Is it more effective for anhedonia and avolition? A systematic review and meta‐analysis of non‐invasive brain stimulation interventions for negative symptoms in schizophrenia
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SUBMITTER: Chen Y
PROVIDER: S-EPMC10909625 | biostudies-literature | 2024 Mar
REPOSITORIES: biostudies-literature
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Project description:BackgroundAnhedonia (a reduced experience of pleasure) and avolition (a reduction in goal-directed activity) are common features of schizophrenia that have substantial effects on functional outcome, but are poorly understood and treated. Here, we examined whether alterations in reinforcement learning may contribute to these symptoms in schizophrenia by impairing the translation of reward information into goal-directed action.Methods38 stable outpatients with schizophrenia or schizoaffective disorder and 37 healthy controls underwent fMRI during a probabilistic stimulus selection reinforcement learning task with dissociated choice- and feedback-related activation, followed by a behavioral transfer task allowing separate assessment of learning from positive versus negative outcomes. A Q-learning algorithm was used to examine functional activation relating to prediction error at the time of feedback and to expected value at the time of choice.ResultsBehavioral results suggested a reduction in learning from positive feedback in patients; however, this reduction was unrelated to anhedonia/avolition severity. On fMRI analysis, prediction error-related activation at the time of feedback was highly similar between patients and controls. During early learning, patients activated regions in the cognitive control network to a lesser extent than controls. Correlation analyses revealed reduced responses to positive feedback in dorsolateral prefrontal cortex and caudate among those patients higher in anhedonia/avolition.ConclusionsTogether, these results suggest that anhedonia/avolition are as strongly related to cortical learning or higher-level processes involved in goal-directed behavior such as effort computation and planning as to striatally mediated learning mechanisms.
| S-EPMC5098503 | biostudies-literature
Project description:ImportanceNegative symptoms have a detrimental impact on functional outcomes and quality of life in people with schizophrenia, and few therapeutic options are considered effective for this symptomatic dimension. Studies have suggested that noninvasive brain stimulation (NIBS) interventions may be effective in treating negative symptoms. However, the comparative efficacy of different NIBS protocols for relieving negative symptoms remains unclear.ObjectiveTo compare the efficacy and acceptability of different NIBS interventions for treating negative symptoms.Data sourcesThe ClinicalKey, Cochrane CENTRAL, Embase, ProQuest, PubMed, ScienceDirect, ClinicalTrials.gov, and Web of Science electronic databases were systematically searched from inception through December 7, 2021.Study selectionA frequentist model network meta-analysis was conducted to assess the pooled findings of trials that evaluated the efficacy of repetitive transcranial magnetic stimulation (rTMS), theta-burst stimulation, transcranial random noise stimulation, transcutaneous vagus nerve stimulation, and transcranial direct current stimulation on negative symptoms in schizophrenia. Randomized clinical trials (RCTs) examining NIBS interventions for participants with schizophrenia were included.Data extraction and synthesisThe Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. Data were independently extracted by multiple observers. The pair-wise meta-analytic procedures were conducted using a random-effects model.Main outcomes and measuresThe coprimary outcomes were changes in the severity of negative symptoms and acceptability (ie, dropout rates owing to any reason). Secondary outcomes were changes in positive and depressive symptoms.ResultsForty-eight RCTs involving 2211 participants (mean [range] age, 38.7 [24.0-57.0] years; mean [range] proportion of female patients, 30.6% [0%-70.0%]) were included. Compared with sham control interventions, excitatory NIBS strategies (standardized mean difference [SMD]: high-definition transcranial random noise stimulation, -2.19 [95% CI, -3.36 to -1.02]; intermittent theta-burst stimulation, -1.32 [95% CI, -1.88 to -0.76]; anodal transcranial direct current stimulation, -1.28 [95% CI, -2.55 to -0.02]; high-frequency rTMS, -0.43 [95% CI, -0.68 to -0.18]; extreme high-frequency rTMS, -0.45 [95% CI, -0.79 to -0.12]) over the left dorsolateral prefrontal cortex with or without other inhibitory stimulation protocols in the contralateral regions of the brain were associated with significantly larger reductions in negative symptoms. Acceptability did not significantly differ between the groups.Conclusions and relevanceIn this network meta-analysis, excitatory NIBS protocols over the left dorsolateral prefrontal cortex were associated with significantly large improvements in the severity of negative symptoms. Because relatively few studies were available for inclusion, additional well-designed, large-scale RCTs are warranted.
