UNASSIGNED: Negative symptoms of schizophrenia (NSS) have been linked with poor functional outcomes. A literature review was performed to identify instruments used to assess functional outcomes and quality of life in clinical trials and observational studies conducted in groups of people with NSS.
UNASSIGNED: Literature search strings were designed using Medical Subject Headings combined with free-text terms and searches were performed using the PubMed, Embase and the Cochrane Library databases. For inclusion, articles were required to be published as full-text articles, in English, over the period 2011-2021, include at least one group or treatment arm of people with NSS and report either functional outcomes or quality of life (QoL).
UNASSIGNED: Literature searches identified a total of 3,268 unique hits. After two rounds of screening, 37 publications (covering 35 individual studies) were included in the review. A total of fourteen different instruments were used to assess functional outcomes and eleven different instruments were used to assess QoL. In studies in people with NSS, the most frequently used functional outcome measures were the Personal and Social Performance scale and the Global Assessment of Functioning. The most frequently used QoL instruments included the Manchester Short Assessment of Quality of Life, the Heinrich Carpenter Quality of Life Scale, the Schizophrenia Quality of Life Scale and the EQ-5D.
UNASSIGNED: A large number of measures have been used to assess functional outcomes and QoL in people with NSS, these include both generic and condition-specific as well as both interviewer-administered and self-reported instruments.

UNASSIGNED: Negative symptoms and cognitive impairments are highly frequent in schizophrenia spectrum disorders (SSD), associated with adverse functional outcomes and quality of life. Repetitive transcranial magnetic stimulation (rTMS) has been considered a promising therapeutic option in SSD. However, placebo effects of rTMS on these symptoms remained unclear.
UNASSIGNED: To investigate placebo effects of rTMS on alleviating negative symptoms and cognitive impairment in patients with SSD and to explore potential moderators.
UNASSIGNED: We systematically searched five electronic databases up to 15 July 2023. Randomized, double-blind, sham-controlled trials investigating effects of rTMS on negative symptoms or cognition in patients with SSD were included. The pooled placebo effect sizes, represented by Hedges\' g, were estimated using the random-effects model. Potential moderators were explored through subgroup analysis and meta-regression.
UNASSIGNED: Forty-four randomized controlled trials with 961 patients (mean age 37.53 years; 28.1% female) in the sham group were included. Significant low-to-moderate pooled placebo effect sizes were observed for negative symptoms (g=0.44, p<0.001), memory (g=0.31, p=0.010), executive function (g=0.35, p<0.001), working memory (g=0.26, p=0.004), and processing speed (g=0.36, p=0.004). Subgroup analysis indicated that placebo effects were affected by sham stimulation methods, rTMS targeting approaches, and stimulation frequency.
UNASSIGNED: Placebo effects of rTMS on negative symptoms and cognition in patients with SSD are significant in a small-to-moderate magnitude, which might be mediated by rTMS parameters. Our findings will provide new insights for practitioners to further optimize and establish standardized rTMS protocols for future RCTs tackling cardinal symptoms in SSD.
UNASSIGNED: https://www.crd.york.ac.uk/prospero/, identifier CRD42023390138.

UNASSIGNED: Negative symptoms, frequently experienced by people with schizophrenia, can impair functional outcomes and quality of life. Negative symptoms typically affect motivation, communication, and the ability to live independently and are difficult to treat. Several meta-analyses suggest that cognitive behavioural therapy results in a modest reduction in negative symptoms. It is unclear if similar effects can be achieved using behavioural activation. Behavioural activation is a derivative of cognitive behavioural therapy that helps to improve social and emotional functioning by encouraging patients to engage in activities that they value whilst modifying the avoidance responses. Behavioural activation can be a standalone treatment for depressive symptoms that is equally as efficacious as cognitive behavioural therapy.
UNASSIGNED: This systematic review aimed to identify and summarise the evidence about the efficacy of behavioural activation in treating negative symptoms.
UNASSIGNED: Systematic review.
UNASSIGNED: Two published studies conducted in South Korea and the United Kingdom recruited 55 patients.
UNASSIGNED: We searched five databases and four trial registries for clinical treatment trials of behavioural activation involving adults diagnosed with negative symptoms of schizophrenia. Studies were screened according to the inclusion criteria and assessed for quality.
UNASSIGNED: We identified 5023 published studies. After removing duplicates and conducting screening, two studies were included in this review. One study used a parallel non-randomised trial design whilst the other adopted a single group test-re-test design. Fifty-five participants were recruited from hospital and community settings. Both studies delivered 10 face-to-face sessions of behavioural activation; these were individual in one study and group sessions in the other. One study involved behavioural activation as the treatment whilst the other delivered behavioural activation with motivational interviewing. Neither study reported harms or adverse events.
UNASSIGNED: Based on the included studies, there is low-quality evidence that behavioural activation may be helpful in the treatment of negative symptoms. Key limitations of the studies include small sample sizes and overall low study quality.
UNASSIGNED: The protocol covering this review was registered with Open Science on 18 February 2022 (Registration DOI 10.17605/OSF.IO/57QSW; Weblink: https://osf.io/57qsw).
UNASSIGNED: Behavioural activation holds promise in supporting patients experiencing negative symptoms of schizophrenia.

Management of negative symptoms is one of the most challenging and important unmet needs of schizophrenia treatment. Negative symptoms together with positive symptoms result in significant psychosocial impairment and poor quality of life. Existing studies on atypical antipsychotics reported limited treatment adherence due to higher prevalence of treatment-emergent adverse events, such as diabetes, weight gain, hyperlipidemia, hyperprolactinemia and hypertension. A compound with greater affinity for dopamine D2/D3 receptors may improve negative symptoms, mood, and cognitive impairment associated with schizophrenia. In 2015, the US FDA has approved cariprazine, a partial D2/D3 agonist for treatment of schizophrenia, mania or mixed episodes. Midlands and Lancashire Commissioning Support Unit, UK (2019) has particularly suggested cariprazine for the treatment of predominant negative symptoms of schizophrenia. India\'s Central Drugs Standard Control Organization (CDSCO) has approved cariprazine in 2021 for the treatment of schizophrenia, manic or mixed episodes associated with bipolar I disorder. A ten-fold greater affinity for D3 receptors and partial agonism to serotonin receptors, along with longer half-life make cariprazine distinct when compared with other atypical antipsychotics. Cariprazine is also reported to have fewer incidents of metabolic and hormonal adverse events, and has been shown to provide better relapse prevention. Recent evidence indicates promising effect of cariprazine in ameliorating negative symptoms as well as psychotic symptoms in patients with schizophrenia. In addition, improved adherence to treatment (adjunctive/monotherapy) with cariprazine in patients having inadequate response to an ongoing antipsychotic treatment has also been clinically established. This review presents the evidence-based safety and efficacy of cariprazine for treatment of predominant negative symptoms of schizophrenia.

BACKGROUND: The clinical profiles of methamphetamine-induced psychosis (MIP) and schizophrenia are largely overlapping making differentiation challenging. In this systematic review and meta-analysis, we aim to compare the positive and negative symptoms of MIP and schizophrenia to better understand the differences between them.
METHODS: In accordance with our pre-registered protocol (CRD42021286619), we conducted a search of English-language studies up to December 16th, 2022, in PubMed, EMBASE, and PsycINFO, including stable outpatients with MIP and schizophrenia. We used the Newcastle-Ottawa Scale to measure the quality of cross-sectional, case-control, and cohort studies.
RESULTS: Of the 2052 articles retrieved, we included 12 studies (6 cross-sectional, 3 case-control, and 2 cohort studies) in our meta-analysis, involving 624 individuals with MIP and 524 individuals with schizophrenia. Our analysis found no significant difference in positive symptoms between the two groups (SMD, -0.01; 95%CI, -0.13 to +0.11; p = 1). However, individuals with MIP showed significantly less negative symptoms compared to those with schizophrenia (SMD, -0.35; 95CI%, -0.54 to -0.16; p = 0.01; I2 = 54 %). Our sensitivity analysis, which included only studies with a low risk of bias, did not change the results. However, our meta-analysis is limited by its cross-sectional approach, which limits the interpretation of causal associations. Furthermore, differences in population, inclusion criteria, methodology, and drug exposure impact our findings.
CONCLUSIONS: Negative symptoms are less prominent in individuals with MIP. While both groups do not differ regarding positive symptoms, raises the possibility of shared and partly different underlying neurobiological mechanisms related to MIP and schizophrenia.

OBJECTIVE: Schizophrenia is often associated with severe difficulties in social functioning, resulting in increased isolation and subsequent loneliness. Interpersonal distance - the amount of space around an individual\'s body during social interaction - can signal such difficulties. However, little is known about how individuals with schizophrenia regulate their interpersonal distance during social encounters. Summarizing the current empirical findings of interpersonal distance regulation in schizophrenia can bring novel perspectives for understanding interpersonal difficulties observed in this clinical population.
METHODS: This systematic review examined empirical studies indexed in Web of Science and PubMed based on a-priori-defined criteria. 1164 studies were screened with the final review consisting of 14 studies. They together included 1145 adult participants, of whom 668 were diagnosed with schizophrenia or psychotic disorder.
RESULTS: The studies clearly showed that patients maintain greater interpersonal distances than do controls. Furthermore, a larger distance was linked to more severe positive and negative symptoms. More specifically, the link to symptoms was more pronounced when patients were being approached by someone else during interactions. On a neurobiological level, the increased activity and functional connectivity of the dorsal inferior parietal sulcus and increased subjective state-dependent stress are further indicated as being potentially related to increase interpersonal distancing in schizophrenia.
CONCLUSIONS: We provided information about the aberrant modulation of interpersonal distance in schizophrenia. Studies showed substantial heterogeneity in tasks used to measure interpersonal distance. Future studies should look at links to social functioning, underlying neurobiology, and neuroendocrinal regulation of interpersonal space in schizophrenia.

BACKGROUND: Yoga is gradually being explored as a potential complementary intervention in addition to psychiatric drugs for schizophrenia. However, there are conflicts on the efficacy of yoga for schizophrenia. This meta-analysis was aimed to evaluate the association of yoga intervention with reductions on clinical symptoms and improvements in quality of life (QoL) as well as social functioning among schizophrenia.
METHODS: Systematic literature search was undertaken to identify all RCTs that compared yoga with active or passive controls for patients with schizophrenia from inception to July 2023. The outcomes were measurements of positive symptoms, negative symptoms, QoL and social functioning. Random-effects models were performed to calculate the effect sizes in the standardized mean differences reporting as Hedges\' s g statistic.
RESULTS: 19 studies enrolling 1274 participants with schizophrenia were included. Yoga had a medium effect on positive symptoms in the short term (Hedges\'s g = 0.31) and small effect in the long term (Hedges\'s g = 0.18). Medium significant effects were also found on negative symptoms in both the short term (Hedges\'s g = 0.44) and the long term (Hedges\'s g = 0.35). Yoga had a significant impact on improving both total QoL (Hedges\'s g = 0.34) and social functioning (Hedges\'s g = 0.45) with medium effect sizes.
CONCLUSIONS: Yoga was associated with significant reductions on negative and positive symptoms, and significant improvements in QoL as well as social functioning in patients with schizophrenia. Future research should explore the long-term efficacy of yoga for schizophrenia, encompassing more diverse populations.

UNASSIGNED: In randomized clinical trials (RCTs) investigating the application of transcranial alternating current stimulation (tACS) in schizophrenia, inconsistent results have been reported. The purpose of this exploratory systematic review of RCTs was to evaluate tACS as an adjunct treatment for patients with schizophrenia based on its therapeutic effects, tolerability, and safety.
UNASSIGNED: Our analysis included RCTs that evaluated adjunctive tACS\' effectiveness, tolerability, and safety in schizophrenia patients. Three independent authors extracted data and synthesized it using RevMan 5.3 software.
UNASSIGNED: Three RCTs involving 76 patients with schizophrenia were encompassed in the analysis, with 40 participants receiving active tACS and 36 receiving sham tACS. Our study revealed a significant superiority of active tACS over sham tACS in improving total psychopathology (standardized mean difference [SMD] = -0.61, 95% confidence interval [CI]: -1.12, -0.10; I2 = 16%, p = 0.02) and negative psychopathology (SMD = -0.65, 95% CI: -1.11, -0.18; I2 = 0%, p = 0.007) in schizophrenia. The two groups, however, showed no significant differences in positive psychopathology, general psychopathology, or auditory hallucinations (all p > 0.05). Two RCTs examined the neurocognitive effects of tACS, yielding varied findings. Both groups demonstrated similar rates of discontinuation due to any reason and adverse events (all p > 0.05).
UNASSIGNED: Adjunctive tACS is promising as a viable approach for mitigating total and negative psychopathology in individuals diagnosed with schizophrenia. However, to gain a more comprehensive understanding of tACS\'s therapeutic effects in schizophrenia, it is imperative to conduct extensive, meticulously planned, and well-documented RCTs.

Negative symptoms in schizophrenia impose a significant burden with limited effective pharmacological treatment options. Recent trials have shown preliminary evidence for the efficacy of using intermittent theta burst stimulation (iTBS) in treating negative symptoms in schizophrenia. We aim to systematically review the current evidence of iTBS in the treatment of the negative symptoms of schizophrenia as an augmentation therapy. The study protocol was developed and registered on Prospero (registration ID: 323381). MEDLINE, EMBASE, Web of Science (Scopus), PsycINFO and Wan Fang databases were searched for sham-controlled, randomized trials of iTBS among patients with schizophrenia. The mean difference in major outcome assessments for negative symptoms was calculated. The quality of evidence was assessed using the Cochrane Risk of Bias Tool (version 1) and the GRADE system. Moreover, 12 studies including a total of 637 participants were included. Compared to sham treatment, the pooled analysis was in favor of iTBS treatment for negative symptoms (mean weight effect size: 0.59, p = 0.03) but not for positive symptoms (mean weight effect size: 0.01, p = 0.91) and depressive symptoms (mean weight effect size: 0.35, p = 0.16). A significant treatment effect was also observed on the iTBS target site left dorsal prefrontal cortex (mean weight effect size: 0.86, p = 0.007) and for stimulation with 80% motor threshold (mean weight effect size: 0.86, p = 0.02). Thus, our synthesized data support iTBS as a potential treatment for negative symptoms among patients with schizophrenia. However, the long-term efficacy and safety issues of iTBS in a larger population have yet to be examined.

The aim of our study was to evaluate the efficacy of cariprazine augmentation of clozapine in treatment-resistant schizophrenia in a retrospective chart review. Among 916 medical records of schizophrenia patients, we identified 12 individuals treated with a combination of those drugs for a duration of 3-60 weeks [median 32 (10-40)]. Clinical Global Impression-Improvement (CGI-I) scores were used to measure the treatment response between the introduction of cariprazine augmentation of clozapine and the last point of observation. The majority of the patients presented treatment response (9/12 patients, 75%) after 4-16 weeks of therapy [median 6 (4-12)]. Treatment was associated with the decrease in positive, negative, affective, and anxiety symptom severity, as well as improvement of patient global functioning. One patient discontinued the treatment due to side effects (akathisia), and two patients halted the therapy due to the exacerbation of psychotic symptoms. Our study presents a thorough clinical description of the largest number of treatment-resistant schizophrenia patients medicated using cariprazine augmentation of clozapine in a \"real-world\" setting. Our results suggest that the use of this combination may lead to the improvement in a broad range of symptoms of patients with this condition.