Cognitive impairment in euthymic major depressive disorder: a meta-analysis
Summary (2 min read)
Introduction
- Major depressive disorder (MDD) is a heterogeneous mental disorder with high prevalence.
- A meta-analytic review of the existing literature is required to identify the most consistent cognitive features of euthymic MDD patients and the relationship of putative cognitive deficits with relevant clinical factors.
Method
- The authors meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (Moher et al. 2009).
- The reference lists of identified published studies were also cross-checked for additional studies.
- Inclusion criteria for studies were that they: (1) included neuropsychological data pertaining to a euthymic adult (age >17 years) MDD patient group and a healthy control group; (2) reported sufficient data to estimate effect sizes (Cohen’s d) ; and (3) used Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD) criteria to diagnose MDD.
- For the purposes of this study, the authors also define a ‘strict euthymia’ category (7<HAMD or 10<MADRS, and being remitted for at least 2 months).
- In addition to task-specific analyses, the authors grouped individual tasks into broader cognitive domains of ‘executive function’, ‘working memory’, ‘attention’, ‘processing speed’, ‘ semantic fluency’, ‘verbal memory’ and ‘visual memory’.
Statistical analysis
- Meta-analyses were performed using MIX software version 1.7 on a Windows platform (Bax et al. 2006).
- Effect sizes were weighted using the inverse variance method.
- When the Q test was significant ‘ I2 ’ – a measure of the degree of inconsistency in the studies’ results – was used to quantify heterogeneity (Higgins & Thompson, 2002).
- The authors also calculated homogeneity statistics using Qbet to test for differences between late-onset (LOD) and earlier-onset adult depression (EOD).
- For studies that reported both EOD and LOD in elderly patients without providing separate data for each group, the study was classified as LOD.
Global cognition
- The authors composite measure of global cognition was significantly different between euthymic MDD patients compared with healthy controls (d=0.47), with patients having lower scores in global cognition (Table 2).
- There was no evidence for publication bias and the distribution of effect sizes was very homogeneous (I2=0).
- When repeating analyses on the basis of more stringent criteria for remission (cut-off score and at least 2 months’ duration), the magnitude of impairment remained similiar (d=0.50).
Cognitive domains
- Healthy controls significantly outperformed euthymic MDD patients in all cognitive domains (d range 0.39–0.59) (Table 2).
- Task-specific analyses indicated that healthy controls performed significantly better than MDD patients in Stroop interference (d=0.74), Trail-Making Test part A (d=0.39), Trail-Making Test part B (d=0.48), digit span backwards (d=0.41), list learning (d=0.42), list recall (d=0.39), and animal naming (d=0.57), but not in phonetic fluency, Wisconson Card Sorting Test (WCST) perseveration, digit span forwards and list recognition.
- There was no evidence of publication bias in any of the cognitive domains or individual tasks.
- The distribution of effect sizes was heterogeneous except the attention domain and three of the individual tasks (Stroop interference, digit backwards, WCST perseveration).
- The magnitudes of this heterogeneoity were quite small (range I2=0 to 0.22) for all measures.
LOD v. controls
- Compared with the whole-sample analyses, specific meta-analyses in LOD patients identified more severe cognitive impairment for global cognition (d=0.64) and for most cognitive domains (range of d=0.42–1.10), with the largest effect size occuring in the domain of verbal memory (Table 2).
- It was not possible to conduct meta-analyses for the attention and semantic fluency domains due to a lack of sufficient studies in LOD patients.
- Unlike the wholesample analyses, the distribution of effect sizes was homogeneous across all domains in LOD patients, apart from the domain of visual memory.
- There was no evidence of publication bias.
EOD v. controls
- For most cognitive domains, the magnitude of cognitive deficits observed in EOD samples was notably smaller (range d=0.21–0.54).
- When analyses were limited to unipolar patients, the magnititude of observed effects (d=0.30–0.49) was very similar to that of the full EOD sample.
- For specific tasks, EOD patients were most prominently impaired in Stroop interference (d=0.82).
- Consistent with the whole-sample analyses, there was significant heterogeneity of the distribution of effect sizes for most cognitive measures, but the magnitude of such heterogeneity was modest (range I2=0–0.29).
EOD v. LOD
- Cognitive deficits in LOD patients were significantly more severe than those in EOD patients in terms of processing speed (Qbet=7.4, p<0.01) and verbal memory (Qbet=30.4, p<0.001) (see online Supplementary Figs S2–S5).
- The between-group differences for executive functions were driven by 4 E .
Discussion
- The authors meta-analytical review has demonstrated overall that cognitive deficits are evident in euthymic MDD patients.
- Another limitation relates to the fact that all but two studies included patients receiving antidepressant medication and most studies did not report medication doses, which the authors were unable to formally examine by metaanalysis.
- Such deficits are more pronounced in patients who experienced their first episode of illness late in life, particularly in the domain of processing speed and verbal memory.
- Within the broad and heterogeneous diagnostic spectrum of MDD, persistent cognitive deficits might be important functional markers of some patient groups.
Yen YC, Rebok GW, Gallo JJ, Jones RN, Tennstedt SL
- Depressive symptoms impair everyday problem-solving ability through cognitive abilities in late life.
- Abnormal neural activity in the patients with remitted geriatric depression : a resting-state functional magnetic resonance imaging study.
- Anterior cingulate subregion volumes and executive function in bipolar disorder.
