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Cited by 7Functional Brain Connectivity StudiesTreatment of Major DepressionTranscranial Magnetic Stimulation Studies

A Treatment-Response Comparison Study of Resting-State Functional Magnetic Resonance Imaging Between Standard Treatment of SSRI and Standard Treatment of SSRI Plus Non-dominant Hand-Writing Task in Patients With Major Depressive Disorder

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Boyraz, Rabia Kevser, Kirpinar, Ismet, Yilmaz, Onur, Özyurt, Onur, Kiliçarslan, Tezer, Aralasmak, Ayse·2021·Frontiers in Psychiatry
DOI 10.3389/fpsyt.2021.698954PMC PMC8446543
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Abstract

Background: Researches have recently shifted from functional/structural imaging studies to functional connectivity (FC) studies in major depressive disorder (MDD). We aimed to compare treatment response of two treatment groups before and after treatment, in terms of both with psychiatric evaluation scales and resting-state functional connectivity (RSFC) changes in order to objectively demonstrate the possible contribution of the non-dominant hand-writing exercise (NHE) effect on depression treatment. Methods: A total of 26 patients who were right-handed women with similar sociodemographic characteristics were enrolled. Their pre-treatment resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychiatric tests were recorded, and then, patients were divided into two groups randomly. A standard treatment (ST) (fix sertraline 50 mg/day) was given to both groups. One randomly selected group was given the NHE in addition to the ST. After 8 weeks of treatment, all patients were reevaluated with rs-fMRI and neuropsychiatric tests. Pre- and post-treatment FC changes within the groups and post-treatment connectivity changes between groups were evaluated. Results: Post-treatment neuropsychiatric tests were significantly different in both groups. Post-treatment, two brain regions' connectivity changed in the ST group, whereas 10 brain regions' connectivity changed significantly in the ST + NHE group. When treatment groups were compared with each other after the treatment, the FC of 13 regions changed in the ST + NHE group compared to the ST group (p-unc/p-PFD <0.05). The density of connectivity changes in the frontal and limbic regions, especially connectivities shown to change in depression treatment, in the ST + NHE group indicates a positive contribution to depression treatment, which is also supported by neuropsychiatric scale changes. Conclusion: NHE, which we developed with inspiration from the Eye Movement Desensitization and Reprocessing (EMDR) method, showed significantly more connecitivity changes related with MDD treatment. Beyond offering a new additional treatment method, our study will also contribute to the current literature with our efforts to evaluate all brain regions and networks that may be related to MDD and its treatment together, without being limited to a few regions. Trial Registration: The rs-fMRI and treatment registers were recorded in the BizMed system, which is the patient registration system of Bezmialem Vakif University Medicine Faculty, under the BAP support project approval code and the registration number 3.2018/8.

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  • For young children, learning to write by hand has been linked to improved letter recognition and reading fluency.

    “For young children, learning to write by hand has been linked to improved letter recognition and reading fluency, emphasizing its role in building foundational literacy skills [37].”

    From The Neuroscience Behind Writing: Handwriting vs. Typing—Who Wins the Battle? (2025) · cites this paper as [37]

    The Materials and Methods section describes a non-dominant-hand writing task for patients with major depressive disorder, while the Introduction frames it as a potential depression treatment. Searches for young children, letter recognition, reading fluency, and literacy found no passage addressing the claimed link. (LLM, conf=0.76)

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  1. [1]Kenny ER O'brien JT Cousins DA Richardson J Thomas AJ Firbank MJ. Functional connectivity in late-life depression using resting-state functional magnetic resonance imaging. Am J Geriatr Psychiatry. (2010) 18: 643– 51. 10.1097/JGP.0b013e3181cabd0e 20220591 · DOI
  2. [2]Wang L Hermens D Hickie I Lagopoulos J. A systematic review of resting-state functional-MRI studies in major depression. J Affect Disord. (2012) 142: 6– 12. 10.1016/j.jad.2012.04.013 22858266 · DOI
  3. [3]Posner J Hellerstein DJ Gat I Mechling A Klahr K Wang Z. Antidepressants normalize the default mode network in patients with dysthymia. JAMA Psychiatry. (2013) 70: 373– 82. 10.1001/jamapsychiatry.2013.455 23389382 PMC3935731 · DOI · Paper page
  4. [4]Wu QZ Li DM Kuang WH Zhang TJ Lui S Huang XQ. Abnormal regional spontaneous neural activity in treatment-refractory depression revealed by resting-state fMRI. Hum Brain Mapp. (2011) 32: 1290– 9. 10.1002/hbm.21108 20665717 PMC6870367 · DOI
  5. [5]Anand A Li Y Wang Y Gardner K Lowe MJ. Reciprocal effects of antidepressant treatment on activity and connectivity of the mood regulating circuit: an FMRI study. J Neuropsychiatry Clin Neurosci. (2007) 19: 274– 82. 10.1176/jnp.2007.19.3.274 17827412 PMC3465666 · DOI · Paper page
  6. [6]Yang R Zhang H Wu X Yang J Ma M Gao Y. Hypothalamus-anchored resting brain network changes before and after sertraline treatment in major depression. Biomed Res.Int. (2014):2014. 10.1155/2014/915026 24772438 PMC3977500 · DOI
  7. [7]Disner SG Beevers CG Haigh EA Beck AT. Neural mechanisms of the cognitive model of depression. Nature Rev Neurosci. (2011) 12: 467. 10.1038/nrn3027 21731066 · DOI · Paper page
  8. [8]Bergmann U. EMDR's neurobiological mechanisms of action: A survey of 20 years of searching. J EMDR Pract Res. (2010) 4: 22– 42. 10.1891/1933-3196.4.1.22 · DOI
  9. [9]Rasolkhani-Kalhorn T Harper ML. EMDR and low frequency stimulation of the brain. Traumatology. (2006) 12: 9– 24. 10.1177/153476560601200102 · DOI
  10. [10]van der Kolk BA Spinazzola J Blaustein ME Hopper JW Hopper EK Korn DL. A randomized clinical trial of eye movement desensitization and reprocessing (EMDR), fluoxetine, and pill placebo in the treatment of posttraumatic stress disorder: treatment effects and long-term maintenance. J Clin Psychiatry. (2007) 68: 37– 46. 10.4088/JCP.v68n0105 17284128 · DOI
  11. [11]Hofmann A Hilgers A Lehnung M Liebermann P Ostacoli L Schneider W. Eye movement desensitization and reprocessing as an adjunctive treatment of unipolar depression: A controlled study. J EMDR Pract Res. (2014) 8: 103– 12. 10.1891/1933-3196.8.3.103 · DOI
  12. [12]Wood E Ricketts T Parry G. EMDR as a treatment for long-term depression: A feasibility study. Psychol Psychother. (2018) 91: 63– 78. 10.1111/papt.12145 28834138 PMC5836996 · DOI
  13. [13]Hall JE. Guyton y Hall. Elsevier Health Sciences Spain (2011). p. 745.
  14. [14]Kaprinis G Nimatoudis J Karavatos A Kandylis D Kaprinis S. Functional brain organization in bipolar affective patients during manic phase and after recovery: a digit dichotic listening study. Percept Mot Skills. (1995) 80: 1275– 82. 10.2466/pms.1995.80.3c.1275 7478888 · DOI
  15. [15]Li M Xu H Lu S. Neural basis of depression related to a dominant right hemisphere: A resting-state fMRI study. Behav. Neurol. (2018) 2018. 10.1155/2018/5024520 29971137 PMC6008682 · DOI
  16. [16]Beck AT Ward CH Mendelson M Mock J Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry. (1961) 4: 561– 71. 10.1001/archpsyc.1961.01710120031004 13688369 · DOI · Paper page
  17. [18]Chapman LJ Chapman JP. The measurement of handedness. Brain Cogn. (1987) 6: 175– 83. 10.1016/0278-2626(87)90118-7 3593557 · DOI
