Skip to main content
    • Aa
    • Aa
  • Get access
    Check if you have access via personal or institutional login
  • Cited by 64
  • Cited by
    This article has been cited by the following publications. This list is generated based on data provided by CrossRef.

    Aker, Martin Bø, Ragnhild Harmer, Catherine Stiles, Tore C. and Landrø, Nils Inge 2016. Inhibition and response to error in remitted major depression. Psychiatry Research, Vol. 235, p. 116.

    Allott, Kelly Fisher, Caroline A. Amminger, Gunther Paul Goodall, Joanne and Hetrick, Sarah 2016. Characterizing neurocognitive impairment in young people with major depression: state, trait, or scar?. Brain and Behavior, Vol. 6, Issue. 10, p. e00527.

    Bora, Emre and Berk, Michael 2016. Theory of mind in major depressive disorder: A meta-analysis. Journal of Affective Disorders, Vol. 191, p. 49.

    Bortolato, Beatrice Miskowiak, Kamilla W. Köhler, Cristiano A. Maes, Michael Fernandes, Brisa S. Berk, Michael and Carvalho, André F. 2016. Cognitive remission: a novel objective for the treatment of major depression?. BMC Medicine, Vol. 14, Issue. 1,

    Brühl, Annette B. and Sahakian, Barbara J. 2016. Drugs, games, and devices for enhancing cognition: implications for work and society. Annals of the New York Academy of Sciences, Vol. 1369, Issue. 1, p. 195.

    Brunoni, André Russowsky Tortella, Gabriel Benseñor, Isabela Martins Lotufo, Paulo Andrade Carvalho, André Ferrer and Fregni, Felipe 2016. Cognitive effects of transcranial direct current stimulation in depression: Results from the SELECT-TDCS trial and insights for further clinical trials. Journal of Affective Disorders, Vol. 202, p. 46.

    Clark, Marci DiBenedetti, Dana and Perez, Vanessa 2016. Cognitive dysfunction and work productivity in major depressive disorder. Expert Review of Pharmacoeconomics & Outcomes Research, Vol. 16, Issue. 4, p. 455.

    Depping, Malte S. Wolf, Nadine D. Vasic, Nenad Sambataro, Fabio Thomann, Philipp A. and Wolf, R. Christian 2016. Common and distinct structural network abnormalities in major depressive disorder and borderline personality disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 65, p. 127.

    Griffiths, Kristi R. Lagopoulos, Jim Hermens, Daniel F. Lee, Rico S.C. Guastella, Adam J. Hickie, Ian B. and Balleine, Bernard W. 2016. Impaired causal awareness and associated cortical–basal ganglia structural changes in youth psychiatric disorders. NeuroImage: Clinical, Vol. 12, p. 285.

    Hammar, Åsa Neto, Emanuel Clemo, Leila Hjetland, Gunnhild J. Hugdahl, Kenneth and Elliott, Rebecca 2016. Striatal hypoactivation and cognitive slowing in patients with partially remitted and remitted major depression. PsyCh Journal, Vol. 5, Issue. 3, p. 191.

    Kandola, Aaron Hendrikse, Joshua Lucassen, Paul J. and Yücel, Murat 2016. Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment. Frontiers in Human Neuroscience, Vol. 10,

    Kassel, Michelle T. Rao, Julia A. Walker, Sara J. Briceño, Emily M. Gabriel, Laura B. Weldon, Anne L. Avery, Erich T. Haase, Brennan D. Peciña, Marta Considine, Ciaran M. Noll, Douglas C. Bieliauskas, Linas A. Starkman, Monica N. Zubieta, Jon-Kar Welsh, Robert C. Giordani, Bruno Weisenbach, Sara L. and Langenecker, Scott A. 2016. Decreased Fronto-Limbic Activation and Disrupted Semantic-Cued List Learning in Major Depressive Disorder. Journal of the International Neuropsychological Society, Vol. 22, Issue. 04, p. 412.

