Cerebral blood flow in schizophrenia: A systematic review and meta-analysis of MRI-based studies

Introduction: Schizophrenia-spectrum disorders (SSD) represent one of the leading causes of disability worldwide and are usually underpinned by neurodevelopmental brain abnormalities observed on a structural and functional level. Nuclear medicine imaging studies of cerebral blood flow (CBF) have already provided insights into the pathophysiology of these disorders. Recent developments in non-invasive MRI techniques such as arterial spin labeling (ASL) have allowed broader examination of CBF across SSD prompting us to conduct an updated literature review of MRI-based perfusion studies. In addition, we conducted a focused meta-analysis of whole brain studies to provide a complete picture of the literature on the topic.Methods: A systematic OVID search was performed in Embase, MEDLINEOvid, and PsycINFO. Studies eligible for inclusion in the review involved: 1) individuals with SSD, first-episode psychosis or clinical-high risk for psy-chosis, or; 2) had healthy controls for comparison; 3) involved MRI-based perfusion imaging methods; and 4) reported CBF findings. No time span was specified for the database queries (last search: 08/2022). Information related to participants, MRI techniques, CBF analyses, and results were systematically extracted. Whole-brain studies were then selected for the meta-analysis procedure. The methodological quality of each included studies was assessed.Results: For the systematic review, the initial Ovid search yielded 648 publications of which 42 articles were included, representing 3480 SSD patients and controls. The most consistent finding was that negative symptoms were linked to cortical fronto-limbic hypoperfusion while positive symptoms seemed to be associated with hyperperfusion, notably in subcortical structures. The meta-analysis integrated results from 13 whole-brain studies, across 426 patients and 401 controls, and confirmed the robustness of the hypoperfusion in the left superior and middle frontal gyri and right middle occipital gyrus while hyperperfusion was found in the left putamen.Conclusion: This updated review of the literature supports the implication of hemodynamic correlates in the pathophysiology of psychosis symptoms and disorders. A more systematic exploration of brain perfusion could complete the search of a multimodal biomarker of SSD.