The influence of personality on the effect of iTBS after being stressed on cortisol secretion

Autoři: Matias M. Pulopulos aff001;  Sara De Witte aff002;  Marie-Anne Vanderhasselt aff002;  Rudi De Raedt aff001;  Johan Schiettecatte aff004;  Ellen Anckaert aff004;  Alicia Salvador aff005;  Chris Baeken aff002
Působiště autorů: Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium aff001;  Department of Head and Skin, Ghent University, Ghent, Belgium aff002;  Ghent Experimental Psychiatry (GHEP) Lab, Ghent, Belgium aff003;  Laboratory of Hormonology and Tumor Markers, University Hospital (UZBrussel), Brussels, Belgium aff004;  Laboratory of Social Cognitive Neuroscience, Department of Psychobiology and IDOCAL, University of Valencia, Valencia, Spain aff005;  Department of Psychiatry, University Hospital (UZBrussel), Brussels, Belgium aff006;  Eindhoven University of Technology, Department of Electrical Engineering, Eindhoven, the Netherlands aff007
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article


Over the last years, individualization of repetitive Transcranial Magnetic Stimulation (rTMS) parameters has been a focus of attention in the field of non-invasive stimulation. It has been proposed that in stress-related disorders personality characteristics may influence the clinical outcome of rTMS. However, the underlying physiological mechanisms as to how personality may affect the rTMS response to stress remains to be clarified. In this sham-controlled crossover study, after being stressed by the Trier Social Stress Test, 38 healthy females received two sessions of intermittent theta burst stimulation (iTBS) applied to the left dorsolateral prefrontal cortex. To take possible personality influences into account, they also completed the Temperament and Character Inventory. Mood and salivary cortisol were assessed throughout the experimental protocol. Overall, two iTBS sessions did not significantly alter mood or influenced cortisol secretion. When taking into account personality features, higher scores on the character dimension Cooperativeness was related to decreased cortisol output, only when active iTBS was administered after the social stressor. In line with other studies, personality features such as the character dimension Cooperativeness may be of particular interest to explain individual neurobiological responses to neurostimulation.

Klíčová slova:

Cortisol – Depression – Emotions – Personality – Personality traits – Psychological stress – Secretion – Transcranial magnetic stimulation


1. Lefaucheur J-P, André-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol. 2014 Nov;125(11):2150–206. doi: 10.1016/j.clinph.2014.05.021 25034472

2. Baeken C, De Raedt R. Neurobiological mechanisms of repetitive transcranial magnetic stimulation on the underlying neuro circuitry in unipolar depression. Dialogues Clin Neurosci. 2011;13(1):139. 21485753

3. De Raedt R. A neurocognitive approach to major depressive disorder: Combining biological and cognitive interventions. In: From Symptom to Synapse: A Neurocognitive Perspective on Clinical Psychology [Internet]. 1st ed. Routledge; 2015 [cited 2019 Jun 17]. Available from:

4. Brunoni AR, Chaimani A, Moffa AH, Razza LB, Gattaz WF, Daskalakis ZJ, et al. Repetitive Transcranial Magnetic Stimulation for the Acute Treatment of Major Depressive Episodes: A Systematic Review With Network Meta-analysis. JAMA Psychiatry. 2017 Feb 1;74(2):143. doi: 10.1001/jamapsychiatry.2016.3644 28030740

5. Schutter DJLG. Antidepressant efficacy of high-frequency transcranial magnetic stimulation over the left dorsolateral prefrontal cortex in double-blind sham-controlled designs: a meta-analysis. Psychol Med. 2009 Jan;39(1):65–75. doi: 10.1017/S0033291708003462 18447962

6. Padberg F, Brem A-K, Palm U, Pogarell O, Hasan A, Brunelin J, et al. Discovering the individual brain: brain stimulation in psychiatry: Editorial I to the supplement from the 2nd European conference on brain stimulation in psychiatry. Eur Arch Psychiatry Clin Neurosci. 2017 Dec;267(S2):109–12.

