The Effects of Bimodal Anodal Transcranial Direct Current Stimulation Over Bilateral Prefrontal Cortex on Illness Severity, Insight, Functional Outcomes, Quality of Life, Neurocognition and Heart Rate Variability (HRV) in Schizophrenia
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Changes from baseline scores of Positive and Negative Syndrome Scale (PANSS) at the timepoint immediately after tDCS, at one month and three months after tDCS.
研究概览
简要总结
The study aimed to investigate the effects of bimodal anodal transcranial direct current stimulation (tDCS) over bilateral dorsolateral prefrontal cortex (DLPFC) on psychopathological symptoms, insight, psychosocial functioning, neurocognitive function and heart rate variability (HRV) in schizophrenia patients
详细描述
Transcranial direct current stimulation encompasses the induction of a relatively weak constant current flow through the cerebral cortex via scalp electrodes . Dependent on stimulation polarity, this results in a modulation of cortical excitability and spontaneous neural activity.The technique was established in the 1950s and 1960s primarily in animals. In these early studies it was shown that subthreshold DC stimulation increases spontaneous neuronal activity if the anode is placed above or within the cortex, while exposure to cathodal polarity results in reduced activity. This is caused by a subthreshold membrane depolarization by anodal and a hyperpolarization by cathodal stimulation. It was demonstrated in humans that the after-effects of tDCS depend on modifications of N-methyl-D-aspartate (NMDA) receptor-efficacy. The after-effects of tDCS are blocked by the NMDA receptor antagonist dextromethorphan, and prolonged by the partial NMDA receptor-agonist D-cycloserine. This tDCS polarity-dependent alteration of NMDA receptor function seems to be initiated by the respective membrane potential shift and probably by the accompanying cortical activity modification,because it is prevented by the sodium channel blocker carbamazepine. Intraneuronal calcium concentration also contributes, because calcium channel antagonists eliminate the excitability-enhancing after-effects of anodal tDCS. Recently, unimodal anodal tDCS over left dorsolateral prefrontal cortex (DLPFC) has been found to improve psychopathological symptoms, cognitive deficits and insight of schizophrenia and also strengthen cardiac autonomic function in healthy subjects. Further studies using bimodal anodal tDCS over bilateral dorsolateral prefrontal cortex (DLPFC) and prefrontal cortex are needed.
Study design: randomized double-blind, sham-controlled study design.
Participants: 60 patients having a diagnosis of schizophrenia or schizoaffective were randomly allocated to receive 20 minutes of active 2-mA tDCS or sham stimulation twice a day on 5 consecutive weekdays. These participants were assessed at baseline, after intervention and in a three-months follow-up.
Active or sham stimulation: The present study used bimodal anodal tDCS over bilateral dorsolateral prefrontal cortex (DLPFC) and prefrontal cortex. One anode was placed with the middle of the electrode over a point midway between International 10-20 electrode positions F3 and Fp1 (left dorsolateral prefrontal cortex and left prefrontal cortex). The other was located over a point midway between F4 and Fp2 (right dorsolateral prefrontal cortex and left prefrontal cortex). An extracephalic positions were used for the reference electrodes (cathodes) in order to avoid confounding effects from inhibitory cathodal effects at other cortical sites. The reference electrodes were placed on bilateral forearms.
Others: see Arms and Interventions, Eligibility Criteria or Outcome Measures.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
盲法说明
In sham stimulation, the current was turned on for 30 sec and then ramped down to 0 mA.
入排标准
- 年龄范围
- 20 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eligible participants aged 20-65 with DSM-IV-TR-defined schizophrenia or schizoaffective disorder.
- •Duration of illness ≧ 1 year.
- •Being on an adequate therapeutic dose of antipsychotics and clinically stable (nonacute phase of illness) but symptomatic for at least 4 weeks prior to enrolment as defined by Clinical Global Impression-Severity of Illness scale (CGI-S) score ≦ 4 (at both screening and baseline).
- •Agreement to participate in the study and provide the written informed consent.
排除标准
- •Having current psychiatric comorbidity or active substance use disorder, in exception to caffeine and/or tobacco.
- •Having history of seizures.
- •Having contraindications for tDCS, e.g., implanted brain medical devices or metal in the head.
- •Having history of intracranial neoplasms or surgery, or a history of severe head injuries or cerebrovascular diseases.
- •Pregnancy or breastfeeding at enrollment.
