Background: Anorexia nervosa (AN) is a life-threatening illness with poor treatment outcomes. Although transcranial direct current stimulation (tDCS) is a promising non-invasive brain stimulation method, its effect in patients with AN remains unclear. Objective: This study investigated changes in maladaptive eating behavior, body mass index (BMI), and depression after 10 sessions of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC). Methods: In this double-blind, randomized controlled trial, 43 inpatients with AN were divided to receive either active (n = 22) or sham (n = 21) tDCS over the left DLPFC (anode F3/cathode Fp2, 2 mA for 30 min). All patients filled the Eating Disorder Examination Questionnaire (EDE-Q) and Zung Self-Rating Depression Scale (ZUNG), and their BMI was measured. These values were obtained repeatedly in four stages: (1) before tDCS treatment, (2) after tDCS treatment, (3) in the follow-up after 2 weeks, and (4) in the follow-up after 4 weeks. Results: Primary outcomes (EDE-Q) based on the ANOVA results do not show any between-group differences either after the active part of the study or in the follow-up. Secondary analysis reveals a reduction in some items of EDE-Q. Compared with sham tDCS, active tDCS significantly improved self-evaluation based on body shape (p < 0.05) and significantly decreased the need of excessive control over calorie intake (p < 0.05) in the 4-week follow-up. However, the results do not survive multiple comparison correction. In both sham and active groups, the BMI values improved, albeit not significantly. Conclusion: We did not observe a significant effect of tDCS over the left DLPFC on complex psychopathology and weight recovery in patients with AN. tDCS reduced the need to follow specific dietary rules and improved body image evaluation in patients with AN. Tests with a larger sample and different positions of electrodes are needed. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03273205.

1st Faculty of Medicine Charles University Prague Czechia

3rd Faculty of Medicine Charles University Prague Czechia

Department of Pediatrics and Inherited Metabolic Disorders 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czechia

Department of Physiology 3rd Faculty of Medicine Charles University Prague Czechia

Department of Psychiatry 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Prague Czechia

Department of Psychotherapy National Institute of Mental Health Klecany Czechia

Department of Steroid Hormones and Proteohormones Institute of Endocrinology Prague Czechia

Zobrazit více v PubMed

Smink FR, van Hoeken D, Hoek HW. Epidemiology of eating disorders: incidence, prevalence and mortality rates. Curr Psychiatry Rep. (2012) 14:406–14. 10.1007/s11920-012-0282-y PubMed DOI PMC

Treasure J, Claudino AM, Zucker N. Eating disorders. Lancet. (2010) 375:583–93. 10.1016/S0140-6736(09)61748-7 PubMed DOI

Smink FR, van Hoeken D, Hoek HW. Epidemiology, course, and outcome of eating disorders. Curr Opin Psychiatry. (2013) 26:543–8. 10.1097/YCO.0b013e328365a24f PubMed DOI

World Health Organization . The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines. Geneva: (1992). Available online at: http://www.who.int/classifications/icd/en/bluebook.pdf

Herpertz-Dahlmann B, Dempfle A, Egberts KM, Kappel V, Konrad K, Vloet JA et al. Outcome of childhood anorexia nervosa-The results of a five- to ten-year follow-up study. Int J Eat Disord. (2018) 51:295–304. 10.1002/eat.22840 PubMed DOI

Fichter MM, Quadflieg N, Crosby RD, Koch S. Long-term outcome of anorexia nervosa: results from a large clinical longitudinal study. Int J Eat Disord. (2017) 50:1018–30. 10.1002/eat.22736 PubMed DOI

Philip NS, Nelson BG, Frohlich F, Lim KO, Widge AS, Carpenter LL. Low-intensity transcranial current stimulation in psychiatry. Am J Psychiatry. (2017) 174:628–39. 10.1176/appi.ajp.2017.16090996 PubMed DOI PMC

Bikson M, Grossman P, Thomas C, Zannou AL, Jiang J, Adnan T et al. Safety of transcranial direct current stimulation: evidence based update 2016. Brain Stimul. (2016) 9:641–61. 10.1016/j.brs.2016.06.004 PubMed DOI PMC

Aparício LVM, Guarienti F, Razza LB, Carvalho AF, Fregni F, Brunoni AR. A systematic review on the acceptability and tolerability of transcranial direct current stimulation treatment in neuropsychiatry trials. Brain Stimul. (2016) 9:671–81. 10.1016/j.brs.2016.05.004 PubMed DOI

