title: Effects of risk for bipolar disorder on brain function: A twin and family study.
abstract: Bipolar disorder (BPD) is associated with altered regional brain function during the performance of cognitive tasks. The relative contribution of genetic and environmental risk factors for BPD to these changes has not yet been quantified. We sought to address this issue in a functional neuroimaging study of people who varied in their risk for BPD. Functional magnetic resonance imaging was used to study 124 subjects (29 twin and 9 sibling pairs with at least one member with BPD, and 24 healthy twin pairs) performing a working memory task. We assessed the influence of risk for BPD on regional brain function during the task in a two stage process. Firstly, we identified areas where there were group differences in activation. Secondly, we estimated the heritability and phenotypic correlation of activation and BPD using genetic modeling. BPD was associated with increased activation in the anterior cingulate, orbitofrontal, medial prefrontal, and left precentral cortices, and in the precuneus. Within these regions, activation in the orbitofrontal cortex rendered the most significant heritability estimate (h2=0.40), and was significantly correlated with BPD phenotype (rph=0.29). A moderate proportion of the genetic influences (rg=0.69) acting on both BPD and on the degree of orbitofrontal activation were shared. These findings suggest that genetic factors that confer vulnerability to BPD alter brain function in BPD.
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King׳s College London, De Crespigny Park, SE5 8AF, UK. Electronic address: genichi.sugihara@kcl.ac.uk.
authors.forename: Genichi
authors.initials: G
authors.lastname: Sugihara
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King׳s College London, De Crespigny Park, SE5 8AF, UK.
authors.forename: Fergus
authors.initials: F
authors.lastname: Kane
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King׳s College London, De Crespigny Park, SE5 8AF, UK; St Andrew׳s Academic Centre, King׳s College London, NN1 5BG, UK.
authors.forename: Marco M
authors.initials: MM
authors.lastname: Picchioni
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King׳s College London, De Crespigny Park, SE5 8AF, UK.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Chaddock
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King׳s College London, De Crespigny Park, SE5 8AF, UK.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Kravariti
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King׳s College London, De Crespigny Park, SE5 8AF, UK.
authors.forename: Sridevi
authors.initials: S
authors.lastname: Kalidindi
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King׳s College London, De Crespigny Park, SE5 8AF, UK.
authors.forename: Fruhling
authors.initials: F
authors.lastname: Rijsdijk
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King׳s College London, De Crespigny Park, SE5 8AF, UK.
authors.forename: Timothea
authors.initials: T
authors.lastname: Toulopoulou
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King׳s College London, De Crespigny Park, SE5 8AF, UK.
authors.forename: Vivienne A
authors.initials: VA
authors.lastname: Curtis
authors.affiliation: Department of Psychiatry, Clinical Science Institute, National University of Ireland, Galway, University Road, Galway, Ireland.
authors.forename: Colm
authors.initials: C
authors.lastname: McDonald
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King׳s College London, De Crespigny Park, SE5 8AF, UK.
authors.forename: Robin M
authors.initials: RM
authors.lastname: Murray
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King׳s College London, De Crespigny Park, SE5 8AF, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: McGuire
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D004200:Diseases in Twins; D005192:Family Health; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors; D014427:Twins / Q000235:genetics; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic
chemical_list: D010100:Oxygen
keywords: Bipolar disorder; Functional magnetic resonance imaging; Genetic modeling; Twin; Working memory