Previous studies in a Finnish family cohort for schizophrenia found significant association with five genes within the DISC1 network; DISC1, NDE1, NDEL1, PDE4B and PDE4D. Here, in sub-samples of these families, we utilised gene expression and psychoactive medication use, in order to translate the role of the DISC1 network into biological consequences and potential treatment implications. Gene expression levels were determined in 63 individuals from 18 families, whilst prescription medication information has been collected over a ten year period for all 931 affected individuals. Replication of the observed changes was sought from the GTEx database and from a Finnish twin cohort ascertained for schizophrenia. We demonstrated that the NDE1 SNP rs2242549 associates with changes in a large number of probes (n=2,908), and with 214 genes that could be replicated in independent cohorts. A significant number of the genes altered (347 out of 2,510, p=3.0x10-8) were predicted targets of microRNA-484, which is located on a 5' non-coding exon of NDE1. Variants within the NDE1 locus also displayed significant association to early cessation of psychoactive medications, specifically a genotype by gender interaction with use of CYP2C19 metabolised medications. Furthermore, we demonstrated that miR-484 can affect the expression of CYP2C19 in a cell culture system. Thus, mutations at the NDE1 locus may alter risk to mental illness, in part through functional modification of miR-484, and that such modification also alters treatment response to specific psychoactive medications, leading to the potential for the NDE1 locus to be used in targeting of treatment for psychiatric illness.