title: Differential transcriptome expression in human nucleus accumbens as a function of loneliness.
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.
authors: Integrative Neuroscience, Department of Psychology, Stony Brook University, Stony Brook, NY, USA.
authors: T
authors: T
authors: Canli
authors: Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, USA.
authors: R
authors: R
authors: Wen
authors: Preventive Medicine, School of Medicine, Stony Brook Medicine, Stony Brook, NY USA.
authors: X
authors: X
authors: Wang
authors: Integrative Neuroscience, Department of Psychology, Stony Brook University, Stony Brook, NY, USA.
authors: A
authors: A
authors: Mikhailik
authors: Rush Alzheimer's Disease Center and Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors: L
authors: L
authors: Yu
authors: Rush Alzheimer's Disease Center and Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors: D
authors: D
authors: Fleischman
authors: Rush Alzheimer's Disease Center and Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors: R S
authors: RS
authors: Wilson
authors: Rush Alzheimer's Disease Center and Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors: D A
authors: DA
authors: Bennett
mesh_terms: D000369:Aged, 80 and over; D001344:Autopsy; D001921:Brain / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D053263:Gene Regulatory Networks / Q000235:genetics; D016678:Genome / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D008132:Loneliness / Q000523:psychology; D008297:Male; D009714:Nucleus Accumbens / Q000737:chemistry* / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics