Prodromal Symptom Severity Predicts Accelerated Gray Matter Reduction and Third Ventricle Expansion among Clinically High-Risk Youth Developing Psychotic Disorders

A recent prospective longitudinal neuroimaging study of 274 prodromal risk syndrome subjects revealed that those who later developed full-blown psychotic symptoms exhibited accelerated gray matter loss and third ventricle expansion around the time of onset of psychosis. Previous studies also indicate that higher levels of unusual thought content during prodromal states are a significant predictor of psychosis in clinically high-risk youth (CHR). However, the relationship between clinical symptoms and changes in neuroanatomical structure has not been previously examined in the North American Prodrome Longitudinal Study (NAPLS) sample at the atlas level. In this report, we investigated whether symptom severity as measured by the Scale of Prodromal Symptoms (SOPS) predicted the accelerated gray matter decline in 274 CHR cases, including 35 who converted to psychosis. Higher levels of unusual thought content (pre-delusional) symptoms at baseline were associated with a steeper rate of gray matter loss in the prefrontal cortex bilaterally among converters. In contrast, there was no association found among non-converters. Steeper gray matter loss seems to be unique to those (CHR) individuals with higher levels of sub-psychotic pre-delusional symptoms that acutely worsen in the ramp-up to full-blown psychosis, and as such may reflect pathophysiological processes driving emergence of psychosis.