Structural and functional impact of clozapine in patients with schizophrenia: systematic review of neuroimaging longitudinal studies

Clozapine structural and functional cerebral impact in patients with schizophrenia: a systematic review of neuroimaging longitudinal studies Objective: This review aimed to identify the cerebral anatomical-functional correlates in a clozapine (CLZ) treatment as well as the anatomical-functional markers predicting response to CLZ. Methods: We have conducted a systematic review of literature in databases MEDLINE and Web of Science to identify and examine all neuroimaging longitudinal studies investigating CLZ cerebral impact. Results: 30 studies were included and analysed. CLZ elicits a reduction of volume and perfusion in the basal ganglia in responding patients. A larger volume of grey matter and perfusion in these structures before starting CLZ were associated with a better treatment response. The reduction of volume and perfusion at the prefrontal cortex (PFC) level is perceived in spite of starting CLZ but in a smaller way in patients on CLZ than in patients on typical antipsychotics. A larger volume at PFC level before starting CLZ is associated with a better clinical response in most studies. Finally, CLZ seems to induce a reduction in alterations at white matter level. Conclusion: CLZ anatomical-functional correlates differ from those of other antipsychotics, with a specific action of CLZ in basal ganglia and PFC possibly participating in its superior clinical response. Many clinical and neuroimaging data bring on the assumption of a better prognosis associated with CLZ started earlier.