title: Altered Brain Activation during Emotional Face Processing in Relation to Both Diagnosis and Polygenic Risk of Bipolar Disorder.
abstract: OBJECTIVE
  Bipolar disorder (BD) is a highly heritable disorder with polygenic inheritance. Among the most consistent findings from functional magnetic imaging (fMRI) studies are limbic hyperactivation and dorsal hypoactivation. However, the relation between reported brain functional abnormalities and underlying genetic risk remains elusive. This is the first cross-sectional study applying a whole-brain explorative approach to investigate potential influence of BD case-control status and polygenic risk on brain activation.
  
  
  METHODS
  A BD polygenic risk score (PGRS) was estimated from the Psychiatric Genomics Consortium BD case-control study, and assigned to each individual in our independent sample (N=85 BD cases and 121 healthy controls (HC)), all of whom participated in an fMRI emotional faces matching paradigm. Potential differences in BOLD response across diagnostic groups were explored at whole-brain level in addition to amygdala as a region of interest. Putative effects of BD PGRS on brain activation were also investigated.
  
  
  RESULTS
  At whole-brain level, BD cases presented with significantly lower cuneus/precuneus activation than HC during negative face processing (Z-threshold=2.3 as cluster-level correction). The PGRS was associated positively with increased right inferior frontal gyrus (rIFG) activation during negative face processing. For amygdala activation, there were no correlations with diagnostic status or PGRS.
  
  
  CONCLUSIONS
  These findings are in line with previous reports of reduced precuneus and altered rIFG activation in BD. While these results demonstrate the ability of PGRS to reveal underlying genetic risk of altered brain activation in BD, the lack of convergence of effects at diagnostic and PGRS level suggests that this relation is a complex one.
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: Martin
authors.initials: M
authors.lastname: Tesli
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: Karolina
authors.initials: K
authors.lastname: Kauppi
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bettella
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: Christine Lycke
authors.initials: CL
authors.lastname: Brandt
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: Tobias
authors.initials: T
authors.lastname: Kaufmann
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway.
authors.forename: Thomas
authors.initials: T
authors.lastname: Espeseth
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Sørlandet Hospital HF, Kristiansand, Norway.
authors.forename: Morten
authors.initials: M
authors.lastname: Mattingsdal
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; HUBIN Project, Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet and Hospital, Stockholm, Sweden; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Agartz
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Melle
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Division of Medical Genetics, Oslo University Hospital, Oslo, Norway.
authors.forename: Srdjan
authors.initials: S
authors.lastname: Djurovic
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway.
authors.forename: Lars T
authors.initials: LT
authors.lastname: Westlye
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: Ole A
authors.initials: OA
authors.lastname: Andreassen
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004644:Emotions / Q000502:physiology; D005149:Facial Expression; D000066499:Facial Recognition / Q000502:physiology*; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D055815:Young Adult