Differential synaptic changes in the striatum of subjects with undifferentiated versus paranoid schizophrenia

Subjects with schizophrenia (SZ) have an increased density of synapses characteristic of corticostriatal or thalamostriatal glutamatergic inputs in the caudate matrix and putamen patches. SZ is a heterogeneous disease in many aspects including symptoms. The purpose of the present study was to determine if the synaptic organization in two different DSM-i.v. subgroups of SZ was differentially affected. Postmortem striatal tissue was obtained from the Maryland Brain Collection from normal controls (NC), chronic paranoid SZs (SZP), and chronic undifferentiated SZs (SZU). Tissue was prepared for calbindin immunocytochemistry to identify patch matrix compartments, prepared for electron microscopy and analyzed using stereological methods. The synaptic density of asymmetric synapses, characteristic of glutamatergic inputs, was elevated equivalently in striatal patches in the SZP and SZU versus NC. The SZU also had an increased density of asymmetric synapses in the striatal matrix compared to NC. Moreover, symmetric axospinous synapses, characteristic of intrinsic inhibitory inputs and dopaminergic afferents, showed a dichotomy in synaptic density between the SZU and SZP in the striatal and caudate matrix. These data show discreet differences in synaptic organization between SZU and SZP and/or NCs. The results suggest that abnormal corticostriatal and/or corticothalamic inputs to striatal patches may be related to limbic dysfunction, which is perturbed in both subtypes of SZ. The selective increase in axospinous synapses in the matrix of the SZU subgroup compared to the SZP may be related to more severe cognitive problems in that subset of SZ compared to SZP.