    Liu, Yansong Zhang, Fuquan Wang, Zhiqiang Cao, Leiming Wang, Jun Na, Aiguo Sun, Yujun and Zhao, Xudong 2016. Overgeneral autobiographical memory at baseline predicts depressive symptoms at follow-up in patients with first-episode depression. Psychiatry Research, Vol. 243, p. 123.

    Mazereeuw, Graham Herrmann, Nathan Oh, Paul I. Ma, David W.L. Wang, Cheng Tao Kiss, Alexander and Lanctôt, Krista L. 2016. Omega-3 Fatty Acids, Depressive Symptoms, and Cognitive Performance in Patients With Coronary Artery Disease. Journal of Clinical Psychopharmacology, Vol. 36, Issue. 5, p. 436.

    Miskowiak, K.W. Ott, C.V. Petersen, J.Z. and Kessing, L.V. 2016. Systematic review of randomized controlled trials of candidate treatments for cognitive impairment in depression and methodological challenges in the field. European Neuropsychopharmacology,

    Miskowiak, K. W. Vinberg, M. Glerup, L. Paulson, O. B. Knudsen, G. M. Ehrenreich, H. Harmer, C. J. Kessing, L. V. Siebner, H. R. and Macoveanu, J. 2016. Neural correlates of improved executive function following erythropoietin treatment in mood disorders. Psychological Medicine, Vol. 46, Issue. 08, p. 1679.

    Osuch, E. A. Manning, K. Hegele, R. A. Théberge, J. Neufeld, R. Mitchell, D. Williamson, P. and Gardner, R. C. 2016. Depression, marijuana use and early-onset marijuana use conferred unique effects on neural connectivity and cognition. Acta Psychiatrica Scandinavica, Vol. 134, Issue. 5, p. 399.

    Ott, Caroline Vintergaard Bjertrup, Anne Juul Jensen, Johan Høy Ullum, Henrik Sjælland, René Purdon, Scot E. Vieta, Eduard Kessing, Lars V. and Miskowiak, Kamilla W. 2016. Screening for cognitive dysfunction in unipolar depression: Validation and evaluation of objective and subjective tools. Journal of Affective Disorders, Vol. 190, p. 607.

    Otte, Christian Gold, Stefan M. Penninx, Brenda W. Pariante, Carmine M. Etkin, Amit Fava, Maurizio Mohr, David C. and Schatzberg, Alan F. 2016. Major depressive disorder. Nature Reviews Disease Primers, Vol. 2, p. 16065.

    Pantzar, Alexandra Atti, Anna Rita Fratiglioni, Laura Fastbom, Johan Bäckman, Lars and Laukka, Erika J. 2016. Cognitive performance in unipolar old-age depression: a longitudinal study. International Journal of Geriatric Psychiatry,


Cognitive impairment in euthymic major depressive disorder: a meta-analysis

  • E. Bora (a1), B. J. Harrison (a1), M. Yücel (a1) (a2) and C. Pantelis (a1)
  • DOI:
  • Published online: 26 October 2012

There is evidence to suggest that cognitive deficits might persist beyond the acute stages of illness in major depressive disorder (MDD). However, the findings are somewhat inconsistent across the individual studies conducted to date. Our aim was to conduct a systematic review and meta-analysis of existing studies that have examined cognition in euthymic MDD patients.


Following a systematic search across several publication databases, meta-analyses were conducted for 27 empirical studies that compared euthymic adult MDD patients (895 participants) and healthy controls (997 participants) across a range of cognitive domains. The influence of demographic variables and confounding factors, including age of onset and recurrent episodes, was examined.


Compared with healthy controls, euthymic MDD patients were characterized by significantly poorer cognitive functions. However, the magnitude of observed deficits, with the exception of inhibitory control, were generally modest when late-onset cases were excuded. Late-onset cases demonstrated significantly more pronounced deficits in verbal memory, speed of information processing and some executive functions.