Did you find this useful? Give us your feedback
Citations
1,728 citations
1,341 citations
Cites background or methods from "Cognitive impairment in euthymic ma..."
...To our knowledge, to date, only two groups have reviewed cognitive function in patients remitted from depression (Hasselbalch et al. 2011; Bora et al. 2013)....
[...]
...Meanwhile, the review by Bora et al. (2013) included 895 remitted patients (and 997 controls) from 27 studies and, using standardized effect sizes, revealed cognitive deficits in a composite measure of global cognition, in individual cognitive domain composites and in a subset of specific tasks....
[...]
643 citations
Cites background from "Cognitive impairment in euthymic ma..."
...This is the case in both unipolar depression (Bora et al., 2013) and bipolar disorder (Baune and Malhi, 2015; Bourne et al....
[...]
...This is the case in both unipolar depression (Bora et al., 2013) and bipolar disorder (Baune and Malhi, 2015; Bourne et al., 2013)....
[...]
257 citations
256 citations
Cites background from "Cognitive impairment in euthymic ma..."
...The inconsistencies in the cognitive control studies between the youth and adult MDD literature may be due, in part, to the fact that cognitive deficits emerge and become more severe with recurrent MDD (Bora et al., 2012), and therefore abnormalities in brain regions subserving cognitive control would be expected more so in older MDD patients compared to patients who have their first episode in early adulthood....
[...]
...Furthermore, cognitive deficits emerge and become more severe with recurrent MDD and are more pronounced in late-onset MDD patients compared to patients who have their first episode of illness in adolescence or early adulthood (Bora et al., 2012)....
[...]
...…the youth and adult MDD literature may be due, in part, to the fact that cognitive deficits emerge and become more severe with recurrent MDD (Bora et al., 2012), and therefore abnormalities in brain regions subserving cognitive control would be expected more so in older MDD patients…...
[...]
References
46,935 citations
31,379 citations
25,460 citations
"Cognitive impairment in euthymic ma..." refers methods in this paper
...When the Q test was significant ‘ I2 ’ – a measure of the degree of inconsistency in the studies’ results – was used to quantify heterogeneity (Higgins & Thompson, 2002)....
[...]
23,203 citations
1,059 citations
"Cognitive impairment in euthymic ma..." refers result in this paper
...These findings contradict other evidence suggesting that hippocampus alterations are among the most robust findings in MDD (Campbell et al. 2004), although it must be said that the vast majority of neuroimaging studies have not compared euthymic versus currently ill patients....
[...]
Related Papers (5)
Frequently Asked Questions (13)
Q2. What are the future works mentioned in the paper "Cognitive impairment in euthymic major depressive disorder: a meta-analysis" ?
Future studies are needed to examine cognitive performance in euthymic MDD patients with a history of melancholic/non-melancholic and psychotic and non-psychotic features. It is clear that further studies of cognition are needed in euthymic and unmedicated MDD patients. Longitudinal studies that are designed to assess cognition in ‘ at-risk ’ and first-episode populations across the age range will be needed to further clarify the precise nature of cognitive deficits in depression.
Q3. What was the effect of I2 values on between-group differences?
Meta-regression analyses were used to estimate the impact of demographic (age, gender) and clinical (number of episodes, age at illness onset, duration of illness, residual depressive symptoms, based on Hamilton Depression Rating Scale) variables on between-group differences.
Q4. What is the reason for the hippocampus alterations in MDD?
It is likely that hippocampus alterations in adult MDD patients are secondary to active stress-related processes and that such alterations might recover in fully remitted patients.
Q5. What are the main characteristics of MDD?
Within the broad and heterogeneous diagnostic spectrum of MDD, persistent cognitive deficits might be important functional markers of some patient groups.
Q6. what is the psychiatric effect of serotonin reuptake inhibitor?
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.
Q7. What was the effect size of the cognitive deficits in euthymic MDD?
In the whole sample, older age of onset was associated with more severe verbal memory deficits (B=0.32, S.E.=0.09, Z=3.77, p=0.0002).
Q8. What is the reason for the heterogeneity in the data?
It is likely that this heterogeneity is due to variance in the proportion of patients with potentially more severe cognitive deficits, for instance, patients with a history of psychosis or melancholic features during active episodes.
Q9. How many studies were included in the meta-analysis?
A total of 27 studies (30 samples) comparing 895 (60.7% female) patients with MDD and 993 (60.1% female) healthy controls were included in the final meta-analysis (Table 1).
Q10. What was the average magnitude of cognitive dysfunction in euthymic MDD patients?
The average magnitude (Cohen’s d) of cognitive dysfunction in euthymic MDD patients was 0.47, indicating nearly 70% overlap of distributions of cognitive performances of MDD patients and healthy controls.
Q11. What is the significance of the effects of the cognitive tests in euthymic MD?
Their findings provide strong evidence for pronounced cognitive deficits in remitted patients who had their first episode of illness late in life (d=0.64, 60% overlap with controls), with the distribution of effect sizes being strikingly homogeneous in this population.
Q12. What is the common definition of euthymia?
Definitions of euthymia varied between studies, with some of them relying solely on cut-off scores on depression scales while others required a minimum temporal duration (e.g. 2 weeks to 6 months) for clinical remission (Table 1).
Q13. What are the main factors that are needed to examine cognitive performance in euthymic?
Future studies are needed to examine cognitive performance in euthymic MDD patients with a history of melancholic/non-melancholic and psychotic and non-psychotic features.