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Original Investigation
December 26, 2018

Cognitive Performance in First-Degree Relatives of Individuals With vs Without Major Depressive Disorder: A Meta-analysis

Author Affiliations
  • 1Department of Psychology and Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada
  • 2Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada
  • 3Nova Scotia Health Authority, Halifax, Nova Scotia, Canada
JAMA Psychiatry. 2019;76(3):297-305. doi:10.1001/jamapsychiatry.2018.3672
Key Points

Question  Is cognitive impairment present in relatives of individuals with depression?

Findings  In this meta-analysis of 54 studies including more than 8000 individuals, first-degree relatives of people with depression performed consistently less well on cognitive tests compared with individuals with no family history of major mental illness. Cognitive impairment generalized to most cognitive domains tested.

Meaning  General cognitive impairment may be associated with familial risk for depression.


Importance  Findings of cognitive impairment in major depressive disorder (MDD), including remitted MDD, raise the question whether impaired cognition is part of preexisting vulnerability rather than a consequence of MDD or its treatment. To our knowledge, no meta-analyses have been published on cognitive impairment in first-degree relatives of individuals with MDD.

Objective  To compare cognitive performance between individuals with and without family history of MDD.

Data Sources  Medline/PubMed, PsycINFO, and Embase using combinations of search terms for depression, first-degree relatives, and cognition from January 1, 1980, to July 15, 2018.

Study Selection  Original articles that reported data on cognition in first-degree relatives of individuals with MDD compared with controls with no family history of major mental illness.

Data Extraction and Synthesis  Means and SDs were extracted, and standardized mean differences (SMD) between relatives and controls were calculated for each measure of cognitive performance. The relative-control differences in overall cognition and in specific cognitive domains were synthesized in random-effects meta-analyses with robust variance estimation that allows including multiple correlated measures of cognition within each study. Heterogeneity was quantified with τ2. Publication bias was assessed with funnel plots and Egger intercept.

Main Outcomes and Measures  Performance on cognitive tests.

Results  Across 284 measures of cognition in 54 nonoverlapping samples including 3246 relatives of people with MDD (mean age 15.38 years, 57.68% females) and 5222 controls (mean age 14.70 years, 55.93% females), relatives of people with MDD performed worse than controls across all measures of cognition (SMD = −0.19; 95% CI, −0.27 to −0.11; P < .001). Domain-specific meta-analyses showed similar size of relative-control difference in most domains of cognition, including Full-Scale IQ (SMD = −0.19), verbal intelligence (SMD = −0.29), perceptual intelligence (SMD = −0.23), memory (SMD = −0.20), academic performance (SMD = −0.40), and language (SMD = −0.29). Study characteristics were not significantly associated with observed between-group differences. There was no evidence of publication bias.

Conclusions and Relevance  A general impairment in cognition is a feature of familial disposition for MDD. Cognition may contribute to early identification of risk for depression and may be examined as potential target for early intervention.