Stability of Cortical Thinning in Persons at Increased Familial Risk for Major Depressive Disorder Across 8 Years

Background A biological marker of vulnerability should precede onset of illness and be independent of disease course. We previously reported that cortical thinning may serve as a potential biomarker for risk for familial depression. We now test stability of cortical thinning across 8 years, and whether thinning mediates associations between familial risk and depressive traits. Methods Participants were from a three-generation family study of depression, where second- and third-generation offspring were characterized as being at high or low risk for depression based on the presence/absence of major depressive disorder in the first generation. The analysis includes 82 offspring with anatomical magnetic resonance imaging scans across two assessment waves conducted 7.8 years apart (SD = 1.3 years; range, 5.2–10.9 years). Results High-risk offspring had thinner bilateral superior and middle frontal gyri and left inferior parietal lobule at both time points. High intrasubject correlation (.60 < r <.91) and intraclass correlation (0.72–0.78) of thickness measures across time points was detected within the above regions; rank order by effect size and region was also preserved across time. The thinning was stable despite changes in scanning platform (Siemens Sonata vs. GE Signa), field strength (1.5T vs. 3T), and participant age and clinical course. Thinning at the first time point predicted anger and hostility at the second time point and mediated the relationship between familial risk and these traits. Conclusions The study provides evidence for cortical thinning as a stable biomarker for familial vulnerability for depressive illness, which supports the ability to detect persistent and clinically relevant anatomical findings regardless of magnetic resonance imaging platform.