Introverts experience greater mood elevations from antidepressant placebos than extraverts

A recent study published in the International Journal of Neuropsychopharmacology indicates that people with natural tendencies toward lower positive moods tend to experience greater mood boosts from both antidepressant placebos and a dopamine-altering drug. The research suggests that an individual’s baseline personality traits, such as introversion and their natural ability to experience pleasure, play a major role in how they respond to treatments aimed at improving mood.

Human beings naturally vary in their daily capacity to experience positive emotions. Some people naturally have high levels of extraversion, meaning they tend to be outgoing, energetic, and cheerful. Others experience higher levels of anhedonia, a psychological term for a reduced ability to feel pleasure, joy, or motivation. Both of these personality dimensions are closely tied to how the human brain processes dopamine, a chemical messenger deeply involved in reward anticipation and motivation.

Past research indicates that expecting a medical treatment to work can trigger the brain’s dopamine system, leading to real improvements in mood. This psychological phenomenon is commonly known as the placebo effect. In the context of depression, the simple belief that a pill will boost mood can sometimes act as its own reward, stimulating dopamine release and alleviating symptoms.

It was not entirely understood whether a person’s baseline dopamine-related traits, such as anhedonia or extraversion, influence the strength of these mood-boosting placebo responses. A research team led by Li-Ching Chuang at the University of Marburg designed an experiment to test this dynamic. The scientists aimed to see how personal differences in baseline emotional traits might change how healthy people react to an actual dopamine-altering drug, as well as their reaction to the mere expectation of receiving an antidepressant.

To explore this, the researchers recruited 293 healthy adults between the ages of 18 and 60 for a randomized, double-blind study. Before the main experiment, participants completed comprehensive questionnaires to measure their baseline personality traits. This included a 30-item survey to measure trait anhedonia, where participants rated their recent lack of positive emotions. They also completed a personality inventory to measure trait extraversion.

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On the day of the experiment, participants arrived at the laboratory in the morning and provided a baseline blood sample. They were then given two identical capsules to swallow. The researchers manipulated treatment expectations through specific verbal instructions. Half of the participants were told that the capsules contained a mood-elevating medication that would begin to take effect in about three hours. The other half were told the capsules contained an inactive, inert substance.

In reality, the physical contents of the capsules were also randomized regardless of what the participants were told. Half of the total participants received actual inactive placebos. The other half received 400 milligrams of sulpiride. Sulpiride is a medication that blocks specific dopamine receptors in the brain. At this specific dosage, it can alter how dopamine functions, sometimes increasing dopamine signaling by blocking the autoreceptors that normally tell the brain to stop producing it.

Following the pill intake, participants rested and were provided a standardized meal. About three hours later, which aligns with when sulpiride reaches its peak concentration in the bloodstream, a second blood sample was drawn. The researchers measured prolactin, a hormone that reliably increases in response to sulpiride, to confirm the drug was physically active in the body.

Over the next several hours, participants completed various computer tasks. At six different time points throughout the session, participants rated their current state of positive affect using a standardized mood scale. This required them to rate how strongly they were currently feeling positive emotions like interest, excitement, and alertness.

The researchers found that neither the expectation of receiving an antidepressant nor the physical sulpiride pill increased positive emotions across the entire sample of participants. Instead, the treatment effects depended heavily on a person’s baseline personality traits.

Specifically, individuals who naturally scored high in trait anhedonia experienced a gradual increase in their current positive emotions when they took the active sulpiride medication. For these individuals, the dopamine-altering drug successfully boosted their mood. On the other hand, participants with naturally low anhedonia experienced a decrease in positive emotions after taking the exact same drug.

A very similar pattern emerged for the psychological expectation of receiving an antidepressant. Participants who scored low in extraversion, commonly known as introverts, experienced a noticeable increase in positive emotions when they were told they were taking a mood-boosting drug. The belief that they were being treated elevated their mood. In contrast, highly extraverted individuals reported reduced positive emotions when given the same antidepressant instructions.

The researchers also statistically combined these overlapping personality traits into a broader category called general positive affectivity. When looking at this combined measure, the scientists noted that individuals who naturally experience fewer positive emotions in their daily lives were the ones most likely to feel a temporary mood boost. Both the physical dopamine-altering drug and the psychological placebo instructions were most effective for those with a lower baseline of positivity.

These findings do not necessarily mean that positive expectations or dopamine treatments are biologically ineffective for generally happy people. Individuals with naturally high levels of positive emotion might simply hit a measurement ceiling effect in a laboratory setting. Because their mood is naturally quite high to begin with, a single dose of a drug or a positive expectation might not be capable of elevating it much further on a standardized rating scale.

The observed decrease in positive emotions among highly extraverted and low-anhedonia individuals under these conditions might also reflect the natural fatigue of participating in a controlled laboratory experiment. Sitting in a clinic for several hours performing computer tasks could naturally drain the enthusiasm of an extraverted person, leading to the observed drop in positive feelings over time.

The study also relied entirely on a healthy sample of adults who do not have clinical diagnoses of depression. Responses to dopamine-altering drugs and placebo expectations operate differently in individuals experiencing severe, clinical depression. The neurological state of a clinically depressed brain often involves more pronounced disruptions in dopamine signaling than what is seen in healthy individuals with mild anhedonia. Future investigations could test these identical procedures on clinical populations to see if the same personality traits dictate treatment success in patients actively seeking psychiatric care.

The study, “Individual differences in dopamine-related traits influence mood effects of dopamine D2-antagonist and antidepressant treatment expectations,” was authored by Li-Ching Chuang, Nick Augustat, Philipp Bierwirth, Ty Lees, Diego A. Pizzagalli, Dominik Endres, and Erik M. Mueller.