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Reduced dopamine transporter functioning induces high-reward risk-preference consistent with bipolar disorder.

ABSTRACT: Individuals with bipolar disorder (BD) exhibit deleterious decision making, negatively impacting their lives. Such aberrant decision making can be quantified using the Iowa Gambling Task (IGT), which requires choosing between advantageous and disadvantageous options based on different reward/punishment schedules. The mechanisms underlying this behavioral deficit are unknown, but may include the reduced dopamine transporter (DAT) functioning reported in BD patients. Using both human and mouse IGTs, we tested whether reduced DAT functioning would recreate patterns of deficient decision making of BD patients. We assessed the IGT performance of 16 BD subjects (7 female) and 17 healthy control (HC) subjects (12 female). We recorded standard IGT performance measures and novel post-reward and post-punishment decision-making strategies. We characterized a novel single-session mouse IGT using C57BL/6J mice (n = 44). The BD and HC IGT performances were compared with the effects of chronic (genetic knockdown (KD; n = 31) and wild-type (n = 28) mice) and acute (C57BL/6J mice (n = 89) treated with the DAT inhibitor GBR12909) reductions of DAT functioning in mice performing this novel IGT. BD patients exhibited impaired decision making compared with HC subjects. Both the good-performing DAT KD and GBR12909-treated mice exhibited poor decision making in the mouse IGT. The deficit of each population was driven by high-reward sensitivity. The single-session mouse IGT measures dynamic risk-based decision making similar to humans. Chronic and acute reductions of DAT functioning in mice impaired decision-making consistent with poor IGT performance of BD patients. Hyperdopaminergia caused by reduced DAT may impact poor decision making in BD patients, which should be confirmed in future studies.

SUBMITTER: van Enkhuizen J

PROVIDER: S-EPMC4229584 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Reduced dopamine transporter functioning induces high-reward risk-preference consistent with bipolar disorder.

van Enkhuizen Jordy J Henry Brook L BL Minassian Arpi A Perry William W Milienne-Petiot Morgane M Higa Kerin K KK Geyer Mark A MA Young Jared W JW

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20140709 13

Individuals with bipolar disorder (BD) exhibit deleterious decision making, negatively impacting their lives. Such aberrant decision making can be quantified using the Iowa Gambling Task (IGT), which requires choosing between advantageous and disadvantageous options based on different reward/punishment schedules. The mechanisms underlying this behavioral deficit are unknown, but may include the reduced dopamine transporter (DAT) functioning reported in BD patients. Using both human and mouse IGT ...[more]

PMID: 25005251

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Project description:Bipolar disorder is characterized by impaired decision-making captured in impulsivity and risk-taking. We sought to determine whether this is driven by a failure to effectively weight the lower-order goal of obtaining a strongly desired reward in relation to higher-order goals, and how this relates to trait impulsivity and risk-taking. We hypothesized that in bipolar disorder the weighting of valuation signals converging on ventromedial prefrontal cortex are more heavily weighted towards ventral striatum inputs (lower-order), with less weighting of dorsolateral prefrontal cortex inputs (higher-order). Twenty euthymic patients with bipolar disorder not in receipt of antipsychotic medication and 20 case-matched controls performed a roulette task during functional magnetic resonance imaging. Activity in response to high-probability ('safe') and low-probability ('risky') prospects was measured during both anticipation, and outcome. In control subjects, anticipatory and outcome-locked activity in dorsolateral prefrontal cortex was greater for safe than risky reward prospects. The bipolar disorder group showed the opposite pattern with preferential response to risky rewards. This group also showed increased anticipatory and outcome-locked activity in ventral striatum in response to rewards. In control subjects, however, ventromedial prefrontal activation was positively associated with both ventral striatum and dorsolateral prefrontal activity; patients evidenced a strong positive association with ventral striatum, but a negative association with dorsolateral prefrontal cortex. Response to high-probability rewards in dorsolateral prefrontal cortex was inversely associated with trait impulsivity and risk-taking in the bipolar disorder group. Our findings suggest that clinically impulsive and risky decision-making are related to subjective valuation that is biased towards lower-order preference, with diminished integration of higher-order goals. The findings extend a functional neuroanatomical account of disorders characterized by clinically impulsive decision-making, and provide targets for evaluating interventions that foster self-control.

Dataset Information

Reduced dopamine transporter functioning induces high-reward risk-preference consistent with bipolar disorder.

Publications

Reduced dopamine transporter functioning induces high-reward risk-preference consistent with bipolar disorder.

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