Effects of High-Frequency rTMS on Negative Symptoms and Cognitive Function in Hospitalized Patients With Chronic Schizophrenia: A Double-Blind, Sham-Controlled Pilot Trial

Chen, Lei; Miao, Xuemeng; Zhang, Min; Zhang, Yaoyao; Liu, Jie; Xu, Yao; Tong, Siyu; Tang, Wei; Wang, Mengpu; Liu, Jiahong; Zhou, Siyao; Fang, Xinyu; Zhao, Ke

doi:10.3389/fpsyt.2021.736094

Cited by 16 publications

(14 citation statements)

References 63 publications

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“…A recent 10-year follow-up study reported that schizophrenia patients with sustained negative symptoms could have a poorer cognitive function and a lower level of global functioning compared to patients with an early illness course characterized by the absence of negative symptoms ( 33 ). In addition, transcranial direct current stimulation (tDCS) or repetitive transcranial magnetic stimulation (rTMS) can ameliorate the negative symptoms and further improve cognitive function in schizophrenia patients ( 34 , 35 ). The greater extent of cognitive deficits among DS patients than among NDS patients found in our present study further supports the above causal relationship.…”

Section: Discussionmentioning

confidence: 99%

Differences in inflammatory marker profiles and cognitive functioning between deficit and nondeficit schizophrenia

Wang

Chen

et al. 2022

Front. Immunol.

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Deficit schizophrenia (DS) patient is a homogenous subtype of schizophrenia that includes primary and enduring negative symptoms. This study aimed to compare the differences in cognitive functioning and plasma levels of C-reactive protein (CRP) and inflammatory cytokines among DS patients, nondeficit schizophrenia (NDS) patients, and healthy controls (HCs). A total of 141 schizophrenia patients and 67 HCs were included in this study. The schizophrenia patients were divided into DS (N= 51) and NDS (N=90) groups based on the Proxy for the Deficit Syndrome Scale (PDS). The Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were used to evaluate the clinical symptoms and cognitive performances, respectively. The plasma level of CRP, IL-1β, Il-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, TNF-α, and IFN-γ were measured using enzyme-linked immunosorbent assays (ELISAs). Our results showed that DS patients had the worst cognitive performance, especially in the immediate memory, attention, and language dimensions, compared to the NDS and HC groups. Compared to the HCs group, DS patients had higher levels of CRP, IL-1β, IL-6, IL-8, IFN-γ, and total proinflammatory cytokines, and NDS patients had higher levels of IL-1β, IFN-γ, and proinflammatory cytokines. We also found that CRP levels were significantly increased in DS patients compared to NDS patients. Moreover, stepwise logistic regression analysis revealed that CRP is an independent risk factor for DS. Sex stratification analysis showed significant differences in almost all cytokines in female samples but not in male samples. The significant differences in cognitive performance and inflammatory components among groups suggest that deficit syndrome is an independent endophenotype of schizophrenia patients with unique immune-inflammatory features, but may have sex characteristics.

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Section: Discussionmentioning

confidence: 99%

Differences in inflammatory marker profiles and cognitive functioning between deficit and nondeficit schizophrenia

Wang

Chen

et al. 2022

Front. Immunol.

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“…B. Although with very high uncertainty, this safety analysis found no effect on positive symptoms (mean [SD] duration, 3.9 [2.0] weeks; 14 studies 53,59,71,[95][96][97][98]105,115,117,119,120,122,123 ; 909 participants; χ 2 = 0.05; df = 2; P = .98; I 2 = 75%). C. Although with very high uncertainty for high dose, a bell-shape curve was obtained (mean [SD] duration, of 1.7 [0.5] weeks; 5 studies 24,34,53,91,122 ; 159 participants; χ 2 = 36.52 df = 2; P < .001; I 2 = 95%).…”

Section: Current Depressive Episodementioning

confidence: 75%

“…We included 110 studies, encompassing a total of 4820 participants . The majority of participants were male (2959 [61.4%] compared with 1861 females [38.6%]), and the mean (SD) age was 43 (8.8) years.…”

Section: Resultsmentioning

confidence: 99%

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Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation Across Mental Disorders

