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Article ; Online: The first steps on the path toward genomic predictors of behavioral therapy for posttraumatic stress disorder.

Enoch, Mary-Anne

2013 Volume 73, Issue 11, Page(s) 1039–1040

MeSH term(s)	Cognitive Behavioral Therapy/methods ; Emotions/physiology ; Female ; Humans ; Male ; Panic Disorder/psychology ; Panic Disorder/rehabilitation
Language	English
Publishing date	2013-05-04
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	209434-4
ISSN	1873-2402 ; 0006-3223
ISSN (online)	1873-2402
ISSN	0006-3223
DOI	10.1016/j.biopsych.2013.04.005
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Article ; Online: Genetic influences on the development of alcoholism.

Enoch, Mary-Anne

Current psychiatry reports

2013 Volume 15, Issue 11, Page(s) 412

Abstract: Alcoholism has a substantial heritability yet the detection of specific genetic influences has largely proved elusive. The strongest findings are with genes encoding alcohol metabolizing enzymes. A few candidate genes such as GABRA2 have shown robust ... ...

Abstract	Alcoholism has a substantial heritability yet the detection of specific genetic influences has largely proved elusive. The strongest findings are with genes encoding alcohol metabolizing enzymes. A few candidate genes such as GABRA2 have shown robust associations with alcoholism. Moreover, it has become apparent that variants in stress-related genes such as CRHR1, may only confer risk in individuals exposed to trauma, particularly in early life. Over the past decade there have been tremendous advances in large scale SNP genotyping technologies allowing for genome-wide associations studies (GWAS). As a result, it is now recognized that genetic risk for alcoholism is likely to be due to common variants in very many genes, each of small effect, although rare variants with large effects might also play a role. This has resulted in a paradigm shift away from gene centric studies toward analyses of gene interactions and gene networks within biologically relevant pathways.
MeSH term(s)	Alcoholism/genetics ; Gene-Environment Interaction ; Genetic Linkage ; Genetic Predisposition to Disease ; Humans ; Polymorphism, Single Nucleotide
Language	English
Publishing date	2013-10-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Review
ZDB-ID	2055376-6
ISSN	1535-1645 ; 1523-3812
ISSN (online)	1535-1645
ISSN	1523-3812
DOI	10.1007/s11920-013-0412-1
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Article ; Online: Genetic influences on response to alcohol and response to pharmacotherapies for alcoholism.

Enoch, Mary-Anne

Pharmacology, biochemistry, and behavior

2013 Volume 123, Page(s) 17–24

Abstract: Although very many individuals drink alcohol at safe levels, a significant proportion escalates their consumption with addiction as the end result. Alcoholism is a common, moderately heritable, psychiatric disorder that is accompanied by considerable ... ...

Abstract	Although very many individuals drink alcohol at safe levels, a significant proportion escalates their consumption with addiction as the end result. Alcoholism is a common, moderately heritable, psychiatric disorder that is accompanied by considerable morbidity and mortality. Variation in clinical presentation suggests inter-individual variation in mechanisms of vulnerability including genetic risk factors. The development of addiction is likely to involve numerous functional genetic variants of small effects. The first part of this review will focus on genetic factors underlying inter-individual variability in response to alcohol consumption, including variants in alcohol metabolizing genes that produce an aversive response (the flushing syndrome) and variants that predict the level of subjective and physiological response to alcohol. The second part of this review will report on genetic variants that identify subgroups of alcoholics who are more likely to respond to pharmacotherapy to reduce levels of drinking or maintain abstinence. Genetic analyses of the level of response to alcohol, particularly of the functional OPRM1 A118G polymorphism and 5' and 3' functional polymorphisms in SLC6A4, are beginning to provide insights into the etiology of alcoholism and also genotype-stratified subgroup responses to naltrexone and SSRIs/ondansetron respectively. Because of large inter-ethnic variation in allele frequencies, the relevance of these functional polymorphisms will vary between ethnic groups. However there are relatively few published studies in this field, particularly with large sample sizes in pharmacogenetic studies, therefore it is premature to draw any conclusions at this stage.
MeSH term(s)	Alcoholism/drug therapy ; Alcoholism/genetics ; Humans ; Naltrexone/therapeutic use ; Narcotic Antagonists/therapeutic use
Chemical Substances	Narcotic Antagonists ; Naltrexone (5S6W795CQM)
Language	English
Publishing date	2013-11-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	191042-5
ISSN	1873-5177 ; 0091-3057
ISSN (online)	1873-5177
ISSN	0091-3057
DOI	10.1016/j.pbb.2013.11.001
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Article ; Online: The influence of gene-environment interactions on the development of alcoholism and drug dependence.

