Neuropsychological Assessments of Cognitive Impairment in Major Depressive Disorder: A Systematic Review and Meta-Analysis with Meta-Regression

<b><i>Introduction:</i></b> Cognitive dysfunction or deficits are common in patients with major depressive disorder (MDD). The current study systematically reviews and meta-analyzes multiple domains of cognitive impairment in patients with MDD. <b><i>Methods:</i></b> PubMed/MEDLINE, PsycINFO, Cochrane Library, Embase, Web of Science, and Google Scholar were searched from inception through May 17, 2023, with no language limits. Studies with the following inclusion criteria were included: (1) patients with a diagnosis of MDD using standardized diagnostic criteria; (2) healthy controls (i.e., those without MDD); (3) neuropsychological assessments of cognitive impairment using Cambridge Neuropsychological Test Automated Battery (CANTAB); and (4) reports of sufficient data to quantify standardized effect sizes. Hedges’ <i>g</i> standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) were used to quantify effect sizes of cognitive impairments in MDD. SMDs were estimated using a fixed- or random-effects models. <b><i>Results:</i></b> Overall, 33 studies consisting of 2,596 subjects (<i>n</i> = 1,337 for patients with MDD and <i>n</i> = 1,259 for healthy controls) were included. Patients with MDD, when compared to healthy controls, had moderate cognitive deficits (SMD, −0.39 [95% CI, −0.47 to −0.31]). In our subgroup analyses, patients with treatment-resistant depression (SMD, −0.56 [95% CI, −0.78 to −0.34]) and older adults with MDD (SMD, −0.51 [95% CI, −0.66 to −0.36]) had greater cognitive deficits than healthy controls. The effect size was small among unmedicated patients with MDD (SMD, −0.19 [95% CI, −0.37 to −0.00]), and we did not find any statistical difference among children. Cognitive deficits were consistently found in all domains, except the reaction time. No publication bias was reported. <b><i>Conclusion:</i></b> Because cognitive impairment in MDD can persist in remission or increase the risk of major neurodegenerative disorders, remediation of cognitive impairment in addition to alleviation of depressive symptoms should be an important goal when treating patients with MDD.