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Does the change in glutamate to GABA ratio correlate with change in depression severity? A randomized, double-blind clinical trial

Molecular Psychiatry volume 27, pages 3833–3841 (2022)Cite this article

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Abstract

Previous proton magnetic resonance spectroscopy (1H-MRS) studies suggest a perturbation in glutamate and/or GABA in Major Depressive Disorder (MDD). However, no studies examine the ratio of glutamate and glutamine (Glx) to GABA (Glx/GABA) as it relates to depressive symptoms, which may be more sensitive than either single metabolite. Using a within-subject design, we hypothesized that reduction in depressive symptoms correlates with reduction in Glx/GABA in the anterior cingulate cortex (ACC). The present trial is a randomized clinical trial that utilized 1H-MRS to examine Glx/GABA before and after 8 weeks of escitalopram or placebo. Participants completed the 17-item Hamilton Depression Rating Scale (HDRS17) and underwent magnetic resonance spectroscopy before and after treatment. Two GABA-edited MEGA-PRESS acquisitions were interleaved with a water unsuppressed reference scan. GABA and Glx were quantified from the average difference spectrum, with preprocessing using Gannet and spectral fitting using TARQUIN. Linear mixed models were utilized to evaluate relationships between change in HDRS17 and change in Glx/GABA using a univariate linear regression model, multiple linear regression incorporating treatment type as a covariate, and Bayes Factor (BF) hypothesis testing to examine strength of evidence. No significant relationship was detected between percent change in Glx, GABA, or Glx/GABA and percent change in HDRS17, regardless of treatment type. Further, MDD severity before/after treatment did not correlate with ACC Glx/GABA. In light of variable findings in the literature and lack of association in our investigation, future directions should include evaluating glutamate and glutamine individually to shed light on the underpinnings of MDD severity. Advancing Personalized Antidepressant Treatment Using PET/MRI, ClinicalTrials.gov, NCT02623205.

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Fig. 1: A sample 1H-MRS spectra (top) showing Glx and GABA (including macromolecules) peaks, acquired from the anterior cingulate cortex (ACC), with voxel size and location shown in the bottom panel in sagittal (left), coronal (middle), and axial (right) views.
Fig. 2: Concentrations (mM) of GABA (left) and Glx (right) as a function of depression (HDRS17) in the ACC.
Fig. 3: Percent change in HDRS17 as a function of % change in Glx (top) and GABA (bottom), n = 60 (placebo: n = 30, escitalopram: n = 30).
Fig. 4: Percent difference in HDRS17 as a function of % change in Glx/GABA, with outlier (top, n = 60; placebo n = 30, escitalopram n = 30) and without outlier (bottom, n = 59; placebo n = 29, escitalopram n = 30).

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References

  1. Brown V, Pecina M. Neuroimaging studies of antidepressant placebo effects: challenges and opportunities. Front Psychiatry. 2019;10:1–8.

    CAS  Google Scholar 

  2. Lener MS, Niciu MJ, Ballard ED, Park M, Park LT, Nugent AC et al. Glutamate and GABA systems in the pathophysiology of major depression and antidepressant response to ketamine. Biol Psychiatry. 2017;81:886–97.

    CAS  PubMed  Google Scholar 

  3. Brennan B, Admon R, Perriello C, LaFlamme E, Athey A, Pizzagalli D, et al. Acute change in anterior cingulate cortex GABA, but not glutamine/glutamate, mediates antidepressant response to citalopram. Psychiatry Res Neuroimaging. 2017;269:9–16.

    PubMed  Google Scholar 

  4. Sanacora G, Gueorguieva R, Epperson C, Wu Y, Appel M, Rothman D, et al. Subtype-specific alterations in gamma-aminobutyric acid and glutamate in patients with major depression. Arch Gen Psychiatry. 2004;61:705–13.

    CAS  PubMed  Google Scholar 

  5. Hashimoto K. The role of glutamate on the action of antidepressants. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35:1558–68.

