Change In Negative Symptoms Research Articles

Psychological interventions for early-phase schizophrenia: protocol for a systematic review and network meta-analysis

Introduction Treating the early phase of schizophrenia is crucial for preventing further episodes and improving quality of life, functioning, and social inclusion. Pharmacotherapies are first-line treatments, but have limitations. There is consensus on the need for non-pharmacological interventions for individuals in the early phase of schizophrenia. Several psychological interventions have shown promising effects; however, their comparative effectiveness remains largely unknown. To address this issue, a network meta-analysis will be performed. We aim to develop a hierarchy of existing psychological treatments concerning their efficacy and tolerability, which will inform treatment guidelines. Protocol Randomized controlled trials (RCTs) investigating psychological interventions for first-episode psychosis, first-episode schizophrenia, or early phase schizophrenia will be included. The primary outcome will be overall schizophrenia symptoms (measured up to 6 and 12 months, and at the longest follow-up) and relapse as a co-primary outcome. Secondary outcomes are premature discontinuation; change in positive, negative, and depressive symptoms of schizophrenia; response; quality of life; overall functioning; satisfaction with care; adherence; adverse events; and mortality. The study selection and data extraction are performed by two independent reviewers. We will assess the risk of bias of each study using the Cochrane Risk of Bias tool 2 and evaluate the confidence in the results using Confidence in Network Meta-Analysis (CINeMA). Subgroup and sensitivity analyses will be conducted to explore heterogeneity and assess the robustness of our findings. Discussion This systematic review and network meta-analysis aims to compare multiple existing psychological interventions, establishing which are best for symptom reduction, relapse prevention, and other important outcomes in early phase schizophrenia. Our results may provide practical guidance concerning the most effective psychological intervention to reduce symptom severity and the societal burden associated with the disorder.

Psychological interventions for early-phase schizophrenia: protocol for a systematic review and network meta-analysis.

Treating the early phase of schizophrenia is crucial for preventing further episodes and improving quality of life, functioning, and social inclusion. Pharmacotherapies are first-line treatments, but have limitations. There is consensus on the need for non-pharmacological interventions for individuals in the early phase of schizophrenia. Several psychological interventions have shown promising effects; however, their comparative effectiveness remains largely unknown. To address this issue, a network meta-analysis will be performed. We aim to develop a hierarchy of existing psychological treatments concerning their efficacy and tolerability, which will inform treatment guidelines. Randomized controlled trials (RCTs) investigating psychological interventions for first-episode psychosis, first-episode schizophrenia, or early phase schizophrenia will be included. The primary outcome will be overall schizophrenia symptoms (measured up to 6 and 12 months, and at the longest follow-up) and relapse as a co-primary outcome. Secondary outcomes are premature discontinuation; change in positive, negative, and depressive symptoms of schizophrenia; response; quality of life; overall functioning; satisfaction with care; adherence; adverse events; and mortality. The study selection and data extraction are performed by two independent reviewers. We will assess the risk of bias of each study using the Cochrane Risk of Bias tool 2 and evaluate the confidence in the results using Confidence in Network Meta-Analysis (CINeMA). Subgroup and sensitivity analyses will be conducted to explore heterogeneity and assess the robustness of our findings. This systematic review and network meta-analysis aims to compare multiple existing psychological interventions, establishing which are best for symptom reduction, relapse prevention, and other important outcomes in early phase schizophrenia. Our results may provide practical guidance concerning the most effective psychological intervention to reduce symptom severity and the societal burden associated with the disorder.

Australian trial of behavioural activation for people with schizophrenia experiencing negative symptoms: a feasibility randomised controlled trial protocol

IntroductionNegative symptoms are frequently experienced by people with schizophrenia. People with negative symptoms often have impaired social functioning and reduced quality of life. There is some evidence that cognitive–behavioural therapy...

Race/ethnicity and socioeconomic status as predictors of outcome following family therapy in youth at clinical high risk for psychosis.