  18. [19]Dubois B Slachevsky A Litvan I Pillon B. The FAB: a frontal assessment battery at bedside. Neurology. (2000) 55: 1621– 6. 10.1212/WNL.55.11.1621 11113214 · DOI · Paper page
  19. [20]Lai C-H Wu Y-T. Frontal regional homogeneity increased and temporal regional homogeneity decreased after remission of first-episode drug-naive major depressive disorder with panic disorder patients under duloxetine therapy for 6 weeks. J Affect Disord. (2012) 136: 453– 8. 10.1016/j.jad.2011.11.004 22137181 · DOI
  20. [21]Yang C Zhang A Jia A Ma JX Sun N Wang Y. Identify abnormalities in resting-state brain function between first-episode, drug-naive major depressive disorder and remitted individuals: a 3-year retrospective study. Neuroreport. (2018) 29: 907– 16. 10.1097/WNR.0000000000001054 29912848 · DOI
  21. [22]Anand A Li Y Wang Y Wu J Gao S Bukhari L. Activity and connectivity of brain mood regulating circuit in depression: a functional magnetic resonance study. Biol Psychiatry. (2005) 57: 1079– 88. 10.1016/j.biopsych.2005.02.021 15866546 · DOI · Paper page
  22. [23]Grodd W Hülsmann E Ackermann H. Functional MRI localizing in the cerebellum. Neurosurgery Clinics. (2005) 16: 77– 99. 10.1016/j.nec.2004.07.008 15561530 · DOI
  23. [24]Schraa-Tam CK Rietdijk WJ Verbeke WJ Dietvorst RC Van Den Berg WE Bagozzi RP. fMRI activities in the emotional cerebellum: a preference for negative stimuli and goal-directed behavior. The Cerebellum. (2012) 11: 233– 45. 10.1007/s12311-011-0301-2 21761197 PMC3311856 · DOI
  24. [25]Guo W-b Liu F Chen J-d Gao K Xue Z-m Xu X-j. Abnormal neural activity of brain regions in treatment-resistant and treatment-sensitive major depressive disorder: a resting-state fMRI study. J Psychiatr Res. (2012) 46: 1366– 73. 10.1016/j.jpsychires.2012.07.003 22835912 · DOI
  25. [27]Park IS Lee NJ Rhyu IJ. Roles of the Declive, Folium, and Tuber Cerebellar Vermian Lobules in Sportspeople. J Clini Neurol. (2018) 14: 1– 7. 10.3988/jcn.2018.14.1.1 29141275 PMC5765239 · DOI
  26. [28]Chen SA Desmond JE. Temporal dynamics of cerebro-cerebellar network recruitment during a cognitive task. Neuropsychologia. (2005) 43: 1227– 37. 10.1016/j.neuropsychologia.2004.12.015 15949507 · DOI
  27. [29]Alalade E Denny K Potter G Steffens D Wang L. Altered cerebellar-cerebral functional connectivity in geriatric depression. PLoS ONE. (2011) 6: e20035. 10.1371/journal.pone.0020035 21637831 PMC3102667 · DOI · Paper page
  28. [30]Fang J Mao N Jiang X Li X Wang B Wang Q. Functional and anatomical brain abnormalities and effects of antidepressant in major depressive disorder: combined application of voxel-based morphometry and amplitude of frequency fluctuation in resting state. J Comput Assist Tomogr. (2015) 39: 766– 73. 10.1097/RCT.0000000000000264 26125296 · DOI
  29. [31]Emam H Steffens DC Pearlson G Wang L. Increased ventromedial prefrontal cortex activity and connectivity predict poor sertraline treatment outcome in late-life depression. Int J Geriatr Psychiatry. (2019). 10.1002/gps.5079 30761621 PMC6480406 · DOI
  30. [32]Cullen KR Gee DG Klimes-Dougan B Gabbay V Hulvershorn L Mueller BA. A preliminary study of functional connectivity in comorbid adolescent depression. Neurosci Lett. (2009) 460: 227– 31. 10.1016/j.neulet.2009.05.022 19446602 PMC2713606 · DOI
  31. [33]Tu Z Jia YY Wang T Qu H Pan JX Jie J. Modulatory interactions of resting-state brain functional connectivity in major depressive disorder. Neuropsychiatr Dis Treat. (2018) 14: 2461. 10.2147/NDT.S165295 30319258 PMC6167995 · DOI
  32. [34]Yao Z Wang L Lu Q Liu H Teng G. Regional homogeneity in depression and its relationship with separate depressive symptom clusters: a resting-state fMRI study. J Affect Disord. (2009) 115: 430– 8. 10.1016/j.jad.2008.10.013 19007997 · DOI · Paper page
