Large-Scale Neuroimaging and Genetic Analyses of the Human Thalamus in Loneliness

Although loneliness is prevalent and significantly impacts society globally, its neural and genetic bases remain poorly understood. The thalamus, which receives sensory information from the environment, may have a more significant role in social interactions than previously recognized. Here, we integrate neuroimaging and genetic approaches to characterize structural differences within the thalamus associated with loneliness.

We obtained thalamic nuclei volumes on brain scans from 45,834 individuals (age range: 45-82 years) in the UK Biobank and grouped them into 6 anatomical groups. We investigated effects of loneliness and social isolation using self-reported data. Then, we performed a genome-wide association study (GWAS) analysis on the genetic overlap between thalamic volumes and loneliness.

The volumes of the whole thalamus and its medial, lateral, and posterior nuclei are significantly reduced in individuals with loneliness compared with those who do not feel lonely. Loneliness with frequent social contact is associated with smaller volumes, whereas social isolation without loneliness shows no such reduction in thalamus volumes. Leveraging data from GWASs on thalamic volumes (n = 30,114) and loneliness (n = 370,342) in the UK Biobank, we identified shared loci between thalamus structure and loneliness.

Our findings support the emerging view that the thalamus plays important roles in social interactions and in the experience of loneliness.