COMT and BDNF Gene Variants Help to Predict Alcohol Consumption in Alcohol-dependent Patients

Klimkiewicz, Anna; Mach, Anna; Jakubczyk, Andrzej; Klimkiewicz, Jakub; Wnorowska, Anna; Kopera, Maciej; Fudalej, Sylwia; Burmeister, Margit; Brower, Kirk J.; Wojnar, Marcin

doi:10.1097/adm.0000000000000277

Cited by 19 publications

(14 citation statements)

References 36 publications

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“…Interestingly, this single point mutation is also associated with an early onset of relapse in alcoholics undergoing treatment (Wojnar et al, 2009), and with an increased likelihood to respond to alcohol cues in adolescents (Nees et al, 2015). The Val66Met BDNF polymorphism can also predict the level of alcohol intake in alcohol-dependent patients when assessed together with polymorphisms for dopaminergic genes (Klimkiewicz et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Differential Correlation of Serum BDNF and microRNA Content in Rats with Rapid or Late Onset of Heavy Alcohol Use

Ehinger

Phamluong

Darevesky

et al. 2019

Preprint

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Heavy alcohol use reduces the levels of the brain-derived neurotrophic factor (BDNF) in the prefrontal cortex of rodents through the upregulation of microRNAs targeting BDNF mRNA. In humans, an inverse correlation exists between circulating blood levels of BDNF and the severity of psychiatric disorders including alcohol abuse. Here, we set out to determine whether a history of heavy alcohol use produces comparable alterations in the blood of rats. We used an intermittent access to 20% alcohol using the 2-bottle choice paradigm (IA20%2BC), and measured circulating levels of BDNF protein and microRNAs in the serum of Long-Evans rats before and after 8-weeks of excessive alcohol intake. We observed that the drinking profile of heavy alcohol users is not unified; Whereas 70% of the rats gradually escalate their alcohol intake (Late Onset), 30% of alcohol users exhibit a very Rapid Onset of drinking (Rapid Onset). We found that serum BDNF levels are negatively correlated with alcohol intake in both Rapid Onset and Late Onset rats. In contrast, increased expression of the microRNAs (miRs) targeting BDNF, miR30a-5p, miR-195-5p, miR191-5p and miR206-3p, was detected only in the Rapid Onset rats. Finally, we report that the alcohol-dependent molecular changes are not due to alterations in platelet number. Our data suggest that rats exhibit both Late and Rapid Onset of alcohol intake. We further show that heavy alcohol use produces comparable changes in BDNF protein levels in both groups. However, circulating microRNAs are responsive to alcohol only in the Rapid Onset rats.

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Section: Introductionmentioning

confidence: 99%

Differential Correlation of Serum BDNF and microRNA Content in Rats with Rapid or Late Onset of Heavy Alcohol Use

Ehinger

Phamluong

Darevesky

et al. 2019

Preprint

View full text Add to dashboard Cite

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“…There has been speculation that because Met/Met individuals have higher consummatory rewards [ 74 ], drinking behavior may also lead to increased cravings relative to Val/Val homozygotes. The relationship between cravings and dopamine should be explored further within the context of chronic alcohol use, which alters dopaminergic transmission and influences drinking motivation [ 75 ].…”

Section: Discussionmentioning

confidence: 99%

Dimensions of Craving Interact with COMT Genotype to Predict Relapse in Individuals with Alcohol Use Disorder Six Months after Treatment

et al. 2021

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(1) Background: Alcohol use disorder (AUD) is associated with poor medical, psychological, and psychosocial outcomes and approximately 60% of individuals with AUD relapse six months after treatment. Craving is a core aspect of AUD and associated with high risk of relapse. One promising avenue to improve outcomes may be in understanding the relationship between COMT genotype, craving, and treatment outcomes. (2) Methods: To this end, we assessed craving, recent drinking history, and impulsivity in 70 individuals with AUD undergoing a standard course of treatment at a regional Veteran Affairs (VA) medical center. Saliva samples were collected to determine COMT genotype. In this prospective observational study, participants were followed for six months to determine who went on to relapse after treatment. (3) Results: Results revealed a significant interaction between craving and catechol-O-methyltransferse (COMT) genotype in predicting relapse. Post hoc exploratory analyses indicated that Met/Met homozygotes reported the highest levels of craving, and craving was associated with recent drinking history. Among Val/Val homozygotes, who had higher rates of relapse, craving was associated with impulsivity. (4) Conclusions: These associations highlight that specific profiles of psychological and biological factors may be important in understanding which individuals are at highest risk of relapse following treatment. Future studies that build on these findings are warranted.

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“…The relevance of BDNF/TrkB signaling in AUD is provided by studies in humans. Polymorphisms in both the NTRK2 and BDNF genes have been associated with AUD [46][47][48], although this association does not always exist [49,50]. Genetic variations in the NTRK2 gene in humans were associated with an AUD diagnosis that co-occurred with antisocial personality disorder (ASPD).…”

Section: Trkbmentioning

confidence: 99%

Receptor Tyrosine Kinases as Therapeutic Targets for Alcohol Use Disorder

Hamada

Lasek

2020

Neurotherapeutics

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The receptor tyrosine kinases (RTKs) are a large family of proteins that transduce extracellular signals to the inside of the cell to ultimately affect important cellular functions such as cell proliferation, survival, apoptosis, differentiation, and migration. They are expressed in the nervous system and can regulate behavior through modulation of neuronal and glial function. As a result, RTKs are implicated in neurodegenerative and psychiatric disorders such as depression and addiction. Evidence has emerged that 5 RTKs (tropomyosin-related kinase B (TrkB), RET proto-oncogene (RET), anaplastic lymphoma kinase (ALK), fibroblast growth factor receptor (FGFR), and epidermal growth factor receptor (EGFR)) modulate alcohol drinking and other behaviors related to alcohol addiction. RTKs are considered highly "druggable" targets and small-molecule inhibitors of RTKs have been developed for the treatment of various conditions, particularly cancer. These kinases are therefore attractive targets for the development of new pharmacotherapies to treat alcohol use disorder (AUD). This review will examine the preclinical evidence describing TrkB, RET, ALK, FGFR, and EGFR modulation of alcohol drinking and other behaviors relevant to alcohol abuse.

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COMT and BDNF Gene Variants Help to Predict Alcohol Consumption in Alcohol-dependent Patients

Cited by 19 publications

References 36 publications

Differential Correlation of Serum BDNF and microRNA Content in Rats with Rapid or Late Onset of Heavy Alcohol Use

Differential Correlation of Serum BDNF and microRNA Content in Rats with Rapid or Late Onset of Heavy Alcohol Use

Dimensions of Craving Interact with COMT Genotype to Predict Relapse in Individuals with Alcohol Use Disorder Six Months after Treatment

Receptor Tyrosine Kinases as Therapeutic Targets for Alcohol Use Disorder

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