Sabé,

Hyde,

Cramer

et al. 2024

JAMA Netw Open

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ImportanceNoninvasive brain stimulation (NIBS) interventions have been shown to be efficacious in several mental disorders, but the optimal dose stimulation parameters for each disorder are unknown.ObjectiveTo define NIBS dose stimulation parameters associated with the greatest efficacy in symptom improvement across mental disorders.Data SourcesStudies were drawn from an updated (to April 30, 2023) previous systematic review based on a search of PubMed, OVID, and Web of Knowledge.Study SelectionRandomized clinical trials were selected that tested transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) for any mental disorder in adults aged 18 years or older.Data Extraction and SynthesisTwo authors independently extracted the data. A 1-stage dose-response meta-analysis using a random-effects model was performed. Sensitivity analyses were conducted to test robustness of the findings. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.Main Outcomes and MeasuresThe main outcome was the near-maximal effective doses of total pulses received for TMS and total current dose in coulombs for tDCS.ResultsA total of 110 studies with 4820 participants (2659 men [61.4%]; mean [SD] age, 42.3 [8.8] years) were included. The following significant dose-response associations emerged with bell-shaped curves: (1) in schizophrenia, high-frequency (HF) TMS on the left dorsolateral prefrontal cortex (LDLPFC) for negative symptoms (χ2 = 9.35; df = 2; P = .009) and TMS on the left temporoparietal junction for resistant hallucinations (χ2 = 36.52; df = 2; P &lt; .001); (2) in depression, HF-DLPFC TMS (χ2 = 14.49; df = 2; P &lt; .001); (3) in treatment-resistant depression, LDLPFC tDCS (χ2 = 14.56; df = 2; P &lt; .001); and (4) in substance use disorder, LDLPFC tDCS (χ2 = 33.63; df = 2; P &lt; .001). The following significant dose-response associations emerged with plateaued or ascending curves: (1) in depression, low-frequency (LF) TMS on the right DLPFC (RDLPFC) with ascending curve (χ2 = 25.67; df = 2; P = .001); (2) for treatment-resistant depression, LF TMS on the bilateral DLPFC with ascending curve (χ2 = 5.86; df = 2; P = .004); (3) in obsessive-compulsive disorder, LF-RDLPFC TMS with ascending curve (χ2 = 20.65; df = 2; P &lt; .001) and LF TMS on the orbitofrontal cortex with a plateaued curve (χ2 = 15.19; df = 2; P &lt; .001); and (4) in posttraumatic stress disorder, LF-RDLPFC TMS with ascending curve (χ2 = 54.15; df = 2; P &lt; .001). Sensitivity analyses confirmed the main findings.Conclusions and RelevanceThe study findings suggest that NIBS yields specific outcomes based on dose parameters across various mental disorders and brain regions. Clinicians should consider these dose parameters when prescribing NIBS. Additional research is needed to prospectively validate the findings in randomized, sham-controlled trials and explore how other parameters contribute to the observed dose-response association.

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“…Numerous studies had reported similar benefits of high-frequency rTMS on negative symptoms in patients with schizophrenia. A double-blind, sham-controlled, high-frequency rTMS study demonstrated that the rTMS group showed effective amelioration of negative symptoms, indicating that rTMS may have potential benefits in improving clinical symptoms and cognitive functions in patients with chronic schizophrenia ( Wen et al, 2021 ). Moreover, a high-frequency (20 Hz) unilateral rTMS over the left DLPFC suggested that rTMS may lead to an improvement in the negative symptoms of schizophrenia ( Kumar et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Reconfiguration of Functional Dynamics in Cortico-Thalamo-Cerebellar Circuit in Schizophrenia Following High-Frequency Repeated Transcranial Magnetic Stimulation

Huang

Zhang

et al. 2022

Front. Hum. Neurosci.

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Schizophrenia is a serious mental illness characterized by a disconnection between brain regions. Transcranial magnetic stimulation is a non-invasive brain intervention technique that can be used as a new and safe treatment option for patients with schizophrenia with drug-refractory symptoms, such as negative symptoms and cognitive impairment. However, the therapeutic effects of transcranial magnetic stimulation remain unclear and would be investigated using non-invasive tools, such as functional connectivity (FC). A longitudinal design was adopted to investigate the alteration in FC dynamics using a dynamic functional connectivity (dFC) approach in patients with schizophrenia following high-frequency repeated transcranial magnetic stimulation (rTMS) with the target at the left dorsolateral prefrontal cortex (DLPFC). Two groups of schizophrenia inpatients were recruited. One group received a 4-week high-frequency rTMS together with antipsychotic drugs (TSZ, n = 27), while the other group only received antipsychotic drugs (DSZ, n = 26). Resting-state functional magnetic resonance imaging (fMRI) and psychiatric symptoms were obtained from the patients with schizophrenia twice at baseline (t1) and after 4-week treatment (t2). The dynamics was evaluated using voxel- and region-wise FC temporal variability resulting from fMRI data. The pattern classification technique was used to verify the clinical application value of FC temporal variability. For the voxel-wise FC temporary variability, the repeated measures ANCOVA analysis showed significant treatment × time interaction effects on the FC temporary variability between the left DLPFC and several regions, including the thalamus, cerebellum, precuneus, and precentral gyrus, which are mainly located within the cortico-thalamo-cerebellar circuit (CTCC). For the ROI-wise FC temporary variability, our results found a significant interaction effect on the FC among CTCC. rTMS intervention led to a reduced FC temporary variability. In addition, higher alteration in FC temporal variability between left DLPFC and right posterior parietal thalamus predicted a higher remission ratio of negative symptom scores, indicating that the decrease of FC temporal variability between the brain regions was associated with the remission of schizophrenia severity. The support vector regression (SVR) results suggested that the baseline pattern of FC temporary variability between the regions in CTCC could predict the efficacy of high-frequency rTMS intervention on negative symptoms in schizophrenia. These findings confirm the potential relationship between the reduction in whole-brain functional dynamics induced by high-frequency rTMS and the improvement in psychiatric scores, suggesting that high-frequency rTMS affects psychiatric symptoms by coordinating the heterogeneity of activity between the brain regions. Future studies would examine the clinical utility of using functional dynamics patterns between specific brain regions as a biomarker to predict the treatment response of high-frequency rTMS.

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Effects of High-Frequency rTMS on Negative Symptoms and Cognitive Function in Hospitalized Patients With Chronic Schizophrenia: A Double-Blind, Sham-Controlled Pilot Trial

Cited by 16 publications

References 63 publications

Differences in inflammatory marker profiles and cognitive functioning between deficit and nondeficit schizophrenia

Differences in inflammatory marker profiles and cognitive functioning between deficit and nondeficit schizophrenia

Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation Across Mental Disorders

Reconfiguration of Functional Dynamics in Cortico-Thalamo-Cerebellar Circuit in Schizophrenia Following High-Frequency Repeated Transcranial Magnetic Stimulation

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