@article {Couvy-DuchesneENEURO.0153-17.2017, author = {Baptiste Couvy-Duchesne and Lachlan T. Strike and Greig I. de Zubicaray and Katie L. McMahon and Paul M. Thompson and Ian B. Hickie and Nicholas G. Martin and Margaret J. Wright}, title = {Lingual Gyrus surface area is associated with anxiety-depression severity in young adults: a genetic clustering approach}, elocation-id = {ENEURO.0153-17.2017}, year = {2018}, doi = {10.1523/ENEURO.0153-17.2017}, publisher = {Society for Neuroscience}, 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).}, URL = {https://www.eneuro.org/content/early/2018/01/11/ENEURO.0153-17.2017}, eprint = {https://www.eneuro.org/content/early/2018/01/11/ENEURO.0153-17.2017.full.pdf}, journal = {eNeuro} }