Cognitive deficits, especially poor response inhibition, are likely to be persistent features, at least of some forms, of adult-onset MDD. More studies are necessary to examine cognitive dysfunction in remitted psychotic, melancholic and bipolar spectrum MDD. Cognitive deficits overall appear to be more common among patients with late-onset depression, supporting the theories suggesting that possible vascular and neurodegenerative factors play a role in a substantial number of these patients.

Corresponding author
*Address for correspondence: Dr E. Bora, Melbourne Neuropsychiatry Centre, Alan Gilbert Building NNF level 3, 161 Barry Street, Carlton South, VIC 3053, Australia. (Email:
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

MP Austin , P Mitchell , K Wilhelm , G Parker , I Hickie , H Brodaty , J Chan , K Eyers , M Milic , D Hadzi-Pavlovic (1999). Cognitive function in depression: a distinct pattern of frontal impairment in melancholia? Psychological Medicine 29, 7385.

K Baba , H Baba , I Noguchi , R Arai , T Suzuki , M Mimura , H Arai (2010). Executive dysfunction in remitted late-life depression: Juntendo University Mood Disorder Projects (JUMP). Journal of Neuropsychiatry and Clinical Neuroscience 22, 7074.

L Bax , LM Yu , N Ikeda , H Tsuruta , KGM Moons (2006). Development and validation of MIX: comprehensive free software for meta-analysis of causal research data. BMC Medical Research Methodology 6, 50.

A Behnken , S Schöning , J Gerss , C Konrad , R de Jong-Meyer , P Zwanzger , V Arolt (2010). Persistent non-verbal memory impairment in remitted major depression – caused by encoding deficits? Journal of Affective Disorders 122, 144148.

RK Bhalla , MA Butters , BH Mulsant , AE Begley , MD Zmuda , B Schoderbek , BG Pollock , CF Reynolds 3rd, JT Becker (2006). Persistence of neuropsychologic deficits in the remitted state of late-life depression. American Journal of Geriatric Psychiatry 14, 419427.

A Bhardwaj , P Wilkinson , C Srivastava , M Sharma (2010). Cognitive deficits in euthymic patients with recurrent depression. Journal of Nervous Mental Disorders 198, 513515.

E Biringer , A Mykletun , K Sundet , R Kroken , KI Stordal , A Lund (2007). A longitudinal analysis of neurocognitive function in unipolar depression. Journal of Clinical and Experimental Neuropsychology 29, 879891.

HP Blumberg , HC Leung , P Skudlarski , CM Lacadie , CA Fredericks , BC Harris , DS Charney , JC Gore , JH Krystal , BS Peterson (2003). A functional magnetic resonance imaging study of bipolar disorder: state- and trait-related dysfunction in ventral prefrontal cortices. Archives of General Psychiatry 60, 601609.

E Bora , A Fornito , C Pantelis , M Yucel (2012 a). Gray matter abnormalities in major depressive disorder: a meta-analysis of voxel based morphometry studies. Journal of Affective Disorders 138, 918.

E Bora , A Fornito , M Yucel , C Pantelis (2010 a). Voxelwise meta-analysis of gray matter abnormalities in bipolar disorder. Biological Psychiatry 67, 10971105.

E Bora , M Yucel , C Pantelis (2009). Cognitive endophenotypes of bipolar disorder: a meta-analysis of neuropsychological deficits in euthymic patients and their first-degree relatives. Journal of Affective Disorders 113, 120.

E Bora , M Yucel , C Pantelis (2010 b). Cognitive impairment in affective psychoses. Schizophrenia Bulletin 36, 112125.

S Campbell , M Marriott , C Nahmias , GM MacQueen (2004). Lower hippocampal volume in patients suffering from depression: a meta-analysis. American Journal of Psychiatry 161, 598607.

L Clark , MJ Kempton , A Scarnà , PM Grasby , GM Goodwin (2005 a). Sustained attention-deficit confirmed in euthymic bipolar disorder but not in first-degree relatives of bipolar patients or euthymic unipolar depression. Biological Psychiatry 57, 183187.

