title: Disturbed anterior prefrontal control of the mesolimbic reward system and increased impulsivity in bipolar disorder.
abstract: Bipolar disorder (BD) is characterized by recurrent mood episodes ranging from severe depression to acute full-blown mania. Both states of this severe psychiatric disorder have been associated with alterations of reward processing in the brain. Here, we present results of a functional magnetic resonance imaging (fMRI) study on the neural correlates and functional interactions underlying reward gain processing and reward dismissal in favor of a long-term goal in bipolar patients. Sixteen medicated patients diagnosed with bipolar I disorder, euthymic to mildly depressed, and sixteen matched healthy controls performed the 'desire-reason dilemma' (DRD) paradigm demanding rejection of priorly conditioned reward stimuli to successfully pursue a superordinate goal. Both groups exhibited significant activations in reward-related brain regions, particularly in the mesolimbic reward system. However, bipolar patients showed reduced neural responses of the ventral striatum (vStr) when exploiting a reward stimulus, and exhibited a decreased suppression of the reward-related activation of the mesolimbic reward system while having to reject immediate reward in favor of the long-term goal. Further, functional interaction between the anteroventral prefrontal cortex and the vStr in the 'DRD' was significantly impaired in the bipolar group. These findings provide evidence for a reduced responsivity of the vStr to reward stimuli in BD, possibly related to clinical features like anhedonia. The disturbed top-down control of mesolimbic reward signals by prefrontal brain regions in BD can be interpreted in terms of a disease-related enhanced impulsivity, a trait marker of BD.
authors.affiliation: Department of Psychiatry and Psychotherapy, Centre for Translational Research in Systems Neuroscience and Clinical Psychiatry, Georg August University, Goettingen, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Trost
authors.affiliation: 1] Department of Psychiatry and Psychotherapy, Centre for Translational Research in Systems Neuroscience and Clinical Psychiatry, Georg August University, Goettingen, Germany [2] Biocenter Grindeland Zoological Museum, Institute for Human Biology, University of Hamburg, Hamburg, Germany.
authors.forename: Esther Kristina
authors.initials: EK
authors.lastname: Diekhof
authors.affiliation: Department of Psychiatry and Psychotherapy, Centre for Translational Research in Systems Neuroscience and Clinical Psychiatry, Georg August University, Goettingen, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Zvonik
authors.affiliation: Department of Psychiatry and Psychotherapy, Centre for Translational Research in Systems Neuroscience and Clinical Psychiatry, Georg August University, Goettingen, Germany.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Lewandowski
authors.affiliation: Department of Psychiatry and Psychotherapy, Centre for Translational Research in Systems Neuroscience and Clinical Psychiatry, Georg August University, Goettingen, Germany.
authors.forename: Juliana
authors.initials: J
authors.lastname: Usher
authors.affiliation: Department of Psychiatry and Psychotherapy, Centre for Translational Research in Systems Neuroscience and Clinical Psychiatry, Georg August University, Goettingen, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Keil
authors.affiliation: Department of Psychiatry and Psychotherapy, Centre for Translational Research in Systems Neuroscience and Clinical Psychiatry, Georg August University, Goettingen, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Zilles
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Falkai
authors.affiliation: Department of Cognitive Neurology, Georg August University, Goettingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Dechent
authors.affiliation: Department of Psychiatry and Psychotherapy, Centre for Translational Research in Systems Neuroscience and Clinical Psychiatry, Georg August University, Goettingen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Gruber
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000503:physiopathology*; D001931:Brain Mapping; D005260:Female; D006801:Humans; D007175:Impulsive Behavior / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000503:physiopathology*; D012201:Reward; D066328:Ventral Striatum / Q000503:physiopathology*; D055815:Young Adult