This is a well-done, prospective imaging study by Arango et al. looking at brain changes in early-onset psychosis. Early-onset psychosis populations in general are less studied, but are important, as they provide a window into earlier neurodevelopmental correlates and are less likely to show environmental influences. As quoted in the paper, a majority of these studies have come from the NIMH childhood schizophrenia sample, so it is nice to see findings being replicated in independent samples.

The sample size is small when divided in subgroups, but they do find significant frontal gray matter (GM) loss in schizophrenia, not shared by psychotic bipolar patients, as was observed in the NIMH psychotic bipolar sample. This is an important observation in favor of careful diagnostic/phenotypic characterization of patients, as increasing evidence from longitudinal studies seems to suggest that underlying brain pathology and trajectories are quite distinct as well. Interestingly, the "other" psychosis group also showed GM loss, and although we do not have further information on the diagnoses in this group, these observations support the increasing discussion of the dimensionality of psychosis. A more or less similar/comparable antipsychotic exposure of all groups also suggests, like in the NIMH studies, that the brain findings may be less due to medication influence.

I am hoping that this group has also collected siblings of patients to address the endophenotype question, and will also do more subregional/cortical thickness analyses rather than just lobar volumes. Finally, many reports publish CSF findings, but there is not enough talk in the literature about what they mean. Is the CSF increase secondary to the loss of GM (or white matter)? Or is it the other way around (increase in CSF resulting in brain substance loss)? Or is it increased gyral folding and hence more space for CSF? What mechanistic/pathophysiologic implications does that have? More elucidation is needed in the field rather than just showing increases in CSF volume.

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