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.
James S. House, Psychosomatic Medicine, 2001, Issue 2, Volume 63, pages 273 - 274
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.