MRI correlates of treatment response in first episode psychosis

It is not known whether the magnitude of the structural brain abnormalities that underlie schizophrenia is a determinant of the extent to which patients respond to antipsychotic medication. This study was undertaken in order to explore this relationship. Twenty-six patients receiving treatment for a first episode of psychosis were involved in both a study measuring treatment response and a magnetic resonance imaging (MRI) study. In the treatment study, haloperidol dose was increased weekly beginning at 2 mg/day until patients showed evidence of a response or extrapyramidal symptoms. MRI scans were analyzed using a computerized volumetric approach to yield estimates of cerebrospinal fluid (CSF), gray-matter and white-matter volumes. Improvement in positive and negative symptoms after 1 week of treatment was significantly correlated with cortical gray-matter volumes. Those patients who were maintained on 2 mg/day of haloperidol had greater cortical gray-matter volume than those who were treated with higher doses. The severity of structural brain abnormalities at the onset of psychosis may contribute to individual variation in response to antipsychotic medication. It remains to be determined whether the degree to which particular domains of symptomatology can improve is related to the severity of structural brain pathology in specific brain regions.