The genetics of addictions: uncovering the genes

Goldman, David; Oroszi, Gábor; Ducci, Francesca

doi:10.1038/nrg1635

Cited by 930 publications

(613 citation statements)

References 137 publications

(80 reference statements)

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“…Addictions to alcohol, nicotine and illicit drugs are heritable disorders influenced by many variants of small effect (Goldman, Oroszi & Ducci 2005; Manolio et al 2009), as are SCZ and BPD (PGC‐Bipolar‐Disorder‐Working‐Group 2011; PGC‐Schizophrenia‐Working‐Group 2014). Using polygenic risk scores (PRSs) from an ensemble of common sequence variants of small effects can aid in elucidating whether co‐morbidity relationships reflect shared genetics.…”

Section: Introductionmentioning

confidence: 99%

Polygenic risk scores for schizophrenia and bipolar disorder associate with addiction

et al. 2017

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We use polygenic risk scores (PRSs) for schizophrenia (SCZ) and bipolar disorder (BPD) to predict smoking, and addiction to nicotine, alcohol or drugs in individuals not diagnosed with psychotic disorders. Using PRSs for 144 609 subjects, including 10 036 individuals admitted for in‐patient addiction treatment and 35 754 smokers, we find that diagnoses of various substance use disorders and smoking associate strongly with PRSs for SCZ (P = 5.3 × 10−50–1.4 × 10−6) and BPD (P = 1.7 × 10−9–1.9 × 10−3), showing shared genetic etiology between psychosis and addiction. Using standardized scores for SCZ and BPD scaled to a unit increase doubling the risk of the corresponding disorder, the odds ratios for alcohol and substance use disorders range from 1.19 to 1.31 for the SCZ‐PRS, and from 1.07 to 1.29 for the BPD‐PRS. Furthermore, we show that as regular smoking becomes more stigmatized and less prevalent, these biological risk factors gain importance as determinants of the behavior.

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Section: Introductionmentioning

confidence: 99%

Polygenic risk scores for schizophrenia and bipolar disorder associate with addiction

et al. 2017

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“…Investigators have often treated typically developing control populations as a monolithic group. However, there is considerable evidence that individual differences in successful, adaptive psychological styles are essential for human development, functioning, social cohesion, and health outcomes (Buss 1991;Goldman et al 2005;Chapman and Goldberg 2011;Braver et al 2010).…”

Section: Etiological Heterogeneitymentioning

confidence: 99%

Attention-Deficit/Hyperactivity Disorder

Nigg

2010

Curr Dir Psychol Sci

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Over the last two decades, there have been numerous technical and methodological advances available to clinicians and researchers to better understand attention deficit hyperactivity disorder (ADHD) and its etiology. Despite the growing body of literature investigating the disorder's pathophysiology, ADHD remains a complex psychiatric disorder to characterize. This chapter will briefly review the literature on ADHD, with a focus on its history, the current genetic insights, neurophysiologic theories, and the use of neuroimaging to further understand the etiology. We address some of the major concerns that remain unclear about ADHD, including subtype instability, heterogeneity, and the underlying neural correlates that define the disorder. We highlight that the field of ADHD is rapidly evolving; the descriptions provided here will hopefully provide a sturdy foundation for which to build and improve our understanding of the disorder.

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“…Alcohol dependence, hereafter called alcoholism, is a complex behavioral disorder in which substantial heritable susceptibility factors interact with the environment to produce and maintain the disease state (2). Alcoholism is clinically characterized by a chronic relapsing course similar to other common medical conditions (3).…”

mentioning

confidence: 99%

Variation at the rat Crhr1 locus and sensitivity to relapse into alcohol seeking induced by environmental stress

Hansson

Cippitelli

Sommer

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

242

280

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Alcoholism is a chronic relapsing disorder with substantial heritability. Uncovering gene-environment interactions underlying this disease process can aid identification of novel treatment targets. Here, we found a lowered threshold for stress-induced reinstatement of alcohol seeking in Marchigian-Sardinian Preferring (msP) rats genetically selected for high alcohol preference. In situ hybridization for a panel of 20 stress-related genes in 16 brain regions was used to screen for differential gene expression that may underlie this behavioral phenotype. An innate up-regulation of the Crhr1 transcript, encoding the corticotropin-releasing hormone receptor 1 (CRH-R1), was found in several limbic brain areas of msP rats genetically selected for high alcohol preference, was associated with genetic polymorphism of the Crhr1 promoter, and was accompanied by increased CRH-R1 density. A selective CRH-R1 antagonist (antalarmin, 10 -20 mg͞kg) was devoid of effects on operant alcohol self-administration in unselected Wistar rats but significantly suppressed this behavior in the msP line. Stressinduced reinstatement of alcohol seeking was not significantly affected by antalarmin in Wistar rats but was fully blocked in msP animals. These data demonstrate that Crhr1 genotype and expression interact with environmental stress to reinstate alcohol-seeking behavior.lcohol use is the number three modifiable cause of death in the United States (1). Alcohol dependence, hereafter called alcoholism, is a complex behavioral disorder in which substantial heritable susceptibility factors interact with the environment to produce and maintain the disease state (2). Alcoholism is clinically characterized by a chronic relapsing course similar to other common medical conditions (3). Relapse, i.e., return to alcohol seeking and uncontrolled drinking after varying intervals of sobriety, is a key phenomenon in this process, making relapse prevention a primary therapeutic objective.Gene-environment interactions are commonly implicated in alcoholism and propensity to relapse, but their exact nature is presently unknown. A behavioral analysis has long pointed to three broad categories of environmental stimuli with an ability to trigger relapse in susceptible individuals (4): consumption of small, ''priming'' doses of alcohol, presentation of conditioned cues associated with prior availability of alcohol, and stress. It is unclear whether, in alcohol-dependent individuals, these stimuli trigger relapse by interacting with preexisting genetic susceptibility factors, acquired CNS neuroadaptations secondary to a prolonged history of alcohol use, or both.Models in experimental animals offer tools in the search for novel alcoholism treatments (5, 6) and may be helpful in addressing this question. Genetic selection for high alcohol preference in rats has resulted in several lines with pharmacologically relevant levels of voluntary intake of alcohol, as well as other alcohol-related phenotypes (7,8), and an improved understanding of mechanisms mediating rel...

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The genetics of addictions: uncovering the genes

Cited by 930 publications

References 137 publications

Polygenic risk scores for schizophrenia and bipolar disorder associate with addiction

Polygenic risk scores for schizophrenia and bipolar disorder associate with addiction

Attention-Deficit/Hyperactivity Disorder

Variation at the rat Crhr1 locus and sensitivity to relapse into alcohol seeking induced by environmental stress

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