale (p<0.001). The SNS is a reliable and valid instrument to self-rate the five domains of negative symptoms in patients with schizophrenia and seems to be appropriate for use in everyday clinical practice as a complementary measure to the evaluation performed by the clinician.

Parasympathetic activity as a potential biomarker of negative symptoms in patients with schizophrenia.

Autonomic dysfunction in patients with schizophrenia has raised concern considering the higher cardiovascular mortality and morbidity rate. This phenomenon has been demonstrated using various measurements and is inferred to be associated with demographics, medical treatment, and psychopathology. However, few have targeted the role of negative symptoms within schizophrenia. Schizophrenia patients with stationary psychopathology were recruited from a chronic ward, a daycare center, and a nonintensive case management program. Demographic data, medication history, the Positive and Negative Syndrome Scale (PANSS) score, the Personal and Social Performance Scale (PSP) score, and the five-minute resting-state heart rate variability (HRV) were collected at trial initiation (Time 1) and a year later (Time 2). The relationships between variables and HRV indices were evaluated using correlation and regression analyses. A total of 63 participants were recruited at Time 1, with 29 participants remaining at Time 2. Correlation analyses showed a negative correlation between the PANSS negative score (PANSS-N) and total power (TP), low-frequency power (LF), and high-frequency power (HF) at Time 1. The results were further examined with multiple linear regression analysis and remained significant between the PANSS-N score and HF (β = -0.306, P = .012). A generalized estimating equation model revealed the above negative association to be significant considering both timepoints. The negative association between negative symptom severity and parasympathetic activity was significant, which may inspire further research into the corresponding treatment, the mechanisms, and the use of HRV as an applicable biomarker for treatment response.

M184. SOCIAL SKILLS TRAINING FOR TREATMENT-RESISTANT SCHIZOPHRENIA WITH PREDOMINANTLY NEGATIVE SYMPTOMS

BackgroundPoor social skills are a core characteristic of schizophrenia and are highly associated with the progression of negative symptoms. While positive symptoms have a good response to antipsychotics, the treatment of negative symptoms remains an unmet need.MethodsA randomized controlled trial to assess the efficacy of a 20-week social skills training (SST) program for the improvement of negative symptoms in patients with treatment-resistant schizophrenia (TRS) with predominantly negative persistent symptoms, with a score > 4 (moderate) in at least 3 items of the Negative Symptom Factor Score (NSFS) (blunted affect, emotional withdrawal, poor rapport, passive social withdrawal, lack of spontaneity, motor retardation and active social avoidance).Each session lasted 60 minutes and included 6 to 9 participants. The SST sessions were conducted by trained psychologists, following topics previously outlined in a manual, and role-playing activities. The non-directive control group was conducted by nurses specialists in mental health, with the same duration but without role-playing activities. Control groups’ therapists were instructed not to give directions to the patients but to listen and redirect questions to the group.TRS was defined as the persistence of psychotic symptoms after at least two adequate trials with two different antipsychotics, All patients were taking clozapine. Blinded raters evaluated the patients at baseline, 20 weeks and after 6 months follow-up by the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI) and the Social Skills Inventory (SSI). Longitudinal comparisons between groups were carried out using a linear mixed-effects model at pre, post and follow-up to assess differences between groups. Cohen’s d effect size was computed at each time point. Primary outcome measure was the PANSS negative subscale score.Social skill were assessed with the Social Skills Inventory.Results62 patients were randomized to SST (N=29) and control group (N=33). Subjects were predominantly male (70.96%) and single (88.70%). At baseline, groups showed no differences in terms of demographic variables and illness duration. Patients were moderately ill, with mean CGI = 4.10 (SD 0.78) in SST group and 4.34 (0.90) in the control group, and had a high baseline PANSS score, with a mean total PANSS 71.90 (10.83) in the SST group and 70.4 (13.8) in the control group. The mean PANSS negative subscale score was 25.48 (4.56) in SST group and 25.13 (6.34) in control group; in the SST group 28 patients completed the 20-week intervention and 24 were assessed after 6 months; in the control group, 18 completed the treatment and 16 were assessed at the follow-up. After the 20-week intervention period, the PANSS negative scores were 24.57 (4.92) in the SST group and 22.67 (6.59) in the control group. At the follow-up, the negative score was 23.92 (5.85) in the SST group and 22.97 (5.32) in the control. There was no improvement at any timepoint (p= 0.162) or any difference between groups (p= 0.864). Patients remained clinically stable during the study. The only symptom which showed a significant improvement was the control of aggressiveness (Cohen’s d at week 20 = 0.445 [IC 95% -0.140; 1.030]), which was maintained at follow-up (Cohen’s d = 0.682 [IC 95% 0.037; 1.327]).DiscussionThe study has limitations: the SSI was not designed to assess social skills in patients with psychosis, and we have not assessed the adherence to pharmacological treatment. Our findings suggest that SST is not effective to improve negative symptoms in patients with TRS with predominantly negative symptoms, but may be potentially useful for the control of aggressiveness in situations such as criticism and mockery, which frequently occur in social interactions.

