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

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Abstract

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 post-mortem nucleus accumbens from donors (N=26) with known loneliness measures. Loneliness was associated with 1710 differentially expressed transcripts and genes from 1599 genes (DEGs; false discovery rate P<0.05, fold change |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 (AD) genes (that 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.

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Acknowledgements

This work was supported by funding from NIA R01 AG034578-01 and NSF BCS-0843346 to TC, and RF1AG15819, R01AG17917 and R01AG36042 to DAB.

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Canli, T., Wen, R., Wang, X. et al. Differential transcriptome expression in human nucleus accumbens as a function of loneliness. Mol Psychiatry 22, 1069–1078 (2017). https://doi.org/10.1038/mp.2016.186

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