    CAS  PubMed  Google Scholar 

  6. Bhagwagar Z, Wylezinska M, Jezzard P, Evans J, Boorman E, Matthews PM, et al. Low GABA concentrations in occipital cortex and anterior cingulate cortex in medication-free, recovered depressed patients. Int J Neuropsychopharm. 2008;15:39–47.

    Google Scholar 

  7. Gabbay V, Mao X, Klein RG, Ely BA, Babb JS, Panzner AM et al. Anterior cingulate cortex γ-aminobutyric acid in depressed adolescents: relationship to anhedonia. Arch Gen Psychiatry. 2012;69:139–49.

    CAS  PubMed  Google Scholar 

  8. Price RB, Shungu DC, Mao X, Nestadt P, Kelly C, Collins KA et al. Amino acid neurotransmitters assessed by 1h mrs: relationship to treatment resistance in major depressive disorder. Biol Psychiatry. 2009;65:792–800.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Abdallah C, Jackowski A, Sato JR, Mao X, Kang G, Cheema R, et al. Prefrontal cortical GABA abnormalities are associated with reduced hippocampal volume in major depressive disorder. Eur Neuropsychopharmacol. 2015;25:1082–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Sanacora G, Treccani G, Popoli M. Towards a glutamate hypothesis of depression: an emerging frontier of neuropsychopharmacology for mood disorders. Neuropharmacology. 2012;62:63–77.

    CAS  PubMed  Google Scholar 

  11. Luykx J, Laban K, van den Heuvel M, Boks M, Mandl R, Kahn R, et al. Region and state specific glutamate downregulation in major depressive disorder: a meta-analysis of (1)H-MRS findings. Neurosci Biobehav Rev. 2012;36:198–205.

    CAS  PubMed  Google Scholar 

  12. Sanacora G, Mason G, Rothman D, Behar K, Hyder F, Petroff O, et al. Reduced cortical gamma-aminobutyric acid levels in depressed patients determined by proton magnetic resonance spectroscopy. Arch Gen Psychiatry. 1999;56:1043–7.

  13. Yildiz-Yesiloglu AA,DP. Review of 1H magnetic resonance spectroscopy findings in major depressive disorder: a meta-analysis. Psychiatry Res Neuroimaging. 2006;147:1–28.

    CAS  Google Scholar 

  14. Gunduz-Bruce H, Silber C, Kaul I, Rothschild A, Riesenberg R, Sankoh A, et al. Trial of SAGE-217 in patients with major depressive disorder. N Engl J Med. 2019;381:903–11.

    CAS  PubMed  Google Scholar 

  15. Godfrey KE, Gardner AC, Kwon S, Chea W, Muthukumaraswamy SD. Differences in excitatory and inhibitory neurotransmitter levels between depressed patients and healthy controls: a systematic review and meta-analysis. J Psychiatr Res. 2018;105:33–44.

    PubMed  Google Scholar 

  16. Romeo BC W, Fossati P, Rotge J. Meta-analysis of central and peripheral γ-aminobutyric acid levels in patients with unipolar and bipolar depression. J Psychiatry Neurosci. 2018;43:58–66.

    Google Scholar 

  17. Abdallah C, Jiang L, DeFeyter H, Fasula M, Krystal J, Rothman D, et al. Glutamate metabolism in major depressive disorder. Am J Psychiatry. 2014;171:1320–7.

    PubMed  PubMed Central  Google Scholar 

  18. Meltzer-Brody S, Colquhoun H, Riesenberg R, Epperson C, Deligiannidis K, Rubinow D, et al. Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet. 2018;392:1058–70.

    CAS  PubMed  Google Scholar 

  19. Bhagwagar Z, Wylezinska M, Taylor M, Jezzard P, Matthews P, Cowen P. Increased brain GABA concentrations following acute administration of a selective serotonin reuptake inhibitor. Am J Psychiatry. 2004;161:368–70.

    PubMed  Google Scholar 

  20. Sanacora G, Mason G, Rothman D, Krystal J. Increased occipital cortex GABA concentrations in depressed patients after therapy with selective serotonin reuptake inhibitors. Am J Psychiatry. 2002;159:663–5.

    PubMed  Google Scholar 

  21. Levine J, Panchalingam K, Rapoport A, Gershon S, McClure R, Pettegrew J. Increased cerebrospinal fluid glutamine levels in depressed patients. Biol Psychiatry. 2000;47:586–93.

    CAS  PubMed  Google Scholar 

  22. Yuksel C, Ongur D. Magnetic resonance spectroscopy studies of glutamate-related abnormalities in mood disorders. Biol Psychiatry. 2010;68:785–94.

    PubMed  PubMed Central  Google Scholar 

  23. Dang YH, Ma XC, Zhang JC, Ren Q, Wu J, Gao CG, et al. Targeting of NMDA receptors in the treatment of major depression. Curr Pharm Des. 2014;20:5151–9.

    CAS  PubMed  Google Scholar 

  24. Kim Y, Na K. Role of glutamate receptors and glial cells in the pathophysiology of treatment-resistant depression. Prog Neuropsychopharmacol Biol Psychiatry. 2016;70:117–26.

    CAS  PubMed  Google Scholar 

  25. Kugaya A, Sanacora G, Verhoeff N, Fujita M, Mason GF, Seneca NM, et al. Cerebral benzodiazepine receptors in depressed patients measured with [123i]iomazenil SPECT. Biol Psychiatry. 2003;54:792–9.

    CAS  PubMed  Google Scholar 

  26. Godlewska B, Near J, Cowen P. Neurochemistry of major depression: a study using magnetic resonance spectroscopy. Psychopharmacology. 2015;232:501–7.

    CAS  PubMed  Google Scholar 

  27. Walter M, Henning A, Grimm S, Schulte R, Beck J, Dydak U, et al. The relationship between aberrant neuronal activation in the pregenual anterior cingulate, altered glutamatergic metabolism, and anhedonia in major depression. Arch Gen Psychiatry. 2009;66:478–86.

    CAS  PubMed  Google Scholar 

  28. Grimm S, Luborzewski A, Schubert F, Merkl A, Kronenberg G, Colla M, et al. Region-specific glutamate changes in patients with unipolar depression. J Psychiatr Res. 2009;46:1059–65.

    Google Scholar 

  29. Godlewska B, Masaki C, Sharpley A, Cowen P, Emir U. Brain glutamate in medication-free depressed patients: a proton MRS study at 7 Tesla. Psychol Med. 2018;48:1731–7.

    PubMed  Google Scholar 

  30. Abdallah C, Hannestad J, Mason G, Holmes S, DellaGioia N, Sanacora G, et al. Metabotropic glutamate receptor 5 and glutamate involvement in major depressive disorder: a multimodal imaging study. Biol Psychiatry. 2017;2:449–56.

    Google Scholar 

  31. Moriguchi S, Takamiya A, Noda Y, Horita N, Wada M, Tsugawa S et al. Glutamatergic neurometabolite levels in major depressive disorder: a systematic review and meta-analysis of proton magnetic resonance spectroscopy studies. Mol Psychiatry. 2019;24:952–64.

    CAS  PubMed  Google Scholar 

  32. Michael N, Erfurth A, Ohrmann P, Arolt V, Heindel W, Pfleiderer B. Metabolic changes within the left dorsolateral prefrontal cortex occurring with electroconvulsive therapy in patients with treatment resistant unipolar depression. Psychol Med. 2003;33:1277–84.

    CAS  PubMed  Google Scholar 

  33. Pfleiderer B, Michael N, Erfurth A, Ohrmann P, Hohmann U, Wolgast M, et al. Effective electroconvulsive therapy reverses glutamate/glutamine deficit in the left anterior cingulum of unipolar depressed patients. Psychiatry Res. 2003;122:185–92.

