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Is cognitive dysfunction involved in difficult-to-treat depression? Characterizing resistance from a cognitive perspective

  • Clara López-Solà (a1) (a2) (a3), Marta Subirà (a1) (a3), Maria Serra-Blasco (a1), Muriel Vicent-Gil (a1) (a4), Guillem Navarra-Ventura (a1) (a5), Eva Aguilar (a1), Siddarta Acebillo (a1), Diego J. Palao (a1) (a3) (a5) and Narcís Cardoner (a1) (a3) (a5)...

Abstract

Background.

This study aimed to identify clinical and cognitive factors associated with increased risk for difficult-to-treat depression (DTD) or treatment-resistant depression (TRD).

Methods.

A total of 229 adult outpatients with major depression were recruited from the mental health unit at a public hospital. Participants were subdivided into resistant and nonresistant groups according to their Maudsley Staging Model score. Sociodemographic, clinical, and cognitive (objective and subjective measures) variables were compared between groups, and a logistic regression model was used to identify the factors most associated with TRD risk.

Results.

TRD group patients present higher verbal memory impairment than the nonresistant group irrespective of pharmacological treatment or depressive symptom severity. Logistic regression analysis showed that low verbal memory scores (odds ratio [OR]: 2.02; 95% confidence interval [CI]: 1.38–2.95) together with high depressive symptom severity (OR: 1.29; CI95%: 1.01–1.65) were associated with TRD risk.

Conclusions.

Our findings align with neuroprogression models of depression, in which more severe patients, defined by greater verbal memory impairment and depressive symptoms, develop a more resistant profile as a result of increasingly detrimental neuronal changes. Moreover, our results support a more comprehensive approach in the evaluation and treatment of DTD in order to improve illness course. Longitudinal studies are warranted to confirm the predictive value of verbal memory and depression severity in the development of TRD.

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Copyright

This is an Open Access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike licence (http://creativecommons.org/licenses/by-nc-sa/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the same Creative Commons licence is included and the original work is properly cited. The written permission of Cambridge University Press must be obtained for commercial re-use.

Corresponding author

Narcís Cardoner, E-mail: ncardoner@tauli.cat

Footnotes

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Clara López-Solà and Marta Subirà should be considered joint first authors.