Enoch, Mary-Anne

Current psychiatry reports

2012 Volume 14, Issue 2, Page(s) 150–158

Abstract: Alcoholism and drug dependence are common psychiatric disorders with a heritability of about 50%; therefore genetic and environmental influences are equally important. Early-life stress is a predictor of adolescent problem drinking/drug use and alcohol/ ... ...

Abstract	Alcoholism and drug dependence are common psychiatric disorders with a heritability of about 50%; therefore genetic and environmental influences are equally important. Early-life stress is a predictor of adolescent problem drinking/drug use and alcohol/drug dependence in adulthood, but moderating factors governing the availability of alcohol/drug are important. The risk-resilience balance for addiction may be due in part to the interaction between genetic variation and environment stressors (G × E); this has been confirmed by twin studies of inferred genetic risk. Measured genotype studies to detect G × E effects have used a range of alcohol consumption and diagnostic phenotypes and stressors ranging from early-life to adulthood past year life events. In this article, the current state of the field is critically reviewed and suggestions are put forth for future research.
MeSH term(s)	Adaptation, Psychological ; Gene-Environment Interaction ; Genetic Variation ; Humans ; Hypothalamo-Hypophyseal System/physiology ; Life Change Events ; Pituitary-Adrenal System/physiology ; Risk Factors ; Stress, Psychological/complications ; Substance-Related Disorders/genetics ; Substance-Related Disorders/physiopathology ; Substance-Related Disorders/psychology
Language	English
Publishing date	2012-02-25
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2055376-6
ISSN	1535-1645 ; 1523-3812
ISSN (online)	1535-1645
ISSN	1523-3812
DOI	10.1007/s11920-011-0252-9
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Article ; Online: Review: Genetic and environmental risk factors for alcohol use disorders in American Indians and Alaskan Natives.

Enoch, Mary-Anne / Albaugh, Bernard J

The American journal on addictions

2016 Volume 26, Issue 5, Page(s) 461–468

Abstract: Background and objectives: Genetic and environmental predictors for alcohol use disorder (AUD) are both important in the general population. As a group, American Indian and Alaskan Native individuals (AI/AN) are at increased risk for alcohol-related ... ...

Abstract	Background and objectives: Genetic and environmental predictors for alcohol use disorder (AUD) are both important in the general population. As a group, American Indian and Alaskan Native individuals (AI/AN) are at increased risk for alcohol-related morbidity /mortality, early onset problem drinking and AUD. Methods: Alcohol consumption behaviors amongst AI/AN tribes, environmental stressors and genetic studies in AI/AN and European-ancestry individuals are reviewed followed by an analysis of unique difficulties for undertaking research with AI/AN. Results: Some AI/AN tribes have high rates of childhood trauma that predict psychopathology including AUD. The deleterious effects of historical trauma and forced placement in boarding schools cross generations to the present day. There are scanty numbers of genetic studies of AUD in AI/AN and these derive from only a few tribes. However, it is important to note that the results are largely similar to findings in European-ancestry individuals indicating that AI/AN do not have increased genetic risk for AUD. Conducting AI/AN genetic studies has been challenging, in part because of tribe disillusionment and mistrust over past experiences and unique hurdles in getting consent from tribes, each a sovereign nation. However, it is encouraging that a new way forward has been established-community-based participatory research with tangible health benefits and a focus on strength-based approaches. Conclusions and scientific significance: Given the high prevalence of AUD in many AI/AN tribes and limited knowledge about genetic risk-resilience factors, it is important for our understanding of prevention and treatment that AI/AN research progresses and that more tribes are represented. (Am J Addict 2017;26:461-468).
MeSH term(s)	Alcoholism/genetics ; Alcoholism/psychology ; Gene-Environment Interaction ; Humans ; Indians, North American/genetics ; Indians, North American/psychology ; Risk Factors
Language	English
Publishing date	2016-09-06
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1141440-6
ISSN	1521-0391 ; 1055-0496
ISSN (online)	1521-0391
ISSN	1055-0496
DOI	10.1111/ajad.12420
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Article ; Online: The role of early life stress as a predictor for alcohol and drug dependence.

Enoch, Mary-Anne

Psychopharmacology

2010 Volume 214, Issue 1, Page(s) 17–31

Abstract: Rationale: Genetic and environmental influences on the development of alcohol and drug dependence are equally important. Exposure to early life stress, that is unfortunately common in the general population, has been shown to predict a wide range of ... ...

