Untreated illness duration correlates with gray matter loss in first-episode psychoses.

Frontolimbic neural circuit dysfunction has been thought to underlie schizophrenia. Prolonged duration of untreated illness (DUI) is associated with frontolimbic structural changes. We present data addressing this question in minimally treated first-episode patients with psychoses. To determine the relationship between DUI and gray matter changes in schizophrenia, we analyzed the structural magnetic resonance images of 82 minimally treated first-episode patients with psychotic disorder by using optimized voxel-based morphometry. DUI inversely correlated with gray matter in the left fusiform gyrus extending into the lingual gyrus, cerebellum, and the parahippocampal gyrus. The observed inverse relationship between DUI and temporal gray matter density is consistent with a progressive process during the early course of schizophrenia.