L Clark , A Sarna , GM Goodwin (2005 b). Impairment of executive function but not memory in first-degree relatives of patients with bipolar I disorder and in euthymic patients with unipolar depression. American Journal of Psychiatry 162, 19801982.

S Fennig , A Mottes , G Ricter-Levin , I Treves , Y Levkovitz (2002). Everyday memory and laboratory memory tests: general function predictors in schizophrenia and remitted depression. Journal of Nervous and Mental Disorders 190, 677682.

SK Fleming , C Blasey , AF Schatzberg (2004). Neuropsychological correlates of psychotic features in major depressive disorders: a review and meta-analysis. Journal of Psychiatry Research 38, 2735.

R Gallassi , R Di Sarro , A Morreale , M Amore (2006). Memory impairment in patients with late-onset major depression: the effect of antidepressant therapy. Journal of Affective Disorders 91, 243250.

P Gorwood , E Corruble , B Falissard , GM Goodwin (2008). Toxic effects of depression on brain function: impairment of delayed recall and the cumulative length of depressive disorder in a large sample of depressed outpatients. American Journal of Psychiatry 165, 731739.

CB Hartberg , K Sundet , LM Rimol , UK Haukvik , EH Lange , R Nesvåg , I Melle , OA Andreassen , I Agartz (2011). Subcortical brain volumes relate to neurocognition in schizophrenia and bipolar disorder and healthy controls. Progress in Neuropsychopharmacology and Biological Psychiatry 35, 11221130.

BJ Hasselbalch , U Knorr , LV Kessing (2011). Cognitive impairment in the remitted state of unipolar depressive disorder: a systematic review. Journal of Affective Disorders 134, 2031.

I Herrera-Guzmán , E Gudayol-Ferré , JE Herrera-Abarca , D Herrera-Guzmán , P Montelongo-Pedraza , F Padrós Blázquez , M Peró-Cebollero , J Guàrdia-Olmos (2010). Major depressive disorder in recovery and neuropsychological functioning: effects of selective serotonin reuptake inhibitor and dual inhibitor depression treatments on residual cognitive deficits in patients with major depressive disorder in recovery. Journal of Affective Disorder 123, 341350.

LL Herrmann , GM Goodwin , KP Ebmeier (2007). The cognitive neuropsychology of depression in the elderly. Psychological Medicine 37, 16931702.

LL Herrmann , M Le Masurier , KP Ebmeier (2008). White matter hyperintensities in late life depression: a systematic review. Journal of Neurology, Neurosurgery and Psychiatry 79, 619624.

JPT Higgins , SG Thompson (2002). Quantifying heterogeneity in a meta-analysis. Statistical Medicine 21, 15391558.

Z Hou , Y Yuan , Z Zhang , F Bai , G Hou , J You (2012). Longitudinal changes in hippocampal volumes and cognition in remitted geriatric depressive disorder. Behaviour and Brain Research 227, 3035.

Y Kaneda (2009). Verbal working memory impairment in patients with current episode of unipolar major depressive disorder and in remission. Clinical Neuropharmacology 32, 346347.

RS Lee , DF Hermens , MA Porter , MA Redoblado-Hodge (2012). A meta-analysis of cognitive deficits in first-episode major depressive disorder. Journal of Affective Disorders 140, 113124.

CT Li , CP Lin , KH Chou , IY Chen , JC Hsieh , CL Wu , WC Lin , TP Su (2010). Structural and cognitive deficits in remitting and non-remitting recurrent depression: a voxel-based morphometric study. Neuroimage 50, 347356.

WR Marchand , D Yurgelun-Todd (2010). Striatal structure and function in mood disorders: a comprehensive review. Bipolar Disorders 12, 764785.

LM McDermott , KP Ebmeier (2009). A meta-analysis of depression severity and cognitive function. Journal of Affective Disorders 119, 18.

D Moher , A Liberati , J Tetzlaff , DG Altman ; PRISMA Group (2009). Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. British Medical Journal 339, b2535.

