Social Withdrawal, Loneliness, and Health in Schizophrenia: Psychological and Neural Mechanisms

Abstract

Background and hypothesis: Some of the most debilitating aspects of schizophrenia and other serious mental illnesses (SMI) are the impairments in social perception, motivation, and behavior that frequently accompany these conditions. These impairments may ultimately lead to chronic social disconnection (ie, social withdrawal, objective isolation, and perceived social isolation or loneliness), which may contribute to the poor cardiometabolic health and early mortality commonly observed in SMI. However, the psychological and neurobiological mechanisms underlying relationships between impairments in social perception and motivation and social isolation and loneliness in SMI remain incompletely understood.

Study design: A narrative, selective review of studies on social withdrawal, isolation, loneliness, and health in SMI.

Study results: We describe some of what is known and hypothesized about the psychological and neurobiological mechanisms of social disconnection in the general population, and how these mechanisms may contribute to social isolation and loneliness, and their consequences, in individuals with SMI.

Conclusions: A synthesis of evolutionary and cognitive theories with the "social homeostasis" model of social isolation and loneliness represents one testable framework for understanding the dynamic cognitive and biological correlates, as well as the health consequences, of social disconnection in SMI. The development of such an understanding may provide the basis for novel approaches for preventing or treating both functional disability and poor physical health that diminish the quality and length of life for many individuals with these conditions.

Fig. 1.

A schematic of the social homeostasis model, as proposed and developed by Matthews and Tye, is presented (figure adapted with permission from). Although the neural correlates of these components of this model are unknown, we speculate that the Detector function in this system may rely on brain networks involved in social perception, such as the amygdala and other areas of the “social brain.” The Control Center may engage brain regions that track social knowledge and memories, such as the hippocampus, the temporal-parietal junction, and the default network, to compare the individual’s current social state with stored expectations. Thus, the Effector System may have several components, perhaps including brainstem projections from the ventral tegmental area, dorsal raphe nucleus, and locus coeruleus, that are stimulated by the hypothalamus, which drives changes in mood, vigilance, and systemic changes in sympathetic nervous system activity and immune system mediators. This is consistent with findings of rodent studies that have shown that social isolation leads to activation of the hypothalamic-pituitary-adrenal axis (HPA) axis via the release of corticotropin-releasing factor by the paraventricular nucleus of the hypothalamus. Thus, the Effector System may generate the psychological signal of loneliness and in parallel a physiologic stress response, with increases in activity of the HPA axis and sympathetic nervous system activity involving the release of glucocorticoids such as cortisol, and epinephrine, as well as increases in the release of pro-inflammatory cytokines and other immunological mediators, such as interleukin-6, C-reactive protein and fibrinogen.^, The activity of the ventral tegmental area and dorsal raphe nucleus dopaminergic neurons may signal both the aversive state of isolation and the rewarding aspects of social contact via distinct projections to the amygdala, striatum, and prefrontal cortex. Loneliness is also associated with a shift in immune function, with enhanced pro-inflammatory activity but a reduced antiviral response, which is thought to prepare an individual for the infections most likely to be encountered when alone (ie, bacterial infections sustained through physical injury but fewer socially transmitted viral infections). Thus, taken together, this model proposes, based on a large body of animal research, that a multi-system response is generated by the brain to respond to discrepancies between expected or desired and actual levels of social bonds, which serves to correct a survival-threatening state of reduced social contact and support.

Fig. 2.

A schematic diagram illustrating the proposed model of this review, incorporating some of the psychological, behavioral, and health correlates of isolation and loneliness in serious mental illnesses (SMI), is shown. Although there is a rapidly growing body of work uncovering important correlates of social disconnection and their associations with health outcomes, the complex and dynamic nature of social isolation and loneliness suggests a multi-method approach will be critical to answering the unresolved questions about the mechanisms of social disconnection in SMI. Studies including assessment of both stable and dynamic correlates of social disconnection at multiple levels of analysis (psychological, behavioral, and neural), combined with measures of health outcomes, collected in longitudinal designs, could inform the development of new interventions that could reverse some of the adverse psychological and systemic consequences of isolation and loneliness.