In addition to GABAergic neuron overproduction, we also find evidence of exuberant cellular overgrowth of neurites and synapses at the transcriptome and cellular levels and an increase in GABAergic synapses, consistent with the increase in GABAergic neuron number found in our preparation. This increase is consistent with increased spine densities found in the postmortem cerebral cortex of ASD patients (Hutsler and Zhang, 2010; Tang et al., 2014) as well as in the fmr1 KO mouse, a model for Fragile X syndrome, one of the most common forms of inherited intellectual disability and ASD (Dolen et al., 2007). Consistent with the cellular phenotype, mRNA for the synaptic adhesion molecules NLGN1, NRXN1, NRXN2, and NRXN3 were all overexpressed in patient-derived organoids. In contrast to the present results, rare loss-of-function mutations in synaptic adhesion molecules (SHANK, NLGN, NRXN) suggest a deficiency in synaptic connections in some individuals with ASD. However, a gain-of-function mutation in NLGN3 (R451C) found in ASD confers an increase in GABAergic synaptic signaling (Etherton et al., 2011; Pizzarelli and Cherubini, 2013; Tabuchi et al., 2007). These apparently discrepant results may
