Hostname: page-component-8448b6f56d-wq2xx Total loading time: 0 Render date: 2024-04-24T12:34:38.671Z Has data issue: false hasContentIssue false
  • English
  • Français

Structural brain plasticity and inflammation are independently related to changes in depressive symptoms six months after an index ECT course

Published online by Cambridge University Press:  05 January 2023

John O. Brooks III Open the ORCID record for John O. Brooks III [Opens in a new window] ,
Jennifer L. Kruse ,
Antoni Kubicki ,
Gerhard Hellemann ,
Randall T. Espinoza ,
Michael R. Irwin  and
Katherine L. Narr
John O. Brooks III*
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA
Jennifer L. Kruse
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA
Antoni Kubicki
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA Department of Neurology, Ahmanson-Lovelace Brain Mapping Center, Geffen School of Medicine at the University of California, Los Angeles, CA, USA
Gerhard Hellemann
Affiliation:
University of Alabama, Birmingham, AL, USA
Randall T. Espinoza
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA
Michael R. Irwin
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA
Katherine L. Narr
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA Department of Neurology, Ahmanson-Lovelace Brain Mapping Center, Geffen School of Medicine at the University of California, Los Angeles, CA, USA
*
Author for correspondence: John O. Brooks, E-mail: john.brooks@ucla.edu
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Electroconvulsive therapy (ECT) is effective for treatment-resistant depression and leads to short-term structural brain changes and decreases in the inflammatory response. However, little is known about how brain structure and inflammation relate to the heterogeneity of treatment response in the months following an index ECT course.

Methods

A naturalistic six-month study following an index ECT course included 20 subjects with treatment-resistant depression. Upon conclusion of the index ECT course and again after six months, structural magnetic resonance imaging scans and peripheral inflammation measures [interleukin-6 (IL-6), IL-8, tumor necrosis factor (TNF-α), and C-reactive protein] were obtained. Voxel-based morphometry processed with the CAT-12 Toolbox was used to estimate changes in gray matter volume.

Results

Between the end of the index ECT course and the end of follow-up, we found four clusters of significant decreases in gray matter volume (p < 0.01, FWE) and no regions of increased volume. Decreased HAM-D scores were significantly related only to reduced IL-8 level. Decreased volume in one cluster, which included the right insula and Brodmann's Area 22, was related to increased HAM-D scores over six months. IL-8 levels did not mediate or moderate the relationship between volumetric change and depression.

Conclusions

Six months after an index ECT course, multiple regions of decreased gray matter volume were observed in a naturalistic setting. The independent relations between brain volume and inflammation to depressive symptoms suggest novel explanations of the heterogeneity of longer-term ECT treatment response.

