People who are naturally predisposed to negative emotions and worry tend to experience more side effects from treatment because they expect it to go wrong. Recent research published in personality journal This self-fulfilling prophecy provides evidence that negative personality traits create a loop in which negative expectations result in very real physical discomfort. The findings suggest that physicians may need to adjust the way they communicate risks to anxious patients to minimize these unintended harms.
The psychological concept of neuroticism is a broad personality trait that reflects a person’s tendency to experience negative emotions. People with high levels of neuroticism frequently experience anxiety, anger, sadness, and emotional instability. They often have a more pessimistic outlook on life and routinely report higher levels of general physical health complaints.
This pessimistic outlook could have tangible implications for healthcare through a phenomenon known as the nocebo effect. The nocebo effect is a negative effect of the well-known placebo effect. This occurs when a person’s negative expectations for a treatment cause them to experience negative side effects, even if the treatment itself is completely ineffective or harmless.
Previous scientific observations point to a link between high neuroticism and a higher likelihood of experiencing the nocebo effect. However, the precise set of psychological events that link generally negative personality traits with specific physical side effects requires further investigation. A team of psychology researchers from the Philipp University of Marburg in Germany designed a project to uncover this relationship. They aimed to test whether specific, conscious expectations about side effects serve as a key bridge between high levels of neuroticism and the experience of actual nocebo responses.
To investigate this psychological pathway, the authors recruited a sample of 275 healthy adult participants. This group consisted of 133 women, 139 men, and 3 individuals who identified as gender diverse. Participants ranged in age from 18 to 65, with an average age of just over 24.
Before the first experiment began, participants completed a comprehensive set of questionnaires. These studies used standardized personality assessments to measure baseline levels of neuroticism. Participants also filled out a form detailing their current daily physical symptoms and rated the number of side effects they would experience from future medical procedures.
The scientists then assigned participants to settings with four different experimental conditions. As for the actual treatment, participants were given two inert placebo pills or 400 milligrams of a drug called sulpiride. Sulpiride is a drug that acts on dopamine receptors in the brain and is often used in psychiatric treatment. However, scientific literature shows that this particular single dose typically does not cause any noticeable physical side effects in healthy people.
Regardless of which pill they actually received, participants were given one of two verbal instructions by medical staff. Some participants were explicitly told that they were being given an inert placebo pill that had no effect on their bodies. Other participants were given the active ingredient sulpiride and were warned that it could sometimes cause side effects.
After ingesting the pills, participants underwent a waiting period of several hours and completed various computer tasks and other laboratory assessments. At the end of the study session, participants rated their physical symptoms again. Researchers compared these final symptom reports to baseline physical complaints to measure sudden increases in physical discomfort.
The data collected revealed some notable patterns regarding personality and physical health. Those with higher levels of neuroticism reported more physical symptoms before the experiment began. These same people reported significantly higher expectations that future treatments would cause side effects.
When looking at changes in physical symptoms after taking the drug, the actual drug and clear verbal instructions had little effect. Participants who took the actual drug reported fewer symptoms than those who took the sugar pill. Instead, the participants’ natural psychological characteristics were the main predictors of how their bodies felt at the end of the day.
Both high neuroticism and high pretreatment expectations independently predicted stronger nocebo responses across groups. This means that people who felt more anxious in general, or simply expected more side effects, experienced a greater increase in physical complaints after taking the pill. This occurred regardless of whether they received the active drug or a placebo.
The scientists then used a statistical method known as path analysis to test whether these expectations acted as mediators. In psychological research, a mediator is an intermediate variable that helps explain the gradual relationship between two other variables. The authors wanted to see if neuroticism causes negative expectations, which in turn lead to physical symptoms.
The analysis showed a partial mediation effect. This data suggests that high neuroticism tends to increase explicit expectations of side effects, which directly increases the likelihood of experiencing harmful bodily sensations. A generally pessimistic worldview translates into a specific fear of medical care, which tricks the body into becoming unwell.
At the same time, neurosis directly increased side effects independently of these conscious expectations. Researchers have proposed that people high in neuroticism may have negative unconscious biases when it comes to their perceptions of their bodies. They pay close attention to normal body fluctuations, such as random rumblings in the stomach or slight headaches, and can misinterpret them as severe drug-induced side effects.
Although these findings provide useful insight into how personality influences medical outcomes, this study has several limitations. The researchers measured anticipation of side effects using a single survey question with a numerical scale. This simple measure may not have fully captured the complexity of patients’ medical concerns and may have mathematically reduced the strength of the relationships observed in the statistical model.
Additionally, the experiment involved one lab visit and a drug that rarely causes side effects. In real-world clinical practice, patients are often repeatedly treated with drugs that carry a much higher risk of actual adverse events. The single and low-risk nature of this controlled study may have resulted in a smaller nocebo effect than would occur naturally in routine medical care.
Future studies should aim to follow patients across multiple visits in a natural clinical setting. Tracking actual doctor visits could reveal how neuroticism and negative expectations worsen over time and affect a person’s overall health. Over the years, a self-reinforcing loop of bad expectations and bad experiences can have a significant impact on patients’ willingness to seek medical care.
Understanding this psychological loop suggests that health care professionals may benefit from identifying high-anxiety patients early on during consultations. Physicians could break the cycle of negative expectations by adjusting how they explain medication risks. Framing side effect statistics positively, such as emphasizing that the majority of patients tolerate the drug well, may help reduce the physical burden of nocebo effects.
The study, “Trait Neuroticism and the Nocebo Effect: The Mediating Role of Side Effect Expectations,” was authored by Anton Fischer, Li-Chin Chuan, Nick Augustadt, Pia von Blankenburg, and Eric M. Muller.