Footnotes

References

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[1]Rush, AJ, Aaronson, ST, Demyttenaere, K. Difficult-to-treat depression: a clinical and research roadmap for when remission is elusive. Aust N Z J Psychiatry. 2019;53:109118.
[2]Fava, M, Papakostas, GI, Petersen, T, Mahal, Y, Quitkin, F, Stewart, J, et al.Switching to bupropion in fluoxetine-resistant major depressive disorder. Ann Clin Psychiatry. 2003;15:1722.
[3]Souery, D, Amsterdam, J, de Montigny, C, Lecrubier, Y, Montgomery, S, Lipp, O, et al.Treatment resistant depression: methodological overview and operational criteria. Eur Neuropsychopharmacol. 1999;9:8391.
[4]Berlim, MT, , Turecki G. Definition, assessment, and staging of treatment-resistant refractory major depression: a review of current concepts and methods. Can J Psychiatry. 2007;52:4654.
[5]Ruhé, HG, Van Rooijen, G, Spijker, J, Peeters, FPML, Schene, AH. Staging methods for treatment resistant depression. A systematic review. J Affect Disord. 2012;137:3545.
[6]Fekadu, A, Wooderson, S, Donaldson, C, Markopoulou, K, Masterson, B, Poon, L, et al.A multidimensional tool to quantify treatment resistance in depression: the Maudsley Staging Method. J Clin Psychiatry. 2009;70:177184.
[7]Caraci, F, Calabrese, F, Molteni, R, Bartova, L, Dold, M, Leggio, GM, et al.International Union of Basic and Clinical Pharmacology CIV: the neurobiology of treatment-resistant depression: from antidepressant classifications to novel pharmacological targets. Pharmacol Rev. 2018;70:475504.
[8]Schwert, C, Stohrer, M, Aschenbrenner, S, Weisbrod, M, Schröder, A. Biased neurocognitive self-perception in depressive and in healthy persons. J Affect Disord. 2018;232:96102.
[9]Miskowiak, KW, Petersen, JZ, Ott, CV, Knorr, U, Kessing, LV, Gallagher, P, et al.Predictors of the discrepancy between objective and subjective cognition in bipolar disorder: a novel methodology. Acta Psychiatr Scand. 2016;134:511521.
[10]Srisurapanont, M, Suttajit, S, Eurviriyanukul, K, Varnado, P. Discrepancy between objective and subjective cognition in adults with major depressive disorder. Sci Rep. 2017;7:17.
[11]Petersen, JZ, Porter, RJ, Miskowiak, KW. Clinical characteristics associated with the discrepancy between subjective and objective cognitive impairment in depression. J Affect Disord. 2019;246:763774.
[12]Serra-Blasco, M, Torres, IJ, Vicent-Gil, M, Goldberg, X, Navarra-Ventura, G, Aguilar, E, et al.Discrepancy between objective and subjective cognition in major depressive disorder. Eur Neuropsychopharmacol. 2019;29:4656.
[13]Gupta, M, Holshausen, K, Best, MW, Jokic, R, Milev, R, Bernard, T, et al.Relationships among neurocognition, symptoms, and functioning in treatment-resistant depression. Arch Clin Neuropsychol. 2013;28:272281.
[14]Snyder, HR. Major depressive disorder is associated with broad impairments on neuropsychological measures of executive function: a meta-analysis and review. Psychol Bull. 2014;139:81132.
[15]McClintock, SM, Husain, MM, Greer, TL, Cullum, CM. Association between depression severity and neurocognitive function in major depressive disorder: a review and synthesis. Neuropsychology. 2010;24:934.
[16]Bortolato, B, Miskowiak, KW, Köhler, CA, Maes, M, Fernandes, BS, Berk, M, et al.Cognitive remission: a novel objective for the treatment of major depression? BMC Med. 2016;14:9.
[17]Evans, VC, Iverson, GL, Yatham, LN, Lam, RW. The relationship between neurocognitive and psychosocial functioning in major depressive disorder: a systematic review. J Clin Psychiatry. 2014;75:13591370.
[18]Goodall, J, Fisher, C, Hetrick, S, Phillips, L, Parrish, EM, Allott, K. Neurocognitive functioning in depressed young people: a systematic review and meta-analysis. Neuropsychol Rev. 2018;28:216231.
[19]Keefe, RSE, McClintock, SM, Roth, RM, Murali Doraiswamy, P, Tiger, S, Madhoo, M. Cognitive effects of pharmacotherapy for major depressive disorder: a systematic review. J Clin Psychiatry. 2014;75:864876.
[20]Allott, K, Fisher, CA, Amminger, GP, Goodall, J, Hetrick, S. Characterizing neurocognitive impairment in young people with major depression: state, trait, or scar? Brain Behav. 2016;6:112.
[21]Stordal, KI, Lundervold, AJ, Egeland, J, Mykletun, A, Asbjørnsen, A, Landrø, NI, et al.Impairment across executive functions in recurrent major depression. Nord J Psychiatry. 2004;58:4147.