There is limited research on the effects of sociodemographic and socioeconomic factors on treatment outcomes in youth at clinical high risk for psychosis (CHRp). This study examined sociodemographic factors that may affect functional outcomes within this population. Specifically, we investigated the influence of race/ethnicity (dichotomized as non-Hispanic whites [NHW] vs. people of colour [POC]), socioeconomic status (SES; operationalized as parental years of education), and their interaction on change in psychosocial functioning and symptoms over 6 months in a randomized trial of family-focused therapy. CHRp youth (N = 128) participated in a randomized trial of family therapy (18 sessions of family therapy vs. 3 sessions of family psychoeducation). Sixty-four participants who self-identified as POC and 64 self-identified NHW participants completed baseline and 6-month follow-up measures of positive and negative symptoms and psychosocial (global, role, and social) functioning. Multiple regression models were conducted to test the main effect of race/ethnicity on changes in positive and negative symptoms and functioning, and whether this effect was moderated by parental education. There was a significant interaction between race/ethnicity and parental education, such that higher parental education was associated with greater improvement in global functioning in NHW participants, but there was no relationship between parental education and global functioning in POC. Additionally, higher parental education was associated with a decrease in negative symptoms in NHW participants but not in POC. There were no significant effects of race/ethnicity or parental education on positive symptoms, nor on social or role functioning. Clinicians may consider tailoring psychosocial treatments according to the needs of diverse families who vary in sociodemographic factors such as educational attainment and race/ethnicity.

485 Investigating the Impact of Inflammation on White Matter Tracts using Diffusion Tensor Imaging that may Contribute to Motivational Deficits and Negative Symptoms in Patients with Schizophrenia

OBJECTIVES/GOALS: Previous research has linked inflammation to changes in brain reward circuitry and subsequent negative symptoms in patients with schizophrenia. This project aims to understand brain-immune interactions using diffusion tensor imaging (DTI) to investigate the impact of inflammatory markers on white matter (WM) tracts. METHODS/STUDY POPULATION: Patients with schizophrenia, ages 18 to 45, were recruited at Grady Hospital in Atlanta, GA. All subjects were stable outpatients and underwent extensive medical screening to rule out medical causes of acute inflammation. DTI data was collected from 39 participants on a 3-Tesla Siemens scanner. Blood was collected between 9-11AM for later assay of serum inflammatory markers. Negative symptoms were assessed using the Brief Negative Symptom Scale (BNSS). A diffusion tensor imaging model will be fitted with the data to generate well-known diffusion tensor measures (fractional anisotropy and mean diffusivity). Linear regression will be used to analyze the relationship between DTI measures and inflammation (C-Reactive Protein, CRP), controlling for possible confounders. RESULTS/ANTICIPATED RESULTS: The hypothesis of this proposal is that decreased microstructural integrity in WM tracts between the nucleus accumbens (NAc) and insula will be associated with increased inflammation, which in turn are associated with increased negative symptoms. Negative symptoms include deficits in motivation/pleasure as well as diminished expressivity, and are strongly associated with poor functional outcomes. Based on previous data from this sample demonstrating relationships between CRP and negative symptoms as well as CRP and fMRI functional connectivity between the NAc and insula, we anticipate results that demonstrate similar relationships with WM microstructural integrity, such as functional anisotropy and mean diffusivity. DISCUSSION/SIGNIFICANCE: Given the lack of treatment options for negative symptoms, this research will provide key data to further our understanding of the potential role of inflammation on neural circuits that underlie these symptoms, including WM integrity. This research also has the potential to inform future anti-inflammatory therapies for patients with schizophrenia.

The management of patients with predominant negative symptoms in Slovakia: A 1-year longitudinal, prospective, multicentric cohort study.

Predominant negative symptoms (PNSs) in schizophrenia can affect the patients' psychosocial functioning immensely and are less responsive to treatment than positive symptoms. The aim of the study was to observe negative symptoms and psychosocial functioning in PNS schizophrenia patients and to understand whether PNS can be improved and with what treatment strategies. This was a 1-year, prospective, multicentric cohort study conducted in Slovakia. Adult outpatients with diagnosis of schizophrenia according to ICD-10 and PNS evaluated using the criteria by the European Psychiatric Association's (EPA) guidance were included. Change in negative symptoms, functionality, and treatment patterns were observed. Treatment effectiveness was evaluated using the modified Short Assessment of Negative Domain (m-SAND), the Self-evaluation of Negative Symptoms (SNS) scale, the Personal and Social Performance (PSP) scale, and the Clinical Global Impression - Severity (CGI-S) and the Clinical Global Impression - Improvement (CGI-I) scales. Least-squares (LS) means were calculated for the change from baseline to final visit for the outcomes. The study included 188 patients. Functionality improved as, by the end of the study, fewer patients were unemployed (53%) and more worked occasionally (21%). PNS improved significantly according to both physicians and patients (LS mean change from baseline in m-SAND total score: -10.0 (p-value <0.0001)). Most patients received polytherapy throughout the study. Cariprazine was utilized most (20% monotherapy and 76% polytherapy). Only a few patients discontinued treatment due to adverse drug reactions. With the right treatment strategy, it is possible to achieve improvement in PNS and everyday functioning in schizophrenia outpatients.

Adjunctive canakinumab reduces peripheral inflammation markers and improves positive symptoms in people with schizophrenia and inflammation: A randomized control trial

BackgroundClinical trials of anti-inflammatories in schizophrenia do not show clear and replicable benefits, possibly because patients were not recruited based on elevated inflammation status. Interleukin 1-beta (IL-1β) mRNA and protein levels are increased in serum, plasma, cerebrospinal fluid, and brain of some chronically ill patients with schizophrenia, first episode psychosis, and clinical high-risk individuals. Canakinumab, an approved anti-IL-1β monoclonal antibody, interferes with the bioactivity of IL-1β and interrupts downstream signaling. However, the extent to which canakinumab reduces peripheral inflammation markers, such as, high sensitivity C-reactive protein (hsCRP) and symptom severity in schizophrenia patients with inflammation is unknown. Trial designWe conducted a randomized, placebo-controlled, double-blind, parallel groups, 8-week trial of canakinumab in chronically ill patients with schizophrenia who had elevated peripheral inflammation. MethodsTwenty-seven patients with schizophrenia or schizoaffective disorder and elevated peripheral inflammation markers (IL-1β, IL-6, hsCRP and/or neutrophil to lymphocyte ratio: NLR) were randomized to a one-time, subcutaneous injection of canakinumab (150 mg) or placebo (normal saline) as an adjunctive antipsychotic treatment. Peripheral blood hsCRP, NLR, IL-1β, IL-6, IL-8 levels were measured at baseline (pre injection) and at 1-, 4- and 8-weeks post injection. Symptom severity was assessed at baseline and 4- and 8-weeks post injection. ResultsCanakinumab significantly reduced peripheral hsCRP over time, F(3, 75) = 5.16, p = 0.003. Significant hsCRP reductions relative to baseline were detected only in the canakinumab group at weeks 1, 4 and 8 (p’s = 0.0003, 0.000002, and 0.004, respectively). There were no significant hsCRP changes in the placebo group. Positive symptom severity scores were significantly reduced at week 8 (p = 0.02) in the canakinumab group and week 4 (p = 0.02) in the placebo group. The change in CRP between week 8 and baseline (b = 1.9, p = 0.0002) and between week 4 and baseline (b = 6.0, p = 0.001) were highly significant predictors of week 8 change in PANSS Positive Symptom severity scores. There were no significant changes in negative symptoms, general psychopathology or cognition in either group. Canakinumab was well tolerated and only 7 % discontinued. ConclusionsCanakinumab quickly reduces peripheral hsCRP serum levels in patients with schizophrenia and inflammation; after 8 weeks of canakinumab treatment, the reductions in hsCRP are related to reduced positive symptom severity. Future studies should consider increased doses or longer-term treatment to confirm the potential benefits of adjunctive canakinumab in schizophrenia.Australian and New Zealand Clinical Trials Registry number: ACTRN12615000635561.

"InMotion"-Mixed physical exercise program with creative movement as an intervention for adults with schizophrenia: study protocol for a randomized controlled trial.

Schizophrenia is among the world's top 10 causes of long-term disability with symptoms that lead to major problems in social and occupational functioning, and in self-care. Therefore, it is important to investigate the efficacy of complementary treatment options for conventionally used antipsychotic medication, such as physical training, and psychosocial interventions. To combine aerobic and strength training with cognitive, emotional and social stimulation in one intervention for people with schizophrenia and test the feasibility and effects of this intervention. The study is a mixed-method randomized controlled trial to evaluate the effects of a 12-week intervention for adults with schizophrenia. The treatment group (30 participants) will receive the intervention in addition to standard care and the control group (30 participants) only standard care. The intervention consists of 24 biweekly sessions with a duration of 60 min. The pre-test (weeks from 4 to 2 prior to the intervention) and post-test (week 12) include clinical measure (PANSS), quality of life, social performance, movement quantity, brain function and eye tracking measures. In addition, a treatment subgroup of 12-15 participants and their family member or other next of kin will complete a qualitative interview as a part of their post-test. Two follow-up tests, including clinical, quality of life, brain function and eye tracking will be made at 6 and 12 months from the completion of the intervention to both study groups. The primary outcome is change in negative symptoms. Secondary outcome measures include general and positive symptoms, quality of life, social performance, movement quantity, brain function and eye tracking. Explorative outcome includes patient and family member or other next of kin interview. Pilot data was collected by June 2023 and the main data collection will begin in September 2023. The final follow-up is anticipated to be completed by 2026. The InMotion study will provide new knowledge on the feasibility, efficacy, and experiences of a novel intervention for adults with schizophrenia. The hypothesis is that regular participation in the intervention will reduce clinical symptoms, normalize physiological measures such as brain activation, and contribute to new active habits for the participants. ClinicalTrials.gov, identifier NCT05673941.

Long-term efficacy of antipsychotic drugs in initially acutely ill adults with schizophrenia: systematic review and network meta-analysis.

Most acute phase antipsychotic drug trials in schizophrenia last only a few weeks, but patients must usually take these drugs much longer. We examined the long-term efficacy of antipsychotic drugs in acutely ill patients using network meta-analysis. We searched the Cochrane Schizophrenia Group register up to March 6, 2022 for randomized, blinded trials of at least 6-month duration on all second-generation and 18 first-generation antipsychotics. The primary outcome was change in overall symptoms of schizophrenia; secondary outcomes were all-cause discontinuation; change in positive, negative and depressive symptoms; quality of life, social functioning, weight gain, antiparkinson medication use, akathisia, serum prolactin level, QTc prolongation, and sedation. Confidence in the results was assessed by the CINeMA (Confidence in Network Meta-Analysis) framework. We included 45 studies with 11,238 participants. In terms of overall symptoms, olanzapine was on average more efficacious than ziprasidone (standardized mean difference, SMD=0.37, 95% CI: 0.26-0.49), asenapine (SMD=0.33, 95% CI: 0.21-0.45), iloperidone (SMD=0.32, 95% CI: 0.15-0.49), paliperidone (SMD=0.28, 95% CI: 0.11-0.44), haloperidol (SMD=0.27, 95% CI: 0.14-0.39), quetiapine (SMD=0.25, 95% CI: 0.12-0.38), aripiprazole (SMD=0.16, 95% CI: 0.04-0.28) and risperidone (SMD=0.12, 95% CI: 0.03-0.21). The 95% CIs for olanzapine versus aripiprazole and risperidone included the possibility of trivial effects. The differences between olanzapine and lurasidone, amisulpride, perphenazine, clozapine and zotepine were either small or uncertain. These results were robust in sensitivity analyses and in line with other efficacy outcomes and all-cause discontinuation. Concerning weight gain, the impact of olanzapine was higher than all other antipsychotics, with a mean difference ranging from -4.58 kg (95% CI: -5.33 to -3.83) compared to ziprasidone to -2.30 kg (95% CI: -3.35 to -1.25) compared to amisulpride. Our data suggest that olanzapine is more efficacious than a number of other antipsychotic drugs in the longer term, but its efficacy must be weighed against its side effect profile.

Treatment of Depression with Vortioxetine and Second Generation Antipsychotics During the Period of Remission Formation in Schizophrenia (Interim Data Analysis).

Depression in patients with schizophrenia worsens the course of the disease by increasing the risk of suicide, by complicating the clinical picture of the disorder, and by reducing the quality of the social functioning; its treatment is difficult, since monotherapy, even when involving modern antipsychotics, does not always prove successful. While the prescription of additional antidepressants (ADs) can improve the likelihood of a better outcome, the effectiveness of such augmentation in many cases is yet to be proven. Therefore, it is still important that one weighs the effectiveness of various combinations between most of the known ADs and some second-generation antipsychotic (SGA) in the treatment of depression that occurs at different stages of schizophrenia. In previous studies, the use of vortioxetine as an adjunct to an antipsychotic yielded a reduction in negative symptoms, a clinically significant improvement in cognitive functions that differed from its antidepressant effect, and good tolerability, which affects how committed to treatment a patient remains. To study the changes that occur over time in the clinical manifestations of depression, negative and cognitive impairment, as well as the social adequacy of patients receiving a combination therapy with second-generation antipsychotics and vortioxetine, which were prescribed in real clinical practice at doses approved in the Russian Federation. We performed a comparative analysis of the changes in depression symptoms and negative symptoms, cognitive impairment, as well as function of 78 patients with severe manifestations of depression at the stage of exacerbation reduction and subsequent remission of paranoid schizophrenia. Combination treatment with SGA and vortioxetine was used in 39 patients, and 39 patients who had similar clinical manifestations received just SGA. During the observation period, the mental disorder severity and depression symptom severity were assessed 3 times (before the start of treatment, after three months, and after six months) using the Clinical Global Impression (CGI) scale and Calgary Depression Scale for Schizophrenia (CDSS), respectively; patients were also assessed using the Negative Symptoms Assessment-5 (NSA-5) scale, Perceived Deficits Questionnaire-20 items (PDQ-20) scale, and Personal and Social Performance (PSP) scale. According to the ANOVA results, by the end of the observation period, patients, regardless of their therapeutic group, showed a statistically significant decrease in the level of depression on the CDSS scale, the severity of negative symptoms on the NSA-5 scale, cognitive symptoms on the PDQ-20 scale, as well as an improvement in personality and society, judging by the increase in the total PSP scores. There were also significant differences between the compared main (SGA + vortioxetine) and control (SGA) groups in terms of the changes in the total score on the CDSS and PSP scales. An interesting aspect of the changes in the clinical scores was a noticeable improvement in the SGA + vortioxetine group after 3 months of treatment, in the absence of a similar improvement in the control group, and the achievement of approximately the same scores in both groups after 6 months. In particular, there were significant differences between the SGA + vortioxetine and SGA groups in terms of the mean CDSS (p 0.001), NSA-5 (p=0.003), PDQ-20 (p 0.001), and PSP (p=0.004) scores after 3 months. Analysis of the time before early withdrawal from the study showed that significantly more patients in the SGA + vortioxetine group completed the study program (n=27, 69.23%) compared with the SGA group (n=13, 33.33%) (2 =14.618, df=1, p 0.001, log-rank test. The mean survival time in the SGA group was significantly (p 0.001) less and amounted to 101.436 days (95% CI: 81.518121.354), and in the SGA + vortioxetine group it amounted to 161.744 days (147.981175.506). The relative risk of full study completion in the vortioxetine + SGA group compared with that in SGA was 3.618 (1.8716.994). The addition of vortioxetine to the SGA therapy accelerates the reduction of the depression symptoms that occur at the stage of psychosis regression and early remission, contributes to the accelerated reduction in negative symptoms, positively affects the subjective assessment of cognitive impairment severity, and has a significant positive effect on the level of psychosocial functioning.

Long-Term Outcome of Clozapine in Treatment-Resistant Schizophrenia.

The favorable effect of clozapine on psychotic symptoms in patients with treatment-resistant (TR) schizophrenia (SCZ) in short-term studies is well established. However, prospective studies of the long-term outcome of clozapine treatment on psychopathology, cognition, quality of life, and functional outcome in TR-SCZ are limited. Here, we have examined the long-term (mean duration of follow-up 14 years) effects of clozapine on those outcomes in a prospective, open label study in 54 TR-SCZ patients. Assessments were performed at baseline, 6 weeks, 6 months, and at the last follow-up. Brief Psychiatric Rating Scale (BPRS) total, positive symptoms, and anxiety/depression at the last follow-up improved significantly from baseline, as well as from the 6-month evaluation ( P < 0.0001), with a 70.5% responder rate (≥20% improvement at the last follow-up from baseline). Quality of Life Scale (QLS) total improved by 72% at the last follow-up, with 24% of patients rated as having "good" functioning compared with 0% at baseline. Suicidal thoughts/behavior was significantly reduced at the last follow-up from the baseline. No significant change in negative symptoms was found at the last follow-up in the total sample. Short-term memory function declined at the last follow-up from baseline, but there was no significant change in processing speed. The QLS total showed a significant negative correlation with BPRS positive symptoms but not with cognitive measures, or negative symptoms, at the last follow-up. For patients with TR-SCZ, improving psychotic symptoms with clozapine seems to have a more significant impact than negative symptoms or cognition on improving psychosocial function.

Negative Symptom Trajectories in Individuals at Clinical High Risk for Psychosis: Differences Based on Deficit Syndrome, Persistence, and Transition Status.

Negative symptom trajectory in clinical high risk (CHR) for psychosis is ill defined. This study aimed to better characterize longitudinal patterns of change in negative symptoms, moderators of change, and differences in trajectories according to clinical subgroups. We hypothesized that negative symptom course will be nonlinear in CHR. Clinical subgroups known to be more severe variants of psychotic illness-deficit syndrome (DS), persistent negative syndrome (PNS), and acute psychosis onset-were expected to show more severe baseline symptoms, slower rates of change, and less stable rates of symptom resolution. Linear, curvilinear, and stepwise growth curve models, with and without moderators, were fitted to negative symptom ratings from the NAPLS-3 CHR dataset (N = 699) and within clinical subgroups. Negative symptoms followed a downward curvilinear trend, with marked improvement 0-6 months that subsequently stabilized (6-24 months), particularly among those with lower IQ and functioning. Clinical subgroups had higher baseline ratings, but distinct symptom courses; DS vs non-DS: more rapid initial improvement, similar stability of improvements; PNS vs non-PNS: similar rates of initial improvement and stability; transition vs no transition: slower rate of initial improvement, with greater stability of this rate. Continuous, frequent monitoring of negative symptoms in CHR is justified by 2 important study implications: (1) The initial 6 months of CHR program enrollment may be a key window for improving negative symptoms as less improvement is likely afterwards, (2) Early identification of clinical subgroups may inform distinct negative symptom trajectories and treatment needs.

Antipsychotics for schizophrenia spectrum disorders with catatonic symptoms.

Antipsychotics for schizophrenia spectrum disorders with catatonic symptoms.

Quality of life after involuntary psychiatric admission

Studies seeking predictors of outcomes after involuntary admission, including quality of life (QoL), are limited and results inconsistent. We aimed to describe QoL 3 months after involuntary psychiatric admission and to investigate associated factors. One hundred and fifty-three involuntarily admitted inpatients were assessed for a range of sociodemographic and clinical variables. Structured scales included the Brief Psychiatric Rating Scale (BPRS), the MacArthur Admission Experience Survey, the Heinrichs Quality of Life Scale and the World Health Organisation Quality of Life Brief Assessment (WHOQOL-BREF, n = 124). The mean total score on the Heinrichs QoL scale at 3 months was 69.3 (SD = 24.1). Predictors of higher 3 month QoL after involuntary admission in a multiple regression model (adjusted R2 = 0.37, F = 7.1 (14, 138), p ≤0.001) were less severe negative symptoms on the BPRS at baseline (B = −4.56, p < 0.001), improvement in negative symptom scores between baseline and follow up (B = 4.58, p < 0.001) and higher current social class (B = −14.31, p = 0.001). Events during involuntary admission, such as being subject to coercive experiences, were not significantly associated with QoL after admission. The results suggest that a core determinant of service users' QoL after involuntary admission is negative symptom severity and change over time.

The Impact of Electroconvulsive Therapy on Negative Symptoms in Schizophrenia and Their Association with Clinical Outcomes.

Objective: The treatment efficacy of electroconvulsive therapy (ECT) for negative symptoms amongst patients with schizophrenia remains unclear. In this study, we aim to examine the effects of ECT on negative symptoms in schizophrenia and their association with other clinical outcomes, including cognition and function. Methods: This is a retrospective data analysis of patients with schizophrenia/schizoaffective disorder treated with ECT at the Institute of Mental Health (IMH), Singapore, between January 2016 and December 2019. Clinical outcomes were assessed by the Brief Psychiatric Rating Scale (BPRS), the Montreal Cognitive Assessment (MoCA), and Global Assessment of Function (GAF). Changes in scores were compared with repeated measures analysis of variance. Sequential structural modelling was utilized to examine the pathway relationships between changes in negative symptoms, global functioning, and cognition functioning after ECT. Results: A total of 340 patients were analysed. Hence, 196 (57.6%), 53 (15.5%), and 91 (26.7%) showed improvements, no change, and deterioration in negative symptoms, respectively. ECT-induced improvement of negative symptoms was significantly associated with improvement of global functioning (direct effect correlation coefficient (r): −0.496; se: 0.152; p = 0.001) and cognition function (indirect effect r: −0.077; se: 0.037; p = 0.035). Moreover, having capacity to consent, more severe baseline negative symptoms, lithium prescription, and an indirect effect of voluntary admission status via consent capacity predicted ECT associated negative symptoms improvement. Conclusion: ECT is generally associated with improvements of negative symptoms in people with schizophrenia, which correlate with improvements of overall function. Possible novel clinical predictors of negative symptom improvement have been identified and will require further research and validation.

What Is the Minimum Clinically Important Change in Negative Symptoms of Schizophrenia? PANSS Based Post-hoc Analyses of a Phase III Clinical Trial.

IntroductionMinimum clinically important difference (MCID) is a measure that defines the minimum amount of change in an objective score of a clinical test that must be reached for that change to be clinically noticeable. We aimed to find the MCID for patients with predominantly negative symptoms of schizophrenia at its earliest occurrence.MethodsData of a 26-week long, double-blind study with 454 patients [Positive and Negative Symptom Scale Negative Factor Score (PANSS-FSNS) ≥24, Positive and Negative Symptom Scale Positive Factor Score (PANSS-FSPS) ≤ 19] treated with cariprazine 4.5 mg/d or risperidone 4 mg/d were analyzed. The Clinical Global Impression—Improvement scale was used to quantify minimum improvement (CGI-I = 3) and no clinical change (CGI-I = 4) on the PANSS-FSNS, and the MCID was estimated with the following methods: as the mean PANSS-FSNS changes corresponding to the first instance of minimal improvement across all visits (MCID1); as the difference between the PANSS-FSNS change associated with the first instance and the PANSS-FSNS changes associated with the last recorded clinically unchanged status across all visits (MCID2); with the effect size approach (MCID3); as the Youden Index based cut-off value between no clinical change and minimal improvement (MCID4); as the relative likelihood of minimal improvement (MCID5).ResultsThe MCID1 and MCID2 resulted in, respectively, a 3.8-point (18.5%) and a 1.5-point (7.3%) decrease from baseline severity on the PANSS-FSNS. Greater values were required for the MCID at later evaluation times. The cut-off between minimum improvement and no clinical change defined by the Youden Index was a−3-point (15%) change in the PANSS-FSNS. The effect size approach indicated the 1.5-point difference between minimally improved and unchanged patients to be a medium effect (ES = 0.6).ConclusionApplying different methods led to different results, ranging between 7.3 and 18.5% improvement from the baseline for the MCID at its earliest occurrence in patients with predominantly negative symptoms of schizophrenia.

Relationship between TNF-\u03b1 levels and psychiatric symptoms in first-episode drug-na\xefve patients with schizophrenia before and after risperidone treatment and in chronic patients

BackgroundThe influence of antipsychotic drugs on tumor necrosis factor-α (TNF-α) levels is unclear, and there is no consensus on the association between TNF-α and psychotic symptoms. This study aimed to investigate the differences in TNF-α levels and clinical correlations in first-episode drug-naïve (FEDN) patients with schizophrenia before and after treatment and in chronic patients.MethodsA total of 103 (51 FEDN and 52 chronic) patients and 114 healthy controls were recruited. Demographic and clinical data, including TNF-α levels, were recorded. We used the Positive and Negative Syndrome Scale (PANSS) to measure the psychopathology of all patients.ResultsTNF-α levels before treatment were significantly higher in FEDN patients than in chronic patients and healthy controls. No significant sex differences were found in the TNF-α levels of patients with schizophrenia. The TNF-α levels before treatment were significantly positively related to changes in PANSS negative symptoms in FEDN patients. The TNF-α levels in chronic patients were significantly negatively correlated with the general psychopathology subscales and PANSS total scores.ConclusionsIncreased TNF-α levels in FEDN patients and their correlation with psychopathology indicate that inflammatory cytokines may play a crucial role in the etiopathogenesis of schizophrenia, and inflammation-directed therapy may, therefore, improve negative symptoms.

Humour-based interventions for people with schizophrenia.

Humour-based interventions are defined as any intervention that promotes health and wellness by stimulating a playful discovery, expression, or appreciation of the absurdity or incongruity of life's situations. Humour-based interventions can be implemented in different settings, including hospitals, nursing homes and day care centres. They have been posed as an adjunct to usual care for people with schizophrenia, but a summary of the evidence is lacking. To examine the effects of humour-based interventions as an add-on intervention to standard care for people with schizophrenia. On 31 July 2019 and 10 February 2021 we searched the Cochrane Schizophrenia Group's study-based register of trials, which is based on CENTRAL, CINAHL, ClinicalTrials.Gov, Embase, ISRCTN, MEDLINE, PsycINFO, PubMed, and WHO ICTRP. We included all randomised controlled trials comparing humour-based interventions with active controls, other psychological interventions, or standard care for people with schizophrenia. We excluded studies fulfilling our prespecified selection criteria but without useable data from further quantitative synthesis. Two review authors independently inspected citations, selected studies, extracted data and appraised study quality, following the guidance from the Cochrane Handbook for Systematic Reviews of Interventions. For binary outcomes we calculated risk ratios (RRs) and their 95% confidence intervals (CIs). For continuous outcomes we calculated the mean differences (MDs) and their 95% CIs. We assessed risks of bias for included studies and created summary of findings tables using the GRADE approach. We included three studies in this review for qualitative synthesis, although one study did not report any relevant outcomes. We therefore include two studies (n = 96) in our quantitative synthesis. No data were available on the following prespecified primary outcomes: clinically-important change in general mental state, clinically-important change in negative symptoms, clinically-important change in overall quality of life, and adverse effects. As compared with active control, humour-based interventions may not improve the average endpoint score of a general mental state scale (Positive and Negative Syndrome Scale (PANSS) total score: MD -1.70, 95% CI -17.01 to 13.61; 1 study, 30 participants; very low certainty of evidence); positive symptoms (PANSS positive symptom score: MD 0.00, 95% CI -2.58 to 2.58; 1 study, 30 participants; low certainty of evidence), negative symptoms (PANSS negative symptom score: MD -0.70, 95% CI -4.22 to 2.82; 1 study, 30 participants; very low certainty of evidence) and anxiety (State-Trait Anxiety Inventory (STAI): MD -2.60, 95% CI -5.76 to 0.56; 1 study, 30 participants; low certainty of evidence). Due to the small sample size, we remain uncertain about the effect of humour-based interventions on leaving the study early as compared with active control (no event, 1 study, 30 participants; very low certainty of evidence). On the other hand, humour-based interventions may reduce depressive symptoms (Beck Depression Inventory (BDI): MD -6.20, 95% CI -12.08 to -0.32; 1 study, 30 participants; low certainty of evidence). Compared with standard care, humour-based interventions may not improve depressive symptoms (BDI second edition: MD 0.80, 95% CI -2.64 to 4.24; 1 study, 59 participants; low certainty of evidence). We are uncertain about the effect of humour-based interventions on leaving the study early for any reason compared with standard care (risk ratio 0.38, 95% CI 0.08 to 1.80; 1 study, 66 participants; very low certainty of evidence). We are currently uncertain whether the evidence supports the use of humour-based interventions in people with schizophrenia. Future research with rigorous and transparent methodology investigating clinically important outcomes is warranted.

