title: The risk variant in ODZ4 for bipolar disorder impacts on amygdala activation during reward processing.
abstract: OBJECTIVE
  Bipolar disorder is a severe mood disorder, which normally begins during adolescence or early adulthood and has a heritability of up to 80%. The largest genome-wide association analysis of bipolar disorder recently identified a new genome-wide associated variant in OZD4 (rs12576775). The aim of the present study was to further elucidate the role of this risk variant in the disease process using an imaging genetics approach. As increased amygdala and striatal responses during the processing of reward and emotion are characteristic for bipolar disorder patients, it was tested whether the risk variant has an influence on this endophenotype in healthy adolescents.
  
  
  METHODS
  We examined the impact of the risk variant rs12576775 on functional magnetic resonance imaging data in an adolescent sample (N = 485). Differential activation between carriers of the risk allele (G-allele) and homozygous A-allele carriers in the amygdala and the striatum during a modification of the monetary incentive delay task (examining reward) and a face task (examining emotion) was analyzed.
  
  
  RESULTS
  Carriers of the risk allele showed an increased blood oxygen level-dependent response in the amygdala during reward sensitivity (p = 0.05) and reward expectation (p < 0.05) but not during the face task. No significant group differences were found in the striatum during both reward and emotion processing.
  
  
  CONCLUSIONS
  Our results indicate that the ODZ4 risk variant influences reward processing in the amygdala. Alterations in the processing of emotion may have different underlying mechanisms and need to be further examined.
authors.affiliation: Department of Cognitive and Clinical Neuroscience; Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Heinrich
authors.forename: Anbarasu
authors.initials: A
authors.lastname: Lourdusamy
authors.forename: Jelka
authors.initials: J
authors.lastname: Tzschoppe
authors.forename: Sabine
authors.initials: S
authors.lastname: Vollstädt-Klein
authors.forename: Mira
authors.initials: M
authors.lastname: Bühler
authors.forename: Sabina
authors.initials: S
authors.lastname: Steiner
authors.forename: Christiane
authors.initials: C
authors.lastname: Bach
authors.forename: Luise
authors.initials: L
authors.lastname: Poustka
authors.forename: Tobias
authors.initials: T
authors.lastname: Banaschewski
authors.forename: Gareth
authors.initials: G
authors.lastname: Barker
authors.forename: Christian
authors.initials: C
authors.lastname: Büchel
authors.forename: Patricia
authors.initials: P
authors.lastname: Conrod
authors.forename: Hugh
authors.initials: H
authors.lastname: Garavan
authors.forename: Jürgen
authors.initials: J
authors.lastname: Gallinat
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinz
authors.forename: Bernd
authors.initials: B
authors.lastname: Ittermann
authors.forename: Eva
authors.initials: E
authors.lastname: Loth
authors.forename: Karl
authors.initials: K
authors.lastname: Mann
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Martinot
authors.forename: Tomáš
authors.initials: T
authors.lastname: Paus
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Pausova
authors.forename: Michael
authors.initials: M
authors.lastname: Smolka
authors.forename: Andreas
authors.initials: A
authors.lastname: Ströhle
authors.forename: Maren
authors.initials: M
authors.lastname: Struve
authors.forename: Stephanie
authors.initials: S
authors.lastname: Witt
authors.forename: Herta
authors.initials: H
authors.lastname: Flor
authors.forename: Gunter
authors.initials: G
authors.lastname: Schumann
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Frauke
authors.initials: F
authors.lastname: Nees
mesh_terms: D000293:Adolescent; D000679:Amygdala / Q000378:metabolism / Q000473:pathology; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D004644:Emotions / Q000502:physiology*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D058027:Neuropsychiatry; D011569:Psychiatric Status Rating Scales; D012201:Reward
chemical_list: D008562:Membrane Glycoproteins; C576539:TENM4 protein, human
keywords: amygdala; bipolar disorder; imaging genetics; reward processing; ventral striatum