T162. THICKER PREFRONTAL CORTEX IS ASSOCIATED WITH SUBCLINICAL NEGATIVE SYMPTOMS IN SCHIZOTYPY - AN ENIGMA CONSORTIUM META-ANALYSIS

BackgroundNegative symptoms can be seen to represent a continuum from subclinical manifestations in the general population to severe symptoms in schizophrenia. Neuroanatomical studies show evidence of fronto-striatal structural abnormalities linked to negative symptoms in patients with schizophrenia (Walton et al. 2018). However, it remains an open question whether these structural associations are also observed in ostensibly healthy individuals reporting subclinical negative symptoms. The present study used structural T1-weighted brain imaging data from the ENIGMA Schizotypy Working Group to investigate the relationship between subclinical negative symptoms and fronto-striatal structural measures.MethodsWe included 2,235 healthy unmedicated individuals with varying levels of schizotypy from 17 centers around the world. The complete sample had a weighted mean (range) age of 29.2 (15.9–39.6) and 59.4% (51–100) were male. Subclinical negative symptoms were assessed at each site separately using factor scores from self-report schizotypy questionnaires (i.e., the Community Assessment of Psychic Experiences, the Oxford-Liverpool Inventory of Feelings and Experiences, or the Schizotypal Personality Questionnaire). Based on prior studies in schizophrenia, we obtained cortical thickness from 22 frontal regions-of-interest (ROIs) and subcortical volumes from 6 striatal ROIs using FreeSurfer. We performed meta-analyses of effect sizes (standardized regression coefficients) from a model predicting mean cortical thickness by subclinical negative symptom scores, adjusting for age, sex, and site. The same analysis was repeated for subcortical volumes including intracranial volume as additional covariate.ResultsMeta-analyses revealed significant positive associations between subclinical negative symptoms and cortical thickness of the left frontal pole (βstd=0.091; pFDR=0.009), right medial orbitofrontal cortex (βstd=0.083; pFDR=0.009) and right anterior cingulate cortex (βstd=0.07; pFDR=0.011).DiscussionUsing a large sample of healthy unmedicated individuals with varying levels of schizotypal personality traits, this ENIGMA meta-analysis showed that subclinical negative symptoms are associated with thicker prefrontal cortex. The present data are contrary to previous findings in schizophrenia, which demonstrates a relationship between negative symptoms and lower prefrontal cortical thickness (Walton et al. 2018). These divergent neural correlates suggest that thicker cortex could be a potential compensatory mechanism preventing individuals with schizotypy from the clinical manifestation of severe negative symptoms. Alternatively, greater prefrontal cortical thickness could also be associated with pathological processes along the negative symptom continuum prior to clinical manifestation.

S36. TREATING NEGATIVE SYMPTOMS OF SCHIZOPHRENIA WITH A MOTIVE-SPECIFIC INTERVENTION: A RANDOMIZED BRIEF INTERVENTION TRIAL

