Serotonergic antidepressants might be more effective in less crowded environments

A new study from the Netherlands suggests that the effectiveness of serotonergic antidepressants may be linked to a patient’s living environment. For individuals with depression taking these medications, living in an area with lower population density was associated with healthier patterns of attention, a key behavioral marker of the disorder. The study’s authors propose that less frequent social contact and reduced sensory stimulation in these environments might interact with the medication in a way that is beneficial for mental health. The research was published in Cognition and Emotion.

Depression is a common and serious mental disorder characterized by persistent sadness, loss of interest, and reduced energy. It is estimated that 5% of the adult population worldwide suffers from it. Over 700,000 people die by suicide each year, with depression being a major contributing factor.

Treatment for depression often involves psychotherapy, medication, or a combination of both. A primary class of these medications is serotonergic antidepressants, which work by increasing the levels of a brain chemical called serotonin.

However, the effectiveness of these medications varies greatly from person to person. A significant number of patients do not achieve full remission. Lead author Kari Bosch and her colleagues wanted to explore whether the effects of serotonergic antidepressants might depend on the patient’s environment.

The researchers conducted a study exploring whether a person’s living environment modulates the effects of antidepressant treatment on attentional bias. People with depression often show a negative attentional bias, meaning they tend to focus more on negative emotional cues (like sad or angry facial expressions) than on positive ones. The authors investigated whether this attentional bias was influenced by the population density of a patient’s neighborhood.

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Study participants were 140 individuals with depression from the ongoing MIND-Set study cohort (Measuring Integrated Novel Dimensions in Neurodevelopmental and Stress-related Mental Disorders). Approximately 49% of the participants were women, and the average age was around 40 years.

The participants were divided into two groups: 71 were taking serotonergic antidepressants, and 69 were not. Approximately 10% of participants not on serotonergic antidepressants were on another type of psychoactive medication.

Participants completed an assessment of their depressive symptoms and performed an eye-tracking task. In the task, they were shown four images of a person’s face simultaneously, each with a different expression (angry, sad, happy, and neutral), and were instructed to view them freely. The researchers recorded how long participants looked at each image and how many times they returned to it, using this data to assess their attentional bias. The team used participants’ postal codes to determine the population density of their neighborhoods.

Results showed that, overall, participants from less populated areas tended to look longer at positive and neutral faces compared to negative ones. A more specific interaction was found between medication and environment: in more densely populated areas, patients taking serotonergic antidepressants spent more total time looking at all the faces combined compared to patients not on these medications.

The most notable finding came from analyzing how many times participants revisited each face. For patients taking serotonergic antidepressants, those in low-density areas revisited positive and neutral faces more often—a healthier pattern. Conversely, those in high-density areas lost this positive bias and paid more attention to angry faces. This pattern was not seen in patients not taking serotonergic drugs. Based on this, the authors suggest that a less populated environment may have a protective effect, enhancing the medication’s ability to normalize attentional patterns.

“Possibly, less frequent unavoidable social contact and reduced overall sensory stimulation, particularly in combination with serotonergic AD [antidepressant] treatment, benefits mental health,” the study authors concluded. “These findings challenge our thinking about (and stimulate research on) taking a patient’s environment into account when prescribing pharmacotherapy for depression.”

The study sheds light on the important interactions between a person’s environment and their mental health. However, because it was not a controlled experiment, the study cannot establish a direct causal link. The researchers analyzed patients based on the medications they were already taking, which means the observed differences could be related to other factors that influenced why a certain medication was prescribed, rather than the effects of the medication itself.

The paper, “Low population density relates to more positive behavioural endophenotype in depressed patients on serotonergic antidepressants,” was authored by Kari Bosch, Dirk Schubert, Judith R. Homberg, Indira Tendolkar, Philip van Eijndhoven, Marloes J.A.G. Henckens, and Janna N. Vrijsen.