7. Drysdale AT, Grosenick L, Downar J, Dunlop K, Mansouri F, Meng Y, et al. Resting-state connectivity biomarkers define neurophysiological subtypes of depression. Nat Med. 2017 Jan;23(1):28–38. doi: 10.1038/nm.4246 27918562

8. Cloninger CR. A Systematic Method for Clinical Description and Classification of Personality Variants: A Proposal. Arch Gen Psychiatry. 1987 Jun 1;44(6):573. doi: 10.1001/archpsyc.1987.01800180093014 3579504

9. Cloninger RC, Przybeck TR, Svrakic DM, Wetzel RD. The Temperament and Character Inventory: A Guide to its Development and Use: Amerikaanse Handleiding. Center for Psychobiology of Personality, Washington University; 1994.

10. Baeken C, Desmyter S, Duprat R, De Raedt R, Van denabbeele D, Tandt H, et al. Self-directedness: An indicator for clinical response to the HF-rTMS treatment in refractory melancholic depression. Psychiatry Res. 2014 Dec;220(1–2):269–74. doi: 10.1016/j.psychres.2014.07.084 25175912

11. McCrae RR, Costa PT. Validation of the five-factor model of personality across instruments and observers. J Pers Soc Psychol. 1987;52(1):81–90. doi: 10.1037//0022-3514.52.1.81 3820081

12. Berlim MT, McGirr A, Beaulieu M-M, Van den Eynde F, Turecki G. Are neuroticism and extraversion associated with the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS)? An exploratory 4-week trial. Neurosci Lett. 2013 Feb;534:306–10. doi: 10.1016/j.neulet.2012.12.029 23291399

13. McGirr A, Van den Eynde F, Chachamovich E, Fleck MPA, Berlim MT. Personality dimensions and deep repetitive transcranial magnetic stimulation (DTMS) for treatment-resistant depression: A pilot trial on five-factor prediction of antidepressant response. Neurosci Lett. 2014 Mar;563:144–8. doi: 10.1016/j.neulet.2014.01.037 24486892

14. De Fruyt F, Van De Wiele L, Van Heeringen C. Cloninger’s Psychobiological Model of Temperament and Character and the Five-Factor Model of Personality. Personal Individ Differ. 2000 Sep;29(3):441–52.

15. Siddiqi SH, Chockalingam R, Cloninger CR, Lenze EJ, Cristancho P. Use of the Temperament and Character Inventory to Predict Response to Repetitive Transcranial Magnetic Stimulation for Major Depression: J Psychiatr Pract. 2016 May;22(3):193–202. doi: 10.1097/PRA.0000000000000150 27123799

16. Singh A, Erwin-Grabner T, Sutcliffe G, Antal A, Paulus W, Goya-Maldonado R. Personalized repetitive transcranial magnetic stimulation temporarily alters default mode network in healthy subjects. Sci Rep. 2019 Dec;9(1):5631. doi: 10.1038/s41598-019-42067-3 30948765

17. Baeken C, Marinazzo D, Wu G-R, Van Schuerbeek P, De Mey J, Marchetti I, et al. Accelerated HF-rTMS in treatment-resistant unipolar depression: Insights from subgenual anterior cingulate functional connectivity. World J Biol Psychiatry. 2014 May;15(4):286–97. doi: 10.3109/15622975.2013.872295 24447053

18. Buck R. The biological affects: a typology. Psychol Rev. 1999;106(2):301. doi: 10.1037/0033-295x.106.2.301 10378015

19. Hori H, Teraishi T, Sasayama D, Hattori K, Hashikura M, Higuchi T, et al. Relationship of temperament and character with cortisol reactivity to the combined dexamethasone/CRH test in depressed outpatients. J Affect Disord. 2013 May;147(1–3):128–36. doi: 10.1016/j.jad.2012.10.022 23178186

20. Schutter DJLG, van Honk J. An endocrine perspective on the role of steroid hormones in the antidepressant treatment efficacy of transcranial magnetic stimulation. Psychoneuroendocrinology. 2010 Jan;35(1):171–8. doi: 10.1016/j.psyneuen.2009.04.009 19443126

21. Keck ME. rTMS as treatment strategy in psychiatric disorders–neurobiological concepts. In: Supplements to Clinical neurophysiology. Elsevier; 2003. p. 100–116.