Keywords

DepressionECTimaginginflammationMRIneuroimaging
Type
Original Article
Information
Psychological Medicine , Volume 54 , Issue 1 , January 2024 , pp. 108 - 116
Check for updates
Copyright
Copyright © The Author(s), 2023. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Bahji, A., Hawken, E. R., Sepehry, A. A., Cabrera, C. A., & Vazquez, G. (2019). ECT beyond unipolar major depression: Systematic review and meta-analysis of electroconvulsive therapy in bipolar depression. Acta Psychiatrica Scandinavica, 139(3), 214–226. doi: 10.1111/acps.12994CrossRefGoogle ScholarPubMed
Baron, R. M., & Kenny, D. A. (1986). The moderator-mediator variable distinction in social psychological research: Conceptual, strategic, and statistical considerations. Journal of Personality and Social Psycholology, 51(6), 1173–1182. doi: 10.1037//0022-3514.51.6.1173CrossRefGoogle ScholarPubMed
Bauer, M., Pfennig, A., Severus, E., Whybrow, P. C., Angst, J., Moller, H. J., & World Federation of Societies of Biological Psychiatry. Task Force on Unipolar Depressive, D. (2013). World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders, part 1: Update 2013 on the acute and continuation treatment of unipolar depressive disorders. World Journal of Biological Psychiatry, 14(5), 334–385. doi: 10.3109/15622975.2013.804195CrossRefGoogle ScholarPubMed
Belge, J. B., van Diermen, L., Sabbe, B., Parizel, P., Morrens, M., Coppens, V., … van Eijndhoven, P. (2020). Inflammation, hippocampal volume, and therapeutic outcome following electroconvulsive therapy in depressive patients: A pilot study. Neuropsychobiology, 79(3), 222–232. doi: 10.1159/000506133CrossRefGoogle ScholarPubMed
Boyle, C. C., Cho, J. H., Eisenberger, N. I., Olmstead, R. E., Piber, D., Sadeghi, N., … Irwin, M. R. (2020). Motivation and sensitivity to monetary reward in late-life insomnia: Moderating role of sex and the inflammatory marker CRP. Neuropsychopharmacology, 45(10), 1664–1671. doi: 10.1038/s41386-020-0735-7CrossRefGoogle ScholarPubMed
Brancati, G. E., Brekke, N., Bartsch, H., Evjenth Sorhaug, O. J., Ousdal, O. T., Hammar, A., … Oltedal, L. (2021). Short and long-term effects of single and multiple sessions of electroconvulsive therapy on brain gray matter volumes. Brain Stimulation, 14(5), 1330–1339. doi: 10.1016/j.brs.2021.08.018CrossRefGoogle Scholar
Brooks, J. O. III, Bonner, J. C., Rosen, A. C., Wang, P. W., Hoblyn, J. C., Hill, S. J., & Ketter, T. A. (2009). Dorsolateral and dorsomedial prefrontal gray matter density changes associated with bipolar depression. Psychiatry Research: Neuroimaging, 172(3), 200–204. doi: 10.1016/j.pscychresns.2008.06.007CrossRefGoogle ScholarPubMed
Brooks, J. O. III, Foland-Ross, L. C., Thompson, P. M., & Altshuler, L. L. (2011). Preliminary evidence of within-subject changes in gray matter density associated with remission of bipolar depression. Psychiatry Research: Neuroimaging, 193(1), 53–55. doi: 10.1016/j.pscychresns.2010.12.012CrossRefGoogle ScholarPubMed
Camilleri, J. A., Hoffstaedter, F., Zavorotny, M., Zollner, R., Wolf, R. C., Thomann, P., … Nickl-Jockschat, T. (2020). Electroconvulsive therapy modulates grey matter increase in a hub of an affect processing network. Neuroimage. Clinical, 25, 102114. doi: 10.1016/j.nicl.2019.102114CrossRefGoogle Scholar
Carlier, A., Berkhof, J. G., Rozing, M., Bouckaert, F., Sienaert, P., Eikelenboom, P., … Exel, E. V. (2019). Inflammation and remission in older patients with depression treated with electroconvulsive therapy; findings from the MODECT study(). Journal of Affective Disorders, 256, 509–516. doi: 10.1016/j.jad.2019.06.040CrossRefGoogle ScholarPubMed