    CAS  PubMed  Google Scholar 

  34. Sanacora G, Mason G, Rothman D, Hyder F, Ciarcia J, Ostroff R, et al. Increased cortical GABA concentrations in depressed patients receiving ECT. Am J Psychiatry. 2003;160:577–9.

    PubMed  Google Scholar 

  35. Taylor MJ, Godlewska BR, Norbury R, Selvaraj S, Near J, Cowen PJ. Early increase in marker of neuronal integrity with antidepressant treatment of major depression: 1H-magnetic resonance spectroscopy of N-acetyl-aspartate. Int J Neuropsychopharmacol. 2012;15:1541–6.

    CAS  PubMed  Google Scholar 

  36. Sanacora G, Fenton L, Fasula M, Rothman D, Levin Y, Krystal J, et al. Cortical GABA concentrations in depressed patients receiving cognitive behavioral therapy. Biol Psychiatry. 2006;59:284–6.

    CAS  PubMed  Google Scholar 

  37. Abdallah C, Niciu M, Fenton L, Fasula M, Jiang L, Black A, et al. Decreased occipital cortical glutamate levels in response to successful cognitive behavioral therapy and pharmacotherapy for major depressive disorder. Psychother Psychosom. 2014;83:298–307.

    PubMed  Google Scholar 

  38. Legarreta MD, Sheth C, Prescot AP, Renshaw PF, McGlade EC, & Yurgelun-Todd DA. An exploratory proton MRS examination of gamma-aminobutyric acid, glutamate, and glutamine and their relationship to affective aspects of chronic pain. Neurosci Res. 2021;163:10–7.

  39. Levar N, van Leeuwen JMC, Denys D, van Wingen GA. Divergent influences of anterior cingulate cortex GABA concentrations on the emotion circuitry. NeuroImage. 2017;158:136–44.

    CAS  PubMed  Google Scholar 

  40. Horn D, Yu C, Steiner J, Buchmann J, Kaufmann J, Osoba A, et al. Glutamatergic and resting-state functional connectivity correlates of severity in major depression—the role of pregenual anterior cingulate cortex and anterior insula. Front Syst Neurosci. 2010;4:1–10.

    Google Scholar 

  41. Northoff GS E. Why are cortical GABA neurons relevant to internal focus in depression? A cross-level model linking cellular, biochemical, and neural network findings. Mol Psychiatry. 2014;19:966–77.

    Google Scholar 

  42. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56–62.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. First MB, Spitzer RL, Miriam G, Williams JBW. Structured clinical interview for DSM-IV-TR axis I disorders, research version, Patient Edition, (SCID-I/P). (Biometric Research Department, New York State Psychiatric Institute: New York, 2002).

  44. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382–9.

    CAS  PubMed  Google Scholar 

  45. Fournier JC, DeRubeis RJ, Hollon SD, Dimidjian S, Amsterdam JD, Shelton RC, et al. Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA. 2010;303:47–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Landin R, DeBrota DJ, DeVries TA, Potter WZ, Demitrack MA. The impact of restrictive entry criterion during the placebo lead-in period. Biometrics. 2000;56:271–8.

    CAS  PubMed  Google Scholar 

  47. Hill KR, Gardus JD, Bartlett EA, Perlman G, Parsey RV, DeLorenzo C. Measuring brain glucose metabolism in order to predict response to antidepressant or placebo: a randomized clinical trial. Neuroimage Clin. 2021;32:102858.

    PubMed  PubMed Central  Google Scholar 

  48. Lin A, Andronesi O, Bogner W, Choi IY, Coello E, Cudalbu C, et al. Minimum reporting standards for in vivo magnetic resonance spectroscopy (MRSinMRS): experts’ consensus recommendations. NMR Biomed. 2021;34:e4484.

    PubMed  PubMed Central  Google Scholar 

  49. Kreis R. The trouble with quality filtering based on relative Cramér‐Rao lower bounds. Magn Reson Med. 2016;75:15–18.