Buchanan DM, Bogdanowicz T, Khanna N, Lockman-Dufour G, Robaey P, D'Angiulli A. Systematic review on the safety and tolerability of transcranial direct current stimulation in children and adolescents. Brain Sci. (2021) 11:212. 10.3390/brainsci11020212 PubMed DOI PMC

Stagg CJ, Nitsche MA. Physiological basis of transcranial direct current stimulation. Neuroscientist. (2011) 17:37–53. 10.1177/1073858410386614 PubMed DOI

Ciechanski P, Kirton A. Transcranial Direct-Current Stimulation (tDCS): principles and emerging applications in children. In: Kirton A, Gilbert DL. editors Pediatric Brain Stimulation. London; San Diego, CA; Oxford; Cambridge: Academic Press; (2016). p. 85–115.

Impey D, de la Salle S, Knott V. Assessment of anodal and cathodal transcranial direct current stimulation (tDCS) on MMN-indexed auditory sensory processing. Brain Cogn. (2016) 105:46–54. 10.1016/j.bandc.2016.03.006 PubMed DOI

Lozano AM, Hallett M. Brain Stimulation. Amsterdam: Newnes; (2013). p. 456.

Lefaucheur JP, Antal A, Ayache SS, Benninger DH, Brunelin J, Cogiamanian F et al. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS). Clin Neurophysiol. (2017) 128:56–92. 10.1016/j.clinph.2016.10.087 PubMed DOI

Kaye WH, Fudge JL, Paulus M. New insights into symptoms and neurocircuit function of anorexia nervosa. Nat Rev Neurosci. (2009) 10:573–84. 10.1038/nrn2682 PubMed DOI

Silvers JA, Weber J, Wager TD, Ochsner KN. Bad and worse: neural systems underlying reappraisal of high-and low-intensity negative emotions. Soc Cogn Affect Neurosci. (2014) 10:172–9. 10.1093/scan/nsu043 PubMed DOI PMC

Ehrlich S, Geisler D, Ritschel F et al. Elevated cognitive control over reward processing in recovered female patients with anorexia nervosa. J Psychiatry Neurosci. (2015) 40:307. 10.1503/jpn.140249 PubMed DOI PMC

Duriez P, Bou Khalil R, Chamoun Y, Maatoug R, Strumila R, Seneque M, et al. . Brain stimulation in eating disorders: state of the art and future perspectives. J Clin Med. (2020) 9:2358. 10.3390/jcm9082358 PubMed DOI PMC

Knyahnytska YO, Blumberger DM, Daskalakis ZJ, Zomorrodi R, Kaplan AS. Insula H-coil deep transcranial magnetic stimulation in severe and enduring anorexia nervosa (SE-AN): a pilot study. Neuropsychiatr Dis Treat. (2019) 15:2247–56. 10.2147/NDT.S207630 PubMed DOI PMC

Woodside DB, Colton P, Lam E, Dunlop K, Rzeszutek J, Downar J. Dorsomedial prefrontal cortex repetitive transcranial magnetic stimulation treatment of posttraumatic stress disorder in eating disorders: an open-label case series. Int J Eat Disord. (2017) 50:1231–4. 10.1002/eat.22764 PubMed DOI

Kane MJ, Engle RW. The role of prefrontal cortex in working-memory capacity, executive attention, and general fluid intelligence: an individual-differences perspective. Psychon Bull Rev. (2002) 9:637–71. 10.3758/BF03196323 PubMed DOI

Ghanavati E, Salehinejad MA, Nejati V, Nitsche MA. Differential role of prefrontal, temporal and parietal cortices in verbal and figural fluency: implications for the supramodal contribution of executive functions. Sci Rep. (2019) 9:3700. 10.1038/s41598-019-40273-7 PubMed DOI PMC

Nejati V, Majdi R, Salehinejad MA, Nitsche MA. The role of dorsolateral and ventromedial prefrontal cortex in the processing of emotional dimensions. Sci Rep. (2021) 11:1971. 10.1038/s41598-021-81454-7 PubMed DOI PMC

