Neurobiology of Loneliness, Isolation, and Loss: Integrating Human and Animal Perspectives

Abstract

In social species such as humans, non-human primates, and even many rodent species, social interaction and the maintenance of social bonds are necessary for mental and physical health and wellbeing. In humans, perceived isolation, or loneliness, is not only characterized by physical isolation from peers or loved ones, but also involves negative perceptions about social interactions and connectedness that reinforce the feelings of isolation and anxiety. As a complex behavioral state, it is no surprise that loneliness and isolation are associated with dysfunction within the ventral striatum and the limbic system – brain regions that regulate motivation and stress responsiveness, respectively. Accompanying these neural changes are physiological symptoms such as increased plasma and urinary cortisol levels and an increase in stress responsivity. Although studies using animal models are not perfectly analogous to the uniquely human state of loneliness, studies on the effects of social isolation in animals have observed similar physiological symptoms such as increased corticosterone, the rodent analog to human cortisol, and also display altered motivation, increased stress responsiveness, and dysregulation of the mesocortical dopamine and limbic systems. This review will discuss behavioral and neuropsychological components of loneliness in humans, social isolation in rodent models, and the neurochemical regulators of these behavioral phenotypes with a neuroanatomical focus on the corticostriatal and limbic systems. We will also discuss social loss as a unique form of social isolation, and the consequences of bond disruption on stress-related behavior and neurophysiology.

The maternal brain is more flexible and responsive at rest: effective connectivity of the parental caregiving network in postpartum mothers

“…In other words, the network can be more responsive, i.e., requires lower levels of input to activate, in mothers with improved social cognition. Consistent with our other analyses, mothers show a more responsive limbic network which supports their responsiveness to affective stimuli that underlie self-referential and other-referential action 33,72,73 .…”

“…Mothers with higher social cognition scores had decreased inhibition from the amygdala to the parahippocampal gyrus, and from the parahippocampal gyrus to the nucleus accumbens, relative to non-mothers. The nucleus accumbens-amygdala-parahippocampal gyrus network forms the affective limbic network that is implicated in social connectedness, and its converse, loneliness 72 . This network overlaps with the subcortical components of the ventromedial emotion regulatory system, which is implicated in early appraisal, encoding, and automatic regulation of emotion 62 .…”

Breaking the vicious cycle: The interplay between loneliness, metabolic illness, and mental health

“…Although the chronic stress of loneliness might lead to poor metabolic and mental health through numerous pathways—including dysregulation of sympathoadrenal or autonomic nervous system function [for reference, see Vitale and Smith ( 20 )]—evidence for the effect of loneliness on these systems remains relatively scant and inconsistent ( 21 ). Here, we focus on the overactivation of the hypothalamic-pituitary-adrenal (HPA) axis and its downstream immunometabolic consequences, particularly as they relate to mitochondrial function dysregulation.…”

Association between Migraine and Workplace Social Support in the Social Context of China: Using a Validated Chinese Version of the DCSQ

“…An integrated review based on human and animal neurobiological studies concluded that social support could help protect against neurological dysfunction [8]. Social support is defined as the availability of assistance from others in times of need or crisis, including emotional, instrumental, informational and companionship support [9,10].…”