22. Baeken C, De Raedt R, Leyman L, Schiettecatte J, Kaufman L, Poppe K, et al. The impact of one HF-rTMS session on mood and salivary cortisol in treatment resistant unipolar melancholic depressed patients. J Affect Disord. 2009 Feb;113(1–2):100–8. doi: 10.1016/j.jad.2008.05.008 18571733

23. Pridmore Saxby. Rapid transcranial magnetic stimulation and normalization of the dexamethasone suppression test. Psychiatry Clin Neurosci. 1999 Feb;53(1):33–7. doi: 10.1046/j.1440-1819.1999.00467.x 10201281

24. Barden N. Implication of the hypothalamic–pituitary–adrenal axis in the physiopathology of depression. J Psychiatry Neurosci. 2004;29(3):185. 15173895

25. Keck ME, Holsboer F. Hyperactivity of CRH neuronal circuits as a target for therapeutic interventions in affective disorders. Peptides. 2001 May;22(5):835–44. doi: 10.1016/s0196-9781(01)00398-9 11337098

26. Baeken C, De Raedt R, Leyman L, Schiettecatte J, Poppe K, Kaufman L, et al. The impact of one session of HF-rTMS on salivary cortisol in healthy female subjects. World J Biol Psychiatry. 2009 Jan;10(4–2):586–90.

27. Baeken C, Vanderhasselt MA, Remue J, Rossi V, Schiettecatte J, Anckaert E, et al. One left dorsolateral prefrontal cortical HF-rTMS session attenuates HPA-system sensitivity to critical feedback in healthy females. Neuropsychologia. 2014 May;57:112–21. doi: 10.1016/j.neuropsychologia.2014.02.019 24593899

28. Baeken C, Vanderhasselt MA, De Raedt R. Baseline ‘state anxiety’ influences HPA-axis sensitivity to one sham-controlled HF-rTMS session applied to the right dorsolateral prefrontal cortex. Psychoneuroendocrinology. 2011 Jan;36(1):60–7. doi: 10.1016/j.psyneuen.2010.06.006 20599325

29. Remue J, Vanderhasselt M-A, Baeken C, Rossi V, Tullo J, De Raedt R. The effect of a single HF-rTMS session over the left DLPFC on the physiological stress response as measured by heart rate variability. Neuropsychology. 2016 Sep;30(6):756–66. doi: 10.1037/neu0000255 26618798

30. Childs E, White TL, de Wit H. Personality traits modulate emotional and physiological responses to stress: Behav Pharmacol. 2014 Jul;1.

31. Hori H, Ozeki Y, Teraishi T, Matsuo J, Kawamoto Y, Kinoshita Y, et al. Relationships between psychological distress, coping styles, and HPA axis reactivity in healthy adults. J Psychiatr Res. 2010 Oct;44(14):865–73. doi: 10.1016/j.jpsychires.2010.02.007 20334880

32. Kudielka BM, Hellhammer DH, Wüst S. Why do we respond so differently? Reviewing determinants of human salivary cortisol responses to challenge. Psychoneuroendocrinology. 2009 Jan;34(1):2–18. doi: 10.1016/j.psyneuen.2008.10.004 19041187

33. Pulopulos MM, Hidalgo V, Puig-Pérez S. Psychophysiological response to social stressors: Relevance of sex and age. Psicothema. 2018 May;(30.2):171–6.

34. Stephens MAC, Mahon PB, McCaul ME, Wand GS. Hypothalamic–pituitary–adrenal axis response to acute psychosocial stress: Effects of biological sex and circulating sex hormones. Psychoneuroendocrinology. 2016 Apr;66:47–55. doi: 10.1016/j.psyneuen.2015.12.021 26773400

35. Xin Y, Wu J, Yao Z, Guan Q, Aleman A, Luo Y. The relationship between personality and the response to acute psychological stress. Sci Rep. 2017 04;7(1):16906. doi: 10.1038/s41598-017-17053-2 29203876

36. Van Schuerbeek P, Baeken C, De Raedt R, De Mey J, Luypaert R. Individual differences in local gray and white matter volumes reflect differences in temperament and character: A voxel-based morphometry study in healthy young females. Brain Res. 2011 Jan;1371:32–42. doi: 10.1016/j.brainres.2010.11.073 21126511

37. Gusnard DA, Ollinger JM, Shulman GL, Cloninger CR, Price JL, Van Essen DC, et al. Persistence and brain circuitry. Proc Natl Acad Sci. 2003 Mar 18;100(6):3479–84. doi: 10.1073/pnas.0538050100 12626765