Y Nakano , H Baba , H Maeshima , A Kitajima , Y Sakai , K Baba , T Suzuki , M Mimura , H Arai (2008). Executive dysfunction in medicated, remitted state of major depression. Journal of Affective Disorders 111, 4651.

P Neu , U Kiesslinger , P Schlattmann , FM Reischies (2001). Time-related cognitive deficiency in four different types of depression. Psychiatry Research 103, 237247.

JT O'Brien , A Lloyd , I McKeith , A Gholkar , N Ferrier (2004). A longitudinal study of hippocampal volume, cortisol levels, and cognition in older depressed subjects. American Journal of Psychiatry 161, 20812090.

Y Paelecke-Habermann , J Pohl , B Leplow (2005). Attention and executive functions in remitted major depression patients. Journal of Affective Disorders 89, 125135.

A Pedersen , K Küppers , A Behnken , K Kroker , S Schöning , BT Baune , F Rist , V Arolt , T Suslow (2009). Implicit and explicit procedural learning in patients recently remitted from severe major depression. Psychiatry Research 169, 16.

MJ Portella , T Marcos , L Rami , V Navarro , C Gastó , M Salamero (2003). Residual cognitive impairment in late-life depression after a 12-month period follow-up. International Journal of Geriatric Psychiatry 18, 571576.

M Preiss , H Kucerova , J Lukavsky , H Stepankova , P Sos , R Kawaciukova (2009). Cognitive deficits in the euthymic phase of unipolar depression. Psychiatry Research 169, 235239.

MA Rogers , JL Bradshaw , C Pantelis , JG Phillips (1998). Frontostriatal deficits in unipolar major depression. Brain Research Bulletin 47, 297310.

J Vilalta-Franch , S López-Pousa , J Llinàs-Reglà , L Calvó-Perxas , J Merino-Aguado , J Garre-Olmo (2012). Depression subtypes and 5-year risk of dementia and Alzheimer disease in patients aged 70 years. International Journal of Geriatric Psychiatry. Published online: 16May2012. doi:10.1002/gps.3826.

CE Wang , M Halvorsen , K Sundet , AL Steffensen , A Holte , K Waterloo (2006). Verbal memory performance of mildly to moderately depressed outpatient younger adults. Journal of Affective Disorders 92, 283286.

P Weiland-Fiedler , K Erickson , T Waldeck , DA Luckenbaugh , D Pike , O Bonne , DS Charney , A Neumeister (2004). Evidence for continuing neuropsychological impairments in depression. Journal of Affective Disorders 82, 253258.

G Xu , K Lin , D Rao , Y Dang , H Ouyang , Y Guo , J Ma , J Chen (2012). Neuropsychological performance in bipolar I, bipolar II and unipolar depression patients: a longitudinal, naturalistic study. Journal of Affective Disorders 136, 328339.

YC Yeh , HY Tsang , PY Lin , YT Kuo , CF Yen , CC Chen , GC Liu , CS Chen (2011). Subtypes of mild cognitive impairment among the elderly with major depressive disorder in remission. American Journal of Geriatric Psychiatry 19, 923931.

YC Yen , GW Rebok , JJ Gallo , RN Jones , SL Tennstedt (2011). Depressive symptoms impair everyday problem-solving ability through cognitive abilities in late life. American Journal of Geriatric Psychiatry 19, 142150.

Y Yuan , Z Zhang , F Bai , H Yu , Y Shi , Y Qian , W Liu , J You , X Zhang , Z Liu (2008). Abnormal neural activity in the patients with remitted geriatric depression: a resting-state functional magnetic resonance imaging study. Journal of Affective Disorders 111, 145152.

ME Zimmerman , MP DelBello , GE Getz , PK Shear , SM Strakowski (2006). Anterior cingulate subregion volumes and executive function in bipolar disorder. Bipolar Disorders 8, 281288.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
Please enter your name
Please enter a valid email address
Who would you like to send this to? *