title: Neurobiology of aggression and violence in schizophrenia.
abstract: There is much evidence that schizophrenia patients have an increased risk for aggression and violent behavior, including homicide. The neurobiological basis and correlates of this risk have not been much studied. While genome-wide association studies are lacking, a number of candidate genes have been investigated. By far, the most intensively studied is the catechol-O-methyltransferase (COMT) gene on chromosome 22. COMT is involved in the metabolism of dopamine, a key neurotransmitter in schizophrenia pathophysiology. Several studies suggest that the Val158Met polymorphism of this gene affects COMT activity. Methionine (Met)/Met homozygote schizophrenia patients show 4- to 5-fold lower COMT activity than valine (Val)/Val homozygotes, and some but not all studies have found an association with aggression and violence. Recently, a new functional single-nucleotide polymorphism in the COMT gene, Ala72Ser, was found to be associated with homicidal behavior in schizophrenia, but this finding warrants further replication. Studies published so far indicate that an association with the monoamine oxidase A, B, or tryptophan hydroxylase 1 genes is unlikely. Data for the brain-derived neurotrophic factor gene are conflicting and limited. Data from the limited number of neuroimaging studies performed to date are interesting. Frontal and temporal lobe abnormalities are found consistently in aggressive schizophrenia patients. Positron emission tomography and single photon-emission computed tomography (SPECT) data indicate deficits also in the orbitofrontal and temporal cortex. Some functional magnetic resonance imaging studies found a negative association of violent behavior with frontal and right-sided inferior parietal activity. Neuroimaging studies may well help further elucidate the interrelationship between neurocognitive functioning, personality traits, and antisocial and violent behavior.
authors.affiliation: Psychiatric Hospital, Ludwig Maximilian University, Nussbaumstrasse 7, 80336 Munich, Germany. michael.soyka@privatklinik-meiringen.ch
authors.forename: Michael
authors.initials: M
authors.lastname: Soyka
mesh_terms: D000374:Aggression / Q000502:physiology*; D002394:Catechol O-Methyltransferase / Q000235:genetics; D006801:Humans; D012559:Schizophrenia / Q000201:enzymology / Q000235:genetics; D014754:Violence / Q000523:psychology*
chemical_list: D002394:Catechol O-Methyltransferase