2.5. ROI definition

Since cross-disorder PGRS indicates shared genetic risks for these five psychiatric disorders, brain regions that showed disruption in all five major psychiatric disorders were chosen as a ROI to investigate the associations between functional connectivity and cross-disorder PGRS and contributions of subscores for each of these five disorders to the cross-disorder impacts using resting-state fMRI. We used statistical inference maps acquired from Neurosynth (Yarkoni et al., n.d.) (http://neurosynth.org/) to define the region of interest (ROI) for further functional connectivity analysis. We searched the meta-analysis results from Neurosynth (Yarkoni et al., n.d.) (http://neurosynth.org/) for the 5 major psychiatric disorders, separately using ADHD, autism, bipolar, depression, and schizophrenia as search terms. If a study used one of the searched keywords, we obtained statistical inference maps displaying z-scores according to the probability of a region's being activated. In other words, these maps displayed the brain regions that were consistently activated in studies that loaded highly on a specific term. A large z-score means that this region was reported more often than expectation under the hypothesis that activations in the brain would be equally likely (Yarkoni et al., 2011). These maps were thresholded at a false discovery rate (FDR) of 0.01 (Fig. 1). The brain regions affected by all 5 disorders were defined as an ROI. This ROI primarily included the bilateral insula, which is reasonable since the insulae have been suggested as being affected by all five major psychiatric disorders (Goodkind et al., 2015). Then we resampled the voxel size of the ROI to 3 × 3 × 3 mm³ to match the voxel size of the fMRI images we acquired after preprocessing (Fig. 1).

Z-score maps of the meta-analysis for five major psychiatric disorders: (A) ADHD, (B) autism, (C) BD, (D) MDD, (E) schizophrenia. (F) is a binary image of our ROI displaying the overlap between the five maps. MNI coordinates were used.