Hypofrontality in schizophrenia: a meta-analysis of functional imaging studies

Objective: Hypofrontality is not a well-replicated finding in schizophrenia either at rest or under conditions of task activation. Method: Studies comparing whole brain and frontal blood flow/metabolism in schizophrenic patients and normal controls were pooled. Voxel-based studies were also combined to examine the pattern of prefrontal activation in schizophrenia. Results: Whole brain flow/metabolism was reduced in schizophrenia to only a small extent. Resting and activation frontal flow/metabolism were both reduced with a medium effect size. Duration of illness significantly moderated resting hypofrontality, but the moderating effects of neuroleptic treatment were consistent with an influence on global flow/metabolism only. Pooling of voxel-based studies did not suggest an abnormal pattern of activation in schizophrenia. Conclusion: Meta-analysis supports resting hypofrontality in schizophrenia. Task-activated hypofrontality is also supported, but there is little from voxel-based studies to suggest that this is associated with an altered pattern of regional functional architecture.