Molavi P, Aziziaram S, Basharpoor S, Atadokht A, Nitsche MA, Salehinejad MA. Repeated transcranial direct current stimulation of dorsolateral-prefrontal cortex improves executive functions, cognitive reappraisal emotion regulation, and control over emotional processing in borderline personality disorder: a randomized, sham-controlled, parallel-group study. J Affect Disord. (2020) 274:93–102. 10.1016/j.jad.2020.05.007 PubMed DOI

Ridderinkhof KR, van den Wildenberg WP, Segalowitz SJ, Carter CS. Neurocognitive mechanisms of cognitive control: the role of prefrontal cortex in action selection, response inhibition, performance monitoring, and reward-based learning. Brain Cogn. (2004) 56:129–40. 10.1016/j.bandc.2004.09.016 PubMed DOI

Miller EK, Cohen JD. An integrative theory of prefrontal cortex function. Annu Rev Neurosci. (2001) 24:167–202. 10.1146/annurev.neuro.24.1.167 PubMed DOI

Hecht D. Transcranial direct current stimulation in the treatment of anorexia. Med Hypotheses. (2010) 74:1044–7. 10.1016/j.mehy.2009.12.032 PubMed DOI

Khedr EM, Elfetoh NA, Ali AM, Noamany M. Anodal transcranial direct current stimulation over the dorsolateral prefrontal cortex improves anorexia nervosa: a pilot study. Restor Neurol Neurosci. (2014) 32:789–97. 10.3233/RNN-140392 PubMed DOI

Costanzo F, Menghini D, Maritato A, Castiglioni MC, Mereu A, Varuzza C et al. New Treatment perspectives in adolescents with anorexia nervosa: the efficacy of non-invasive brain-directed treatment. Front Behav Neurosci. (2018) 12:133. 10.3389/fnbeh.2018.00133 PubMed DOI PMC

Strumila R, Thiebaut S, Jaussent I, Seneque M, Attal J, Courtet P et al. Safety and efficacy of transcranial direct current stimulation (tDCS) in the treatment of Anorexia Nervosa. The open-label STAR study. Brain Stimul. (2019) 12:1325–7. 10.1016/j.brs.2019.06.017 PubMed DOI

Mares T, Ceresnakova S, Albrecht J, Buday J, Klasova J, Horackova K et al. The onset of diabetes during transcranial direct current stimulation treatment of anorexia nervosa - a case report. Front Psychiatry. (2020) 11:40. 10.3389/fpsyt.2020.00040 PubMed DOI PMC

Berg KC, Peterson CB, Frazier P, Crow SJ. Psychometric evaluation of the eating disorder examination and eating disorder examination-questionnaire: a systematic review of the literature. Int J Eat Disord. (2012) 45:428–38. 10.1002/eat.20931 PubMed DOI PMC

Gabrys JB, Peters K. Reliability, discriminant and predictive validity of the Zung Self-rating Depression Scale. Psychol Rep. (1985) 57(Pt 2):1091–6. 10.2466/pr0.1985.57.3f.1091 PubMed DOI

de Jonghe JF, Baneke JJ. The Zung Self-rating depression scale: a replication study on reliability, validity and prediction. Psychol Rep. (1989) 64:833–34. 10.2466/pr0.1989.64.3.833 DOI

Thielscher A, Antunes A, Saturnino GB. Field modeling for transcranial magnetic stimulation: a useful tool to understand the physiological effects of TMS? Annu Int Conf IEEE Eng Med Biol Soc. (2015) 2015:222–5. 10.1109/EMBC.2015.7318340 PubMed DOI

Hill M, Bicíková M, Parízek A, Havlíková H, Klak J, Fajt T et al. Neuroactive steroids, their precursors and polar conjugates during parturition and postpartum in maternal blood: 2. Time profiles of pregnanolone isomers. J Steroid Biochem Mol Biol. (2001) 78:51–7. 10.1016/S0960-0760(01)00073-5 PubMed DOI

Meloun M, Militký J. Statistická Analýza Experimentálních Dat. Prague: Academia; (2004).