| S-EPMC9218931 | biostudies-literature
Project description:The negative symptoms have been described in association with schizophrenia since the early days of it being recognized as an entity. However, their elusive nature kept them unacknowledged until there was a revival of interest in them following the development of specific quantifying measures. Over the past three decades, there has been a tremendous surge in research on their types, measurements, status in the present classificatory system, and their implications. The developments in modern investigatory methods have provided the researchers with fresh insights into the underlying mechanisms, and a distributed functioning of the neuronal networks has emerged as the major abnormality. Accordingly, a variety of pharmacological and other treatment modalities have been developed which go beyond the traditional. Nevertheless, a lot remain unanswered. The present paper summarizes important concepts with regard to negative symptoms in schizophrenia.
| S-EPMC5479085 | biostudies-literature
Project description:Optimal noninvasive brain stimulation parameters for the treatment of negative symptoms of schizophrenia remain unclear. Here, we aimed to investigate the clinical and biological effects of intermittent theta burst transcranial magnetic stimulation (iTBS) in patients with treatment-resistant negative symptoms of schizophrenia (NCT00875498). In a randomized sham-controlled 2-arm study, 22 patients with schizophrenia and treatment-resistant negative symptoms received 20 sessions of either active (n = 12) or sham (n = 10) iTBS. Sessions were delivered twice a day on 10 consecutive working days. Negative symptom severity was assessed 5 times using the Scale for the Assessment of Negative Symptoms (SANS): before iTBS, after iTBS, and 1, 3, and 6 months after iTBS. As a secondary objective, we explored the acute effects of iTBS on functional connectivity of the left dorsolateral prefrontal cortex (DLPFC) using seed-based resting-state functional connectivity MRI (rsFC fMRI) images acquired before and after iTBS. Active iTBS over the left DLPFC significantly decreased negative symptoms severity compared to sham iTBS (F(3,60) = 3.321, p = 0.026). Post hoc analyses revealed that the difference between groups was significant 6 months after the end of stimulation sessions. Neuroimaging revealed an increase in rsFC between the left DLPFC and a brain region encompassing the right lateral occipital cortex and right angular gyrus and a right midbrain region that may encompass dopamine neuron cell bodies. Thus, iTBS over the left DLPFC can alleviate negative symptoms of schizophrenia. The effect might be driven by significant modulation of dopamine transmission.
| S-EPMC7880987 | biostudies-literature
Project description:ObjectiveSchizophrenia may be the result of a failure of the normal lateralization process of the brain. However, whole-brain asymmetry has not been assessed up to date. Here, we propose a novel measure of global brain asymmetry based on the Dice coefficient to quantify similarity between brain hemispheres.MethodGlobal gray and white matter asymmetry was calculated from high-resolution T1 structural images acquired from 24 patients with schizophrenia and 26 healthy controls, age- and sex-matched. Some of the analyses were replicated in a much larger sample (n = 759) obtained from open-access online databases.ResultsPatients with schizophrenia had more global gray matter asymmetry than controls. Additionally, increased gray matter asymmetry was associated with avolition, whereas the inverse relationship was found for anxiety at a trend level. These analyses were replicated in a larger sample and confirmed previous results.ConclusionOur findings suggest that global gray matter asymmetry is related to the concept of developmental stability and is a useful indicator of perturbations during neurodevelopment.
| S-EPMC5407086 | biostudies-literature
Project description:BackgroundCurrently there is no first-line treatment recommended for the negative symptoms of schizophrenia. Psychosocial and behavioural interventions are widely used to reduce the burden of negative symptoms. Meta-analytic studies have summarised the evidence for specific approaches but not compared evidence quality and benefit.AimTo review and evaluate the evidence from meta-analytic studies of psychosocial and behavioural interventions for the negative symptoms of schizophrenia.MethodA systematic literature search was undertaken to identify all meta-analyses evaluating psychosocial and behavioural interventions reporting on negative symptom outcomes in people with schizophrenia. Data on intervention, study characteristics, acceptability and outcome were extracted. Risk of bias was evaluated. Results were summarised descriptively, and evidence ranked on methodological quality.ResultsIn total, 31 systematic reviews met the inclusion criteria evaluating the efficacy of negative symptom interventions on 33 141 participants. Exercise interventions showed effect sizes (reduction in negative symptoms) ranging from -0.59 to -0.24 and psychological interventions ranging from -0.65 to -0.04. Attrition ranged between 12% to 32%. Across the studies considered heterogeneity varied substantially (range 0-100). Most of the reviews were of very low to low methodological quality. Methodological quality ranking suggested that the effect size for cognitive remediation and exercise therapy may be more robust compared with other approaches.ConclusionsMost of the interventions considered had a small-to-moderate effect size, good acceptability levels but very few had negative symptoms as the primary intervention target. To improve the confidence of these effect sizes being replicated in clinical settings future studies should minimise risk of bias.
| S-EPMC10331321 | biostudies-literature
Project description:Several trials have shown preliminary evidence for the efficacy of transcranial magnetic stimulation (TMS) as a treatment for negative symptoms in schizophrenia. Here, we synthesize this literature in a systematic review and quantitative meta-analysis of double-blind randomized controlled trials of TMS in patients with schizophrenia. Specifically, MEDLINE, EMBASE, Web of Science, and PsycINFO were searched for sham-controlled, randomized trials of TMS among patients with schizophrenia. The effect of TMS vs. sham on negative symptoms in each study was quantified by the standardized mean difference (SMD, Cohen's d) with 95% confidence intervals (95%CI) and pooled across studies using an inverse variance random effects model. We identified 57 studies with a total of 2633 participants that were included in the meta-analysis. The pooled analysis showed statistically significant superiority of TMS (SMD = 0.41, 95%CI: 0.26; 0.56, p-value < 0.001), corresponding to a number needed to treat of 5. Furthermore, stratified analyses suggested that TMS targeting the left dorsolateral prefrontal cortex and using a stimulation frequency >1 Hz was most efficacious. There was, however, substantial heterogeneity and high risk of bias among the included studies. In conclusion, TMS appears to be an efficacious treatment option for patients with schizophrenia suffering from negative symptoms, but the optimal TMS parameters are yet to be established.
| S-EPMC9261093 | biostudies-literature
Project description:ImportanceNegative 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.ObjectiveTo determine the efficacy and safety of tDCS vs sham as an add-on treatment for patients with schizophrenia and predominant negative symptoms.Design, setting, and participantsThe 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.InterventionsTen 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.Main outcomes and measuresChange in the PANSS negative symptoms subscale score at week 6 was the primary outcome. Patients were followed-up for an additional 6 weeks.ResultsOf 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).Conclusions and relevanceTranscranial direct current stimulation was effective and safe in ameliorating negative symptoms in patients with schizophrenia.Trial registrationClinicalTrials.gov identifier: NCT02535676.
| S-EPMC6802484 | biostudies-literature
Project description:BackgroundThe "Avolition-apathy" domain of the negative symptoms was found to include different symptoms by factor analytic studies on ratings derived by different scales. In particular, the relationship of anhedonia with this domain is controversial. Recently introduced negative symptom rating scales provide a better assessment of anhedonia, allowing the distinction of anticipatory and consummatory aspects, which might be related to different psychopathological dimensions. The study of associations with external validators, such as electrophysiological, brain imaging or cognitive indices, might shed further light on the status of anhedonia within the Avolition-apathy domain.ObjectivesWe used brain electrical microstates (MSs), which represent subsecond periods of quasi-stable scalp electrical field, associated with resting-state neural networks (and thus with global patterns of functional connectivity), to test whether the component symptoms of Avolition-apathy share the same correlates.MethodWe analyzed multichannel resting EEGs in 142 individuals with schizophrenia (SCZ) and in 64 healthy controls (HC), recruited within the add-on EEG study of the Italian Network for Research on Psychoses. Relative time contribution, duration and occurrence of four MS classes (MS-A/-B/-C/-D) were calculated. Group differences on MS parameters (contribution and duration) and their associations with negative symptom domains (assessed using the Brief Negative Symptoms Scale) were investigated.ResultsSCZ, in comparison to HC, showed increased contribution and duration of MS-C. The contribution of MS-A positively correlated with Avolition-apathy, but not with Expressive deficit. Within the Avolition-apathy domain, anticipatory anhedonia, avolition and asociality, but not consummatory anhedonia, showed the same correlations with MS-A contribution.ConclusionOur findings support the existence of distinct electrophysiological correlates of Avolition-apathy with respect to Expressive deficit, and lend support to the hypothesis that only the anticipatory component of anhedonia shares the same pathophysiological underpinnings of the Avolition-apathy domain.
| S-EPMC6128100 | biostudies-literature
Project description:ImportanceNegative symptoms are associated with a range of poor clinical outcomes, and currently available treatments generally do not produce a clinically meaningful response. Limited treatment progress may be owing in part to poor clarity regarding latent structure. Prior studies have inferred latent structure using exploratory factor analysis, which has led to the conclusion that there are 2 dimensions reflecting motivation and pleasure (MAP) and diminished expressivity (EXP) factors. However, whether these conclusions are statistically justified remains unclear because exploratory factor analysis does not test latent structure. Confirmatory factor analysis (CFA) is needed to test competing models regarding the latent structure of a construct.ObjectiveTo evaluate the fit of 4 models of the latent structure of negative symptoms in schizophrenia using CFA.Design, setting, and participantsThree cross-sectional studies were conducted on outpatients with schizophrenia who were rated on the 3 most conceptually contemporary measures: Scale for the Assessment of Negative Symptoms (SANS), Brief Negative Symptom Scale (BNSS), and Clinical Assessment Interview for Negative Symptoms (CAINS). Confirmatory factor analysis evaluated the following 4 models: (1) a 1-factor model; (2) a 2-factor model with EXP and MAP factors; (3) a 5-factor model with separate factors for the 5 domains of the National Institute of Mental Health consensus development conference (blunted affect, alogia, anhedonia, avolition, and asociality); and (4) a hierarchical model with 2 second-order factors reflecting EXP and MAP and 5 first-order factors reflecting the 5 consensus domains.Main outcomes and measuresOutcomes included CFA model fit statistics derived from symptom severity scores on the SANS, BNSS, and CAINS.ResultsThe study population included 860 outpatients with schizophrenia (68.0% male; mean [SD] age, 43.0 [11.4] years). Confirmatory factor analysis was conducted on each scale, including 268 patients for the SANS, 192 for the BNSS, and 400 for the CAINS. The 1- and 2-factor models provided poor fit for the SANS, BNSS, and CAINS as indicated by comparative fit indexes (CFIs) and Tucker Lewis indexes (TLIs) less than 0.950, RMSEAs that exceeded the 0.080 threshold, and WRMRs greater than 1.00. The 5-factor and hierarchical models provided excellent fit, with the 5-factor model being more parsimonious. The CFIs and TLIs met the 0.95 threshold and the 1.00 threshold for both factor models with all 3 measures. Interestingly, the RMSEAs for the 5-factor model and the hierarchical model fell under the 0.08 threshold for the BNSS and the CAINS but not the SANS.Conclusions and relevanceThese findings suggest that the recent trend toward conceptualizing the latent structure of negative symptoms as 2 distinct dimensions does not adequately capture the complexity of the construct. The latent structure of negative symptoms is best conceptualized in relation to the 5 consensus domains. Implications for identifying pathophysiological mechanisms and targeted treatments are discussed.
| S-EPMC6583036 | biostudies-literature