Given that stress and major depression are putative causal factors in alcohol consumption, the exploration of the genes and the associated neurobiological mechanisms that influence the relationship between stress, depression, and alcohol dependence (AD) is a first step toward the development of novel medications for AD. The tachykinin receptor 1 (TACR1) gene is a promising candidate gene, showing an association with stress-related behaviors (Thorsell et al., 2010), major depression (Kramer et al., 2004), and AD treatment outcome (George et al., 2008). The purpose of the current study was to determine if TACR1 single nucleotide polymorphisms (SNPs) are associated with (1) blood oxygen level dependent (BOLD) activation in response to alcohol cues, (2)DSM-IV-TR AD symptom count,(3) DSM-IV-TR depression diagnoses, and (4) DSM-IV-TR AD symptom count in a large, publicly available dataset. To address these questions, the current study examined relationships between neural responses during a craving task in 326 individuals with alcohol use disorders and SNPs within the TACR1 gene. Of the 70 SNPs tested, rs3771863 was predictive of AD symptom count and BOLD activation in response to alcohol cues, regardless of major depression status, as well as AD symptom count in the SAGE dataset. Additionally, rs3771810 and rs12477553 also predicted BOLD activation in response to alcohol cues, but the relationship between these SNPs and AD symptom count was moderated by major depression status. Finally, rs1106855 is a SNP associated with BOLD activation that should be explored for possible functional significance due to its location within a stop codon. The exploration of TACR1 receptor antagonism as a form of AD treatment should be further examined in less heterogeneous samples, as it might be most effective for those with primary or secondary alcohol dependence in addition to a diagnosis of major depression.
Level of Degree
First Committee Member (Chair)
Second Committee Member
Alcoholism--Genetic aspects, Depression, Mental--Genetic aspects, Stress (Physiology)--Genetic aspects, Tachykinins.
Blaine, Sara Keelan. "The role of TACR1 genotypes in craving, depression, and alcohol dependence.." (2011). http://digitalrepository.unm.edu/psy_etds/11