Gray matter alterations related to P300 abnormalities in subjects at high risk for psychosis: longitudinal MRI-EEG study

Background: Psychotic disorders are characterized by gray matter and volumetric and electrophysiological abnormalities. The relationship between these factors in the onset of psychotic illness is unclear.

Methods: Eighty English-native right-handed subjects (39 subjects at ultra high risk for psychosis "ARMS" and 41 healthy volunteers) were scanned with MRI, and studied using EEG during an oddball task. Both assessments were performed at first clinical presentation. The ARMS subjects were then followed clinically, with the MRI and EEG assessments repeated in a subgroup of each sample.

Results: The P300 amplitude at presentation was significantly lower in the ARMS subjects than in controls. At baseline, the ARMS group showed reduced gray matter volume relative to controls in the right superior frontal gyrus, left medial frontal gyrus, left inferior frontal gyrus, right orbital gyrus and right supramarginal gyrus. Transition to psychosis (26%) was associated with reduced gray matter in the right inferior parietal lobule and in the left parahippocampal gyrus. Within the ARMS group, there was a positive correlation between P300 amplitude and gray matter volume in the right supramarginal gyrus. A significant group by P300 by gray matter interaction was detected in the left medial frontal gyrus. Longitudinal assessment revealed progressive gray matter alterations in prefrontal and subcortical areas of the ARMS but no significant changes in P300 amplitude over time.

Conclusions: P300 abnormalities in the ARMS are related to alterations in regional gray matter volume and represent a correlate of an increased vulnerability to psychosis.