Abstract
Here we aimed to identify cortical endophenotypes for anxiety-depression. Our data-driven approach used vertex-wise genetic correlations (estimated from a twin sample: 157 monozygotic and 194 dizygotic twin pairs) to parcellate cortical thickness (CT) and surface area (SA) into genetically homogeneous regions (Chen et al., 2013). In an overlapping twin and sibling sample (n = 834; aged 15–29, 66% female), in those with anxiety-depression Somatic and Psychological Health Report (SPHERE) scores (Hickie et al., 2001) above median, we found a reduction of SA in an occipito-temporal cluster, which comprised part of the right lingual, fusiform and parahippocampal gyrii. A similar reduction was observed in the Human Connectome Project (HCP) sample (n = 890, age 22–37, 56.5% female) in those with Adult Self Report (ASR) DSM-oriented scores (Achenbach et al., 2005) in the 25–95% quantiles. A post hoc vertex-wise analysis identified the right lingual and, to a lesser extent the fusiform gyrus. Overall, the surface reduction explained by the anxiety-depression scores was modest (r = −0.10, 3rd order spline, and r = −0.040, 1st order spline in the HCP). The discordant results in the top 5% of the anxiety-depression scores may be explained by differences in recruitment between the studies. However, we could not conclude whether this cortical region was an endophenotype for anxiety-depression as the genetic correlations did not reach significance, which we attribute to the modest effect size (post hoc statistical power <10%).
Footnotes
The authors declare no competing financial interests.
The MRI imaging of QTIM was supported by grants from National Institute of Health (NIH; R01 HD050735) and the National Health and Medical Research Council (NHMRC; 496682 and 1009064). Zygosity typing and collection of SPHERE data were funded by Australian Research Council Grants A7960034, A79906588, A79801419, and DP0212016. Genotyping was funded by the NHMRC Grant 389891. Replication data were provided by the Human Connectome Project, WU-Minn Consortium (Principal Investigators: David Van Essen and Kamil Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and Centres that support the NIH Blueprint for Neuroscience Research; and by the McDonnell Centre for Systems Neuroscience at Washington University.
B.C.D. is supported by a University of Queensland International Scholarship and L.T.S. by an Australian Postgraduate Award Scholarship. P.M.T. and M.J.W. are supported in part by the NIH Grant U54 EB020403 to the ENIGMA Center for Worldwide Medicine, Imaging & Genomics.
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