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Family History of Depression Tied to Descendant Cognitive Decline
Depression in previous generations was associated with lower cognitive performance in descendants, according to a cohort study published in JAMA Psychiatry.
“This study provides evidence for lower cognitive performance in people with familial risk of depression, which appears to manifest differently across the life span,” researchers noted. “Although there was a dose effect for depression itself, with participants with 2 prior generations affected showing greater odds of depression, this effect was not clearly evident with regard to the strength of association with cognitive performance.”
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Researchers conducted cross-sectional analyses of data collected from the Three Generations at High and Low Risk of Depression Followed Longitudinally (TGS) family study and 3 population cohorts, including the Adolescent Brain Cognitive Development (ABCD) study, the National Longitudinal Study of Adolescent to Adult Health, and the UK Biobank. Individuals both with and without familial depression risk were included. Analysis was conducted from March to June 2022.
In total, 57,308 individuals were included, 51% women, with a mean age of 33 years. In younger participants, family history of depression was primarily associated with poorer memory function and tied to possible educational and socioeconomic factors. In the older cohort, family depression history was associated with processing speed, attention, and executive function and had no apparent ties to educational or socioeconomic influences. Effect sizes between familial risk of depression and neurocognitive test performance were largest in TGS; the largest standardized mean differences in primary analyses were −0.55 (95% CI, −1.49 to 0.38) in TGS, −0.09 (95% CI, −0.15 to −0.03) in ABCD, −0.16 (95% CI, −0.31 to −0.01) in Add Health, and −0.10 (95% CI, −0.13 to −0.06) in UK Biobank.
This study had several limitations. Only 1 cohort, TGS, had confirmed depression diagnoses across all generations, but there is no available polygenic risk score data for this group. The study primarily focused on biological family history and did not consider the influence of nonbiological relatives such as step-parents within households. Additionally, the researchers were unable to conduct a detailed analysis of the number of affected biological relatives, such as determining if one or both parents had a history of depression, due to substantial missing data.
“The next challenge is to elucidate the pathways by which this arises, which may include genetic and environmental determinants and moderators of brain development and brain aging, and potentially modifiable social and lifestyle factors at play across the life span,” researchers concluded. “These and other cohorts enable such research at a scale and depth never before possible, opening new research directions for prevention and early intervention in at-risk individuals.”
