One of the primary challenges in the field of psychiatric genetics is the lack of an in vivo model system in which to functionally validate candidate neuropsychiatric risk genes (NRGs) in a rapid and cost-effective manner. To overcome this obstacle, we performed a candidate-based RNAi screen in which C. elegans orthologs of human NRGs were assayed for dendritic arborization and cell specification defects using C. elegans PVD neurons. Of 66 NRGs, identified via exome sequencing of autism (ASD) or schizophrenia (SCZ) probands and predicted to result in a loss of protein function, the C. elegans orthologs of 6 NRGs were found to be required for proper neuronal development and represent a variety of functional classes, including transcriptional regulators and chromatin remodelers, molecular chaperones, and cytoskeleton-related proteins. We find that RNAi phenotypes associated with the depletion of NRG orthologs is recapitulated in genetic mutant animals, and, via genetic interaction studies, we place a subset of NRG orthologs in the SAX-7/MNR-1/DMA-1 signaling pathway. Collectively, our studies demonstrate that C. elegans PVD neurons are a tractable model in which to discover and dissect the fundamental molecular mechanisms underlying neuropsychiatric disease pathogenesis.