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 had exhibited accelerated gray matter loss and third ventricle expansion around the time of psychosis onset. Previous studies also indicate that higher levels of unusual thought content during prodromal states are a significant predictor of psychosis in clinically high-risk (CHR) youth. 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 whole-brain 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 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 nonconverters. Steeper gray matter loss seems to be unique to those (CHR) individuals with higher levels of subpsychotic predelusional symptoms that acutely worsen in the ramp-up to full-blown psychosis, and as such may reflect pathophysiological processes driving the emergence of psychosis.