Study Helps Explains Why Dopamine Drugs Not Effective For Depression Interview with:

Robb B. Rutledge, PhD Max Planck University College London Centre for Computational Psychiatry  and Ageing Research University College London London, England

Dr. Rutledge

Robb B. Rutledge, PhD
Max Planck University College London Centre for Computational Psychiatry
and Ageing Research
University College London
London, England What is the background for this study? What are the main findings?

Response: Depression is associated with deficits in how the brain responds to rewards, something the neurotransmitter dopamine is strongly implicated in.

Dopamine represents what is called a reward prediction error, the difference between experienced and predicted reward. This error signal is used for learning. For example, if the outcome of a decision is better than expected, you can update your expectations using this error signal and you should expect more next time. Previous research has shown that depression reduces these signals in the brain when people are learning about the world around them. We designed a task where participants did not have to learn anything during the experiment and we found that in this situation reward prediction error signals were not affected by depression. The signals we measured in the ventral striatum, a brain area with a lot of input from the dopamine neurons, looked the same in depressed and non-depressed individuals. We also found that the emotional impacts of reward prediction errors were similar in depressed and non-depressed individuals when we eliminated the need for learning during the task in both the lab and using a smartphone experiment with 1833 participants. What should clinicians and patients take away from your report?

Response: Our results suggest that depression does not affect the reward-related signals that dopamine carries. Learning and adapting to new environments may be affected in depression, but our research suggests that the dopamine system is probably functioning normally in depression. This might explain why dopamine drugs are not effective antidepressants for most depressed individuals. What recommendations do you have for future research as a result of this study?

Response: Because the dopamine system appears to be largely intact in depression, this means that some aspects of learning may not be affected by depression. However, there are many situations in which the beliefs of depressed individuals may be different and future research needs to develop computational models that allow us to determine where those beliefs come from. Is there anything else you would like to add?

Response: Our results also show that the smartphones that we all carry around in our pockets might be very useful for mental health research. Using our equations, we were able to predict how happiness will go up and down during the course of a cognitive task, and this kind of approach may help us understand why mood changes, either for better or worse. If researchers start building more smartphone apps, the general public can contribute to important mental health research just by answering questions on their phones and playing carefully designed games that tell us about how we make decisions and how we feel about the outcomes of those decisions. Thank you for your contribution to the community.

Rutledge RB, Moutoussis M, Smittenaar P, Zeidman P, Taylor T, Hrynkiewicz L, Lam J, Skandali N, Siegel JZ, Ousdal OT, Prabhu G, Dayan P, Fonagy P, Dolan RJ. Association of Neural and Emotional Impacts of Reward Prediction Errors With Major Depression. JAMA Psychiatry. Published online July 05, 2017. doi:10.1001/jamapsychiatry.2017.1713

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Last Updated on July 6, 2017 by Marie Benz MD FAAD