Aberrant neurogenesis in the adult brain may have a role in schizophrenia, hints a study in mice (Cell 130, 1146–1158).

Xin Duan et al. examined the function of disrupted in schizophrenia-1 (DISC1) a schizophrenia susceptibility gene expressed in regions of the adult brain that undergo continuous neurogenesis, including the hippocampus. The researchers knocked down the gene with small hairpin RNAs targeted to DISC1.

Neurons lacking DISC1 sport abnormally large cell bodies. DNA in blue, immature neurons in red and cells expressing shRNAs to DISC1 in green; inset shows size of neuron with intact DISC1 expression. Credit: Reprinted with permission of Cell Press

DISC1 knockdown resulted in accelerated morphological development of adult-born neurons, including the enlargement of neuronal cell bodies, as shown here. Additional defects included mispositioning of new neurons, more mature neuronal firing patterns, and accelerated dendritic development and synapse formation. The researchers conclude that DISC1 helps control the timing of neuronal integration in the adult brain.

DISC1 also operates during embryonic development, which is consistent with the view that schizophrenia originates during early brain formation. But whether the embryonic or the adult activity of the gene holds sway in the development of disease remains to be seen.