[22]Paradiso, S, Lamberty, GJ, Garvey, MJ, Robinson, RG. Cognitive impairment in the euthymic phase of chronic unipolar depression. J Nerv Ment Dis. 1997;185:748754.
[23]Jaeger, J, Berns, S, Uzelac, S, Davis-Conway, S. Neurocognitive deficits and disability in major depressive disorder. Psychiatry Res. 2006;145:3948.
[24]Bruder, GE, Alvarenga, JE, Alschuler, D, Abraham, K, Keilp, JG, Hellerstein, DJ, et al.Neurocognitive predictors of antidepressant clinical response. J Affect Disord. 2014;166:108114.
[25]Gallagher, P, Robinson, LJ, Gray, JM, Young, AH, Porter, RJ. Neurocognitive function following remission in major depressive disorder: potential objective marker of response? Aust N Z J Psychiatry. 2007;41:5461.
[26]Story, TJ, Potter, GG, Attix, DK, Welsh-Bohmer, KA, Steffens, DC. Neurocognitive correlates of response to treatment in late-life depression. Am J Geriatr Psychiatry. 2008;16:752759.
[27]Potter, GG, Kittinger, JD, Wagner, HR, Steffens, DC, Krishnan, KRR. Prefrontal neuropsychological predictors of treatment remission in late-life depression. Neuropsychopharmacology. 2004;29:22662271.
[28]Fournier, JC, DeRubeis, RJ, Shelton, RC, Hollon, SD, Amsterdam, JD, Gallop, R. Prediction of response to medication and cognitive therapy in the treatment of moderate to severe depression. J Consult Clin Psychol. 2009;77:775787.
[29]Dunkin, JJ, Leuchter, AF, Cook, IA, Kasl-Godley, JE, Abrams, M, Rosenberg-Thompson, S. Executive dysfunction predicts nonresponse to fluoxetine in major depression. J Affect Disord. 2000;60:1323.
[30]Gorlyn, M, Keilp, JG, Grunebaum, MF, Taylor, BP, Oquendo, MA, Bruder, GE, et al.Neuropsychological characteristics as predictors of SSRI treatment response in depressed subjects. J Neural Transm. 2008;115:12131219.
[31]Malhi, GS, Byrow, Y. Is treatment-resistant depression a useful concept? Evid Based Ment Health. 2016;19:13.
[32]Lezak, MD, Howieson, DB, Loring, DW, with Hannay, HJ, Fischer, JS. Neuropsychological assessment. 4th ed.Oxford, UK: Oxford University Press, 2004.
[33]Sackeim, HA. The definition and meaning of treatment-resistant depression. J Clin Psychiatry. 2001;62(suppl 16):1017.
[34]Hamilton, M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:5662.
[35]Lam, RW, Saragoussi, D, Danchenko, N, Rive, B, Lamy, FX, Brevig, T. Psychometric validation of Perceived Deficits Questionnaire–Depression (PDQ-D) in patients with major depressive disorder (MDD). Value Heal. 2013;16:A330.
[36]Strober, LB, Binder, A, Nikelshpur, OM, Chiaravalloti, N, DeLuca, J. The perceived deficits questionnaire: perception, deficit, or distress? Int J MS Care. 2016;18:183190.
[37]Sullivan, M, Edgley, K, Dehoux, E. A survey of multiple sclerosis: I. Perceived cognitive problems and compensatory strategy use. Can J Rehabil. 1990;4:99105.
[38]Dickson, AL. Book review: Lezak, Muriel Deutsch, (1983). Neuropsychological assessment (2nd ed.). New York: Oxford University Press. J Psychoeduc Assess. 1986;4:9192.
[39]Strauss, E, Sherman, E, Spreen, O. A compendium of neuropsychological tests: administration, norms, and commentary. 3rd ed. New York, NY: Oxford University Press, 2006.
[40]Casals-Coll, M, Sánchez-Benavides, G, Quintana, M, Manero, RM, Rognoni, T, Calvo, L, et al.Estudios normativos españoles en población adulta joven (proyecto NEURONORMA jóvenes): normas para los test de fluencia verbal. Neurología. 2013;28:3340.
[41]Peña-Casanova, J, Quiñones-Úbeda, S, Gramunt-Fombuena, N, Quintana-Aparicio, M, Aguilar, M, Badenes, D, et al.Spanish multicenter normative studies (NEURONORMA project): norms for verbal fluency tests. Arch Clin Neuropsychol. 2009;24:395411.
[42]Nemeroff, CB. Prevalence and management of treatment-resistant depression. J Clin Psychiatry. 2007;68(suppl 8):1725.
[43]Schosser, A, Serretti, A, Souery, D, Mendlewicz, J, Zohar, J, Montgomery, S, et al.European Group for the Study of Resistant Depression (GSRD)—where have we gone so far: review of clinical and genetic findings. Eur Neuropsychopharmacol. 2012;22:453468.
[44]Kautzky, A, Baldinger-Melich, P, Kranz, GS, Vanicek, T, Souery, D, Montgomery, S, et al.A new prediction model for evaluating treatment-resistant depression. J Clin Psychiatry. 2017;78:215222.
[45]Zheng, W, Zhou, Y-L, Liu, W-J, Wang, C-Y, Zhan, Y-N, Li, H-Q, et al.Neurocognitive performance and repeated-dose intravenous ketamine in major depressive disorder. J Affect Disord. 2019;246:241247.
