Originally published by 2 Minute Medicine® (view original article). Reused on AccessMedicine with permission.

1. In this systematic review and meta-analysis, there were significantly lower cognitive functioning scores for those who were first-degree relatives of patients with a history of major depressive disorder (MDD).

2. The lower scores for cognitive testing were demonstrated across multiple domains of cognition including IQ, verbal intelligence, perceptual intelligence, and memory.

Evidence Rating Level: 2 (Good)

Study Rundown:

Cognitive impairment has been observed in those with Major Depressive Disorder (MDD) and cognitive effects can persist despite resolution of the acute episodes of depression. Possible explanations for the connection between cognitive impairment and MDD include direct consequence of the psychopathology, side effects of pharmacotherapy, or underlying shared genetic and socioeconomic risk factors. The current study sought to better evaluate the connection between MDD and cognitive impairment by evaluating the cognitive performance of those with and without first-degree relatives with MDD. The systematic review and meta-analysis found that those with a first-degree relatives with MDD had lower scores on cognitive testing across all domains.

The main strengths of the study include large pooled sample size with minimal evidence of publication bias. The limitations of the study include the inability to evaluate differences in all sub-domains of cognition due to sample size. Further, this study was a meta-analysis of cross-sectional data, making it difficult to establish causality.

In-Depth [systematic review and meta-analysis]:

This study included articles published from January 1, 1980 to July 15, 2018 that reported original data on cognition in first-degree relatives of individuals with MDD along with a control group of individuals without relatives with MDD. Participants were included if they were 69 years of age or younger, and the diagnosis of MDD in the relative was established through a validated diagnostic instrument. Studies were excluded if they had overlapping data with other included studies, where comparisons were matched based on global cognitive performance, or if measures had no clear distinction for better/worse outcomes.

The study included 90 published articles covering 54 non-overlapping study samples which comprised a study sample of 3246 individuals with a relative with MDD and 5222 individuals in the control group without a first-degree relative with MDD. Those with a relative with MDD had lower measures of overall cognition (standard mean difference [SMD] = −0.19; 95%CI, −0.27 to −0.11; P <0.001) and domain specific measures: verbal intelligence (SMD = −0.29, p=.03), perceptual intelligence (SMD = −0.23, p=.02), memory (SMD = −0.20, p=.02), academic performance (SMD = −0.40, p=.02), and language (SMD = −0.29, p=.03).

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