Family History of Depression Associated With Worse Cognition in First-Degree Relatives

General impairment in cognition is a feature of first-degree relatives of family members with major depressive disorder.

Relatives of individuals with major depressive disorder (MDD) may perform less well on cognitive tests compared with individuals with no family history of MDD, according to results of a meta-analysis published in JAMA Psychiatry.

Investigators performed a systematic search of Medline, PubMed, PsycINFO, and Embase for studies published between January 1, 1980, and July 15, 2018, with the key terms “depression,” “first-degree relatives,” and “cognition.” Articles selected for inclusion reported data on cognition in first-degree relatives of individuals with MDD compared with cognition in control subjects without a family history of major mental illness. Cognition was separated for evaluation into the following domains: full-scale IQ, verbal IQ, perceptual IQ, attention, memory, processing speed, executive function, hot cognition, psychomotor skills, academic performance, and language. For each cognitive test, investigators computed the standardized mean difference (SMD) between first-degree relatives and controls.

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Of 4828 articles identified through database searches, 90 were included in the meta-analysis. These 90 studies comprised 54 independent samples with 3246 first-degree relatives (57.68% women) and 5222 controls (55.93% women). First-degree relatives were of mean (standard deviation) age 15.38 (12.37) years, and controls were of mean (standard deviation) age 14.70 (12.37) years. The majority (63.0%) of samples were recruited in North America, and 72.2% studied the offspring of parents with depression.

The overall cognitive performance of first-degree relatives of individuals with MDD was worse than the performance of controls (SMD, -0.19; 95% CI, -0.27 to -0.11; P <.001). Specifically, first-degree relatives of individuals with MDD performed worse than controls in the domains of cognition, including: full-scale IQ (SMD, -0.19; 95% CI, -0.31 to -0.08; P =.001), verbal IQ (SMD, -0.29; 95% CI, -0.56 to -0.03), perceptual IQ (SMD, -0.23; 95% CI, -0.41 to -0.05), memory (SMD, -0.20; 95% CI, -0.35 to -0.05), academic performance (SMD, -0.40; 95% CI, -0.66 to -0.14), and language (SMD, -0.29; 95% CI, -0.55 to -0.04; P <.05 for all). According to meta-regression, type of relative, participants’ age, socioeconomic status, study publication year, and study geographic location had no significant association with the difference in cognitive performance between relatives of individuals with MDD and controls. Moderate heterogeneity was observed among studies (I2 =0.296). Funnel plots and the Egger intercept test were used to investigate publication bias, which was nonsignificant.

These data suggest that cognitive impairment may be a feature of familial predisposition to MDD. In addition, cognition may allow early identification of depression risk. “Efforts should focus on the development of early interventions for individuals with a first-degree relative with MDD,” the researchers concluded.  


MacKenzie LE, Uher R, Pavlova B. Cognitive performance in first-degree relatives of individuals with vs without major depressive disorder: a meta-analysis [published online December 26, 2018]. JAMA Psychiatry. doi: 0.1001/jamapsychiatry.2018.3672