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

Area of Science:

• Neuroscience
• Psychiatry
• Behavioral Science

Background:

• Individuals with bipolar disorder (BD) often exhibit impaired decision-making, affecting their quality of life.
• The Iowa Gambling Task (IGT) quantifies decision-making deficits by assessing choices between advantageous and disadvantageous options.
• Reduced dopamine transporter (DAT) functioning is observed in BD patients, but its role in decision-making deficits is unclear.

Purpose of the Study:

• To investigate if reduced dopamine transporter (DAT) functioning recreates the decision-making deficits observed in bipolar disorder (BD).
• To compare human BD patient performance on the IGT with mouse models exhibiting reduced DAT functioning.

Main Methods:

• Assessed IGT performance in 16 BD patients and 17 healthy controls (HC).
• Developed and utilized a single-session mouse IGT.
• Compared human IGT data with mouse models of chronic (DAT knockdown) and acute (DAT inhibitor GBR12909) DAT reduction.

Main Results:

• BD patients demonstrated significantly impaired decision-making compared to HC subjects.
• Mice with reduced DAT functioning (both chronic knockdown and acute inhibition) exhibited poor decision-making on the mouse IGT.
• The decision-making deficits in both BD patients and DAT-reduced mice were characterized by high sensitivity to rewards.

Conclusions:

• Reduced DAT functioning in mice successfully models the impaired decision-making observed in bipolar disorder (BD) patients.
• The findings suggest that hyperdopaminergia, resulting from reduced DAT functioning, may contribute to poor decision-making in BD.
• The developed mouse IGT effectively measures dynamic, risk-based decision-making comparable to human performance.