Social isolation contributes to abnormal hippocampal development via specific alterations to microtubule stability and decreased MAP-2 expression.[16] Social isolation contributes to decreased expression of the synaptic protein synaptophysin[17] and decreased dendritic length and dendritic spine density of pyramidal cells.[18] The underlying molecular mechanism of these structural neuronal alterations are microtubule stabilizations, which impair the remodeling and extension of axons[19] and dendrites.[20]
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.[21] This finding is paralleled by decreased lymphocyte sensitivity to physiological regulation by the HPA axis in lonely individuals. This, together with evidence of increased activity of the HPA axis, suggests the development of glucocorticoid resistance in chronically lonely individuals.[22]
Social isolation can be a precipitating factor for suicidal behavior. A large body of literature suggests that individuals who experience isolation in their lives are more vulnerable to suicide than those who have strong social ties with others.[23] A study found social isolation to be among the most common risk factors identified by Australian men who attempt suicide. Professor Ian Hickie of the University of Sydney said that social isolation was perhaps the most important factor contributing to male suicide attempts. Hickie said there was a wealth of evidence that men had more restricted social networks than women, and that these networks were heavily work-based.[24]
A lack of social relationships negatively impacts the development of the brain's structure. In extreme cases of social isolation, studies of young mice and monkeys have shown how the brain is strongly affected by a lack of social behaviour and relationships