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 and surface area 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 SPHERE scores (Hickie et al., 2001) above median we found a reduction of surface area 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 sample (N = 890, age 22-37, 56.5% female) in those with Adult Self Report 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 and especially medication screening as anti-depressants may increase the lingual gyrus volume (Jung et al., 2014). 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%).
Significance Statement Endophenotypes may help shed light on the etiology, cognitive impairment and genetics of psychiatric disorders. Here, we report a non-linear negative association between anxiety-depression and smaller surface area of the occipito-temporal region, which comprises most of the right lingual and fusiform gyri (N = 834). This cluster was defined by applying a fuzzy clustering algorithm to a matrix of vertex-wise genetic correlations among cortical surface measures. We replicated this association in an independent sample from the Human Connectome Project (N = 890). We could not confirm the presence of a genetic correlation as the effect size of the association was modest (r=-0.10).
- cortical surface area
- depression anxiety
- endophenotype
- genetic clustering
- Lingual gyrus
- non-linear effect
Footnotes
Authors report no conflict of interest.
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, 1009064]. Zygosity typing and collection of SPHERE data were funded by the Australian Research Council (ARC) [A7960034, A79906588, A79801419, DP0212016]. Genotyping was funded by the NHMRC [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.
BCD is supported by a UQ International scholarship and LS by an Australian Postgraduate Award scholarship. PT and MJW are supported in part by NIH grant U54 EB020403 to the ENIGMA Center for Worldwide Medicine, Imaging & Genomics.
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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