Cavaleri, D., & Bartoli, F. (2022). Biomolecular research on electroconvulsive therapy for mental disorders: State of the art and future directions. Alpha Psychiatry, 23(2), 57–58. https://doi.org/10.5152/alphapsychiatry.2022.0003.CrossRefGoogle ScholarPubMed
Dierckx, B., Heijnen, W. T., van den Broek, W. W., & Birkenhager, T. K. (2012). Efficacy of electroconvulsive therapy in bipolar versus unipolar major depression: A meta-analysis. Bipolar Disorders, 14(2), 146–150. doi: 10.1111/j.1399-5618.2012.00997.xCrossRefGoogle ScholarPubMed
Espinoza, R. T., & Kellner, C. H. (2022). Electroconvulsive therapy. New England Journal of Medicine, 386(7), 667–672. doi: 10.1056/NEJMra2034954CrossRefGoogle ScholarPubMed
Fava, M. (2003). Diagnosis and definition of treatment-resistant depression. Biological Psychiatry, 53(8), 649–659. doi: 10.1016/s0006-3223(03)00231-2CrossRefGoogle ScholarPubMed
Gaser, C., Dahnke, R., Kurth, K., Luders, E., & Initiative, A. S. D. N. (2021). A Computational Anatomy Toolbox for the Analysis of Structural MRI Data. Unpublished.Google Scholar
Gaynes, B. N., Lux, L., Gartlehner, G., Asher, G., Forman-Hoffman, V., Green, J., … Lohr, K. N. (2020). Defining treatment-resistant depression. Depression and Anxiety, 37(2), 134–145. doi: 10.1002/da.22968CrossRefGoogle ScholarPubMed
Gbyl, K., Rostrup, E., Raghava, J. M., Carlsen, J. F., Schmidt, L. S., Lindberg, U., … Videbech, P. (2019). Cortical thickness following electroconvulsive therapy in patients with depression: A longitudinal MRI study. Acta Psychiatrica Scandinavica, 140(3), 205–216. doi: 10.1111/acps.13068CrossRefGoogle ScholarPubMed
Gbyl, K., & Videbech, P. (2018). Electroconvulsive therapy increases brain volume in major depression: A systematic review and meta-analysis. Acta Psychiatrica Scandinavica, 138(3), 180–195. doi: 10.1111/acps.12884CrossRefGoogle ScholarPubMed
Gill, S. P., & Kellner, C. H. (2019). Clinical practice recommendations for continuation and maintenance electroconvulsive therapy for depression: Outcomes from a review of the evidence and a consensus workshop held in Australia in May 2017. The Journal of ECT, 35(1), 14–20. doi: 10.1097/YCT.0000000000000484CrossRefGoogle Scholar
Hamilton, M. (1960). A rating scale for depression. Journal of Neurology, Neurosurgery, and Psychiatry, 23(1), 56–62. doi: 10.1136/jnnp.23.1.56CrossRefGoogle ScholarPubMed
Haroon, E., Daguanno, A. W., Woolwine, B. J., Goldsmith, D. R., Baer, W. M., Wommack, E. C., … Miller, A. H. (2018). Antidepressant treatment resistance is associated with increased inflammatory markers in patients with major depressive disorder. Psychoneuroendocrinology, 95, 43–49. doi: 10.1016/j.psyneuen.2018.05.026CrossRefGoogle ScholarPubMed
Haroon, E., Fleischer, C. C., Felger, J. C., Chen, X., Woolwine, B. J., Patel, T., … Miller, A. H. (2016). Conceptual convergence: Increased inflammation is associated with increased basal ganglia glutamate in patients with major depression. Molecular Psychiatry, 21(10), 1351–1357. doi: 10.1038/mp.2015.206CrossRefGoogle ScholarPubMed
Howren, M. B., Lamkin, D. M., & Suls, J. (2009). Associations of depression with C-reactive protein, IL-1, and IL-6: A meta-analysis. Psychosomatic Medicine, 71(2), 171–186. doi: 10.1097/PSY.0b013e3181907c1bCrossRefGoogle ScholarPubMed
Irwin, M. R., Olmstead, R., Kruse, J., Breen, E. C., & Haque, R. (2022). Association of interleukin-8 and risk of incident and recurrent depression in long-term breast cancer survivors. Brain, Behavior, and Immunity, 105, 131–138. doi: 10.1016/j.bbi.2022.07.003CrossRefGoogle ScholarPubMed
