Lower density of calretinin-immunopositive neurons in the putamen of subjects with schizophrenia

Schizophrenia (SCH) is a chronic and serious mental illness which puts an enormous burden on the individual, families, and society. It is well established that altered dopamine signaling and excitatory-inhibitory imbalance contributes to the symptoms of schizophrenia. Recent neuroimaging and histological studies suggest that the striatum is a key area involved in SCH, however, our knowledge of how specific cell neuronal subtypes of certain subcortical structures may be impaired is incomplete. To this date, no detailed investigation of the putamen has ever been published regarding neuroanatomical changes in SCH. Here we tested whether the density of calretinin immunopositive (CR+) neurons and DARPP32+ neurons is altered in the putamen of patients with SCH. We used immunohistochemistry to reveal CR+ and DARPP32+ neurons in six samples from patients with SCH and six age- and gender-matched control subjects. In line with previous studies, we detected small, medium, and large CR+ neurons. The density of small CR+ neurons was significantly lower in SCH (p = 0.0076). Medium and large CR+ and DARPP32+ neuronal density was not significantly different between groups. The present study substantiates previous results showing significantly lower density of small CR+ interneurons in the caudate nucleus in samples from patients with schizophrenia, highlighting the involvement of the striatum in the disorder. Our results warrant further studies focusing on the role of CR+ interneurons in the regulation of information processing in the fronto-striatal networks, evidently key structures in schizophrenia.