Abstract	Rationale: Genetic and environmental influences on the development of alcohol and drug dependence are equally important. Exposure to early life stress, that is unfortunately common in the general population, has been shown to predict a wide range of psychopathology, including addiction. Objective: This review will look at the characteristics of early life stress that may be specific predictors for adolescent and adult alcohol and drug dependence and will focus on studies in humans, non-human primates and rodents. Results: Experiencing maltreatment and cumulative stressful life events prior to puberty and particularly in the first few years of life is associated with early onset of problem drinking in adolescence and alcohol and drug dependence in early adulthood. Early life stress can result in permanent neurohormonal and hypothalamic-pituitary-adrenal axis changes, morphological changes in the brain, and gene expression changes in the mesolimbic dopamine reward pathway, all of which are implicated in the development of addiction. However, a large proportion of children who have experienced even severe early life stress do not develop psychopathology indicating that mediating factors such as gene-environment interactions and family and peer relationships are important for resilience. Conclusions: There appears to be a direct pathway from chronic stress exposure in pre-pubertal children via adolescent problem drinking to alcohol and drug dependence in early adulthood. However, this route can be moderated by genetic and environmental factors. The role that gene-environment interactions play in the risk-resilience balance is being increasingly recognized.
MeSH term(s)	Adolescent ; Adult ; Age Factors ; Alcoholism/etiology ; Alcoholism/genetics ; Animals ; Child ; Forecasting ; Humans ; Life Change Events ; Primates ; Resilience, Psychological ; Rodentia ; Stress, Psychological/complications ; Substance-Related Disorders/etiology ; Substance-Related Disorders/genetics
Language	English
Publishing date	2010-07-02
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Review
ZDB-ID	130601-7
ISSN	1432-2072 ; 0033-3158
ISSN (online)	1432-2072
ISSN	0033-3158
DOI	10.1007/s00213-010-1916-6
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Article: The role of GABA(A) receptors in the development of alcoholism.

Enoch, Mary-Anne

Pharmacology, biochemistry, and behavior

2008 Volume 90, Issue 1, Page(s) 95–104

Abstract: Alcoholism is a common, heritable, chronic relapsing disorder. GABA(A) receptors undergo allosteric modulation by ethanol, anesthetics, benzodiazepines and neurosteroids and have been implicated in the acute as well as the chronic effects of ethanol ... ...

Abstract	Alcoholism is a common, heritable, chronic relapsing disorder. GABA(A) receptors undergo allosteric modulation by ethanol, anesthetics, benzodiazepines and neurosteroids and have been implicated in the acute as well as the chronic effects of ethanol including tolerance, dependence and withdrawal. Medications targeting GABA(A) receptors ameliorate the symptoms of acute withdrawal. Ethanol induces plasticity in GABA(A) receptors: tolerance is associated with generally decreased GABA(A) receptor activation and differentially altered subunit expression. The dopamine (DA) mesolimbic reward pathway originating in the ventral tegmental area (VTA), and interacting stress circuitry play an important role in the development of addiction. VTA GABAergic interneurons are the primary inhibitory regulators of DA neurons and a subset of VTA GABA(A) receptors may be implicated in the switch from heavy drinking to dependence. GABA(A) receptors modulate anxiety and response to stress; important elements of sustained drinking and relapse. The GABA(A) receptor subunit genes clustered on chromosome 4 are highly expressed in the reward pathway. Several recent studies have provided strong evidence that one of these genes, GABRA2, is implicated in alcoholism in humans. The influence of the interaction between ethanol and GABA(A) receptors in the reward pathway on the development of alcoholism together with genetic and epigenetic vulnerabilities will be explored in this review.
MeSH term(s)	Alcohol Drinking/genetics ; Alcohol Drinking/psychology ; Alcoholism/drug therapy ; Alcoholism/genetics ; Alcoholism/physiopathology ; Animals ; Chromosomes, Human, Pair 4/genetics ; Chromosomes, Human, Pair 4/physiology ; Chromosomes, Human, Pair 5/genetics ; Chromosomes, Human, Pair 5/physiology ; Dopamine/physiology ; Gene Expression Regulation/physiology ; Humans ; Neuronal Plasticity/physiology ; Receptors, GABA-A/chemistry ; Receptors, GABA-A/drug effects ; Receptors, GABA-A/genetics ; Receptors, GABA-A/physiology ; Receptors, Presynaptic/drug effects ; Reward ; Steroids/physiology
Chemical Substances	Receptors, GABA-A ; Receptors, Presynaptic ; Steroids ; Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2008-03-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Review
ZDB-ID	191042-5
ISSN	1873-5177 ; 0091-3057
ISSN (online)	1873-5177
ISSN	0091-3057
DOI	10.1016/j.pbb.2008.03.007
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Article: Genetic and environmental influences on the development of alcoholism: resilience vs. risk.