Jehna, M., Wurm, W., Pinter, D., Vogel, K., Holl, A., Hofmann, P., … Enzinger, C. (2021). Do increases in deep grey matter volumes after electroconvulsive therapy persist in patients with major depression? A longitudinal MRI-study. Journal of Affective Disorders, 281, 908–917. doi: 10.1016/j.jad.2020.11.035CrossRefGoogle ScholarPubMed
Joshi, S. H., Espinoza, R. T., Pirnia, T., Shi, J., Wang, Y., Ayers, B., … Narr, K. L. (2016). Structural plasticity of the hippocampus and amygdala induced by electroconvulsive therapy in Major depression. Biological Psychiatry, 79(4), 282–292. doi: 10.1016/j.biopsych.2015.02.029CrossRefGoogle ScholarPubMed
Kaster, T. S., Vigod, S. N., Gomes, T., Sutradhar, R., Wijeysundera, D. N., & Blumberger, D. M. (2021). Risk of serious medical events in patients with depression treated with electroconvulsive therapy: A propensity score-matched, retrospective cohort study. The Lancet. Psychiatry, 8(8), 686–695. doi: 10.1016/S2215-0366(21)00168-1CrossRefGoogle ScholarPubMed
Kruse, J. L., Boyle, C. C., Olmstead, R., Breen, E. C., Tye, S. J., Eisenberger, N. I., & Irwin, M. R. (2022). Interleukin-8 and depressive responses to an inflammatory challenge: Secondary analysis of a randomized controlled trial. Scientific Reports, 12(1), 12627. doi: 10.1038/s41598-022-16364-3CrossRefGoogle Scholar
Kruse, J. L., Congdon, E., Olmstead, R., Njau, S., Breen, E. C., Narr, K. L., … Irwin, M. R. (2018). Inflammation and improvement of depression following electroconvulsive therapy in treatment-resistant depression. Journal of Clinical Psychiatry, 79, 2. doi: 10.4088/JCP.17m11597Google ScholarPubMed
Kruse, J. L., Olmstead, R., Hellemann, G., Breen, E. C., Tye, S. J., Brooks, J. O. III, … Irwin, M. R. (2021). Interleukin-8 and lower severity of depression in females, but not males, with treatment-resistant depression. Journal Psychiatric Research, 140, 350–356. doi: 10.1016/j.jpsychires.2021.06.009CrossRefGoogle Scholar
Kruse, J. L., Olmstead, R., Hellemann, G., Wade, B., Jiang, J., Vasavada, M. M., … Irwin, M. R. (2020). Inflammation and depression treatment response to electroconvulsive therapy: Sex-specific role of interleukin-8. Brain, Behavior, and Immunity, 89, 59–66. doi: 10.1016/j.bbi.2020.05.069CrossRefGoogle ScholarPubMed
Kubicki, A., Leaver, A. M., Vasavada, M., Njau, S., Wade, B., Joshi, S. H., … Narr, K. L. (2019). Variations in hippocampal white matter diffusivity differentiate response to electroconvulsive therapy in major depression. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 4(3), 300–309. doi: 10.1016/j.bpsc.2018.11.003Google ScholarPubMed
Leaver, A. M., Vasavada, M., Joshi, S. H., Wade, B., Woods, R. P., Espinoza, R., & Narr, K. L. (2019). Mechanisms of antidepressant response to electroconvulsive therapy studied with perfusion magnetic resonance imaging. Biological Psychiatry, 85(6), 466–476. doi: 10.1016/j.biopsych.2018.09.021CrossRefGoogle ScholarPubMed
Leaver, A. M., Vasavada, M., Kubicki, A., Wade, B., Loureiro, J., Hellemann, G., … Narr, K. L. (2021). Hippocampal subregions and networks linked with antidepressant response to electroconvulsive therapy. Molecular Psychiatry, 26, 4288–4299. doi: 10.1038/s41380-020-0666-z.CrossRefGoogle ScholarPubMed
Leonard, B. E. (2018). Inflammation and depression: A causal or coincidental link to the pathophysiology? Acta Neuropsychiatrica, 30(1), 1–16. doi: 10.1017/neu.2016.69CrossRefGoogle ScholarPubMed
Maldjian, J. A., Laurienti, P. J., Kraft, R. A., & Burdette, J. H. (2003). An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. Neuroimage, 19(3), 1233–1239. doi: 10.1016/s1053-8119(03)00169-1CrossRefGoogle ScholarPubMed
