Cognitive impairment in euthymic major depressive disorder: a meta-analysis
Open accessAbstract
Background: 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. Method: 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. Results: 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. Conclusions: 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.
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Many patients suffering from MDD present some form of dysfunction in certain cognitive domains; this affects >60% of all depressed patients and significantly impacts treatment outcomes.
“Many patients suffering from MDD present some form of dysfunction in certain cognitive domains; this affects >60% of all depressed patients and significantly impacts treatment outcomes (Bora et al, 2013; Gualtieri and Morgan, 2008; Lee et al, 2012; Murrough et al, 2011; Rock et al, 2014; Trivedi and Greer, 2014).”
From A Randomized, Placebo-Controlled, Active-Reference, Double-Blind, Flexible-Dose Study of the Efficacy of Vortioxetine on Cognitive Function in Major Depressive Disorder (2015) · cites this paper as Bora et al, 2013
The Introduction and Cognitive domains sections support the claim that cognitive dysfunction occurs in MDD across several domains. The Discussion’s 60% figure describes overlap in cognitive performance between late-onset patients and controls, not the proportion of all depressed patients affected. The paper does not establish that cognitive dysfunction significantly impacts treatment outcomes. (LLM, conf=0.90)
Experimental — accuracy not yet measuredSeveral cognitive domains, including executive function, attention, memory, processing speed, and psychomotor skills, are affected during both symptomatic and remitted phases in MDD.
“Several cognitive domains, including executive function, attention, memory, processing speed, and psychomotor skills, are affected during both symptomatic as well as “remitted” phases in MDD (Marazziti et al., 2010; Lee et al., 2012; Bora et al., 2013; Bortolato et al., 2014).”
From The Cognitive Effects of Antidepressants in Major Depressive Disorder: A Systematic Review and Meta-Analysis of Randomized Clinical Trials (2016) · cites this paper as Bora et al., 2013
The Cognitive domains results (page not provided) report poorer performance in euthymic MDD patients across the domains studied, including executive function, attention, memory, and processing speed. The Introduction says cognitive functions are often impaired in MDD, but this meta-analysis does not establish that every listed domain is affected during symptomatic phases; the Discussion addresses psychomotor inhibitory control specifically, not psychomotor skills broadly. (LLM, conf=0.84)
Experimental — accuracy not yet measuredEvidence varies regarding the domain most impacted by depression across the lifespan and includes executive function, processing speed, and verbal memory.
“Although some have demonstrated that individuals experiencing depression perform worse across all neurocognitive domains (e.g., Bora et al., 2013;Parkinson et al., 2020), evidence varies regarding the domain most impacted by depression across the lifespan and include executive function (Alexopoulos, 2021), processing speed (Göke et al., 2024), and verbal memory (Bora et al., 2013;Goodall et al., 2”
From Neurocognitive effects of theta burst stimulation for treatment-resistant depression in adults: A systematic review and recommendations for future research (2025) · cites this paper as Bora et al., 2013
The Cognitive domains section reports that healthy controls outperformed euthymic MDD patients in every cognitive domain examined. The Discussion identifies verbal memory as a particularly pronounced deficit in patients whose depression began late in life. The citing sentence extends these findings to people experiencing depression generally, whereas this meta-analysis concerns patients in remission. (LLM, conf=0.84)
Experimental — accuracy not yet measuredMDD is associated with impairments in cognitive functioning in domains such as executive function, working memory, visuospatial short-term memory, immediate and delayed free recall, psychomotor speed, and verbal learning.
“Mood disorders are also associated with impairments in cognitive functioning.”
From A Randomized, Placebo-Controlled, Active-Reference, Double-Blind, Flexible-Dose Study of the Efficacy of Vortioxetine on Cognitive Function in Major Depressive Disorder (2015) · cites this paper as Bora et al, 2013
Neurocognitive dysfunction is commonly reported during depressive episodes and even during remission.
“Neurocognitive dysfunction is commonly reported during depressive episodes and even during remission (Bora et al., 2013;Conradi et al., 2011;Hasselbalch et al., 2011).”