38. Barrash J, Tranel D, Anderson SW. Acquired Personality Disturbances Associated With Bilateral Damage to the Ventromedial Prefrontal Region. Dev Neuropsychol. 2000 Dec;18(3):355–81. doi: 10.1207/S1532694205Barrash 11385830

39. Herman JP, Ostrander MM, Mueller NK, Figueiredo H. Limbic system mechanisms of stress regulation: Hypothalamo-pituitary-adrenocortical axis. Prog Neuropsychopharmacol Biol Psychiatry. 2005 Dec;29(8):1201–13. doi: 10.1016/j.pnpbp.2005.08.006 16271821

40. Hermans EJ, Henckens MJAG, Joëls M, Fernández G. Dynamic adaptation of large-scale brain networks in response to acute stressors. Trends Neurosci. 2014 Jun;37(6):304–14. doi: 10.1016/j.tins.2014.03.006 24766931

41. Duprat R, Desmyter S, Rudi DR, van Heeringen K, Van den Abbeele D, Tandt H, et al. Accelerated intermittent theta burst stimulation treatment in medication-resistant major depression: A fast road to remission? J Affect Disord. 2016 Aug;200:6–14. doi: 10.1016/j.jad.2016.04.015 27107779

42. Schulze L, Feffer K, Lozano C, Giacobbe P, Daskalakis ZJ, Blumberger DM, et al. Number of pulses or number of sessions? An open-label study of trajectories of improvement for once-vs. twice-daily dorsomedial prefrontal rTMS in major depression. Brain Stimulat. 2018 Mar;11(2):327–36.

43. Blumberger DM, Vila-Rodriguez F, Thorpe KE, Feffer K, Noda Y, Giacobbe P, et al. Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. The Lancet. 2018 Apr;391(10131):1683–92.

44. Bakker N, Shahab S, Giacobbe P, Blumberger DM, Daskalakis ZJ, Kennedy SH, et al. rTMS of the Dorsomedial Prefrontal Cortex for Major Depression: Safety, Tolerability, Effectiveness, and Outcome Predictors for 10 Hz Versus Intermittent Theta-burst Stimulation. Brain Stimulat. 2015 Mar;8(2):208–15.

45. Kirschbaum C, Pirke K-M, Hellhammer DH. The ‘Trier Social Stress Test’–A Tool for Investigating Psychobiological Stress Responses in a Laboratory Setting. Neuropsychobiology. 1993;28(1–2):76–81. doi: 10.1159/000119004 8255414

46. Allen AP, Kennedy PJ, Dockray S, Cryan JF, Dinan TG, Clarke G. The Trier Social Stress Test: Principles and practice. Neurobiol Stress. 2017 Feb;6:113–26. doi: 10.1016/j.ynstr.2016.11.001 28229114

47. Kudielka BM, Buske-Kirschbaum A, Hellhammer DH, Kirschbaum C. HPA axis responses to laboratory psychosocial stress in healthy elderly adults, younger adults, and children: impact of age and gender. Psychoneuroendocrinology. 2004 Jan;29(1):83–98. doi: 10.1016/s0306-4530(02)00146-4 14575731

48. Liu JJW, Ein N, Peck K, Huang V, Pruessner JC, Vickers K. Sex differences in salivary cortisol reactivity to the Trier Social Stress Test (TSST): A meta-analysis. Psychoneuroendocrinology. 2017 Aug;82:26–37. doi: 10.1016/j.psyneuen.2017.04.007 28486178

49. Zorn JV, Schür RR, Boks MP, Kahn RS, Joëls M, Vinkers CH. Cortisol stress reactivity across psychiatric disorders: A systematic review and meta-analysis. Psychoneuroendocrinology. 2017 Mar;77:25–36. doi: 10.1016/j.psyneuen.2016.11.036 28012291

50. Pruessner JC, Kirschbaum C, Meinlschmid G, Hellhammer DH. Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change. Psychoneuroendocrinology. 2003 Oct;28(7):916–31. doi: 10.1016/s0306-4530(02)00108-7 12892658

51. Fekedulegn DB, Andrew ME, Burchfiel CM, Violanti JM, Hartley TA, Charles LE, et al. Area Under the Curve and Other Summary Indicators of Repeated Waking Cortisol Measurements: Psychosom Med. 2007 Sep;69(7):651–9. doi: 10.1097/PSY.0b013e31814c405c 17766693

52. Baeken C, De Raedt R, Van Schuerbeek P, Vanderhasselt MA, De Mey J, Bossuyt A, et al. Right prefrontal HF-rTMS attenuates right amygdala processing of negatively valenced emotional stimuli in healthy females. Behav Brain Res. 2010 Dec;214(2):450–5. doi: 10.1016/j.bbr.2010.06.029 20600336

53. Van Schuerbeek P, Baeken C, Luypaert R, De Raedt R, De Mey J. Does the amygdala response correlate with the personality trait ‘harm avoidance’ while evaluating emotional stimuli explicitly? Behav Brain Funct. 2014;10(1):18.