Mindt, S., Neumaier, M., Hoyer, C., Sartorius, A., & Kranaster, L. (2020). Cytokine-mediated cellular immune activation in electroconvulsive therapy: A CSF study in patients with treatment-resistant depression. World Journal of Biological Psychiatry, 21(2), 139–147. doi: 10.1080/15622975.2019.1618494CrossRefGoogle ScholarPubMed
Mulders, P. C. R., Llera, A., Beckmann, C. F., Vandenbulcke, M., Stek, M., Sienaert, P., … Tendolkar, I. (2020). Structural changes induced by electroconvulsive therapy are associated with clinical outcome. Brain Stimulation, 13(3), 696–704. doi: 10.1016/j.brs.2020.02.020CrossRefGoogle ScholarPubMed
Nordanskog, P., Larsson, M. R., Larsson, E. M., & Johanson, A. (2014). Hippocampal volume in relation to clinical and cognitive outcome after electroconvulsive therapy in depression. Acta Psychiatrica Scandinavica, 129(4), 303–311. doi: 10.1111/acps.12150CrossRefGoogle ScholarPubMed
Oltedal, L., Narr, K. L., Abbott, C., Anand, A., Argyelan, M., Bartsch, H., … Dale, A. M. (2018). Volume of the human hippocampus and clinical response following electroconvulsive therapy. Biological Psychiatry, 84(8), 574–581. doi: 10.1016/j.biopsych.2018.05.017CrossRefGoogle ScholarPubMed
Osimo, E. F., Pillinger, T., Rodriguez, I. M., Khandaker, G. M., Pariante, C. M., & Howes, O. D. (2020). Inflammatory markers in depression: A meta-analysis of mean differences and variability in 5166 patients and 5083 controls. Brain, Behavior, and Immunity, 87, 901–909. doi: 10.1016/j.bbi.2020.02.010CrossRefGoogle Scholar
Ousdal, O. T., Argyelan, M., Narr, K. L., Abbott, C., Wade, B., Vandenbulcke, & M., … Gemric, . (2020). Brain changes induced by electroconvulsive therapy are broadly distributed. Biological Psychiatry, 87(5), 451–461. doi: 10.1016/j.biopsych.2019.07.010CrossRefGoogle ScholarPubMed
Ousdal, O. T., Brancati, G. E., Kessler, U., Erchinger, V., Dale, A. M., Abbott, C., & Oltedal, L. (2021). The neurobiological effects of electroconvulsive therapy studied through magnetic resonance: What have we learned, and where do we go? Biological Psychiatry, in press. doi: 10.1016/j.biopsych.2021.05.023Google ScholarPubMed
Petralia, M. C., Mazzon, E., Fagone, P., Basile, M. S., Lenzo, V., Quattropani, M. C., … Nicoletti, F. (2020). The cytokine network in the pathogenesis of major depressive disorder. Close to translation? Autoimmunity Reviews, 19(5), 102504. doi: 10.1016/j.autrev.2020.102504CrossRefGoogle ScholarPubMed
Pirnia, T., Joshi, S. H., Leaver, A. M., Vasavada, M., Njau, S., Woods, R. P., … Narr, K. L. (2016). Electroconvulsive therapy and structural neuroplasticity in neocortical, limbic and paralimbic cortex. Translational Psychiatry, 6(6), e832. doi: 10.1038/tp.2016.102CrossRefGoogle ScholarPubMed
Qiu, H., Li, X., Zhao, W., Du, L., Huang, P., Fu, Y., … Luo, Q. (2016). Electroconvulsive therapy-induced brain structural and functional changes in major depressive disorders: A longitudinal study. Medical Science Monitor : International Medical Journal of Experimental and Clinical Research, 22, 4577–4586. doi: 10.12659/msm.898081CrossRefGoogle ScholarPubMed
Roman, M., & Irwin, M. R. (2020). Novel neuroimmunologic therapeutics in depression: A clinical perspective on what we know so far. Brain, Behavior, and Immunity, 83, 7–21. doi: 10.1016/j.bbi.2019.09.016CrossRefGoogle ScholarPubMed
Rush, A. J., Trivedi, M. H., Wisniewski, S. R., Nierenberg, A. A., Stewart, J. W., Warden, D., … Fava, M. (2006). Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: A STAR*D report. American Journal of Psychiatry, 163(11), 1905–1917. doi: 10.1176/ajp.2006.163.11.1905CrossRefGoogle ScholarPubMed