From Neurocognitive effects of theta burst stimulation for treatment-resistant depression in adults: A systematic review and recommendations for future research (2025) · cites this paper as Bora et al., 2013
Cognitive dysfunction is a core symptom of depression that can persist during the remitted state, worsens with increasing numbers of depressive episodes, and results in disrupted psychosocial functioning.
“As cognitive dysfunction is a core symptom of depression that can persist during the remitted state (Bora et al., 2013;Hasselbalch et al., 2011;Kaser et al., 2017), worsens with increasing numbers of depressive episodes (Hasselbalch et al., 2013), and results in disrupted psychosocial functioning (Hasselbalch et al., 2011;Kaser et al., 2017;McCall and Dunn, 2003)”
From Neurocognitive effects of theta burst stimulation for treatment-resistant depression in adults: A systematic review and recommendations for future research (2025) · cites this paper as Bora et al., 2013
DBS is typically reserved for patients with the most severe forms of TRD.
“As pointed out by Fitzgerald 195 , DBS is typically reserved for patients with the most severe forms of TRD”
From Major depressive disorder (2016) · cites this paper as [195]
The Discussion and results passages address cognitive impairment in euthymic major depressive disorder, not eligibility for deep brain stimulation. Searches for DBS, treatment-resistant depression, and Fitzgerald found no passage in our copy supporting the claim. (LLM, conf=0.76)
Experimental — accuracy not yet measuredEven after remission following successful antidepressant treatment, most MDD patients continue to experience cognitive deficits, particularly in executive function, memory, and attention.
“Even after remission following successful antidepressant treatment, most patients continue to experience cognitive deficits, particularly within domains of executive function, memory, and attention (Hammar and Ardal, 2009; Bora et al., 2013; Rock et al., 2013; Popovic et al., 2015; Solé et al., 2015).”
From Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment (2016) · cites this paper as Bora et al., 2013
Age is a correlate of poor cognitive performance in major depressive disorder.
“Moreover, these analyses noted an effect of age as a correlate of poor cognitive performance in MDD, introducing disparate etiopathogenic mechanisms (e.g. vascular and neurodegenerative factors).”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [39]
Executive dysfunction, namely lower inhibitory control, can persist after improvement of depressive symptoms in euthymic adult subjects with major depressive disorder.
“Finally, a meta-analysis of 27 studies investigating euthymic adult subjects with MDD showed that executive dysfunction (namely lower inhibitory control) could persist after improvement of depressive symptoms [39].”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [39]
Subjects with late-onset depression (i.e. >60 years old) are likely to experience increased impairment in verbal memory, processing speed, and executive function with respect to depressed adults.
“Subjects with late-onset depression (i.e. >60 years old) are likely to experience increased impairment in verbal memory, processing speed, and executive function with respect to depressed adults [39].”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [39]
Cognitive symptoms persist beyond the symptoms of low mood.
“Cognitive symptoms are seen in first-episode depression [6,8], persist beyond the symptoms of low mood [9-11], contribute to the risk of relapse [12], and worsen with repeated depressive episodes [13,14].”
From Wearable technology for high-frequency cognitive and mood assessment in major depressive disorder: longitudinal observational study (2019) · cites this paper as [11]
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- Authors
- Bora, E., Harrison, B. J., Yücel, M., & Pantelis, C.
- Affiliations
- The University of Melbourne (AU)
- Corresponding author
- Bora, E.
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2012-10-26
- Volume
- 43
- Issue
- 10
- Pages
- 2017-2026
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- OpenAlex
- W2020449419
- Cited by
- 551
- References
- 56
- Citations by year
- 2026: 31 · 2025: 38 · 2024: 32 · 2023: 42 · 2022: 57 · 2021: 51 · 2020: 50 · 2019: 51 · 2018: 50 · 2017: 37 · 2016: 44 · 2015: 41 · 2014: 15 · 2013: 11 · 2012: 1
- FWCI
- 2.49
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- Medical Research Council
- National Health and Medical Research Council (628509, 1021973, 566529, 628386)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- major depressive disorder, cognitive impairment, late-onset depression, response inhibition, verbal memory, processing speed, executive function, age of onset, recurrent depression
- MeSH terms
- Cognition Disorders, Major Depressive Disorder, Depressive Disorder, Major, Humans
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