研究组 & 干预措施
Active tDCS
Direct current (DC) generated by a Eldith DC stimulator was bilaterally delivered through a pair of saline-soaked surface sponge electrodes (35 square centimeter). One anode was placed with the middle of the electrode over a point midway between International 10-20 electrode positions F3 and Fp1 (left dorsolateral prefrontal cortex and left prefrontal cortex). The other was located over a point midway between F4 and Fp2 (right dorsolateral prefrontal cortex and left prefrontal cortex). The reference electrodes were placed on bilateral forearms. Stimulation was applied at an intensity of 2 mA for 20 min, twice-daily on 5 consecutive weekdays. All patients in the active tDCS group were maintained on their antipsychotic medications throughout the study period.
干预措施: tDCS (Device)
Sham tDCS
In sham stimulation, the current was turned on for 30 sec and then ramped down to 0 mA. All patients in the sham tDCS group were maintained on their antipsychotic medications throughout the study period.
干预措施: tDCS (Device)
结局指标
主要结局
Changes from baseline scores of Positive and Negative Syndrome Scale (PANSS) at the timepoint immediately after tDCS, at one month and three months after tDCS.
时间窗: Three months
A clinician-administered rating scale to measure the severity of psychopathological symptoms of the patients with schizophrenia spectrum disorder. The patient is rated from 1 to 7 on 30 different symptom items. All items scores are summed up to yield a total PANSS score, which ranges from 30 to 210. A higher score indicates greater psychopathological symptom severity. Then, five main symptom dimension subscales of PANSS can be calculated from 26 of 30 items of PANSS: positive (5 items, score 5-35) , negative (8 items, score 8-56), grandiosity/excitement (4 items, score 4-28), disorganization (5 items, score 5-35), and depression (4 items, score 4-28).
次要结局
- Changes from baseline scores at Personal and Social Performance scale (PSP) at the timepoint immediately after tDCS, at one month and three months after tDCS.(Three months)
- Changes from baseline scores of the Global Assessment of Functioning (GAF) Scale of the DSM-IV at the timepoint immediately after tDCS, at one month and three months after tDCS.(Three months.)
- Changes from baseline scores of the Clinical Global Impression (CGI) rating scales at the timepoint immediately after tDCS, at one month and three months after tDCS.(Three months.)
- Changes from baseline scores of the self-reported version of the graphic personal and social performance scale (SRG-PSP) at the timepoint immediately after tDCS and at one month after tDCS.(One month.)
- Changes from baseline scores of the abbreviated version of the Scale to Assess Unawareness in Mental Disorder in schizophrenia (SUMD) at the timepoint immediately after tDCS, at one month and three months after tDCS.(Three months.)
- Changes from baseline scores of the Taiwanese version of the Beck Cognitive Insight Scale (BCIS) at the timepoint immediately after tDCS and at one month after tDCS.(One month.)
- Changes from baseline scores of the Taiwanese version of the Self-Appraisal of Illness Questionnaire (SAIQ) at the timepoint immediately after tDCS and at one month after tDCS.(One month.)
- Changes from baseline scores of the self-administered WHOQOL-BREF at the timepoint immediately after tDCS and at one month after tDCS.(One month.)
- Changes from baseline results of Digit span (forward and backward) at the timepoint immediately after tDCS and at one month after tDCS.(One month)
- Changes from baseline results of Finger tapping test at the timepoint immediately after tDCS and at one month after tDCS.(One month)
- Changes from baseline results of Continuous Performance (CPT, version 2.0) at the timepoint immediately after tDCS and at one month after tDCS.(One month)
- Changes from baseline results of Wisconsin Card Sorting Test (WCST) at the timepoint immediately after tDCS and at one month after tDCS.(One month.)
- Changes from baseline results of Trail Making Test (TMT) at the timepoint immediately after tDCS and at one month after tDCS.(One month.)
- Changes from baseline results of Tower of London test at the timepoint immediately after tDCS and at one month after tDCS.(One month.)
- Changes from baseline heart rate variability (HRV) at the timepoint immediately after tDCS and at one month after tDCS.(One month.)
- Changes from baseline scores of the Mini-Mental State Examination (MMSE) at the timepoint immediately after tDCS, at one month and three months after tDCS.(Three months.)
研究者
Hsin-An Chang, MD
Attending Psychiatrist, Department of Psychiatry, Principal Investigator, Assistant Professor
Tri-Service General Hospital