Loneliness

Loneliness is a state of perceived social isolation that produces measurable biochemical changes. It activates stress pathways that increase morbidity and mortality risk on par with smoking or chronic disease.

Mortality and health risk

A meta-analysis of 148 studies and 308,849 people, followed for an average of 7.5 years, found people with weaker social relationships were 50% less likely to survive the study period than those with strong ones, an effect size comparable to quitting smoking and larger than obesity or physical inactivity. A larger 2023 meta-analysis covering 90 cohort studies and over 2.2 million people found social isolation raised all-cause mortality risk by 32% and loneliness by 14%, with social isolation also raising cancer mortality by 24%. The US Surgeon General's 2023 advisory put the mortality risk of lacking social connection on par with smoking up to 15 cigarettes a day. Isolation is also linked to hypertension, cardiovascular disease, cancer, and cognitive decline, and loneliness predicts later depression independent of demographics, marital status, or perceived stress. A UK Biobank study of 322,558 people found sex differences in how isolation and loneliness affect all-cause, cardiovascular, and cancer mortality over an 11.8-year median follow-up. The Tromsø Study, a Norwegian population cohort followed from 1994 to 2023 (up to 29 years), found the most socially isolated adults had 37% (women) to 41% (men) higher all-cause mortality than the least isolated, after adjusting for smoking and other risk factors; the effect was larger still in adults under 50 at baseline (55% higher in women, 76% higher in men). A newer study found that feeling unhappy, hopeless, and lonely accelerated biological aging on an epigenetic aging clock more than smoking did. Joining a group activity reduces the risk of depression relapse by 24-63%. For a broader survey of the neuroscience behind connection and its opposite, see neuroscientist Ben Rein's discussion of the topic.

Biochemical effects

HPA axis overactivation

Loneliness is a very strong predictor of future development of depression. The neuroendocrine system becomes an important system through which perceived social isolation may operate, at least in part, to affect morbidity and mortality.

Allopregnanolone levels initially rise and then plummet as a result of chronic stress. This pattern matches that observed with the steroid DHEA/DHEA-S. Given that both DHEA and allopregnanolone are potent inhibitors of the HPA response, the loss of these steroids due to chronic stress leads to HPA overactivation. HPA overactivation has been causally linked to pretty much every major mental health condition such as depression, bipolar disorder, PTSD, schizophrenia, and suicidal ideation.

Neurosteroid depletion

In animals stressed by social isolation, similar features emerge, under the influence of decreased neurosteroids, and increased serotonin and activity of the glucocorticoid system.

In darkness and isolation, for example, the stress hormones increase, and the brain-protective steroids decrease. The memory improvement that results from taking pregnenolone or thyroid (which is needed for synthesizing pregnenolone from cholesterol) is the result of turning off the dulling and brain-dissolving stress hormones, allowing normal responsiveness to be restored.

— Ray Peat

Serotonin elevation

Isolation might be another factor contributing to depression and alcoholism, since it decreases the formation of the protective neurosteroid.

Aggression, helplessness, and reduced ability to learn are typically produced in animals by social isolation, and certain kinds of family environment produce the same conditions in children. Schools seldom help, and often hinder, recovery from such early experiences.

Psychological and behavioral mechanisms

Beyond the biochemical pathways above, one account (not a formal study) frames isolation's damage as running through several distinct behavioral routes:

• Impairment: lowered stimulation lowers energy requirements, which can atrophy perception and physiological function over time, with psychosis, Alzheimer's, and dementia as extreme cases.
• Isolation itself: avoidance or withdrawal deepens despair, but gradual re-exposure to people rebuilds resilience.
• Lack of accountability: with no one around and nothing testing you, there's no stimulus pushing you to improve.
• Decadence and dissociation: isolation makes it easier to hold onto vain, self-reinforcing delusions or fantasy instead of confronting reality.

Avoidance and withdrawal are a misguided survival strategy under stress, the short-term relief they provide is a form of negative reinforcement, especially in a modern environment where it's possible to get by on few responsibilities and a life that's merely "good enough." Regular social contact exposes your flaws; isolated, you can live inside a self-flattering delusion without real awareness of your own problems.

Involvement with other people forces you out of rumination and into action. Without that kind of testing there's no pressure to change, so chronic isolation ends up reinforcing whatever dysfunction is already there. Regularly sharing your life, within reason, with people who care about you (family, friends, a spiritual father) and actively cultivating relationships supports both spiritual development and health. Shared experience doesn't require losing your own uniqueness.

Lifespan effects

Sidis, who grew up under intense pressure and social isolation and in extreme poverty, died at the age of 46. Mill, who was educated mainly by his father, in secure financial circumstances, experienced social isolation and moderate pressure, and lived about 20 years longer than Sidis did. Russell, who grew up in the highest circles of the ruling class, experienced no pressure, and only the mild kind of social isolation that wasn't exceptional for his class. He lived to be 97.

— Ray Peat

Social status and community

Social status is one of the strongest predictors of human disease risk and mortality. It is the relative difference of social status that matters. Even though a person in a Western country may have more material goods than a person in a third world country, if the Western person is separated with a bigger distance from the top class then that person would be in poorer health. The low social status resulted in immune system overactivation, with subsequent rise in inflammation.

The bulk of the immune response was mediated through the endotoxin (TLR4) receptor, which both suggests a role of endotoxin in chronic stress and chronic diseases.

Selfishness as consequence

Selfishness may simply be a self-preservation mechanism as a result of extended periods of loneliness. The resulting selfishness triggers further loneliness likely because the selfish people are both being avoided more by others and also because they actively isolate themselves from others. When humans are at their best they are very helpful and cooperative. Cooperation and altruism are the natural state of human affairs when health is good and we are surrounded by good people.

Potential mitigations

Given the animal and human trials showing elevation of allopregnanolone levels leading to suppression of HPA overactivation, supplementation with pregnenolone has been proposed as a reliable method to raise allopregnanolone levels. Supplementation with allopregnanolone or other precursors such as progesterone are also likely to lead to the same outcome.

Other substances that may help offset the biochemical effects include:

• Niacinamide (enhances 11β-HSD activity, deactivating cortisol)
• Vitamin D (acts as glucocorticoid antagonist)
• Thyroid hormone (supports pregnenolone synthesis)

However, these should not be considered substitutes for genuine social connection.

See also

• Stress
• Cortisol
• Pregnenolone
• Serotonin
• Depression