Lisoni Jacopo, Baldacci Giulia, Nibbio Gabriele, Zucchetti Andrea, Butti Lemmi Gigli Elena, Savorelli Arianna, Facchi Michele, Miotto Paola, Deste Giacomo, Barlati Stefano, Vita Antonio
Department of Mental Health and Addiction Services, ASST Spedali Civili of Brescia, Brescia, Italy.
Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
J Psychiatr Res. 2022 Nov;155:430-442. doi: 10.1016/j.jpsychires.2022.09.011. Epub 2022 Sep 21.
Negative symptoms (NS), conceived as Avolition-Apathy (AA) and Expressive Deficit (EXP) domains, and neurocognitive impairments represent unmet therapeutic needs for patients with schizophrenia. The present study investigated if bilateral bipolar-nonbalanced frontal transcranial Direct Current Stimulation (tDCS) could improve these psychopathological dimensions. This randomized, double-blind, sham-controlled study (active-tDCS versus sham-tDCS, both, n = 25) included 50 outpatients diagnosed with schizophrenia clinically stabilized. Patients received 20-min 2 mA active-tDCS or sham-tDCS (anode: left Dorsolateral Prefrontal Cortex; cathode: right orbitofrontal region). Primary outcomes included: PANSS-Negative subscale, Negative Factor (Neg-PANSS), AA and EXP domains; neurocognitive performance at Brief Assessment of Cognition in Schizophrenia. Secondary outcomes included: PANSS subscales and total score, Disorganized/Concrete (DiscC-PANSS) and Positive Factors, Clinical Global Impression (CGI) scores, clinical insight at Scale to Assess Unawareness of Mental Disorder (SUMD). Analysis of covariance (ANCOVA) was performed evaluating between-group changes over time. Significant improvements following active-tDCS were observed for all NS measures (all, p < 0.001; d > 0.8) and for working memory (p = 0.025, d = 0.31). Greater variations following to active treatment emerged also for PANSS-General Psychopathology subscale (p < 0.001; d = 0.54), PANSS total score (p < 0.001; d = 0.69), CGI indexes (all, p < 0.001; d > 0.6), DiscC-PANSS (p < 0.001; d = 0.80) and SUMD-general Unawareness index (p = 0.005; d = 0.15) but not for positive symptoms and others insight measures. Good safety/tolerability profiles were found. Bilateral bipolar-nonbalanced frontal-tDCS is a non-pharmacological approach in schizophrenia effectively improving NS, particularly the AA and EXP domains, probably acting by modulating dysfunctional cortical-subcortical networks. Preliminary results also suggest working memory improvements following tDCS. Further studies are needed to confirm the neurobiological basis of these results.
阴性症状（NS），被定义为意志缺乏-淡漠（AA）和表达缺陷（EXP）两个维度，以及神经认知障碍，是精神分裂症患者尚未得到满足的治疗需求。本研究调查了双侧双相非平衡额叶经颅直流电刺激（tDCS）是否能改善这些精神病理维度。这项随机、双盲、假对照研究（活性tDCS与假tDCS，每组n = 25）纳入了50名临床病情稳定的精神分裂症门诊患者。患者接受20分钟、2毫安的活性tDCS或假tDCS（阳极：左侧背外侧前额叶皮质；阴极：右侧眶额叶区域）。主要结局指标包括：阳性和阴性症状量表（PANSS）阴性分量表、阴性因子（Neg-PANSS）、AA和EXP维度；精神分裂症认知简短评估中的神经认知表现。次要结局指标包括：PANSS各分量表及总分、紊乱/具体（DiscC-PANSS）和阳性因子、临床总体印象（CGI）评分、精神障碍自知力评定量表（SUMD）中的临床自知力。采用协方差分析（ANCOVA）评估组间随时间的变化。活性tDCS治疗后，所有NS测量指标（均p < 0.001；d > 0.8）以及工作记忆（p = 0.025，d = 0.31）均有显著改善。活性治疗后，PANSS一般精神病理分量表（p < 0.001；d = 0.54）、PANSS总分（p < 0.001；d = 0.69）、CGI指数（均p < 0.001；d > 0.6）、DiscC-PANSS（p < 0.001；d = 0.80）和SUMD一般无自知力指数（p = 0.005；d = 0.15）也出现了更大的变化，但阳性症状和其他自知力测量指标未出现变化。研究发现该治疗具有良好的安全性/耐受性。双侧双相非平衡额叶tDCS是一种治疗精神分裂症的非药物方法，可有效改善NS，尤其是AA和EXP维度，可能是通过调节功能失调的皮质-皮质下网络发挥作用。初步结果还表明tDCS后工作记忆有所改善。需要进一步研究来证实这些结果的神经生物学基础。
