Stability of cortical thinning in persons at increased familial risk for major depression across eight years

Xuejun Hao1,2, Ardesheer Talati1,2, *Stewart A. Shankman6, Jun Liu1,2, Jürgen Kayser1,2, Craig E. Tenke1,2, Virginia Warner1,2, David Semanek, 3, Priya J. Wickramaratne1,2,5, Myrna M. Weissman1,2,4, Jonathan Posner1,3

1Department of Psychiatry, Columbia University Medical Center, New York, NY; 2Divisions of Epidemiology; 3Child Psychiatry, New York State Psychiatric Institute, New York, NY; 4Department of Epidemiology; 5Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY; 6Department of Psychology and Psychiatry, University of Illinois at Chicago, Chicago, IL

Received 14 February 2017; revised 12 April 2017; accepted 24 April 2017; available online 10 May 2017.

Abstract

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 the cortical thinning across 8 years, and whether thinning mediates associations between familial risk and depressive traits. Method. 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. Results. High-risk offspring had thinner bilateral superior and middle frontal gyri, and left inferior parietal lobule, at both time-points. High intra-subject correlation (0.60 < r < 0.91) 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. Conclusion. 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.

Key Words:high-risk; biomarker; depression; MRI; Freesurfer; stability

doi:10.1016/j.bpsc.2017.04.009