Association between loneliness and hippocampal responses to dynamic social stimuli in psychotic disorders

Abstract

Background. Rates of loneliness have increased over the past several decades worldwide, particularly among people with serious mental illnesses. A better understanding of the neurocognitive mechanisms underlying loneliness could provide useful information for the efforts to address this public health problem. Methods. To investigate these mechanisms, a functional magnetic resonance imaging (fMRI) study was conducted which accounted for known cognitive biases associated with loneliness. Participants with (n = 40) and without (n = 60) psychotic disorders (PD) viewed images of faces that appeared to approach or withdraw from the participants while fMRI data were collected. Following the scanning, participants rated the trustworthiness of the faces, and these ratings were included as weights in the fMRI analyses. Neural responses to approaching versus withdrawing faces were measured, and whole-brain regression analyses, with loneliness as the regressor, were performed. Results. In the PD and full samples, a higher level of loneliness was significantly associated with greater responses of the hippocampus and areas of the basal ganglia to withdrawing (versus approaching) face stimuli. Moreover, the effects in the hippocampus, but not the basal ganglia, remained significant after controlling for potential confounds such as social activity levels, depression and social anhedonia. Finally, in a subset of the full sample (n = 66), greater hippocampal responses to withdrawing faces predicted greater loneliness 1 year later. Conclusions. Heightened responses of the hippocampus to withdrawing faces may represent a candidate neurobiological marker of loneliness that could be modified by interventions targeting loneliness.