Lingual Gyrus Surface Area Is Associated with Anxiety-Depression Severity in Young Adults: A Genetic Clustering Approach

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%).