Social isolation has similar characteristics in both temporary instances and for those with a historical lifelong isolation cycle. All types of social isolation can include staying home for lengthy periods of time, having no communication with family, acquaintances or friends, and/or willfully avoiding any contact with other humans when those opportunities do arise.
True social isolation over years and decades can be a chronic condition affecting all aspects of a person's existence. Social isolation can lead to feelings of loneliness, fear of others, or negative self-esteem. Lack of consistent human contact can also cause conflict with the (peripheral) friends the socially isolated person may occasionally talk to or cause problems with family members.
In the case of mood-related isolation, the individual may isolate during a depressive episode only to 'surface' when their mood improves. The individual may attempt to justify their reclusive or isolating behavior as enjoyable or comfortable. There can be an inner realization on the part of the individual that there is something wrong with their isolating responses which can lead to heightened anxiety. Relationships can be a struggle, as the individual may reconnect with others during a healthier mood only to return to an isolated state during a subsequent low or depressed mood.
Research by Cole and colleagues showed that perceived social isolation is associated with gene expression — specifically, the under-expression of genes bearing anti-inflammatory glucocorticoid response elements and over-expression of genes bearing response elements for pro-inflammatory NF-κB/Rel transcription factors. This finding is paralleled by decreased lymphocyte sensitivity to physiological regulation by the hypothalamic pituitary adrenocortical (HPA) axis in lonely individuals, which together with evidence of increased activity of the HPA axis, suggests the development of glucocorticoid resistance in chronically lonely individuals.
In a hypothesis proposed by Cacioppo and colleagues, the isolation of a member of a social species has detrimental biological effects. In a 2009 review, Cacioppo and Hawkley noted that the health, life, and genetic legacy of members of social species are threatened when they find themselves on the social perimeter. For instance, social isolation decreases lifespan in the fruit fly; promotes obesity and Type 2 diabetes in mice; exacerbates infarct size and oedema and decreases post-stroke survival rate following experimentally induced stroke in mice; promotes activation of the sympatho-adrenomedullary response to an acute immobilisation or cold stressor in rats; delays the effects of exercise on adult neurogenesis in rats; decreases open field activity, increases basal cortisol concentrations, and decreases lymphocyte proliferation to mitogens in pigs; increases the 24 hr urinary catecholamines levels and evidence of oxidative stress in the aortic arch of rabbits; and decreases the expression of genes regulating glucocorticoid response in the frontal cortex.