BackgroundMotivational deficits seem to be one of the main barriers in the recovery process among psychosis patients and have been shown to be very treatment resistant. Motives are conscious and unconscious affect-based needs that influence behavior toward specific incentives. Thus, they constitute the basis of motivated behavior or the lack thereof. In this study, we investigated how individual differences in social motives relate to the phenomenology of motivational negative symptoms in patients with schizophrenia.MethodsFifty-nine patients with a diagnosis of schizophrenia were included into the sample. Negative symptoms were measured with the Brief Negative Symptom Scale and social motives with the Questionnaire for the Zurich Model of Social Motivation. Between-group differences, Pearson correlations and regression analysis were calculated. We replicated and extended the results in a second sample of forty-five psychosis patients, using the same methods.ResultsA comparison of healthy controls and schizophrenia patients revealed significant differences in social motives. Within the patient group, relationships between the characteristics of the individual motives, in particular the achievement motive, and the severity of the motivational negative symptoms, i.e. of asociality, avolition and anhedonia, could be described. In contrast, social motives cannot be associated with diminished expression, the non-motivational dimension of negative symptoms.The duration of the disease seems to be an additional influencing factor: When comparing the motivational dispositions of first episode patients with those of healthy people, no differences were found. However, a relationship between the duration of the disease and the characteristics of social motives can be described.DiscussionExplicit social motives stand in a relationship with motivational negative symptoms. Since implicit and explicit motives may diverge, the aim of our future research is to additionally investigate the association with implicit motives.The inclusion of psychological factors helps to extend and improve psychotherapeutic interventions for psychosis patients. Since negative symptoms do not respond well to pharmacotherapy, further efforts in this direction are needed to understand the underlying mechanisms of this disease and to develop effective psychotherapy tools in the future.

Validation of the Arabic version of the \u201cself-evaluation of negative symptoms\u201d scale (SNS)

BackgroundThe self-evaluation of negative symptoms scale (SNS) is a new easy-to-use self-administered questionnaire allowing clinicians to understand the clinical and genetic factors affecting the negative symptoms in patients with schizophrenia. There was a need to translate and validate this scale in Arabic so that Arab-speaking patients benefit from it. Therefore, the aim of our study was to validate the Arabic version of the SNS in a sample of Lebanese patients with schizophrenia.MethodsThe Arabic SNS was used to quantify the disability associated with negative symptoms in patients with schizophrenia (n = 206). Six weeks after completing the SNS, the participants were interviewed again to assess test-retest reproducibility. The validity was confirmed by factor analyses using the principal component analysis technique with a varimax rotation. The Positive and Negative Syndrome Scale (PANSS) was also assessed.ResultsNone of the items of the SNS scale were removed; all items converged over a solution of five factors that had an eigenvalue > 1, explaining a total of 66.01% of the variance (Cronbach’s alpha = 0.879; test part). The mean total SNS score was 17.33 ± 8.43 for the “test”, and 16.35 ± 7.50 for the “retest”. The correlation coefficients between the SNS total score and the PANSS scale and subscales were as follows: total PANSS (r = 0.044; p = 0.530), positive PANSS score (r = − 0.106; p = 0.131), negative PANSS score (r = 0.204; p = 0.003), and general psychopathological PANSS score (r = 0.03; p = 0.530).ConclusionThis study is the first to validate the Arabic version of the SNS in patients with schizophrenia. Using this scale would help improve treatment by correctly assessing negative symptoms, thus optimizing treatment options.

Ten-year trajectory and outcomes of negative symptoms of patients with first-episode schizophrenia spectrum disorders

This study explored the 10-year trajectories and outcomes of negative symptoms in patients with first-episode schizophrenia-spectrum disorder. Patients were from the historical control study comparing 10-year outcomes between standard care and early intervention services. A total of 298 patients were identified, 214 were successfully interviewed at 10-year follow-up for clinical and functional outcomes and 209 patients were included for final analyses. Information from clinical records were obtained systematically using standardized data entry forms. These information including negative symptoms, hospitalization and employment, monthly for year 1–3 and trimonthly for the year 4–10. Hierarchical cluster analysis was used to explore the 10-year negative symptom clusters. Demographics and early clinical characteristics related to the cluster memberships and different components of negative symptom at 10-year follow-up were further explored. The cluster analysis identified three longitudinal clusters of negative symptoms and 15% of patients were in the relapsed group. There was no difference in cluster membership between the intervention groups. Male gender and duration of hospitalizations in year four were found to be significant determinants of relapse negative symptoms. Lower education level, higher year-one negative symptom score and more months of unemployment during the first 3 years predicted overall negative symptoms at 10-year follow-up. Male gender was found to be a predictor only for avolition and anhedonia and duration of untreated psychosis only predicted anhedonia. These results highlighted the heterogeneity of longitudinal outcomes and the importance of personalized interventions.

A randomized controlled trial of social skills training for patients with treatment-resistant schizophrenia with predominantly negative symptoms

We conducted a randomized controlled trial to assess the effectiveness of social skills training (SST) in improving negative symptoms in patients with treatment-resistant schizophrenia with predominantly negative symptoms. Patients were randomized to receive SST (n = 29) or to a control group (n = 33), in a 20-week program with weekly group sessions. Patients were assessed at baseline, post-treatment (20 weeks) and 6-month follow-up with the Positive and Negative Syndrome Scale. There was no significant improvement in the negative symptoms in either group, at any timepoint. Caution is warranted to interpret the results due to small sample size.

