Neuroscientists uncover how serotonin alters “belief stickiness”

A recent study published in Nature Mental Health suggests that the brain chemical serotonin plays a key role in helping people update their beliefs when situations change. The findings provide evidence that higher levels of serotonin reduce “belief stickiness,” making it easier to adapt to new information, while obsessive traits are linked to more rigid thinking. This research offers a new understanding of how common antidepressants might alleviate symptoms of obsessive-compulsive disorder by promoting cognitive flexibility.

Serotonin is a chemical messenger in the brain that helps regulate mood, sleep, and learning. Medical professionals frequently prescribe medications called selective serotonin reuptake inhibitors, or SSRIs, to treat mental health conditions like depression and obsessive-compulsive disorder, commonly known as OCD. These drugs work by increasing the amount of serotonin available in the brain.

Tiago V. Maia, an associate professor in the Faculty of Medicine at the University of Lisbon in Portugal, explained the specific rationale for the experiment. “This study had two interrelated motivations,” Maia told PsyPost. “The first was that serotonin has long been known to increase flexibility in thought and behavior, but the precise mechanisms by which it does so had remained unclear.”

“The second was that selective serotonin reuptake inhibitors, which increase serotonin, are the first-line pharmacological treatment for obsessive-compulsive disorder, but it was also unclear why they should help specifically with OCD,” Maia continued.

People with OCD often display cognitive inflexibility, meaning they have a hard time adapting their thoughts or behaviors when their environment changes. The authors suspected that serotonin helps reduce belief stickiness, which is the tendency to hold onto a belief about the state of the world even when new evidence suggests that the original belief is no longer accurate.

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If serotonin reduces belief stickiness, it would allow a person to more easily perform state inference. State inference is the mental process of figuring out the current hidden conditions of the environment based on available clues. Humans constantly adjust their behavior to optimize positive outcomes, and making accurate inferences about the state of the world is necessary for adapting to new situations.

In stable environments, people learn by slowly associating a specific action with a specific reward, a process known as reinforcement learning. Sometimes, environmental rules change abruptly, requiring quick behavioral adjustments to avoid negative consequences. To test whether serotonin helps people infer these changing rules and abandon sticky beliefs, the researchers designed an experiment combining medication, behavioral tasks, and advanced mathematical models.

To conduct the experiment, the researchers recruited 50 healthy adult men. They chose to study only men to prevent natural hormonal changes during the menstrual cycle from affecting serotonin levels. Before the final data analysis, six participants were excluded for various reasons, such as not understanding the task instructions, leaving a final sample of 44 men.

The researchers randomly assigned 20 participants to receive a single 15-milligram dose of escitalopram, a common SSRI. The remaining 24 participants received a placebo, which is an inactive pill that looks exactly like the real medication. The study used a double-blind design, meaning neither the participants nor the researchers interacting with them knew who received the real drug.

The scientists measured the actual levels of escitalopram in the participants’ blood plasma during the experiment. They also asked the participants to complete a standardized questionnaire called the Obsessive-Compulsive Inventory-Revised to assess any obsessive traits. Studying people from the general population allowed the researchers to look at obsessive tendencies on a natural continuum, rather than focusing solely on diagnosed patients.

During the main part of the experiment, participants completed a computer game called the shell task. The game presented different shells on the screen, and participants had to decide whether to collect the shell or let it pass. Collecting a shell could result in gaining a pearl, losing points by finding dirt, or finding nothing at all.

Unbeknownst to the participants, the shells went through hidden seasons, or states. In a rewarding season, a shell was more likely to contain a pearl, while in a punishing season, it was more likely to contain dirt. The seasons changed unexpectedly, requiring participants to infer the current state of each shell based on the outcomes they experienced.

The shell task is a specific type of reversal learning experiment. In reversal learning, initial rules are established and then suddenly flipped. By having seasons that reversed back and forth, the scientists could see if participants were simply relearning rules from scratch or actually inferring that a previous state had returned.

To analyze the behavioral data, the authors used computational modeling. This technique uses mathematics to simulate the mental processes behind human decision-making. The models helped the scientists measure exactly how sticky a participant’s beliefs were when the shell seasons changed.

The computational models separated simple action-and-reward learning from higher-level state inference. The mathematical model proved that participants were not just blindly reacting to rewards. Instead, they were actively forming and updating beliefs about the hidden seasons controlling the shells.

“We found that increasing serotonin through an SSRI decreases what we call belief stickiness, the tendency to get ‘stuck’ in a belief even when the incoming evidence suggests that belief to be incorrect,” Maia said. “We also found that the degree to which participants had obsessions related positively to belief stickiness: the greater participants’ belief stickiness, the more obsessions they had.”

“This finding is intuitive because obsessions can be seen as the prototypical example of belief stickiness,” Maia added. “For example, someone obsessed with whether they locked the door is stuck in a felt belief that the door may be unlocked, even after extensive checking shows ample evidence that the door is locked.”

“This felt belief may differ from the person’s explicit declarative beliefs, as patients with OCD often have insight into the unreasonableness of their obsessions,” Maia explained. “Putting the two findings together, obsessions relate to belief stickiness, and increasing serotonin decreases belief stickiness, suggests that SSRI may work for OCD by reducing the belief stickiness that underpins obsessions.”

Interestingly, simply being in the escitalopram group did not guarantee lower belief stickiness compared to the placebo group. The data showed that the medication only reduced belief stickiness if the participant’s blood plasma levels of escitalopram were sufficiently high. At lower levels, the single dose of the drug did not provide the same cognitive benefit.

When an SSRI is first introduced to the body, it can trigger feedback loops in the brain that temporarily reduce the natural firing of serotonin neurons. A sufficiently high dose is required to overcome this initial drop and successfully increase the amount of serotonin in the target areas of the brain. The participants who achieved these high plasma levels were better at updating their beliefs and adapting their behavior when a shell’s season shifted.

But the authors pointed out a few caveats. “Although our findings suggest a compelling explanation for the mechanism of action of SSRIs in the treatment of OCD, that explanation should be considered tentative, for two reasons,” Maia noted. “First, we did not include patients with OCD in our study, as we were interested in studying obsessions on a continuum in the general population.”

“Second, we used an acute dose of an SSRI, rather than the chronic SSRI administration that is used in the treatment of OCD,” Maia said. In psychiatric treatment, patients typically take SSRIs daily for weeks or months before seeing medical benefits. Chronic treatment consistently increases serotonin levels in the brain, which might reduce belief stickiness even more effectively than a single dose.

Another limitation is that the sample consisted entirely of men. It is essential for future research to include women to see if these effects on belief stickiness apply equally across different sexes. The overall sample size of 44 participants is also relatively small, meaning some statistical findings should be interpreted with a degree of caution.

“The logical immediate steps in this line of research are to address the two limitations noted above: extending this work to patients with OCD and investigating the effects of chronic, rather than acute, SSRI administration,” Maia said. “If that work confirms that SSRIs seem to work for OCD by decreasing belief stickiness, that will open the possibility of investigating other ways of decreasing belief stickiness as an alternative treatment for OCD.” Those interested in learning more about this ongoing scientific work can visit Maia’s academic website at tiagomaia.org.

The study, “Serotonin reduces belief stickiness“, was authored by Vasco A. Conceição, Frederike H. Petzschner, David M. Cole, Katharina V. Wellstein, Daniel Müller, Sudhir Raman, and Tiago V. Maia.