How Loneliness Impacts Metabolic Health and Mental Well-being

Frontiers in Psychiatry | 2023, Vol. 14, p. 1-11

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

Minhal Ahmed; Harvard Medical School, Boston, MA, United States

Ivo Cerda; Harvard Medical School, Boston, MA, United States

Molly Maloof; Adamo Bioscience, Inc., Fernandina Beach, FL, United States

Loneliness, or perceived social isolation, is a leading predictor of all-cause mortality and is increasingly considered a public health epidemic afflicting significant portions of the general population. Chronic loneliness is itself associated with two of the most pressing public health epidemics currently facing the globe: the rise of mental illness and metabolic health disorders. Here, we highlight the epidemiological associations between loneliness and mental and metabolic health disorders and argue that loneliness contributes to the etiology of these conditions by acting as a chronic stressor that leads to neuroendocrine dysregulation and downstream immunometabolic consequences that manifest in disease. Specifically, we describe how loneliness can lead to overactivation of the hypothalamic-pituitary-adrenal axis and ultimately cause mitochondrial dysfunction, which is implicated in mental and metabolic disease. These conditions can, in turn, lead to further social isolation and propel a vicious cycle of chronic illness. Finally, we outline interventions and policy recommendations that can reduce loneliness at both the individual and community levels. Given its role in the etiology of the most prevalent chronic diseases of our time, focusing resources on alleviating loneliness is a vitally important and cost-effective public health strategy.

Loneliness; social isolation; metabolic syndrome; mental health; depression; chronic stress; HPA axis; mitochondria

“Loneliness, or perceived social isolation, is the subjective feeling of a mismatch between one’s desired and actual levels of social connection. Loneliness differs from social disconnection in that the latter is an objective measure of connectivity, while the former is a subjective state. Loneliness is widely recognized as a major risk factor for morbidity and premature mortality; by some estimates, lack of social connection increases the odds of death by as much as 50%... Epidemiological studies have associated loneliness with some of the most pressing public health challenges of our time, namely, the epidemics of chronic diseases like mental illness and the metabolic syndrome (MetS), which includes hypertension, dyslipidemia, obesity, and insulin resistance” (p. 1-2).

“Individuals experiencing prolonged loneliness exhibit a range of psychological and behavioral changes. Feelings of unsafety, which stem from loneliness, result in a chronic hypervigilant state, leading to increased anxiety, altered stress responsiveness, and social withdrawal. Functional magnetic resonance imaging (fMRI) studies of the visual cortex and ventral striatal area revealed that lonely individuals are more likely to pay attention to and remember negative interactions and derive less reward from social stimuli. Importantly, these negative cognitive biases in lonely individuals can thus perpetuate social isolation in a vicious cycle in which loneliness begets loneliness, irrespective of the presence of metabolic or psychiatric conditions. Lonely individuals get less salubrious sleep, have diminished executive function compared to non-lonely individuals, and are more likely to engage in impulsive and unhealthy behaviors” (p. 2-3).

Additionally, “studies of loneliness and chronic social isolation in humans and animal models have consistently found an overactivation of the HPA axis, supported by findings of higher cortisol awakening responses (CAR), greater total GC output (area under the curve; AUC), and flattened diurnal cortisol rhythms in lonely individuals. Persistently high cortisol levels are associated with far reaching physiological consequences, including hyperglycemia, increased vascular resistance, redistribution of body fat to the viscera, and accelerated biological aging. These changes can directly lead to insulin resistance and hypertension and thus represent a mechanism by which loneliness may drive the development of metabolic syndrome” (p. 3).

“While loneliness and social isolation may activate the HPA axis as a stressor, social connection may dampen this activation and impart anti-stress effects through the release of oxytocin. Oxytocin is released within the hypothalamus during positive social interactions and acts as both a neurotransmitter and hormone with far-reaching effects on the body. Importantly, oxytocin has a well-established role in suppressing HPA activity by inhibiting the release of corticotropin-releasing hormone from hypothalamic neurons. Thus, the absence of social interactions may increase HPA activation through a decrease in oxytocin-mediated neurotransmission” (p. 3). 

Furthermore, “prolonged subjection to stressful stimuli and their corresponding metabolic oversupply leads to the accumulation of mitochondrial damage and disruption of structural and functional integrity, eventually reaching a threshold in which the energetic demands of the stress response can no longer be met efficiently” (p. 4). 

“Thus, biobehavioral and psychosocial maladaptive changes associated with mental health conditions and poor metabolic health might expose individuals to acute social isolation, predispose individuals to fail to adapt to this acute stressor, and facilitate the progression and maintenance of the chronic stress of loneliness” (p. 4).

“Practices that encourage self-reflection, like journaling, can help in identifying stress arising from loneliness by improving interoception and increasing self-awareness and emotional regulation. Journaling has been associated with decreased mental distress among general medical patients with anxiety symptoms in a preliminary randomized controlled trial. Once the stress state is identified, deploying relaxation and stress management techniques known to dampen the stress response, like diaphragmatic breathing or loving-kindness and compassion meditation, might improve emotional regulation and help prevent the progression of maladaptive physiological processes tied to loneliness. Indeed, unlike control subjects, individuals practicing diaphragmatic breathing show reductions in cortisol levels following a single session. In a classic study, Fredrickson et al. found that practicing loving-kindness meditation is associated with increased social support in the long term, hinting at its potential value in addressing loneliness specifically” (p. 6).

“Akin to a viral pandemic, loneliness spreads through social networks via a contagious process. Critically, loneliness appears in clusters of people closely interacting with one another and is more severe at the periphery of social networks. These observations point to the multiplicative public health impact interventions might have if they lead to the strengthening and conservation of social connections, even at the individual and small community level. Thus, addressing loneliness resulting from widespread social disconnection emerges as an actionable, cost-effective, and influential target for intervention. Keeping the chronic stress paradigm laid out above in mind, two general approaches to prevent the progression from social disconnection to loneliness and, furthermore, address the deleterious downstream effects of loneliness are building psychological and bioenergetic capacity to adequately respond and adapt to stress and removing or minimizing the stressor. While the former can be achieved most effectively through interventions at the individual level, the latter calls for interventions at the community and societal level. By building stress resilience at the individual level, increasing social connectedness at the community level, and advancing policies that support a public health infrastructure that increases connectedness at a societal level, the interventions recommended below might help break the vicious cycle linking social disconnection to the development and progression of metabolic and mental health disorders” (p. 5 -6).