Distinct grey matter volume alterations in adult patients with panic disorder and social anxiety disorder: A systematic review and voxel-based morphometry meta-analysis

• Structural neuroimaging revealed largely different neuropathological substrates of PD and SAD. • PD and SAD may present distinct anxiety subentities at the level of neuroanatomical phenotypes. • Right inferior frontal gyrus deficit was specific to PD, and left striatum-thalamus deficits could be specific to SAD. The paradox of similar diagnostic criteria but potentially different neuropathologies in panic disorder (PD) and social anxiety disorder (SAD) needs to be clarified. We performed a qualitative systematic review and a quantitative whole-brain voxel-based morphometry (VBM) meta-analysis with an anisotropic effect-size version of seed-based D mapping (AES-SDM) to explore whether the alterations of grey matter volume (GMV) in PD are similar to or different from those in SAD, together with potential confounding factors. A total of thirty-one studies were eligible for inclusion, eighteen of which were included in the meta-analysis. Compared to the respective healthy controls (HC), qualitative and quantitative analyses revealed smaller cortical-subcortical GMVs in PD patients in brain areas including the prefrontal and temporal-parietal cortices, striatum, thalamus and brainstem, predominantly right-lateralized regions, and larger GMVs in the prefrontal and temporal-parietal-occipital cortices, and smaller striatum and thalamus in SAD patients. Quantitatively, the right inferior frontal gyrus (IFG) deficit was specifically implicated in PD patients, whereas left striatum-thalamus deficits were specific to SAD patients, without shared GMV alterations in both disorders. Sex, the severity of clinical symptoms, psychiatric comorbidity, and concomitant medication use were negatively correlated with smaller regional GMV alterations in PD patients. PD and SAD may represent different anxiety sub-entities at the neuroanatomical phenotypes level, with different specific neurostructural deficits in the right IFG of PD patients, and the left striatum and thalamus of SAD patients. This combination of differences and specificities can potentially be used to guide the development of diagnostic biomarkers for these disorders.