Changes in negative symptoms are linked to white matter changes in superior longitudinal fasciculus in individuals at ultra-high risk for psychosis

AimGrowing evidence suggests that subtle white matter (WM) alterations are associated with psychopathology in individuals at ultra-high risk for psychosis (UHR). However, the longitudinal relationship between symptom progression and WM changes over time remains under-explored. Here, we examine associations between changes in clinical symptoms and changes in WM over six months in a large UHR-cohort. Methods110 UHR-individuals and 59 healthy controls underwent diffusion weighted imaging at baseline and after six months. Group × time effects on fractional anisotropy (FA) were tested globally and in four predefined regions of interest (ROIs) bilaterally using linear modelling with repeated measures. Correlations between the changes in clinical symptoms and FA changes in the ROIs were examined with Pearson's correlation. A partial least squares correlation-technique (PLS-C) explored multivariate associations between patterns of changes in psychopathology, regional FA and additional WM indices. ResultsAt baseline, UHR-individuals displayed significantly lower FA globally (p = 0.018; F = 12.274), in right superior longitudinal fasciculus (p = 0.02; Adj R2 = 0.07) and in left uncinate fasciculus (p = 0.048; Adj R2 = 0.058) compared to controls (corrected). We identified a group × time interaction in global FA and right superior longitudinal fasciculus, but the finding did not survive multiple comparisons. However, an increase of negative symptoms in UHR-individuals correlated with FA increase in right superior longitudinal fasciculus (p = 0.048, corrected, r = 0.357), and this finding was supported by the multivariate PLS-C. ConclusionWe found a positive correlation with a moderate effect between change in negative symptoms and FA change over 6 months in right superior longitudinal fasciculus. This link appeared mainly to reflect a subgroup of UHR-individuals, which already at baseline presented as vulnerable.

Intranasal Oxytocin for Negative Symptoms of Schizophrenia: Systematic Review, Meta-Analysis, and Dose-Response Meta-Analysis of Randomized Controlled Trials.

BackgroundNegative symptoms are a core aspect of psychopathology in schizophrenia. Currently available pharmacological agents have proven minimally efficacious for remediating negative symptoms. A promising treatment avenue is the intranasal administration of the neuropeptide oxytocin. However, there have been inconsistencies in effects of oxytocin on negative symptoms throughout the literature, and factors leading to inconsistent effects are unclear.MethodsWe conducted a systematic review and meta-analysis of randomized clinical trials to compare the effectiveness of oxytocin with placebo for the treatment of negative symptoms and determine moderators of treatment effect. Random effects meta-analyses and dose-response meta-analysis were performed on mean changes in negative symptoms.ResultsIn an initial analysis of all 9 identified randomized clinical trials, intranasal oxytocin showed no significant effect on negative symptoms. For higher doses (>40–80 IU), a beneficial effect on negative symptoms was found with a moderate effect size, but this effect disappeared after exclusion of 1 outlier study. The dose-response meta-analysis predicted that higher doses of oxytocin may be more efficacious for negative symptoms. For positive symptoms, no beneficial effect of oxytocin was found in the main meta-analysis, but the dose-response meta-analysis suggested a potential advantage of higher doses.ConclusionsThe present results show no consistent beneficial effect of intranasal oxytocin for the treatment of negative and positive symptoms. The dose-response meta-analysis does not allow drawing any firm conclusions but suggests that high doses of intranasal oxytocin may be more efficacious. If future studies are conducted, an effort to reach adequate CNS concentrations for a sufficient duration is required.