Schizophrenia May Be Caused By Dense Underlying Neurocircuits

An increased density of certain cortical chandelier cell (ChC) axon cartridges in the prefrontal cortex of the brain may underlie cognitive impairments in patients with schizophrenia, according to a recent study. These findings reverse a previous hypothesis that cognitive impairments were related to decreased production of the inhibitory transmitter gamma-aminobutyric acid (GABA).

Previous studies have suggested that GABA deficits across cortical layers 2 to 5 in the brains of patients with schizophrenia were relatively universal, leading researchers to presume it was a compensatory mechanism for lower GABA signaling associated with schizophrenia.
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In this study, the researchers compared the postmortem brain tissue of 20 individuals with schizophrenia with 20 comparison subjects. Specifically, they analyzed GABA synthesizing and packaging proteins within ChC cartridges, as well as the density of these cartridges in the prefrontal cortex.

Additionally, the researchers immunolabeled prefrontal cortex tissue sections from each group for vesicular GABA transporters (vGAT), glutamic acid decarboxylase (GAD67), and calbindin (CB).

Results showed that the ability of ChCs to synthesize and release GABA within the prefrontal cortex is unaltered in schizophrenia patients. However, the researchers found that the ChC cartridges in the brains of patients with schizophrenia were denser than those of the comparison subjects.

“Our findings of a greater density of [calbindin] ChC cartridges in prefrontal cortex layer 2 from schizophrenia subjects suggests that the normal developmental pruning of these cartridges is blunted in the illness,” the researchers concluded.

—Christina Vogt

Reference:

Rocco BR, DeDionisio AM, Lewis DA, Fish KN. Alterations in a unique class of cortical chandelier cell axon cartridges in schizophrenia. Biol Psychiatry. 2017;82(1): 40-48. doi:10.1016/j.biopsych.2016.09.018.