title: Altered amygdala-prefrontal response to facial emotion in offspring of parents with bipolar disorder.
abstract: This study aimed to identify neuroimaging measures associated with risk for, or protection against, bipolar disorder by comparing youth offspring of parents with bipolar disorder versus youth offspring of non-bipolar parents versus offspring of healthy parents in (i) the magnitude of activation within emotional face processing circuitry; and (ii) functional connectivity between this circuitry and frontal emotion regulation regions. The study was conducted at the University of Pittsburgh Medical Centre. Participants included 29 offspring of parents with bipolar disorder (mean age = 13.8 years; 14 females), 29 offspring of non-bipolar parents (mean age = 13.8 years; 12 females) and 23 healthy controls (mean age = 13.7 years; 11 females). Participants were scanned during implicit processing of emerging happy, sad, fearful and angry faces and shapes. The activation analyses revealed greater right amygdala activation to emotional faces versus shapes in offspring of parents with bipolar disorder and offspring of non-bipolar parents than healthy controls. Given that abnormally increased amygdala activation during emotion processing characterized offspring of both patient groups, and that abnormally increased amygdala activation has often been reported in individuals with already developed bipolar disorder and those with major depressive disorder, these neuroimaging findings may represent markers of increased risk for affective disorders in general. The analysis of psychophysiological interaction revealed that offspring of parents with bipolar disorder showed significantly more negative right amygdala-anterior cingulate cortex functional connectivity to emotional faces versus shapes, but significantly more positive right amygdala-left ventrolateral prefrontal cortex functional connectivity to happy faces (all P-values corrected for multiple tests) than offspring of non-bipolar parents and healthy controls. Taken together with findings of increased amygdala-ventrolateral prefrontal cortex functional connectivity, and decreased amygdala-anterior cingulate cortex functional connectivity previously shown in individuals with bipolar disorder, these connectivity patterns in offspring of parents with bipolar disorder may be risk markers for, rather than markers conferring protection against, bipolar disorder in youth. The patterns of activation and functional connectivity remained unchanged after removing medicated participants and those with current psychopathology from analyses. This is the first study to demonstrate that abnormal functional connectivity patterns within face emotion processing circuitry distinguish offspring of parents with bipolar disorder from those of non-bipolar parents and healthy controls.
authors.affiliation: 1 Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA anna.manelis@gmail.com.
authors.forename: Anna
authors.initials: A
authors.lastname: Manelis
authors.affiliation: 1 Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Cecile D
authors.initials: CD
authors.lastname: Ladouceur
authors.affiliation: 1 Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Simona
authors.initials: S
authors.lastname: Graur
authors.affiliation: 1 Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Monk
authors.affiliation: 1 Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Bonar
authors.affiliation: 1 Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Hickey
authors.affiliation: 1 Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Dwojak
authors.affiliation: 2 Department of Psychiatry, Nationwide Children's Hospital and The Ohio State College of Medicine, Columbus, Ohio, USA.
authors.forename: David
authors.initials: D
authors.lastname: Axelson
authors.affiliation: 3 Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto, Faculty of Medicine, Toronto, Ontario, Canada.
authors.forename: Benjamin I
authors.initials: BI
authors.lastname: Goldstein
authors.affiliation: 1 Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Tina R
authors.initials: TR
authors.lastname: Goldstein
authors.affiliation: 1 Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Genna
authors.initials: G
authors.lastname: Bebko
authors.affiliation: 1 Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Michele A
authors.initials: MA
authors.lastname: Bertocci
authors.affiliation: 1 Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Danella M
authors.initials: DM
authors.lastname: Hafeman
authors.affiliation: 1 Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Mary Kay
authors.initials: MK
authors.lastname: Gill
authors.affiliation: 1 Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Boris
authors.initials: B
authors.lastname: Birmaher
authors.affiliation: 1 Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Phillips
mesh_terms: D000293:Adolescent; D000679:Amygdala / Q000098:blood supply* / Q000473:pathology; D001714:Bipolar Disorder / Q000473:pathology*; D001931:Brain Mapping; D002648:Child; D016241:Child of Impaired Parents / Q000523:psychology; D005149:Facial Expression; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000098:blood supply*; D010100:Oxygen / Q000097:blood; D010290:Parents; D010364:Pattern Recognition, Visual; D010775:Photic Stimulation; D017397:Prefrontal Cortex / Q000098:blood supply* / Q000473:pathology; D011569:Psychiatric Status Rating Scales
chemical_list: D010100:Oxygen
keywords: biological markers; emotion processing; emotion regulation; functional MRI; risk of bipolar disorder; youth offspring of parents with bipolar disorder