Improvement of Negative Symptoms in Schizophrenia with Paliperidone Palmitate 1-Month and 3-Month Long-Acting Injectables: Results from a Phase 3 Non-Inferiority Study.

BackgroundNegative symptoms in schizophrenia are associated with impairments in social and cognitive functioning leading to substantial long-term disability. Available antipsychotic treatments have demonstrated only modest benefit in the improvement of negative symptoms.ObjectiveTo compare improvements in negative symptoms among patients treated with paliperidone palmitate 3-month (PP3M) or paliperidone palmitate 1-month (PP1M) long-acting injectable (LAI) formulations.MethodsData from a randomized double-blind (DB), phase-3, non-inferiority study in patients with schizophrenia were analyzed. Following screening, patients entered a 17-week open-label (OL) phase to receive flexibly dosed PP1M followed by a 48-week DB phase where patients were randomized (1:1) to receive either PP1M or PP3M. Positive and Negative Syndrome Scale (PANSS) total scores with emphasis on 7-item negative subscale scores for PP1M vs PP3M were assessed.ResultsOf 1429 patients enrolled, 1016 were randomized to receive PP3M (n=504) or PP1M (n=512). At baseline, mean (SD) PANSS negative subscale was 23.2 (4.60) and negative symptom factor score was 22.3 (4.87), indicating moderate-to-severe negative symptoms. Negative subscale and symptoms factor scores showed continuous improvements throughout OL (15.9 [4.99]) and DB (14.9 [4.81]) phases. Mean (SD) changes from DB baseline in the PANSS negative subscale score were comparable between PP1M (–1.4 [3.67]) and PP3M (–1.4 [3.63]) treatment groups.ConclusionTreatment with PP3M or PP1M demonstrated comparable improvement in negative symptoms in patients with moderate-to-severe negative symptoms and in patients with prominent negative symptoms. Long-term treatment with PP3M demonstrated benefit, suggesting that continuous antipsychotic medication treatment for >1 year is needed to achieve greater benefit for negative symptoms.Trial RegistrationClinicalTrials.gov Identifier: NCT01515423.

Inflammation and Negative Symptoms of Schizophrenia: Implications for Reward Processing and Motivational Deficits.

Negative symptoms of schizophrenia are debilitating and chronic in nature, are difficult to treat, and contribute to poor functional outcomes. Motivational deficits are a core negative symptom and may involve alterations in reward processing, which involve subcortical regions such as the basal ganglia. More specifically, dopamine-rich regions like the ventral striatum, have been implicated in these reward-processing deficits. Inflammation is one mechanism that may underlie negative symptoms, and specifically motivational deficits, via the effects of inflammatory cytokines on the basal ganglia. Previous work has demonstrated that inflammatory stimuli decrease neural activity in the ventral striatum and decrease connectivity in reward-relevant neural circuitry. The immune system has been shown to be involved in the pathophysiology of schizophrenia, and inflammatory cytokines have been shown to be altered in patients with the disorder. This paper reviews the literature on associations between inflammatory markers and negative symptoms of schizophrenia as well as the role of anti-inflammatory drugs to target negative symptoms. We also review the literature on the role of inflammation and reward processing deficits in both healthy controls and individuals with depression. We use the literature on inflammation and depression as a basis for a model that explores potential mechanisms responsible for inflammation modulating certain aspects of negative symptoms in patients with schizophrenia. This approach may offer novel targets to treat these symptoms of the disorder that are significant barriers to functional recovery and do not respond well to available antipsychotic medications.

The safety and efficacy of adjunctive 20-Hz repetitive transcranial magnetic stimulation for treatment of negative symptoms in patients with schizophrenia: A double-blinded, randomized, sham-controlled study.

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.

Semantic processing event-related potential features in patients with schizophrenia and bipolar disorder.

Impairment in semantic association has been reported in bipolar disorder (BD) and schizophrenia (SZ) patients and could underlie abnormal speech patterns in both disorders. In this study, we compared the electrophysiological semantic processing features in patients with these two disorders. Participants (n = 61; BD = 19; SZ = 19; healthy controls [HCs] = 23) were administered a semantic judgment task and event-related potentials (ERPs) were recorded. Responses of the two patient groups were significantly slower than HCs, but comparable behavioral semantic priming effects were observed in both patient groups. The N400 priming effect was observed in all groups, with a delayed peak in the two patient groups. The N400 effect was enhanced for both BD and SZ patients over the left frontal and frontal pole region, but SZ patients showed additional reduction of N400 over the right posterior and occipital regions. The N400 mean amplitudes for related targets correlated with less severe negative symptoms in patients with SZ. Discriminant functional analysis using reaction time and N400 measures successfully classified 82% of the participants into their respective clinical groups. These results suggest that patients with BD and SZ have both overlapping and distinctive semantic processing dysfunction. These findings are consistent with the continuum conceptualization of these disorders, but also offer some support for the traditional Kraepelinian dichotomy.

Efficacy and Safety of Transcranial Direct Current Stimulation for Treating Negative Symptoms in Schizophrenia

Negative symptoms represent a substantial burden in schizophrenia. Although preliminary studies have suggested that transcranial direct current stimulation (tDCS) is effective for some clusters of symptoms, the clinical benefits for negative symptoms are unclear. To determine the efficacy and safety of tDCS vs sham as an add-on treatment for patients with schizophrenia and predominant negative symptoms. The double-blind Schizophrenia Treatment With Electric Transcranial Stimulation (STARTS) randomized clinical trial was conducted from September 2014 to March 2018 in 2 outpatient clinics in the state of São Paulo, Brazil. Patients with schizophrenia with stable negative and positive symptoms and a minimum score of 20 points in the negative symptoms subscale of the Positive and Negative Syndrome Scale (PANSS) were included. Ten sessions of tDCS performed twice a day for 5 days or a sham procedure. The anode and the cathode were positioned over the left prefrontal cortex and the left temporoparietal junction, respectively. Change in the PANSS negative symptoms subscale score at week 6 was the primary outcome. Patients were followed-up for an additional 6 weeks. Of the 100 included patients, 20 (20.0%) were female, and the mean (SD) age was 35.3 (9.3) years. A total of 95 patients (95.0%) finished the trial. In the intention-to-treat analysis, patients receiving active tDCS showed a significantly greater improvement in PANSS score compared with those receiving the sham procedure (difference, 2.65; 95% CI, 1.51-3.79; number needed to treat, 3.18; 95% CI, 2.12-6.99; P < .001). Response rates for negative symptoms (20% improvement or greater) were also higher in the active group (20 of 50 [40%]) vs the sham group (2 of 50 [4%]) (P < .001). These effects persisted at follow-up. Transcranial direct current stimulation was well tolerated, and adverse effects did not differ between groups, except for burning sensation over the scalp in the active group (43.8%) vs the sham group (14.3%) (P = .003). Transcranial direct current stimulation was effective and safe in ameliorating negative symptoms in patients with schizophrenia. ClinicalTrials.gov identifier: NCT02535676.

Religiosity and Severity of Symptoms in Croatian Patients With Major Depressive Disorder or Schizophrenia.

We examined and compared the relationship between religiosity and symptom severity in patients with major depressive disorder (MDD) rated by the Hamilton Depression Rating Scale) and schizophrenia (rated by the Positive and Negative Syndrome Scale). The Duke University Religion Index, the Santa Clara Strength of Religious Faith (SCSORF) questionnaire, and the Brief Religious Coping scale scores were similar between patients with MDD (n = 50) and patients with schizophrenia (n = 50). In patients with MDD, higher organizational religious activity (ORA) (estimate = 2.28, 95% confidence interval [CI] = 0.37-4.19; p = 0.020) and higher negative religious coping (estimate = 0.43, 95% CI = 0.03-0.84; p = 0.037) were independently associated with more severe symptoms. In patients with schizophrenia, higher ORA was associated with lower negative symptoms (estimate = -1.99, 95% CI = -3.94 to -0.03; p = 0.046). Higher SCSORF was associated with lower ORA in both patient subsets, and thus indirectly with milder symptoms in patients with MDD and with more severe negative symptoms in patients with schizophrenia. The relationship between religiosity and symptom severity apparently differs in patients with MDD and those with schizophrenia.

Efficacy of Equine Assisted Therapy on Negative Symptoms in Patients With Schizophrenia

Efficacy of Equine Assisted Therapy on Negative Symptoms in Patients With Schizophrenia