Neurobiology of loneliness: a systematic review

Loneliness is associated with increased morbidity and mortality. Deeper understanding of neurobiological mechanisms underlying loneliness is needed to identify potential intervention targets. We did not find any systematic review of neurobiology of loneliness. Using MEDLINE and PsycINFO online databases, we conducted a search for peer-reviewed publications examining loneliness and neurobiology. We identified 41 studies (n = 16,771 participants) that had employed various methods including computer tomography (CT), structural magnetic resonance imaging (MRI), functional MRI (fMRI), electroencephalography (EEG), diffusion tensor imaging (DTI), single-photon emission computed tomography (SPECT), positron emission tomography (PET), and post-mortem brain tissue RNA analysis or pathological analysis. Our synthesis of the published findings shows abnormal structure (gray matter volume or white matter integrity) and/or activity (response to pleasant versus stressful images in social versus nonsocial contexts) in the prefrontal cortex (especially medial and dorsolateral), insula (particularly anterior), amygdala, hippocampus, and posterior superior temporal cortex. The findings related to ventral striatum and cerebellum were mixed. fMRI studies reported links between loneliness and differential activation of attentional networks, visual networks, and default mode network. Loneliness was also related to biological markers associated with Alzheimer's disease (e.g., amyloid and tau burden). Although the published investigations have limitations, this review suggests relationships of loneliness with altered structure and function in specific brain regions and networks. We found a notable overlap in the regions involved in loneliness and compassion, the two personality traits that are inversely correlated in previous studies. We have offered recommendations for future research studies of neurobiology of loneliness.