SHANK3 and major depressive disorder: Post-mortem single-nucleus RNA-seq in >450 brains has revealed a concerted down-shift of genes that build and maintain excitatory synapses, PSD95 (DLG4), SHANK3, GRIA2, and an up-shift of microglial phagocytic genes in both subgenual cingulate and amygdala, pointing to activity-dependent synapse pruning as a canonical lesion in MDD [166].