Familial depression linked to poorer cognitive performance in offspring

Familial depression is associated with lower cognitive performance in offspring, a cohort study has shown.

A prior meta-analysis found general impairment in cognition among first-degree relatives of people with depression, indicating that a family history of depression may be a useful risk marker for cognitive impairment. [JAMA Psychiatry 2019;76:297-305] To determine whether family history (across one or two prior generations) and polygenic risk of depression are associated with cognitive impairment in offspring, the researchers used data from four cohorts for cross-sectional analysis. [JAMA Psychiatry 2023;doi:10.1001/jamapsychiatry.2023.0716]

A total of 57,308 participants were included from four cohorts, including 87 from the Three Generations at High and Low Risk of Depression Followed Longitudinally (TGS) family study (mean age, 19.7 years; female, 48 percent), 10,258 from the Adolescent Brain Cognitive Development (ABCD) study (mean age, 12.0 years; female, 48 percent), 1,064 from the National Longitudinal Study of Adolescent to Adult Health (Add Health; mean age, 37.8 years; female, 49 percent), and 45,899 from UK Biobank (mean age, 64.0 years; female, 51 percent).

Family history of depression was primarily associated with lower performance in the memory domain in the younger cohorts (ie, TGS, ABCT, Add Health) and lower performance in the domains of processing speed, attention and executive function, but not memory, in the older UK Biobank cohort.

“[Notably,] associations were similar in polygenic risk score analyses and were evident even in participants who had never been depressed themselves but had a family history of depression,” highlighted the researchers.

The memory domain findings in the younger cohorts are congruent with neuroimaging markers in depression that also underpin memory function. For example, hippocampal volume is smaller and cortical grey matter is thinner on average in various regions, including the temporal lobes, in people with depression. In contrast, speed, attention and executive function findings in the older UK Biobank cohort may point to differences in brain ageing such as white matter disease.

“To our knowledge, this study is the first to examine both polygenic risk and family history of depression in multiple cohorts,” said the researchers. “Results provide evidence for lower cognitive performance in people with familial risk of depression, which appears to manifest differently across the life span.” 

“Lifetime experience of depression may have some influence on cognitive outcomes, especially in older adults, but other factors must be at play,” they noted. The next challenge for the researchers is to elucidate the pathways, which may include genetic and environmental determinants, moderators of brain development and brain ageing, and potentially modifiable social and lifestyle factors at play across the life span.