Antipsychotic medication and prefrontal cortex activation: a review of neuroimaging findings.
Decreased prefrontal activation (hypofrontality) in schizophrenia is thought to underlie negative symptoms and cognitive impairments, and may contribute to poor social outcome. Hypofrontality does not always improve during treatment with antipsychotics. We hypothesized that antipsychotics, which share antagonism at dopamine receptors, with a relatively low dopamine receptor affinity and high serotonin receptor affinity may have a sparing effect on prefrontal function compared to strong dopamine receptor antagonists. We systematically investigated the relation between serotonin and dopamine antagonism of antipsychotics and prefrontal functioning by reviewing neuroimaging studies. The weight of the evidence was consistent with our hypothesis that antipsychotics with low dopaminergic receptor affinity and moderate to high serotonergic affinity were associated with higher activation of the prefrontal cortex. However, clozapine, a weak dopamine and strong serotonin antagonist, was associated with decrease in prefrontal activation. Future studies should further elucidate the link between prefrontal activation and negative symptoms using prospective designs and advanced neuroimaging techniques, which may ultimately benefit the development of treatments for disabling negative symptoms.
Neuroimaging Center, Department of Neuroscience, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 2 9713 AW Groningen, The Netherlands. e.j.liemburg@umcg.nl
Edith J
EJ
Liemburg
Henderikus
H
Knegtering
Hans C
HC
Klein
Rudie
R
Kortekaas
André
A
Aleman
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D016208:Databases, Factual / Q000706:statistics & numerical data; D006801:Humans; D059906:Neuroimaging; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011859:Radiography; D011877:Radionuclide Imaging; D011954:Receptors, Dopamine / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy / Q000473:pathology
D014150:Antipsychotic Agents; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin