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

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 the cortical thinning across 8 years, and whether thinning mediates associations between familial risk and depressive traits.Participants were from a 3-generation family study of depression, where 2nd and 3rd generation offspring were characterized as being at high- or low-risk for depression based on the presence/absence of major depression in the 1st generation. The analysis includes 82 offspring with anatomical MRI scans across two assessment waves, 7.8 (S.D.1.3, range: 5.2-10.9) years apart.High-risk offspring had thinner bilateral superior and middle frontal gyri, and left inferior parietal lobule, at both time-points. High intra-subject correlation (0.60r0.91) and intra-class 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 (1.5 vs. 3T), and participant age and clinical course. Thinning at the first time-point predicted anger and hostility at the second, and mediated the relationship between familial risk and these traits.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 irrespective of MRI platform.