The calcium-binding proteins parvalbumin (PVB)-immunoreactive (-IR) neurons have been shown to be unsheathed by perineuronal nets (PNN). It is shown that PVB is expressed in large subpopulations of amygdala interneurons. The number of Parvalbumin-positive interneurons and parvalbumin mRNA expression were reduced in schizophrenic patients’ hippocampus. Perineuronal nets are extracellular matrix structures that enwrap many neurons in the brain. They regulate the postnatal experience-dependent maturation of brain circuits and maintain their functional integrity in the mature brain by stabilizing their synaptic architecture. The densities of PNNs were decreased by 70%–76% in layers 3 and 5 of the PFC in schizophrenia, compared with the normal control subjects. Orthodenticle homeobox 2 (Otx2) homeoprotein is synthesized and secreted globally from the choroid plexus. After eye opening, Otx2 homeoprotein is transferred into the primary visual cortex, thus triggering PV cell maturation 3. Because of the relationship of OTX2 expression to development and maintenance of PVB neurons and PNNs, it is a good candidate to analyze in SZ and BP brain tissue. Because little is known about its expression in adult human brain, we characterized its expression in two brain regions where PNNs are known to be affected in SZ, the amygdale and PFCx, in adult human subject. OTX2 is broadly expressed in neurons in several regions within the adult human brain. OTx2 mRNA is virtually undetectable in neural parenchyma, but expressed at high levels in the choroid plexus. The choroid plexus, through its synthesis and secretion of OTx2, may play a key role in affecting adult neuronal functions and regulating plasticity in human. Ongoing investigations are testing the hypothesis that altered OTX2 expression in schizophrenia may occur in association with perineuronal nets and parvalbumin neuron abnormalities.