CREB‐BDNF pathway influences alcohol cue‐elicited activation in drinkers. Issue 8 (4th May 2015)

• Record Type: Journal Article
• Authors: Chen, Jiayu; Hutchison, Kent E.; Calhoun, Vince D.; Claus, Eric D.; Turner, Jessica A.; Sui, Jing; Liu, Jingyu
• Is Part Of: Human brain mapping. Volume 36:Issue 8(2015:Aug.)
• Page Start: 3007
• Page End: 3019
• Publication Date: 2015-05-04
• Subjects: Brain mapping -- Periodicals; 611.81
• DOI: 10.1002/hbm.22824
• Languages: English
• ISSNs: 1065-9471

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>Alcohol use disorder (AUD) is suggested to have polygenic risk factors and also exhibits neurological complications, strongly encouraging a translational study to explore the associations between aggregates of genetic variants and brain function alterations related to alcohol use. In this study, we used a semiblind multivariate approach, parallel independent component analysis with multiple references (pICA‐MR) to investigate relationships of genome‐wide single nucleotide polymorphisms with alcohol cue‐elicited brain activations in 315 heavy drinkers, where pICA‐MR assesses multiple reference genes for their architecture and functional influences on neurobiological conditions. The genetic component derived from the cAMP‐response element‐binding protein and ‐brain derived neurotrophic factor (CREB‐BDNF) pathway reference was significantly associated (<italic>r</italic> = −0.38, <italic>P</italic> = 3.98 × 10<sup>−12</sup>) with an imaging component reflecting hyperactivation in precuneus, superior parietal lobule, and posterior cingulate for drinkers with more severe alcohol dependence symptoms. The highlighted brain regions participate in many cognitive processes and have been robustly implicated in craving‐related studies. The genetic factor highlighted the <italic>CREB</italic> and <italic>BDNF</italic> references, as well as other genes including <italic>GRM5</italic>, <italic>GRM7</italic>, <italic>GRID1</italic>, <italic>GRIN2A</italic>, <italic>PRKCA</italic>, and <italic>PRKCB</italic>. Ingenuity Pathway Analysis indicated that the genetic component was enriched in synaptic plasticity, GABA, and protein kinase A signaling. Collectively, our findings suggest that genetic variations in various neural plasticity and signaling pathways partially explain the variance of precuneus reactivity to alcohol cues which appears to be associated with AUD severity. <italic>Hum Brain Mapp 36:3007–3019, 2015</italic>. © <bold>2015 Wiley Periodicals, Inc</bold>.</p> </abstract>