Common and Distinct Gray Matter Alterations in Social Anxiety Disorder and Major Depressive Disorder

http://dx.doi.org/10.1016/j.ebiom.2017.06.021 2352-3964/© 2017 The Author. Published by Elsevier B.V Mood and anxiety disorders are impairing and costly psychiatric conditions with considerable comorbidity (Chartier et al., 2003) and pathophysiological overlap. In a study in this issue of EBioMedicine, Zhao and co-workers (Zhao et al., 2017) show that major depressive disorder (MDD) and social anxiety disorder (SAD) are associated with both common and specific abnormalities in brain morphology, further supporting the pathophysiological overlap between these disorders, but at the same time demonstrating that there are distinct brain mechanisms separating them. The authors reported common reductions in gray matter volume and/or cortical thickness in regions encompassing cortico-striatothalamo-cortical circuitry and the salience and dorsal attention networks. MDD-specific alterations in cortical thickness were found in regions involved in visual processing and superior frontal cortex, and SAD patients had thinner preand postcentral cortices. All participants weremedication-naïve, strengthening the conclusion that the gray matter alterations were related to the disorders and not biased by effects of pharmacological treatment. Surprisingly, Zhao et al. (Zhao et al., 2017) did not replicate findings from large-scale and meta-analytic MDD studies of reduced cortical thickness in the ACC and insular cortex (Schmaal et al., 2017). Rather, the findings were in the opposite direction. This is also surprising given the recent report of reduced gray matter volume in these regions being a common neural substrate across a range of psychiatric disorders including MDD and SAD (Goodkind et al., 2015). The inconsistencies may probably be explained by many different factors including differences in study populations (e.g. non-comorbid and medication-naïve in Zhao et al.). We must also be open for the possibility of spurious findings given the relatively small sample size in Zhao et al., although the authors do safeguard against this as best as possible with a stringent statistical threshold. The findings from Zhao et al. (Zhao et al., 2017) support the extension of neural models of SAD from fear circuitry and amygdala-centered models to models including additional brain regions and networks such as cortico-striato-thalamic-cortical circuitry and the salience and attention networks. Indeed, there is rather limited evidence of changes in amygdala volume in the SAD literature. It should also be noted that the findings from previous studies investigating gray matter alterations in