Abstract：
:We endeavored to identify objective blood biomarkers for pain, a subjective sensation with a biological basis, using a stepwise discovery, prioritization, validation, and testing in independent cohorts design. We studied psychiatric patients, a high risk group for co-morbid pain disorders and increased perception of pain. For discovery, we used a powerful within-subject longitudinal design. We were successful in identifying blood gene expression biomarkers that were predictive of pain state, and of future emergency department (ED) visits for pain, more so when personalized by gender and diagnosis. MFAP3, which had no prior evidence in the literature for involvement in pain, had the most robust empirical evidence from our discovery and validation steps, and was a strong predictor for pain in the independent cohorts, particularly in females and males with PTSD. Other biomarkers with best overall convergent functional evidence for involvement in pain were GNG7, CNTN1, LY9, CCDC144B, and GBP1. Some of the individual biomarkers identified are targets of existing drugs. Moreover, the biomarker gene expression signatures were used for bioinformatic drug repurposing analyses, yielding leads for possible new drug candidates such as SC-560 (an NSAID), and amoxapine (an antidepressant), as well as natural compounds such as pyridoxine (vitamin B6), cyanocobalamin (vitamin B12), and apigenin (a plant flavonoid). Our work may help mitigate the diagnostic and treatment dilemmas that have contributed to the current opioid epidemic.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Niculescu AB,Le-Niculescu H,Levey DF,Roseberry K,Soe KC,Rogers J,Khan F,Jones T,Judd S,McCormick MA,Wessel AR,Williams A,Kurian SM,White FAdoi
10.1038/s41380-018-0345-5subject
Has Abstractpub_date
2019-04-01 00:00:00pages
501-522issue
4eissn
1359-4184issn
1476-5578pii
10.1038/s41380-018-0345-5journal_volume
24pub_type
杂志文章abstract：:Emerging evidence suggests that psychiatric disorders are associated with disturbances in structural brain networks. Little is known, however, about brain networks in those at high risk (HR) of bipolar disorder (BD), with such disturbances carrying substantial predictive and etiological value. Whole-brain tractography...
journal_title：Molecular psychiatry
pub_type： 杂志文章
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abstract：:The prefrontal cortex (PFC), seat of the highest-order cognitive functions, constitutes a conglomerate of highly specialized brain areas and has been implicated to have a role in the onset and installation of various neurodevelopmental disorders. The development of a properly functioning PFC is directed by transcripti...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
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更新日期：2015-07-01 00:00:00
abstract：:Circulating inflammatory mediators can signal neurons through a pathway in which cytokine activation of the cells of the blood-brain barrier causes the induction of the nuclear factor kappa B (NF-kappaB), leading to the transcription of target genes, such as the one encoding cyclooxygenase 2 (COX-2), the enzyme that i...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：
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journal_title：Molecular psychiatry
pub_type： 杂志文章
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更新日期：2018-12-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章
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journal_title：Molecular psychiatry
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journal_title：Molecular psychiatry
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journal_title：Molecular psychiatry
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journal_title：Molecular psychiatry
pub_type： 杂志文章
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