Prediction Error, Depression & How Ketamine Works to Treat Depression


We live in a wildly uncertain world right now, but there are some things we always know for sure. When we approach a local coffee shop and wait in line to pay, we can reasonably predict that we will eventually receive a coffee. We can accurately predict such a thing because we have done it before. When we wake up in the morning and go about our morning routine, we have to believe that someone will not jump out from behind our shower curtain and try to attack us.

If we walked around 24 hours a day, unable to predict our environment—afraid of being ambushed in our bathroom—life would be pretty hard. We make predictions about our environment all day long—it is simply part of our evolution.

What about when our predictions are wrong, though? When you teach a dog to sit and give it a treat to reward its obedience, dopamine fires in its brain. If you continue to give the dog treats each time it sits, it will begin to associate sitting with a reward—dopamine, and then, begin to fire when it sits…not when it gets the treat. If you told the dog to sit and didn’t give it a treat, though, that interaction would register as a “negative prediction error”—the dog was predicting a treat, but didn’t receive one. Humans, also get upset when our patterns of reward are interrupted.

Negative prediction errors happen all the time in the human world. What if Netflix decides to remove your favorite show? Or if, one day, your partner stops surprising you with flowers on your anniversary?

When we hold too tightly onto our predictions, our view of the world becomes rigid, and when that rigidity is interrupted, we become highly disappointed. We may begin to doubt our ability to predict reality. If this neural pathway is reinforced, it could lead to apathy or depression.

In a double-blind, placebo-controlled study, new research suggests that ketamine decreased depressive symptoms in 70% of patients—up to 50% of those patients within just one day of ketamine treatment. Ketamine could also reverse sensitivity to prediction errors as related to depression, and increase neuroplasticity. This means the brain may become less rigid when our routines—our predictions—are interrupted. Curious about the benefits of ketamine in treating depression?


Our clinical team is here to answer your questions, address your concerns, and help you choose the depression treatment that is right for you. If you or someone you love is looking to improve their mental health, contact our staff to answer any questions you may have about ketamine infusion therapy.

Contact us for more information about our IV Therapies at 530-208-9355 or by filling out the contact form below.

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