Enoch, Mary-Anne

Annals of the New York Academy of Sciences

2006 Volume 1094, Page(s) 193–201

Abstract: The physiological changes of adolescence may promote risk-taking behaviors, including binge drinking. Approximately 40% of alcoholics were already drinking heavily in late adolescence. Most cases of alcoholism are established by the age of 30 years with ... ...

Abstract	The physiological changes of adolescence may promote risk-taking behaviors, including binge drinking. Approximately 40% of alcoholics were already drinking heavily in late adolescence. Most cases of alcoholism are established by the age of 30 years with the peak prevalence at 18-23 years of age. Therefore the key time frame for the development, and prevention, of alcoholism lies in adolescence and young adulthood. Severe childhood stressors have been associated with increased vulnerability to addiction, however, not all stress-exposed children go on to develop alcoholism. Origins of resilience can be both genetic (variation in alcohol-metabolizing genes, increased susceptibility to alcohol's sedative effects) and environmental (lack of alcohol availability, positive peer and parental support). Genetic vulnerability is likely to be conferred by multiple genes of small to modest effects, possibly only apparent in gene-environment interactions. For example, it has been shown that childhood maltreatment interacts with a monoamine oxidase A (MAOA) gene variant to predict antisocial behavior that is often associated with alcoholism, and an interaction between early life stress and a serotonin transporter promoter variant predicts alcohol abuse in nonhuman primates and depression in humans. In addition, a common Met158 variant in the catechol-O-methyltransferase (COMT) gene can confer both risk and resilience to alcoholism in different drinking environments. It is likely that a complex mix of gene(s)-environment(s) interactions underlie addiction vulnerability and development. Risk-resilience factors can best be determined in longitudinal studies, preferably starting during pregnancy. This kind of research is important for planning future measures to prevent harmful drinking in adolescence.
MeSH term(s)	Adaptation, Psychological ; Adolescent ; Alcoholism/etiology ; Alcoholism/genetics ; Alcoholism/psychology ; Child ; Environment ; Female ; Humans ; Male ; Risk Factors
Language	English
Publishing date	2006-12
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	211003-9
ISSN	1749-6632 ; 0077-8923
ISSN (online)	1749-6632
ISSN	0077-8923
DOI	10.1196/annals.1376.019
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Article ; Online: Gene expression in the addicted brain.

Zhou, Zhifeng / Enoch, Mary-Anne / Goldman, David

International review of neurobiology

2014 Volume 116, Page(s) 251–273

Abstract: Addiction is due to changes in the structure and function of the brain, including neuronal networks and the cells that comprise them. Within cells, gene expression changes can track and help explain their altered function. Transcriptional changes induced ...

Abstract	Addiction is due to changes in the structure and function of the brain, including neuronal networks and the cells that comprise them. Within cells, gene expression changes can track and help explain their altered function. Transcriptional changes induced by addictive agents are dynamic and divergent and range from signal pathway-specific perturbations to widespread molecular and cellular dysregulation that can be measured by "omic" methods and that can be used to identify new pathways. The molecular effects of addiction depend on timing of exposure or withdrawal, the stage of adaptation, the brain region, and the behavioral model, there being many models of addiction. However, the molecular neural adaptations across different drug exposures, conditions, and regions are to some extent shared and can reflect common actions on pathways relevant to addiction. Epigenetic studies of DNA methylation and histone modifications and studies of regulatory RNA networks have been informative for elucidating the mechanisms of transcriptional change in the addicted brain.
MeSH term(s)	Animals ; Brain/metabolism ; Gene Expression ; Gene Expression Regulation/drug effects ; Gene Regulatory Networks ; Humans ; Signal Transduction/drug effects ; Signal Transduction/physiology ; Substance-Related Disorders/pathology
Language	English
Publishing date	2014-08-31
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	209876-3
ISSN	2162-5514 ; 0074-7742
ISSN (online)	2162-5514
ISSN	0074-7742
DOI	10.1016/B978-0-12-801105-8.00010-2
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Article: How can I help my patient stop drinking?

Enoch, Mary-Anne

American family physician

2002 Volume 65, Issue 7, Page(s) 1475–1476

MeSH term(s)	Alcoholism/pathology ; Alcoholism/rehabilitation ; Family Practice ; Female ; Humans ; Middle Aged ; Physician-Patient Relations ; Treatment Refusal
Language	English
Publishing date	2002-04-01
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	412694-4
ISSN	0002-838X ; 0572-3612
ISSN	0002-838X ; 0572-3612
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