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White matter predicts tDCS antidepressant effects in a sham-controlled clinical trial study

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Abstract

Transcranial direct current stimulation (tDCS) has been used as treatment for depression, but its effects are heterogeneous. We investigated, in a subsample of the clinical trial Escitalopram versus Electrical Direct Current Therapy for Depression Study (ELECTTDCS), whether white matter areas associated with depression disorder were associated with tDCS response. Baseline diffusion tensor imaging data were analyzed from 49 patients (34 females, mean age 41.9) randomized to escitalopram 20 mg/day, tDCS (2 mA, 30 min, 22 sessions), or placebo. Antidepressant outcomes were assessed by Hamilton Depression Rating Scale-17 (HDRS) after 10-week treatment. We used whole-brain tractography for extracting white matter measures for anterior corpus callosum, and bilaterally for cingulum bundle, striato-frontal, inferior occipito-frontal fasciculus and uncinate. For the rostral body, tDCS group showed higher MD associated with antidepressant effects (estimate = −5.13 ± 1.64, p = 0.002), and tDCS significantly differed from the placebo and the escitalopram group. The left striato-frontal tract showed higher FA associated with antidepressant effects (estimate = −2.14 ± 0.72, p = 0.003), and tDCS differed only from the placebo group. For the right uncinate, the tDCS group lower AD values were associated with higher HDRS decrease (estimate = −1.45 ± 0.67, p = 0.031). Abnormalities in white matter MDD-related areas are associated with tDCS antidepressant effects. Suggested better white matter microstructure of the left prefrontal cortex was associated with tDCS antidepressant effects. Future studies should investigate whether these findings are driven by electric field diffusion and density in these areas.

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Abbreviations

DTI:

Diffusion tensor imaging

ELECT-TDCS:

Escitalopram versus electrical current therapy for treating depression clinical study

FA:

Fractional anisotropy

HDRS-17:

Hamilton depression rating scale

MDD:

Major depressive disorder

MRI:

Magnetic resonance imaging

tDCS:

Transcranial direct current stimulation

WM:

White matter

MD:

Mean diffusivity

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Acknowledgements

This study was primarily supported by a FAPESP grant (2012/20911-5). ARB is a recipient of a UK Newton Advanced Fellow (2020–2022)—Oxford University and FAPESP grant (2019/06009-6); TZ and MSL are recipient of FAPESP grants (2020/03235-2 and 2021/10574-0, respectively).

Funding

ELECT-TDCS funding: Sao Paulo Research State Foundation (FAPESP) and others. Registration: ClinicalTrials.gov NCT01894815.

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Authors and Affiliations

  1. Department of Internal Medicine, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

    Tamires A. Zanao, Matthias S. Luethi, Paulo Suen & Andre R. Brunoni

  2. Department and Institute of Psychiatry, Faculdade de Medicina da Universidade de São Paulo, Laboratory of Neurosciences LIM-27), São Paulo, Brazil

    Stephan Goerigk

  3. Department of Psychological Methodology and Assessment, LMU Munich, Munich, Germany

    Stephan Goerigk

  4. Hochschule Fresenius, University of Applied Sciences, Munich, Germany

    Alexandre P. Diaz & Jair C. Soares

  5. Hospital Universitário, Departamento de Clínica Médica, Faculdade de Medicina da USP, São Paulo, Brazil

    Andre R. Brunoni

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  1. Tamires A. Zanao
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Zanao, T.A., Luethi, M.S., Goerigk, S. et al. White matter predicts tDCS antidepressant effects in a sham-controlled clinical trial study. Eur Arch Psychiatry Clin Neurosci 273, 1421–1431 (2023). https://doi.org/10.1007/s00406-022-01504-7

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