Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2021 Apr;6(4):449-458. doi: 10.1016/j.bpsc.2020.11.011. Epub 2020 Nov 28.
There are currently no approved treatments for working memory deficits in schizophrenia spectrum disorders (SSDs). The objective of the present study was to assess whether repetitive transcranial magnetic stimulation (rTMS) to the bilateral dorsolateral prefrontal cortex (DLPFC) in people with SSDs 1) improves working memory deficits and 2) changes brain structure.
We conducted a double-blind, parallel, randomized, sham-controlled study at the Centre for Addiction and Mental Health in Toronto, Canada. We randomized 83 participants with SSDs to receive either active 20 Hz rTMS applied to the bilateral DLPFC or sham rTMS for 4 weeks. The participants also completed pre/posttreatment magnetic resonance imaging. Clinical and cognitive assessments were performed at baseline, treatment end, and 1 month later. The primary outcome was change in verbal n-back working memory performance accuracy (d-prime). The secondary outcome measures were change in DLPFC thickness and fractional anisotropy of white matter tracts connecting to the DLPFC. Prespecified exploratory outcome measures were changes in general cognition; positive, negative, and depressive symptoms.
Compared with sham treatment, active rTMS did not lead to significant change in working memory performance; it was associated with an increase in right DLPFC thickness but not fractional anisotropy. Prespecified exploratory analysis showed a significant decrease in depressive symptoms in the active group; the decrease in depressive symptoms was correlated with an increase in right DLPFC thickness.
Although rTMS applied to the bilateral DLPFC was not efficacious in treating working memory deficits in SSDs, it did increase right DLPFC thickness and decrease depressive symptoms. These findings deserve further study given the lack of efficacy of antidepressant medications in SSDs.
目前，精神分裂症谱系障碍（SSDs）患者的工作记忆缺陷尚无获批的治疗方法。本研究旨在评估经颅重复磁刺激（rTMS）双侧背外侧前额叶皮质（DLPFC）是否：1）改善工作记忆缺陷，以及 2）改变大脑结构。
我们在加拿大多伦多的成瘾和心理健康中心开展了一项双盲、平行、随机、假刺激对照研究。我们将 83 名 SSD 患者随机分为接受双侧 DLPFC 20 Hz rTMS 或假刺激治疗 4 周的两组。参与者还完成了治疗前后的磁共振成像。在基线、治疗结束时和 1 个月后进行临床和认知评估。主要结局是言语 n-back 工作记忆表现准确性（d-prime）的变化。次要结局指标为 DLPFC 厚度和连接 DLPFC 的白质束分数各向异性的变化。预设的探索性结局指标为一般认知、阳性、阴性和抑郁症状的变化。
与假刺激治疗相比，rTMS 治疗并未导致工作记忆表现显著改善；它与右侧 DLPFC 厚度增加有关，但与白质束分数各向异性无关。预设的探索性分析显示，rTMS 治疗组的抑郁症状显著下降；抑郁症状的下降与右侧 DLPFC 厚度增加相关。
尽管双侧 DLPFC 的 rTMS 治疗对 SSD 患者的工作记忆缺陷无效，但确实增加了右侧 DLPFC 的厚度并降低了抑郁症状。鉴于抗抑郁药在 SSD 中疗效不佳，这些发现值得进一步研究。
