Low population density relates to more positive behavioural endophenotype in depressed patients on serotonergic antidepressants.

Depression is a severe mental disorder most often treated with serotonergic antidepressants (ADs). Unfortunately, pharmacotherapeutic responses differ greatly between patients, and our mechanistic understanding of AD modulators is limited. According to the undirected susceptibility of change hypothesis, the effects of ADs on depressive behaviour can be influenced by the patient's environment. Using population density as an index of social environment, we investigated in depressed patients whether their living environment modulated the AD treatment effect on a behavioural marker for depression: eye tracking-based attentional bias for socially relevant information (i.e. facial expressions). Our data indicate a significant role for the environment moderating attention bias in depressed patients. Specifically, the interaction between population density and the attention for different emotional facial expressions indicated that a low population density could have a protective effect on automatic depressotypic behaviour; an effect most prominent in patients on serotonergic ADs. Possibly, less frequent unavoidable social contact and reduced overall sensory stimulation, particularly in combination with serotonergic AD treatment, benefits mental health. These findings challenge our thinking about (and stimulate research on) taking a patient's environment into account when prescribing pharmacotherapy for depression.