    PubMed  Google Scholar 

  50. Landheer K, Juchem C. Are Cramér‐Rao lower bounds an accurate estimate for standard deviations in in vivo magnetic resonance spectroscopy? NMR Biomed. 2021;34:e4521.

    CAS  PubMed  Google Scholar 

  51. Mescher M, Merkle H, Kirsch J, Garwood M, Gruetter R. Simultaneous in vivo spectral editing and water suppression. NMR Biomed. 1998;11:266–72.

    CAS  PubMed  Google Scholar 

  52. Saleh MG, Edden RAE, Chang L, Ernst T. Motion correction in magnetic resonance spectroscopy. Magn Reson Med. 2020;84:2312–26.

    PubMed  PubMed Central  Google Scholar 

  53. Harris AD, Puts NA, Edden RA. Tissue correction for GABA-edited MRS: considerations of voxel composition, tissue segmentation, and tissue relaxations. J Magn Reson Imaging. 2015;42:1431–40.

    PubMed  PubMed Central  Google Scholar 

  54. Harris AD, Nicolaas AJP, Edden RAE. Tissue correction for GABA‐edited MRS: considerations of voxel composition, tissue segmentation, and tissue relaxations. J Magn Reson Imaging. 2015;42:1431–40.

    PubMed  PubMed Central  Google Scholar 

  55. Edden RA, Puts NA, Harris AD, Barker PB, Evans CJ. Gannet: a batch-processing tool for the quantitative analysis of gamma-aminobutyric acid-edited MR spectroscopy spectra. J Magn Reson Imaging. 2014;40:1445–52.

    PubMed  Google Scholar 

  56. Klose U. In vivo proton spectroscopy in presence of eddy currents. Magn Reson Med. 1990;14:26–30.

    CAS  PubMed  Google Scholar 

  57. Near J, Edden R, Evans CJ, Paquin R, Harris A, Jezzard P. Frequency and phase drift correction of magnetic resonance spectroscopy data by spectral registration in the time domain. Magn Reson Med. 2015;73:44–50.

    PubMed  Google Scholar 

  58. Wilson M, Reynolds G, Kauppinen RA, Arvanitis TN, Peet AC. A constrained least-squares approach to the automated quantitation of in vivo (1)H magnetic resonance spectroscopy data. Magn Reson Med. 2011;65:1–12.

    CAS  PubMed  Google Scholar 

  59. Keysers C, Gazzola V, Wagenmakers E. Using Bayes factor hypothesis testing in neuroscience to establish evidence of absence. Nat Neurosci. 2020;23:788–99.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Colloca L, Barsky A. Placebo and nocebo effects. N Engl J Med. 2020;382:554–61.

    CAS  PubMed  Google Scholar 

  61. Whiteford HA, Harris MG, McKeon G, Baxter A, Pennell C, Barendregt JJ, et al. Estimating remission from untreated major depression: a systematic review and meta-analysis. Psychol Med. 2013;43:1569–85.

    CAS  PubMed  Google Scholar 

  62. Yang J, Zhang M, Ahn H, Zhang Q, Jin T, Li I, et al. Development and evaluation of a multimodal marker of major depressive disorder. Hum Brain Mapp. 2018;39:4420–39.

    PubMed  PubMed Central  Google Scholar 

  63. Draganov M, Vives-Gilabert Y, Diego-Adelino J, Vicent-Gil M, Puigdemont D, Portella M. Glutamatergic and GABA-ergic abnormalities in First-episode depression. A 1-year follow-up 1H-MR spectroscopic study. J Affect Disord. 2020;266:572–7.

    CAS  PubMed  Google Scholar 

  64. Njau S, Joshi S, Espinoza R, Leaver A, Vasavada M, Marquina A, et al. Neurochemical correlates of rapid treatment response to electroconvulsive therapy in patients with major depression. J Psychiatr Neurosci. 2017;42:6–16.

