Alcohol dependence with comorbid drug dependence: genetic and phenotypic associations suggest a more severe form of the disorder with stronger genetic contribution to risk*

Dick, Danielle M.; Agrawal, Arpana; Wang, Jen C.; Hinrichs, Anthony L.; Bertelsen, Sarah; Bucholz, Kathleen K.; Schuckit, Marc A.; Kramer, John; Nürnberger, John I.; Tischfield, Jay A.; Edenberg, Howard J.; Goate, Alison M.; Bierut, Laura J.

doi:10.1111/j.1360-0443.2007.01871.x

Cited by 103 publications

(78 citation statements)

References 46 publications

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“…A history of psychiatric disorders such as internalizing (mood and anxiety disorders-e.g., Burns and Teesson, 2002) and externalizing (drug use disorders, antisocial personality disorder; Dick et al, 2007), mania (Goodwin and Jamison, 2007), and posttraumatic stress disorder (Bremner et al, 1996) are associated with a chronic course of problem drinking among individuals with AUD (Finney and Moos, 1992;Sher et al, 2005;Zucker et al, 2006). Furthermore, prior twin research, including prospective studies (e.g., Edwards et al, 2011;Hicks et al, 2007), has found that genetic effects contribute to signifi cant variation in these disorders as well as covariation with AUDs (Krueger et al, 2002;Pickens et al, 1995;Todorov et al, 2006).…”

Section: Untangling Genetic and Environmental Infl Uences In The Predmentioning

confidence: 99%

Psychiatric Morbidity is Linked to Problem Drinking in Midlife Among Alcohol-Dependent Men: A Co-Twin Control Study

Blonigen

Burroughs

Haber³

et al. 2013

J. Stud. Alcohol Drugs

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ABSTRACT. Objective: Prior research on predictors of problem drinking has been limited because of an inability to attribute an unambiguous environmental explanation to observed fi ndings. Using a prospective co-twin control design, we examined the extent to which a history of psychiatric symptoms exerts an environmental infl uence on problem drinking in midlife that is unconfounded by genetic underpinnings. Method: Participants were 367 complete male twin pairs (208 monozygotic, 159 dizygotic) from the Vietnam Era Twin Registry who were assessed in midlife as part of the Family Twin Study (M age = 51.4 years, SD = 2.8). Twin pairs who were concordant for a lifetime diagnosis of an alcohol use disorder (AUD) in 1992 were selected for participation and were reinterviewed in 2001 to measure symptoms of AUD (i.e., problem drinking) since the prior assessment (past 10 years). Results: Within-pair differences in lifetime symptom counts of several psychiatric disorders measured in 1992 (i.e., major depression, dysthymia, generalized anxiety disorder, panic disorder, antisocial personality, mania, and posttraumatic stress disorder) were signifi cantly associated with within-pair differences in AUD symptoms in the subsequent 10 years. Conclusions: A history of psychiatric problems, particularly one marked by internalizing symptoms, appears to be linked to problem drinking in midlife above and beyond the confounding infl uence of genetic effects and underscores the potential value of integrated interventions for comorbidity to address problem drinking among individuals during this period of the life course. (J. Stud. Alcohol Drugs, 74, 136-140, 2013)

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Section: Untangling Genetic and Environmental Infl Uences In The Predmentioning

confidence: 99%

Psychiatric Morbidity is Linked to Problem Drinking in Midlife Among Alcohol-Dependent Men: A Co-Twin Control Study

Blonigen

Burroughs

Haber³

et al. 2013

J. Stud. Alcohol Drugs

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“…Further support for a role for the cholinergic system in addiction come from studies looking at the association of gene sequence variation, with changes in the M5 receptor gene sequence being associated with increased smoking and increased risk of developing cannabis dependence [88]. Variations in the M2 gene sequence were associated with a combination of alcohol and comorbid drug dependence, but not alcohol dependence alone [89]. More recently, variations in the M2 receptor gene sequence have been associated with an increased risk of smoking/nicotine dependence [90].…”

Section: Muscarinic Receptors and Substance Abusementioning

confidence: 99%

Muscarinic Receptors: Their Roles in Disorders of the Central Nervous System and Potential as Therapeutic Targets

Scarr

2011

CNS Neuroscience & Therapeutics

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SUMMARYPhylogenetically, acetylcholine is an ancient neurochemical. Therefore, it is not surprising that cholinergic neurons project extensively throughout the central nervous system, innervating a wide range of structures within the brain. In fact, acetylcholine is involved in processes that underpin some of our most basic central functions. Both muscarinic and nicotinic receptor families, which mediate cholinergic transmission, have been implicated in the pathophysiology of psychiatric and neurological disorders. The question that remains to be definitively answered is whether or not these receptors are viable targets for the development of future therapeutic agents.

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“…Genes for both muscarinic and nicotinic cholinergic receptors play a significant role in concurrent alcohol and opioid dependence (22,23) between subjects with heroin addiction, alcohol addiction, or controls. This study also did not find an association between HTR2A A-1438G polymorphism and alcohol or opioid addiction (25).…”

Section: Cholinergicmentioning

confidence: 99%

Genetic pre-determinants of concurrent alcohol and opioid dependence: A critical review

Martin¹,

Klimas²,

Dunne³

et al. 2013

OA Alcohol

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Concurrent alcohol dependence poses a significant burden to health and wellbeing of people with established opioid dependence. Although previous research indicates that both genetic and environmental risk factors contribute to the development of drug or alcohol dependence, the role of genetic determinants in development of concurrent alcohol and opioid dependence has not been scrutinised.To search for genetic pre-determinants of concurrent alcohol and opioid dependence, electronic literature searches were completed using MEDLINE (PubMed) and EBSCO (Academic Search Complete) databases. Reference lists of included studies were also searched. In this discussion paper, we provide an overview of the genes (n=33) which are associated with the opioid, serotonergic, dopaminergic, GABA-ergic, cannabinoid, and metabolic systems for each dependency (i.e., alcohol or opioid) separately.The current evidence base is inconclusive regarding an exclusively genetic pre-determinant of concurrent alcohol and opioid dependence. Further search strategies and original research are needed to determine the genetic basis for concurrent alcohol and opioid dependency.

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Alcohol dependence with comorbid drug dependence: genetic and phenotypic associations suggest a more severe form of the disorder with stronger genetic contribution to risk*

Abstract: These analyses provide specific genetic evidence suggesting that alcohol dependence with comorbid drug dependence represents a particularly severe form of the disorder, with higher genetic contribution to vulnerability.

Cited by 103 publications

References 46 publications

Psychiatric Morbidity is Linked to Problem Drinking in Midlife Among Alcohol-Dependent Men: A Co-Twin Control Study

Psychiatric Morbidity is Linked to Problem Drinking in Midlife Among Alcohol-Dependent Men: A Co-Twin Control Study

Muscarinic Receptors: Their Roles in Disorders of the Central Nervous System and Potential as Therapeutic Targets

Genetic pre-determinants of concurrent alcohol and opioid dependence: A critical review

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