Meloun M, Militký J, Hill M, Brereton RG. Crucial problems in regression modelling and their solutions. Analyst. (2002) 127:433–50. 10.1039/b110779h PubMed DOI

Meloun M, Hill M, Militký J, Vrbíková J, Stanická S, Skrha J. New methodology of influential point detection in regression model building for the prediction of metabolic clearance rate of glucose. Clin Chem Lab Med. (2004) 42:311–22. 10.1515/CCLM.2004.057 PubMed DOI

Trygg J, Holmes E, Lundstedt T. Chemometrics in metabonomics. J Proteome Res. (2007) 6:469–79. 10.1021/pr060594q PubMed DOI

Trygg J, Wold S. Orthogonal projections to latent structures (O-PLS). J Chemometr J Chemometr Soc. (2002) 16:119–28. 10.1002/cem.695 DOI

Madsen R, Lundstedt T, Trygg J. Chemometrics in metabolomics–a review in human disease diagnosis. Anal Chim Acta. (2010) 659:23–33. 10.1016/j.aca.2009.11.042 PubMed DOI

Czech C, Berndt P, Busch K, Schmitz O, Wiemer J, Most V, et al. . Metabolite profiling of Alzheimer's disease cerebrospinal fluid. PLoS One. (2012) 7:e31501. 10.1371/journal.pone.0031501 PubMed DOI PMC

Eryilmaz G, Sayar GH, Ünsalver BÖ, Gül IG, Özten E, Saglam E. Adverse effects of Transcranial Direct Current Stimulation (TDCS) in a group of psychiatric patients. Scholars J Appl Med Sci. (2014) 2:294–7. Available online at: https://www.researchgate.net/profile/Gokben-HizliSayar/publication/260554152_Adverse_Effects_of_Transcranial_Direct_Current_Stimulation_TDCS_in_a_Group_of_Psychiatric_Patients/links/00b7d5318e1660f599000000/Adverse-Effects-ofTranscranial-Direct-Current-Stimulation-TDCS-in-a-Group-of-Psychiatric-Patients.pdf

Kessler SK, Turkeltaub PE, Benson JG, Hamilton RH. Differences in the experience of active and sham transcranial direct current stimulation. Brain Stimul. (2012) 5:155–62. 10.1016/j.brs.2011.02.007 PubMed DOI PMC

Jog MV, Wang DJJ, Narr KL. A review of transcranial direct current stimulation (tDCS) for the individualized treatment of depressive symptoms. Pers Med Psychiatry. (2019) 17–18:17–22. 10.1016/j.pmip.2019.03.001 PubMed DOI PMC

Dejong H, Broadbent H, Schmidt U. A systematic review of dropout from treatment in outpatients with anorexia nervosa. Int J Eat Disord. (2012) 45:635–47. 10.1002/eat.20956 PubMed DOI

Charvet LE, Shaw MT, Bikson M, Woods AJ, Knotkova H. Supervised transcranial direct current stimulation (tDCS) at home: a guide for clinical research and practice. Brain Stimul. (2020) 13:686–93. 10.1016/j.brs.2020.02.011 PubMed DOI

Boggio PS, Nunes A, Rigonatti SP, Nitsche MA, Pascual-Leone A, Fregni F. Repeated sessions of noninvasive brain DC stimulation is associated with motor function improvement in stroke patients. Restor Neurol Neurosci. (2007) 25:123–9. Available online at: https://www.researchgate.net/publication/6114610_Repeated_sessions_of_noninvasive_brain_DC_stimulation_is_associated_with_motor_function_improvement_in_stoke_patients PubMed

Im JJ, Jeong H, Bikson M, Woods AJ, Unal G, Oh JK, et al. . Effects of 6-month at-home transcranial direct current stimulation on cognition and cerebral glucose metabolism in Alzheimer's disease. Brain Stimul. (2019) 12:1222–8. 10.1016/j.brs.2019.06.003 PubMed DOI PMC

Clayton AM, Howard J, Dobbs B, Shaw MT, Charvet LE. Remotely supervised transcranial direct current stimulation after ECT improves mood and cognition in a patient with multiple sclerosis: a case study. J ECT. (2018) 34:e15. 10.1097/YCT.0000000000000474 PubMed DOI

Pilloni G, Shaw M, Feinberg C, Clayton A, Palmeri M, Datta A et al. Long term at-home treatment with transcranial direct current stimulation (tDCS) improves symptoms of cerebellar ataxia: a case report. J Neuroeng Rehabil. (2019) 16:41. 10.1186/s12984-019-0514-z PubMed DOI PMC