54. Van Schuerbeek P, Baeken C, De Mey J. The Heterogeneity in Retrieved Relations between the Personality Trait ‘Harm Avoidance’ and Gray Matter Volumes Due to Variations in the VBM and ROI Labeling Processing Settings. He H, editor. PLOS ONE. 2016 Apr 20;11(4):e0153865. doi: 10.1371/journal.pone.0153865 27096608

55. Lecrubier Y, Sheehan D, Weiller E, Amorim P, Bonora I, Harnett Sheehan K, et al. The Mini International Neuropsychiatric Interview (MINI). A short diagnostic structured interview: reliability and validity according to the CIDI. Eur Psychiatry. 1997;12(5):224–31.

56. Beck AT, Steer RA, Brown G. Beck Depression Inventory–II [Internet]. American Psychological Association; 2011 [cited 2019 Jun 17]. Available from:

57. Van der Does A. Manual of the Dutch version of the Beck Depression Inventory (BDI-II-NL). Amst NL Harcourt. 2002;

58. de la Rie SM, Duijsens IJ, Cloninger CR. Temperament, Character, and Personality Disorders. J Personal Disord. 1998 Dec;12(4):362–72.

59. McCormack HM, de L. Horne DJ, Sheather S. Clinical applications of visual analogue scales: a critical review. Psychol Med. 1988 Nov;18(4):1007–19. doi: 10.1017/s0033291700009934 3078045

60. Kirschbaum C, Wüst S, Hellhammer D. Consistent sex differences in cortisol responses to psychological stress.: Psychosom Med. 1992 Nov;54(6):648–57. doi: 10.1097/00006842-199211000-00004 1454958

61. Goodman WK, Janson J, Wolf JM. Meta-analytical assessment of the effects of protocol variations on cortisol responses to the Trier Social Stress Test. Psychoneuroendocrinology. 2017 Jun;80:26–35. doi: 10.1016/j.psyneuen.2017.02.030 28292684

62. Remue J, Baeken C, De Raedt R. Does a single neurostimulation session really affect mood in healthy individuals? A systematic review. Neuropsychologia. 2016;85:184–198. doi: 10.1016/j.neuropsychologia.2016.03.012 26988115

63. Bayon C, Hill K, Svrakic DM, Przybeck TR, Cloninger CR. Dimensional assessment of personality in an out-patient sample: Relations of the systems of Millon and Cloninger. J Psychiatr Res. 1996 Sep;30(5):341–52. doi: 10.1016/0022-3956(96)00024-6 8923338

64. Cloninger CR, Bayon C, Svrakic DM. Measurement of temperament and character in mood disorders: a model of fundamental states as personality types. J Affect Disord. 1998 Oct;51(1):21–32. doi: 10.1016/s0165-0327(98)00153-0 9879800

65. Svrakic DM, Whitehead C, Przybeck TR, Cloninger CR. Differential Diagnosis of Personality Disorders by the Seven-Factor Model of Temperament and Character. Arch Gen Psychiatry. 1993 Dec 1;50(12):991–9. doi: 10.1001/archpsyc.1993.01820240075009 8250685

66. Huber TJ, Schneider U, Rollnik J. Gender differences in the effect of repetitive transcranial magnetic stimulation in schizophrenia. Psychiatry Res. 2003 Aug;120(1):103–5. doi: 10.1016/s0165-1781(03)00170-7 14500119

67. Zafar N, Paulus W, Sommer M. Comparative assessment of best conventional with best theta burst repetitive transcranial magnetic stimulation protocols on human motor cortex excitability. Clin Neurophysiol. 2008 Jun;119(6):1393–9. doi: 10.1016/j.clinph.2008.02.006 18400556

Článek vyšel v časopise


2019 Číslo 10
Nejčtenější tento týden