A systematic review and meta-analysis of the effects of antipsychotic medications on regional cerebral blood flow (rCBF) in schizophrenia: Association with response to treatment

• We review studies investigating rCBF in schizophrenia during antipsychotic treatment.
• Antipsychotics have regional effects on rCBF in frontal and basal ganglia regions.
• Resting cerebral blood flow (rCBF) is a potential predictive biomarker of treatment response.

Evaluating the short- and long-term effects of antipsychotics on brain physiology is a key factor in advancing our understanding of neurophysiological changes in psychosis and improving prediction of treatment response. Understanding the nature of such changes is crucial to the interpretation of neuroimaging findings in patients with schizophrenia and psychoses in general. This review has systematically appraised existing evidence on resting cerebral blood flow (rCBF) in schizophrenia, before and after antipsychotic treatment, relating the findings to symptom severity. The review shows that antipsychotics exert regional effects on rCBF, particularly in frontal and basal ganglia regions, and that different antipsychotic generations have differential effects on rCBF. These findings are supported by an exploratory meta-analysis of a subset of studies. The review also highlights the relative lack of studies that use a priori definitions of treatment response, which is an important step in identifying testable hypotheses and ensuring clinical relevance of remission criteria. Finally, the review highlights important considerations for future psychopharmacological studies investigating the potential for rCBF to predict symptomatic improvement, which could inform the management of treatment in schizophrenia.