Andrade C. Once- to twice-daily, 3-year domiciliary maintenance transcranial direct current stimulation for severe, disabling, clozapine-refractory continuous auditory hallucinations in schizophrenia. J ECT. (2013) 29:239–42. 10.1097/YCT.0b013e3182843866 PubMed DOI

Phillipou A, Rossell SL, Castle DJ. The neurobiology of anorexia nervosa: a systematic review. Aust N Z J Psychiatry. (2014) 48:128–52. 10.1177/0004867413509693 PubMed DOI

Phillipou A, Rossell SL, Castle DJ, Gurvich C, Abel LA. Square wave jerks and anxiety as distinctive biomarkers for anorexia nervosa. Invest Ophthalmol Vis Sci. (2014) 55:8366–70. 10.1167/iovs.14-15807 PubMed DOI

Phillipou A, Kirkovski M, Castle DJ, Gurvich C, Abel LA, Miles S, et al. . High-definition transcranial direct current stimulation in anorexia nervosa: a pilot study. Int J Eat Disord. (2019) 52:1274–80. 10.1002/eat.23146 PubMed DOI

Depue BE, Orr JM, Smolker HR, Naaz F, Banich MT. The organization of right prefrontal networks reveals common mechanisms of inhibitory regulation across cognitive, emotional, and motor processes. Cereb Cortex. (2016) 26:1634–46. 10.1093/cercor/bhu324 PubMed DOI PMC

Swann NC, Tandon N, Pieters TA, Aron AR. Intracranial electroencephalography reveals different temporal profiles for dorsal- and ventro-lateral prefrontal cortex in preparing to stop action. Cereb Cortex. (2013) 23:2479–88. 10.1093/cercor/bhs245 PubMed DOI PMC

Friehs MA, Frings C, Hartwigsen G. Effects of single-session transcranial direct current stimulation on reactive response inhibition. Neurosci Biobehav Rev. (2021) 128:749–65. 10.1016/j.neubiorev.2021.07.013 PubMed DOI

Faria P, Hallett M, Miranda PC. A finite element analysis of the effect of electrode area and inter-electrode distance on the spatial distribution of the current density in tDCS. J Neural Eng. (2011) 8:066017. 10.1088/1741-2560/8/6/066017 PubMed DOI PMC

Frings C, Brinkmann T, Friehs MA, van Lipzig T. Single session tDCS over the left DLPFC disrupts interference processing. Brain Cogn. (2018) 120:1–7. 10.1016/j.bandc.2017.11.005 PubMed DOI

Treasure J, Duarte TA, Schmidt U. Eating disorders. Lancet. (2020) 395:899–911. 10.1016/S0140-6736(20)30059-3 PubMed DOI

Poutanen O, Huuhka K, Perko K. Severe anorexia nervosa, co-occurring major depressive disorder and electroconvulsive therapy as maintenance treatment: a case report. Cases J. (2009) 2:9362. 10.1186/1757-1626-2-9362 PubMed DOI PMC

Saglam T, Aksoy Poyraz C, Poyraz BÇ, Tosun M. Successful use of electroconvulsive therapy in a patient with anorexia nervosa and severe acute-onset obsessive-compulsive disorder. Int J Eat Disord. (2018) 51:1026–8. 10.1002/eat.22923 PubMed DOI

Villalba Martínez G, Justicia A, Salgado P, Ginés JM, Guardiola R, Cedrón C, et al. . A randomized trial of deep brain stimulation to the subcallosal cingulate and nucleus accumbens in patients with treatment-refractory, chronic, and severe anorexia nervosa: initial results at 6 months of follow up. J Clin Med. (2020) 9:1946. 10.3390/jcm9061946 PubMed DOI PMC

Cancelli A, Cottone C, Giordani A, Asta G, Lupoi D, Pizzella V et al. MRI-guided regional personalized electrical stimulation in multisession and home treatments. Front Neurosci. (2018) 12:284. 10.3389/fnins.2018.00284 PubMed DOI PMC

Hasanzadeh F, Mohebbi M, Rostami R. Prediction of rTMS treatment response in major depressive disorder using machine learning techniques and nonlinear features of EEG signal. J Affect Disord. (2019) 256:132–42. 10.1016/j.jad.2019.05.070 PubMed DOI

Zobrazit více v PubMed

ClinicalTrials.gov
NCT03273205