Sackeim, H. A. (2001). The definition and meaning of treatment-resistant depression. Journal of Clinical Psychiatry, 62(Suppl 16), 10–17. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/11480879, https://www.psychiatrist.com/read-pdf/4083/.Google ScholarPubMed
Sartorius, A., Demirakca, T., Bohringer, A., Clemm von Hohenberg, C., Aksay, S. S., Bumb, J. M., … Ende, G. (2016). Electroconvulsive therapy increases temporal gray matter volume and cortical thickness. European Neuropsychopharmacology, 26(3), 506–517. doi: 10.1016/j.euroneuro.2015.12.036CrossRefGoogle ScholarPubMed
Sartorius, A., Demirakca, T., Bohringer, A., Clemm von Hohenberg, C., Aksay, S. S., Bumb, J. M., … Ende, G. (2019). Electroconvulsive therapy induced gray matter increase is not necessarily correlated with clinical data in depressed patients. Brain Stimulation, 12(2), 335–343. doi: 10.1016/j.brs.2018.11.017CrossRefGoogle Scholar
Sheehan, D. V., Lecrubier, Y., Sheehan, K. H., Amorim, P., Janavs, J., Weiller, E., … Dunbar, G. C. (1998). The Mini-international neuropsychiatric interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. Journal of Clinical Psychiatry, 59(Suppl 20), 22–33.Google ScholarPubMed
Souery, D., Amsterdam, J., de Montigny, C., Lecrubier, Y., Montgomery, S., Lipp, O., … Mendlewicz, J. (1999). Treatment resistant depression: Methodological overview and operational criteria. European Neuropsychopharmacology, 9(1–2), 83–91. doi: 10.1016/s0924–977x(98)00004-2CrossRefGoogle ScholarPubMed
Stippl, A., Kirkgoze, F. N., Bajbouj, M., & Grimm, S. (2020). Differential effects of electroconvulsive therapy in the treatment of Major depressive disorder. Neuropsychobiology, 79(6), 408–416. doi: 10.1159/000505553CrossRefGoogle ScholarPubMed
Thirumangalakudi, L., Yin, L., Rao, H. V., & Grammas, P. (2007). IL-8 induces expression of matrix metalloproteinases, cell cycle and pro-apoptotic proteins, and cell death in cultured neurons. Journal of Alzheimers Disease, 11(3), 305–311. doi: 10.3233/jad-2007-11307CrossRefGoogle ScholarPubMed
Tisdall, M. D., Hess, A. T., Reuter, M., Meintjes, E. M., Fischl, B., & van der Kouwe, A. J. (2012). Volumetric navigators for prospective motion correction and selective reacquisition in neuroanatomical MRI. Magnetic Resonance in Medicine, 68(2), 389–399. doi: 10.1002/mrm.23228CrossRefGoogle ScholarPubMed
Wise, T., Radua, J., Via, E., Cardoner, N., Abe, O., Adams, T. M., … Arnone, D. (2017). Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: Evidence from voxel-based meta-analysis. Molecular Psychiatry, 22(10), 1455–1463. doi: 10.1038/mp.2016.72CrossRefGoogle ScholarPubMed
Yrondi, A., Sporer, M., Peran, P., Schmitt, L., Arbus, C., & Sauvaget, A. (2018). Electroconvulsive therapy, depression, the immune system and inflammation: A systematic review. Brain Stimulation, 11(1), 29–51. doi: 10.1016/j.brs.2017.10.013CrossRefGoogle ScholarPubMed
Yuksel, D., Engelen, J., Schuster, V., Dietsche, B., Konrad, C., Jansen, A., … Krug, A. (2018). Longitudinal brain volume changes in major depressive disorder. Journal of Neural Transmission, 125(10), 1433–1447. doi: 10.1007/s00702-018-1919-8CrossRefGoogle ScholarPubMed
Zhdanava, M., Pilon, D., Ghelerter, I., Chow, W., Joshi, K., Lefebvre, P., … Sheehan, J. J. (2021). The prevalence and national burden of treatment-resistant depression and major depressive disorder in the United States. Journal of Clinical Psychiatry, 82(2), 20m13699. doi: 10.4088/JCP.20m13699.Google ScholarPubMed
Supplementary material: File

Brooks et al. supplementary material

Brooks et al. supplementary material
Download Brooks et al. supplementary material(File)
File 14.4 KB