Familial depression risk associated with lower cognitive function

Key takeaways:

• Family history of and genetic risk for depression were associated with worse cognitive function.
• These associations were present regardless of personal depression history.

People with a family history of or genetic risk for depression had worse cognitive performance compared with people with a lower depression risk profile, according to data published in JAMA Psychiatry.

Breda Cullen, PhD, a senior lecturer in clinical psychology at the University of Glasgow in Scotland, and colleagues assessed data from four studies:

• the Three Generations at High and Low Risk of Depression Followed Longitudinally (TGS) study, which collected data from 1982 to 2015;
• the Adolescent Brain Cognitive Development (ABCD) study, which collected data from 2016 to 2021;
• the National Longitudinal Study of Adolescent to Adult Health (Add Health), which collected data from 1994 to 2018); and
• the U.K. Biobank, which collected data from 2006 to 2022.

The researchers included study participants with and without a familial risk for depression, which was defined as family history or polygenic risk. Participants in the TGS reported history of depression in the previous one or two generations through direct interviews, while all other participants or their parents retrospectively reported that information. Additionally, polygenic depression risk data were available in the ABCD, Add Health and U.K. Biobank studies.

At follow-up, participants completed a series of tests to evaluate cognitive performance.

In total, 57,308 participants were included for analyses. Of these, 87 (mean age, 19.7 years) were TGS participants, 10,258 (mean age, 12 years) were ABCD participants, 1,064 (mean age, 37.8 years) were Add Health participants and 45,899 (mean age, 64 years) were U.K. Biobank participants.

Within the U.K. Biobank cohort, the researchers identified associations between family history of depression and processing speed, attention and executive function.

In the three younger cohorts, family history of depression was associated with worse performance in the memory domain compared with no family history of depression. However, education and socioeconomic factors may play a role in this association.

Analyses of associations revealed that the largest standardized mean difference was 0.55 (95% CI, 1.49 to 0.38) in TGS, followed by 0.16 (95% CI, 0.31 to 0.01) in Add Health, 0.1 (95% CI, 0.13 to 0.06) in the U.K. Biobank and 0.09 (95% CI, 0.15 to 0.03) in ABCD, according to the researchers.

“Larger effect sizes in TGS may reflect the criterion-standard assessments used for both family history and cognitive testing, which increases measurement reliability, as well as the strict eligibility criteria in the first generation at cohort inception,” Cullen and colleagues wrote.

There were similar associations between polygenic risk and cognitive function.

Moving forward, the researchers said studies should investigate the pathways responsible for these associations.