Response to clozapine in treatment resistant schizophrenia related to alterations in regional cerebral blood flow

Abstract Neuroimaging studies indicate that in treatment resistant schizophrenia (TRS), alterations in regional cerebral blood flow (CBF) during clozapine treatment may vary according to the clinical response. To date, these studies have involved radiotracers. Here, we used arterial spin labelling (ASL) to compare CBF in participants with TRS (N=36) before starting treatment with clozapine and in healthy volunteers (N=16). We then compared CBF before and after 12 weeks of treatment with clozapine in TRS participants (N=24), in relation to changes in Positive and Negative Syndrome Scale for Schizophrenia (PANSS) scores over the treatment period. At baseline, global CBF and CBF in frontal, temporal, and parietal regions were lower in participants with TRS than in healthy volunteers. After covarying for global CBF and age, lower CBF in frontal, temporal, and parietal regions was still evident. In the TRS group, higher striatal CBF at baseline was associated with greater improvement in total and general symptoms, and higher hippocampal CBF was associated with greater improvement in total and positive symptoms. Over the course of treatment there were longitudinal decreases in CBF in the anterior cingulate cortex (ACC) and increases in the left postcentral area. Longitudinal reductions in CBF in the ACC and thalamus were associated with less improvement in negative (ACC), positive (thalamus), and total (thalamus) symptoms. These findings indicate that the effect of clozapine in people with TRS may be related to regional CBF, and that assessing CBF has the potential to help in the stratification of this group according to clozapine response.