Previous studies have described abnormal expression of molecules involved in glutamatergic signaling in psychiatric illnesses, including proteins associated with receptor signaling complexes in the postsynaptic density (PSD). In particular the N-methyl-D-aspartate (NMDA) receptor complex has been associated with these illnesses. Several subcortical structures including the striatum are innervated by direct glutamatergic projections from the prefrontal cortex, and these connections may be affected in severe psychiatric illnesses. Abnormal expression of molecules critical for glutamatergic signaling in subcortical structures may thus be associated with the pathophysiology of severe psychiatric illnesses. In the present study postmortem tissue from patients with schizophrenia, bipolar disorder and major depression was used to examine striatal expression of transcripts encoding NMDA receptor interacting proteins of the PSD required for trafficking, membrane targeting and synaptic function of this receptor. We found decreased striatal expression of transcripts encoding PSD-95 and SAP-102 in bipolar disorder and of SAP-102 in major depression and schizophrenia, while no significant changes in NF-L and PSD-93 mRNAs were observed. Abnormal expression of SAP-102 in schizophrenia and SAP-102 and PSD-95 in mood disorders in subcortical structures receiving afferent glutamatergic innervation from frontal cortex suggests dysregulation of cortical-subcortical circuitry in these illnesses. © 2005 Elsevier B.V. All rights reserved.