title: Altered cerebral response during cognitive control: a potential indicator of genetic liability for schizophrenia.
abstract: Aberrant activity in brain regions underlying various aspects of executive cognition has been reported in patients with schizophrenia and in their healthy relatives, suggesting an association with genetic liability. The aim of this study was to investigate brain responses to selective aspects of cognitive control in unaffected siblings who are at increased genetic risk of schizophrenia. Altogether, 65 non-affected siblings, 70 patients with schizophrenia spectrum disorders, and 235 normal controls participated in this study. Blood-oxygen-level-dependent functional magnetic resonance imaging was conducted while participants performed a cognitive control task ('flanker task') to identify brain activity and connectivity associated with response inhibition and conflict monitoring, and suppression. Behaviorally, similar to patients with schizophrenia, siblings were less accurate when inhibiting prepotent responses relative to normal controls. During response inhibition, again similar to patients with schizophrenia, siblings showed decreased activity in the anterior cingulate (ACC), along with increased functional coupling with the dorsolateral prefrontal cortex (PFC) when compared to normal controls. Our findings show altered ACC activity and PFC connectivity in unaffected siblings and patients with schizophrenia during response inhibition. These results suggest that such changes in the neural activity underlying aspects of cognitive control may represent a potential intermediate phenotype for the investigation of the genetic basis of schizophrenia.
authors.affiliation: Brain Center for Motor and Social Cognition, Istituto Italiano di Tecnologia@UNIPr, Parma, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Sambataro
authors.forename: Venkata S
authors.initials: VS
authors.lastname: Mattay
authors.forename: Kristina
authors.initials: K
authors.lastname: Thurin
authors.forename: Martin
authors.initials: M
authors.lastname: Safrin
authors.forename: Roberta
authors.initials: R
authors.lastname: Rasetti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Blasi
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Callicott
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Weinberger
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D002540:Cerebral Cortex / Q000098:blood supply / Q000503:physiopathology*; D016009:Chi-Square Distribution; D003072:Cognition Disorders / Q000209:etiology*; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010100:Oxygen; D011569:Psychiatric Status Rating Scales; D011930:Reaction Time / Q000502:physiology; D012559:Schizophrenia / Q000150:complications* / Q000235:genetics*; D035781:Siblings; D055815:Young Adult
chemical_list: D010100:Oxygen