Schizophrenia (SCH) and autism spectrum disorder (ASD) share several common aetiological
and symptomatic features suggesting they may be included in a common spectrum. For
example, recent results suggest that excitatory/inhibitory imbalance is relevant in
the etiology of SCH and ASD. Numerous studies have investigated this imbalance in
regions like the ventromedial and dorsolateral prefrontal cortex (DLPFC). However,
relatively little is known about neuroanatomical changes that could reduce inhibition
in subcortical structures, such as the caudate nucleus (CN), in neuropsychiatric disorders.
We recently showed a significant decrease in calretinin-immunopositive (CR-ip) interneuronal
density in the CN of patients with ASD without significant change in the density of
neuropeptide Y-immunopositive (NPY-ip) neurons. These subtypes together constitute
more than 50% of caudate interneurons and are likely necessary for maintaining excitatory/inhibitory
balance. Consequently, and since SCH and ASD share characteristic features, here we
tested the hypothesis, that the density of CR-ip neurons in the CN is decreased in
patients with SCH. We used immunohistochemistry and qPCR for CR and NPY in six patients
with schizophrenia and six control subjects. As expected, small, medium and large
CR-ip interneurons were detected in the CN. We found a 38% decrease in the density
of all CR-ip interneurons (P < 0.01) that was driven by the loss of the small CR-ip
interneurons (P < 0.01) in patients with SCH. The densities of the large CR-ip and
of the NPY-ip interneurons were not significantly altered. The lower density detected
could have been due to inflammation-induced degeneration. However, the state of microglial
activation assessed by quantification of ionized calcium-binding adapter molecule
1 (Iba1)- and transmembrane protein 119 (TMEM119)-immunopositive cells showed no significant
difference between patients with SCH and controls. Our results warrant further studies
focussing on the role of CR-ip neurons and on the striatum being a possible hub for
information selection and regulation of associative cortical fields whose function
have been altered in SCH.
