Differential transcriptome expression in human nucleus accumbens as a function of loneliness. Homo sapiens

Loneliness is associated with impaired mental and physical health. Studies of lonely individuals reported differential expression of inflammatory genes in peripheral leukocytes and diminished activation in brain reward regions such as nucleus accumbens, but could not address gene expression in the human brain. Here, we examined genome-wide RNA expression in postmortem nucleus accumbens from donors (N = 26) with known loneliness measures. Loneliness was associated with 1 710 differentially expressed transcripts from 1 599 genes (DEGs; FDR p |2|, controlling for confounds) previously associated with behavioral processes, neurological disease, psychological disorders, cancer, organismal injury, and skeletal and muscular disorders, as well as networks of upstream RNA regulators. Furthermore, a number of DEGs were associated with Alzheimer’s disease genes (which was correlated with loneliness in this sample, although gene expression analyses controlled for AD diagnosis). These results identify novel targets for future mechanistic studies of gene networks in nucleus accumbens and gene regulatory mechanisms across a variety of diseases exacerbated by loneliness. Overall design: Gene expression in postmortem nucleus accumbens was examined as a function of loneliness. Twenty-six White, non-Hispanic individuals without a clinical diagnosis of depression (i.e., excluding individuals who were rated “probable” or “highly probable” to be depressed by a clinician) at baseline were selected out of a pool of 247 MAP participants with reported loneliness data by stratified random sub-sampling from a convenience sample from the top and bottom quartiles of loneliness scores (N=13 each), and matched for the number of females (N=6) in these quartiles.