  33. [39]Clasen PC Beevers CG Mumford JA Schnyer DM. Cognitive control network connectivity in adolescent women with and without a parental history of depression. Dev Cogn Neurosci. (2014) 7: 13– 22. 10.1016/j.dcn.2013.10.008 24270043 PMC4209722 · DOI
  34. [40]Cao J Chen X Chen J Ai M Gan Y Wang W. Resting-state functional MRI of abnormal baseline brain activity in young depressed patients with and without suicidal behavior. J Affect Disord. (2016) 205: 252– 63. 10.1016/j.jad.2016.07.002 27467529 · DOI · Paper page
  35. [42]Hou Z Gong L Zhi M Yin Y Zhang Y Xie C. Distinctive pretreatment features of bilateral nucleus accumbens networks predict early response to antidepressants in major depressive disorder. Brain Imaging Behav. (2018) 1– 11. 10.1007/s11682-017-9773-0 28971301 · DOI
  36. [43]Dichter GS Gibbs D Smoski MJ. A systematic review of relations between resting-state functional-MRI and treatment response in major depressive disorder. J Affect Disord. (2015) 172: 8– 17. 10.1016/j.jad.2014.09.028 25451389 PMC4375066 · DOI · Paper page
  37. [44]Wu H Sun H Xu J Wu Y Wang C Xiao J. Changed hub and corresponding functional connectivity of subgenual anterior cingulate cortex in major depressive disorder. Front Neuroanat. (2016) 10: 120. 10.3389/fnana.2016.00120 28018183 PMC5159433 · DOI
  38. [45]Smith DV Sip KE Delgado MR. Functional connectivity with distinct neural networks tracks fluctuations in gain/loss framing susceptibility. Hum Brain Mapp. (2015) 36: 2743– 55. 10.1002/hbm.22804 25858445 PMC4736507 · DOI
  39. [46]Spechler PA Chaarani B Orr C Mackey S Higgins ST Banaschewski T. Neuroimaging evidence for right orbitofrontal cortex differences in adolescents with emotional and behavioral dysregulation. J Am Acad Child Psy. (2019) 58: 1092– 103. 10.1016/j.jaac.2019.01.021 31004740 · DOI
  40. [47]Phillips ML Drevets WC Rauch SL Lane R. Neurobiology of emotion perception I: The neural basis of normal emotion perception. Biol Psychiatry. (2003) 54: 504– 14. 10.1016/S0006-3223(03)00168-9 12946879 · DOI · Paper page
  41. [48]Serafini G. Neuroplasticity and major depression, the role of modern antidepressant drugs. World J Psychiatry. (2012) 2: 49. 10.5498/wjp.v2.i3.49 24175168 PMC3782176 · DOI
  42. [49]Greicius MD Supekar K Menon V Dougherty RF. Resting-state functional connectivity reflects structural connectivity in the default mode network. Cerebral cortex. (2009) 19: 72– 8. 10.1093/cercor/bhn059 18403396 PMC2605172 · DOI · Paper page
  43. [50]Chen Y Wang C Zhu X Tan Y Zhong Y. Aberrant connectivity within the default mode network in first-episode, treatment-naive major depressive disorder. J Affect Disord. (2015) 183: 49– 56. 10.1016/j.jad.2015.04.052 26001663 · DOI
  44. [51]Teng S Lu CF Wu YT Wang PS Yeh TC Su TP. Investigation of differences on functional connectivity in major depressive disorder using functional magnetic resonance imaging. In 2010 International Conference on Bioinformatics and Biomedical Technology. IEEE. (2010). p. 115– 9.
  45. [52]Rolls ET. The Brain, Emotion, and Depression. Oxford University Press. (2018).
  46. [53]Kong L Chen K Tang Y Wu F Driesen N Womer F. Functional connectivity between the amygdala and prefrontal cortex in medication-naive individuals with major depressive disorder. J Psychiatry Neurosci. (2013) 38: 417. 10.1503/jpn.120117 24148846 PMC3819156 · DOI · Paper page
  47. [54]Rushworth MF Paus T Sipila PK. Attention systems and the organization of the human parietal cortex. J Neurosci. (2001) 21: 5262– 71. 10.1523/JNEUROSCI.21-14-05262.2001 11438601 PMC6762864 · DOI
