Supplement: Neurobehavioral mechanisms of social isolation and loneliness in serious mental illness

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Summary Some of the most debilitating and harmful aspects of serious mental illnesses (SMI) are the 1) social isolation (low numbers of social contacts) and 2) the subjective experiences of social disconnection (loneliness) that frequently accompany these conditions. Social isolation and loneliness greatly impact day-to-day functioning and are associated with poor cardiometabolic health and early mortality in SMI, and currently there are no available treatments that can prevent or reverse these devastating consequences of having these illnesses. This may be in part because the neural and psychological mechanisms underlying social isolation and loneliness in SMI, and how they impact health outcomes, are poorly understood. However, recent clues from studies employing advanced neuroimaging and digital assessments have formed the basis of a novel approach to investigating such mechanisms, outlined in this proposal. Prior work has indicated that objective isolation and loneliness are correlated but also somewhat independent. Recent neuroimaging findings support this model, revealing that social isolation and loneliness have both shared and distinct neural correlates. However, it is also clear that these are not static phenomena; smartphone-based assessments have revealed transient, dynamic changes in social isolation and loneliness. Individual differences in the anticipation of rejection are associated with momentary experiences of loneliness, greater avoidance and subsequent increases in social isolation. Thus, in the current application, we propose to comprehensively measure both the relatively stable neural and behavioral predictors of social isolation and loneliness, as well as the moment-to-moment changes in these experiences, in 60 individuals with SMI and 60 control subjects. In Aim 1 of the proposed project, we will show that the higher levels of social isolation and loneliness in SMI are linked to shared and distinct neural responses to social stimuli, with deficient responses of social perception-related circuitry (medial temporal lobe regions) linked to social isolation, and deficient responses of reward-related circuitry (basal ganglia regions) linked to loneliness. In Aim 2, we will measure transient changes in social isolation and loneliness with smartphone assessments using a longitudinal “burst” design. Lastly, in Aim 3, we will determine how the quantitative markers of social isolation and loneliness identified in Aims 1 and 2 predict indices of cardiometabolic health, measuring the stability of these associations over time. Thus, in this project, we will show that fundamental neural and behavioral processes drive momentary variation in the experience of social isolation and loneliness, and directly impact cardiometabolic health in SMI. In follow-up work, these findings can be used as objective targets in studies of novel interventions which aim to address these major causes of early mortality.