    Google Scholar 

  65. Colic L, von During F, Denzel D, Demenescu LR, Lord AR, Martens L, et al. Rostral anterior cingulate glutamine/glutamate disbalance in major depressive disorder depends on symptom severity. Biol Psychiatry Cogn Neurosci Neuroimaging. 2019;4:1049–58.

    PubMed  Google Scholar 

  66. Yang J, Shen J. In vivo evidence for reduced cortical glutamate-glutamine cycling in rats treated with the antidepressant/antipanic drug phenelzine. Neuroscience. 2005;135:927–37.

    CAS  PubMed  Google Scholar 

  67. Taylor MJ, Mannie Z, Norbury R, Near J, Cowen P. Elevated cortical glutamate in young people at increased familial risk of depression. Int J Neuropsychopharmacol. 2011;14:255–9.

    CAS  PubMed  Google Scholar 

  68. Bobo WV, Angleró GC, Jenkins G, Hall-Flavin DK, Weinshilboum R, Biernacka JM. Validation of the 17-item Hamilton Depression Rating Scale definition of response for adults with major depressive disorder using equipercentile linking to Clinical Global Impression scale ratings: analysis of Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) data. Hum Psychopharmacol. 2016;31:185–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Bespalov A, Steckler T, Skolnick P. Be positive about negatives-recommendations for the publication of negative (or null) results. Eur Neuropsychopharmacol. 2019;29:1312–20.

    CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to thank the Biostatistical Consulting Core at the Stony Brook University Renaissance School of Medicine, and the clinical team who coordinated participant screening and symptom scale rating: Greg Perlman, Juhayer Alam, Kate Bartolotta, Dr. Yashar Yousefzadeh-Fard, Michala Godstrey, Qurat-ul-ain Gulamhussein, Nichole Hoehn, Dan Holzmacher, Dr. Sridhar Kadiyala, Colleen Oliva, Nehal Vadhan, Jennifer Rubinstein, Dr. Laura Kunkel, and Dr. Lucian Manu. This study (ID # 570152) was approved by the IRB (3/20/2015–12/21/2021).

Funding

This study is funded by NIMH (National Institute of Mental Health) R01MH104512, Brain & Behavior Research Foundation, The Dana Foundation, and NYS Faculty Development Grant.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Health, Stony Brook University, Stony Brook, NY, USA

    G. Anjali Narayan, Kathryn R. Hill, Ramin V. Parsey & Christine DeLorenzo

  2. Department of Psychiatry, Columbia University and New York State Psychiatric Institute, New York, NY, USA

    Kenneth Wengler & Christine DeLorenzo

  3. Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA

    Kenneth Wengler & Christine DeLorenzo

  4. Department of Radiology, North Shore University Hospital, Manhasset, NY, USA

    Xiang He

  5. Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, USA

    Junying Wang

  6. Department of Preventive Medicine, Stony Brook University, Stony Brook, NY, USA

    Jie Yang

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Contributions

CD and RVP designed the study and completed data collection. KW, XH, JW, and JY analyzed the data. GAN, KRH, and CD interpreted data and drafted the manuscript. All authors reviewed and edited the manuscript.

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Correspondence to G. Anjali Narayan.

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GAN has no financial disclosures or conflicts of interest to declare. KRH has no financial disclosures or conflicts of interest to declare. XH has no financial disclosures or conflicts of interest to declare. KW has no financial disclosures or conflicts of interest to declare. JY has no financial disclosures or conflicts of interest to declare. JW has no financial disclosures or conflicts of interest to declare. RVP has no financial disclosures or conflicts of interest to declare. CD has no financial disclosures or conflicts of interest to declare.

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Narayan, G.A., Hill, K.R., Wengler, K. et al. Does the change in glutamate to GABA ratio correlate with change in depression severity? A randomized, double-blind clinical trial. Mol Psychiatry 27, 3833–3841 (2022). https://doi.org/10.1038/s41380-022-01730-4

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