  48. [55]Ye M Yang T Qing P Lei X Qiu J Liu G. Changes of functional brain networks in major depressive disorder: a graph theoretical analysis of resting-state fMRI. PLoS ONE. (2015) 10: e0133775. 10.1371/journal.pone.0133775 26327292 PMC4556670 · DOI
  49. [56]Gusnard DA Akbudak E Shulman GL Raichle ME. Medial prefrontal cortex and self-referential mental activity: relation to a default mode of brain function. Proc Nat Acad Sci. (2001) 98: 4259– 64. 10.1073/pnas.071043098 11259662 PMC31213 · DOI · Paper page
  50. [57]Sheline YI Price JL Yan Z Mintun MA. Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus. Proc Nat Acad Sci. (2010) 107: 11020– 5. 10.1073/pnas.1000446107 20534464 PMC2890754 · DOI · Paper page
  51. [58]Brakowski J Spinelli S Dörig N Bosch OG Manoliu A Holtforth MG. Resting state brain network function in major depression–depression symptomatology, antidepressant treatment effects, future research. J Psychiatr Res. (2017) 92: 147– 59. 10.1016/j.jpsychires.2017.04.007 28458140 · DOI
  52. [59]Wang W Zhao Y Hu X Huang X Kuang W Lui S. Conjoint and dissociated structural and functional abnormalities in first-episode drug-naive patients with major depressive disorder: a multimodal meta-analysis. Sci Rep. (2017) 7: 10401. 10.1038/s41598-017-08944-5 28871117 PMC5583354 · DOI
  53. [60]Jing B Liu C-H Ma X Yan H-G Zhuo Z-Z Zhang Y. Difference in amplitude of low-frequency fluctuation between currently depressed and remitted females with major depressive disorder. Brain Res. (2013) 1540: 74– 83. 10.1016/j.brainres.2013.09.039 24121137 · DOI
  54. [61]Zhou M Hu X Lu L Zhang L Chen L Gong Q. Intrinsic cerebral activity at resting state in adults with major depressive disorder: a meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. (2017) 75: 157– 64. 10.1016/j.pnpbp.2017.02.001 28174129 · DOI
  55. [62]Schmahmann JD. Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome. J Neuropsychiatry Clin Neurosci. (2004) 16: 367– 78. 10.1176/jnp.16.3.367 15377747 · DOI
  56. [63]Phillips JR Hewedi DH Eissa AM Moustafa AA. The cerebellum and psychiatric disorders. Frontiers in public health. (2015) 3: 66. 10.3389/fpubh.2015.00066 26000269 PMC4419550 · DOI
  57. [64]Landin-Romero R Novo P Vicens V McKenna PJ Santed A Pomarol-Clotet E. EMDR therapy modulates the default mode network in a subsyndromal, traumatized bipolar patient. Neuropsychobiology. (2013) 67: 181– 4. 10.1159/000346654 23548794 · DOI
  58. [65]Pagani M Di Lorenzo G Verardo AR Nicolais G Monaco L Lauretti G. Neurobiological correlates of EMDR monitoring–an EEG study. PLoS ONE. (2012) 7: e45753. 10.1371/journal.pone.0045753 23049852 PMC3458957 · DOI · Paper page
  59. [66]Matsuo K Kasai K Kato T Kato N. Hemodynamic responses of eye movement desensitization and reprocessing in posttraumatic stress disorder. Neurosci Res. (2009) 65: 375– 83. 10.1016/j.neures.2009.08.014 19729044 · DOI

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Authors
Boyraz, R. K., Kirpinar, I., Yilmaz, O., Özyurt, O., Kiliçarslan, T., & Aralasmak, A.
Affiliations
  • Bezmiâlem Vakıf Üniversitesi (TR)
  • Boğaziçi University (TR)
Corresponding author
Boyraz, Rabia Kevser
ORCID
Venue
Frontiers in Psychiatry
Publisher
Frontiers Media SA
Published
2021-09-03
Volume
12
Pages
698954-698954
ISSN
1664-0640 (ISSN-L)
DOI
10.3389/fpsyt.2021.698954
PMC
PMC8446543
OpenAlex
W3196672528
Cited by
7
References
6
Citations by year
2026: 2 · 2025: 2 · 2024: 1 · 2022: 2
FWCI
0.39
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Psychiatry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
Keywords
major depressive disorder, resting-state functional connectivity, sertraline, treatment response, depression treatment, neuropsychiatric outcomes, brain networks

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