[46]Raes, F, Sienaert, P, Demyttenaere, K, Peuskens, J, Williams, JMG, Hermans, D. Overgeneral memory predicts stability of short-term outcome of electroconvulsive therapy for depression. J ECT. 2008;24:8183.
[47]Kavanaugh, BC, Aaronson, ST, Clarke, GN, Holtzheimer, PE, Johnson, CW, McDonald, WM, et al.Neurocognitive effects of repetitive transcranial magnetic stimulation with a 2-coil device in treatment-resistant major depressive disorder. J ECT. 2018;34:258265.
[48]Romeo, B, Choucha, W, Fossati, P, Rotge, J-Y. Clinical and biological predictors of ketamine response in treatment-resistant major depression: review. Encephale. 2017;43:354362.
[49]Campbell, S, MacQueen, G. The role of the hippocampus in the pathophysiology of major depression. J Psychiatry Neurosci. 2004, 2004;29:417426.
[50]Shah, PJ, Ebmeier, KP, Glabus, MF, Goodwin, GM. Cortical grey matter reductions associated with treatment-resistant chronic unipolar depression. Controlled magnetic resonance imaging study. Br J Psychiatry. 1998;172:527532.
[51]Seeberg, I, Kjaerstad, HL, Miskowiak, KW. Neural and behavioral predictors of treatment efficacy on mood symptoms and cognition in mood disorders: a systematic review. Front Psychiatry. 2018;9:337.
[52]Dickerson, BC, Eichenbaum, H. The episodic memory system: neurocircuitry and disorders. Neuropsychopharmacology. 2010;35:86104.
[53]Rolls, ET. The storage and recall of memories in the hippocampo-cortical system. Cell Tissue Res. 2018;373:577604.
[54]MacQueen, G, Frodl, T. The hippocampus in major depression: evidence for the convergence of the bench and bedside in psychiatric research? Mol Psychiatry. 2011;16:252264.
[55]Joober, R, Rouleau, GA, Lal, S, Dixon, M, O’Driscoll, G, Palmour, R, et al.Neuropsychological impairments in neuroleptic-responder vs. non-responder schizophrenic patients and healthy volunteers. Schizophr Res. 2002;53:229238.
[56]de Bartolomeis A, , Balletta, R, Giordano, S, Buonaguro, EF, Latte, G, Iasevoli, F. Differential cognitive performances between schizophrenic responders and non-responders to antipsychotics: correlation with course of the illness, psychopathology, attitude to the treatment and antipsychotics doses. Psychiatry Res. 2013;210:387395.
[57]Wild, J, Gur, RC. Verbal memory and treatment response in post-traumatic stress disorder. Br J Psychiatry. 2008;193:254255.
[58]Chao, LL. Evidence of objective memory impairments in deployed Gulf War veterans with subjective memory complaints. Mil Med. 2017;182:e1625e1631.
[59]Scott, JC, Matt, GE, Wrocklage, KM, Crnich, C, Jordan, J, Southwick, SM, et al.A quantitative meta-analysis of neurocognitive functioning in posttraumatic stress disorder. Psychol Bull. 2015;141:105140.
[60]Hammar, Å, Årdal, G. Verbal memory functioning in recurrent depression during partial remission and remission-brief report. Front Psychol. 2013;4:652.
[61]Peters, AT, Jacobs, RH, Crane, NA, Ryan, KA, Weisenbach, SL, Ajilore, O, et al.Domain-specific impairment in cognitive control among remitted youth with a history of major depression. Early Interv Psychiatry. 2017;11:383392.
[62]Huang, CL-C. Residual cognitive deficit in adults with depression who recovered after 6-month treatment: stable versus state-dependent markers. J Clin Med Res. 2009;1:202206.
[63]Miskowiak, KW, Vinberg, M, Macoveanu, J, Ehrenreich, H, Køster, N, Inkster, B, et al.Effects of erythropoietin on hippocampal volume and memory in mood disorders. Biol Psychiatry. 2015;78:270277.

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Is cognitive dysfunction involved in difficult-to-treat depression? Characterizing resistance from a cognitive perspective

  • Clara López-Solà (a1) (a2) (a3), Marta Subirà (a1) (a3), Maria Serra-Blasco (a1), Muriel Vicent-Gil (a1) (a4), Guillem Navarra-Ventura (a1) (a5), Eva Aguilar (a1), Siddarta Acebillo (a1), Diego J. Palao (a1) (a3) (a5) and Narcís Cardoner (a1) (a3) (a5)...

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Is cognitive dysfunction involved in difficult-to-treat depression? Characterizing resistance from a cognitive perspective

  • Clara López-Solà (a1) (a2) (a3), Marta Subirà (a1) (a3), Maria Serra-Blasco (a1), Muriel Vicent-Gil (a1) (a4), Guillem Navarra-Ventura (a1) (a5), Eva Aguilar (a1), Siddarta Acebillo (a1), Diego J. Palao (a1) (a3) (a5) and Narcís Cardoner (a1) (a3) (a5)...
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