Recent research published in natural mental health It suggests that the brain chemical serotonin plays an important role in helping people update their beliefs when circumstances change. The findings provide evidence that obsessive-compulsive traits are associated with more rigid thinking, while high serotonin levels reduce “belief fixation” and make it easier to adapt to new information. This study provides new understanding that common antidepressants may reduce 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 drugs called selective serotonin reuptake inhibitors (SSRIs) to treat mental health conditions such as 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, associate professor of medicine at the University of Lisbon in Portugal, explained the specific rationale for the experiment. “There were two interrelated motivations for this study,” Maia told PsyPost. “First, it has long been known that serotonin increases flexibility in thought and behavior, but the exact mechanism has remained unclear.”
“Second, selective serotonin reuptake inhibitors, which increase serotonin, are the first-line drug treatment for obsessive-compulsive disorder, but it was also unclear why they were particularly effective for OCD,” Maia continued.
People with OCD often exhibit cognitive inflexibility, which means they have difficulty adapting their thoughts and behaviors when their environment changes. The authors suspected that serotonin might help reduce belief perseveration, the tendency to cling to beliefs about the state of the world even when new evidence suggests that the original belief is no longer accurate.
If serotonin reduces belief persistence, people will be able to engage in state reasoning more easily. State inference is the mental process of figuring out the current hidden state of the environment based on available cues. Humans constantly adjust their behavior to optimize positive outcomes, and adapting to new situations requires accurate reasoning about the state of the world.
In stable environments, people learn by slowly associating certain behaviors with certain rewards. This is a process known as reinforcement learning. In some cases, environmental rules may change suddenly, requiring quick behavioral adjustments to avoid negative consequences. To test whether serotonin can help people second-guess these changing rules and abandon entrenched beliefs, researchers designed an experiment that combined medication, behavioral tasks, and sophisticated mathematical models.
To conduct the experiment, 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 final data analysis, six participants were excluded for various reasons, including not understanding the task instructions, leaving a final sample of 44 men.
Researchers randomly assigned 20 participants to receive a single 15-milligram dose of escitalopram, a common SSRI. The remaining 24 participants were given a placebo, an inert pill that looks exactly like the real drug. The study used a double-blind design, meaning neither the participants nor the researchers interacting with them knew who was receiving the real drug.
Scientists measured the actual levels of escitalopram in participants’ plasma during the experiment. They also asked participants to complete a standardized questionnaire called the Revised Obsessive-Compulsive Survey to assess obsessive-compulsive traits. By studying people in the general population, researchers were able to look at obsessive-compulsive tendencies on a natural continuum, rather than just focusing on diagnosed patients.
In the main part of the experiment, participants completed a computer game called the shell task. The game showed different seashells on the screen and participants had to decide whether to collect them or let them pass. Collecting shells can earn you pearls, find dirt and lose points, or find nothing at all.
Unbeknownst to the participants, the shells were going through hidden seasons, or states. In seasons of reward, shells are more likely to contain pearls, and in seasons of punishment, they are more likely to contain dirt. The seasons changed unexpectedly, and participants had to infer the current status of each shell based on the results they experienced.
A shell task is a specific type of reversal learning experiment. In reversal learning, an initial rule is established and then suddenly reversed. By flipping the seasons back and forth, the scientists were able to see whether the participants were simply relearning the rules from scratch, or whether they were actually inferring a return to the previous state.
To analyze the behavioral data, the authors used computational modeling. This technique uses mathematics to simulate the mental processes behind human decision-making. The model helped scientists accurately measure how much participants’ beliefs held firm as shellfish seasons changed.
Computational models have separated simple behavior and reward learning from higher-level state inference. The mathematical model proved that participants were not simply responding to rewards blindly. Instead, they were actively forming and updating their beliefs about the hidden seasons that controlled shells.
“We found that increasing serotonin with SSRIs reduces what is called belief stickiness, or the tendency to ‘stick’ to a belief even when incoming evidence suggests that the belief is false,” Maia said. “We also found that participants’ degree of obsession was positively related to belief perseveration. The greater a participant’s belief perseveration, the more obsessive they were.”
“This finding is intuitive because obsessions can be considered a classic example of belief perseveration,” Maia added. “For example, someone who is obsessed with whether or not the door is locked is stuck in the belief that the door may not be locked, even if thorough checks have found sufficient evidence that the door is locked.”
“Because people with OCD often have insight into the irrationality of their obsessions, this felt belief may differ from the person’s explicit declarative beliefs,” Maia explained. “Taken together, the results of the two studies suggest that obsessions are associated with belief perseveration, and that increasing serotonin decreases belief perseveration, suggesting that SSRIs may have an effect on OCD by reducing the belief perseveration that underlies obsessions.”
Interestingly, simply being in the escitalopram group does not guarantee that beliefs will be less persistent compared to those in the placebo group. The data showed that the drug reduced belief persistence only when participants’ plasma concentrations of escitalopram were high enough. At lower levels, a single dose of the drug did not produce the same cognitive effects.
When SSRIs are first introduced to the body, they trigger a feedback loop in the brain that temporarily reduces the natural firing of serotonin neurons. A sufficiently high dose is required to overcome this initial drop and successfully increase serotonin levels in targeted areas of the brain. Participants who achieved these high plasma levels were better at updating their beliefs and adapting their behavior when shellfish season changed.
However, the authors pointed out some caveats. “While our findings suggest a plausible explanation for the mechanism of action of SSRIs in the treatment of OCD, this explanation should be considered tentative for two reasons,” Maia said. “First, we did not include OCD patients in the study because 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 used to treat OCD,” Maia said. In psychiatric treatment, patients typically take SSRIs daily for several weeks to months until medical benefit is achieved. Because chronic treatment consistently increases serotonin levels in the brain, it may reduce belief persistence even more effectively than a single dose.
Another limitation is that the sample consisted only of men. In future studies, it is essential to include women to see if these effects on belief persistence apply similarly across genders. The overall sample size of 44 participants was also relatively small, so some statistical results should be interpreted with some caution.
“The logical immediate steps in this series of studies are to address the two limitations mentioned above: to extend this study to OCD patients and to investigate the effects of chronic rather than acute SSRI administration,” Maia said. “If this study confirms that SSRIs are effective in OCD by reducing belief preoccupation, it would open the possibility of investigating other ways to reduce belief preoccupation as alternative treatments for OCD.” To learn more about this ongoing scientific research, visit Maia’s academic website (tiagomaia.org).
The study, “Serotonin Reduces Belief Persistence,” was authored by Vasco A. Conceição, Frederike H. Petzschner, David M. Cole, Katharina V. Werstein, Daniel Müller, Sudhir Raman, and Tiago V. Maia.
