Family-based and case-control study of DRD2, DAT, 5HTT, COMT genes polymorphisms in alcohol dependence

Samochowiec, Jerzy; Kucharska-Mazur, Jolanta; Grzywacz, Anna; Jabłoński, Marcin; Rommelspacher, Hans; Samochowiec, Agnieszka; Sznabowicz, Mariusz; Horodnicki, J; Sagan, Leszek; Pełka-Wysiecka, Justyna

doi:10.1016/j.neulet.2006.05.005

Cited by 81 publications

(56 citation statements)

References 41 publications

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“…However, the current study found no significant relationships between 5-HTT genotype and age of onset of alcoholism, which is consistent with family-based studies reporting no differential association of the L or S allele with early onset of alcoholism in offspring (Samochowiec et al, 2006). Previous reports have suggested that the SS genotype is associated with increased anxiety and affective liability (Olsson et al, 2005) and may be associated with subtypes of alcoholism complicated by a comorbid psychiatric condition (Feinn et al, 2005).…”

Section: Discussionsupporting

confidence: 88%

Can serotonin transporter genotype predict serotonergic function, chronicity, and severity of drinking?

Johnson

Javors

Roache

et al. 2008

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Serotonin transporter (5-HTT) activity is greater in carriers of the long (L) vs. short (S) alleles of the 5-HTT-linked polymorphic region (5′-HTTLPR) among healthy control subjects but not alcoholdependent adults. In 198 alcoholics, we determined the relationship between current or lifetime drinking and platelet 5-HTT function and density among allelic variants of the 5′-HTTLPR. SS subjects were younger than L-carriers (LL and LS) (p < 0.0085) and had fewer years of lifetime drinking. For L-carriers, the mean of B max for paroxetine binding, but not V max for serotonin (5-HT) uptake, was lower than that for SS subjects (p < 0.05). More L-carriers than their SS counterparts had V max for 5-HT uptake below 200 nmol/10 7 platelets-min (p < 0.05) and B max for paroxetine binding below 600 nmol/mg protein (p < 0.06). Current drinking (drinks per day during the past 14 days) correlated positively with K m and V max of platelet 5-HT uptake (p < 0.05) and negatively with B max , but not K d , of paroxetine binding (p < 0.05) for L-carriers alone. Years of lifetime drinking correlated negatively with K m and V max of platelet 5-HT uptake (p < 0.05) and B max , but not K d , of paroxetine binding (p < 0.05) for L-carriers alone. Among L-carriers alone, there were higher levels of platelet 5-HT uptake and lower levels of platelet paroxetine binding with increased drinking, and more lifetime drinking was associated with modestly lower levels of 5-HT uptake and paroxetine binding. Thus, 5-HTT expression varies with current and lifetime drinking in L-carriers alone.

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Section: Discussionsupporting

confidence: 88%

Can serotonin transporter genotype predict serotonergic function, chronicity, and severity of drinking?

Johnson

Javors

Roache

et al. 2008

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…Such genetically driven variation in COMT function and subsequent fronto-parietal function may also contribute to other forms of impulsive behavior (Cools and Robbins, 2004;Congdon and Canli, 2005;Kreek et al, 2005). Studies linking COMT to alcoholism have been equivocal (Ishiguro et al, 1999;Kauhanen et al, 2000;Kim et al, 2006;Samochowiec et al, 2006;Sery et al, 2006), although some data suggest that alcoholic subphenotypes may associate with specific COMT diplotypes (Tiihonen et al, 1999;Wang et al, 2001;Kweon et al, 2005;Enoch et al, 2006). We did not find a significantly skewed distribution of AA subjects across COMT genotypes; however, the possibility remains that the 158…”

Section: Lateral Ofc and Choosing To Wait For Bigger Payoffsmentioning

confidence: 50%

Immediate Reward Bias in Humans: Fronto-Parietal Networks and a Role for the Catechol-O-Methyltransferase 158^Val/ValGenotype

et al. 2007

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The tendency to choose lesser immediate benefits over greater long-term benefits characterizes alcoholism and other addictive disorders. However, despite its medical and socioeconomic importance, little is known about its neurobiological mechanisms. . These studies assume "hot" and "cool" response selection systems, with the hot system proposed to generate impulsive choices in the presence of a proximate reward. However, to date, brain regions in which the magnitude of activity during decision making reliably predicts intertemporal choice behavior have not been identified. Here we address this question in sober alcoholics and non-substance-abusing control subjects and show that immediate reward bias directly scales with the magnitude of functional magnetic resonance imaging bold oxygen leveldependent (BOLD) signal during decision making at sites within the posterior parietal cortex (PPC), dorsal prefrontal cortex (dPFC), and rostral parahippocampal gyrus regions. Conversely, the tendency of an individual to wait for a larger, delayed reward correlates directly with BOLD signal in the lateral orbitofrontal cortex. In addition, genotype at the Val158Met polymorphism of the catechol-Omethyltransferase gene predicts both impulsive choice behavior and activity levels in the dPFC and PPC during decision making. These genotype effects remained significant after controlling for alcohol abuse history. These results shed new light on the neurobiological underpinnings of temporal discounting behavior and identify novel behavioral and neural consequences of genetic variation in dopamine metabolism.

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“…These studies were then filtered to ensure conformity with the inclusion criteria. Four studies (Foley et al, 2004;Galeeva et al, 2002;Pastorelli et al, 2001) were excluded because no diagnostic criteria was described explicitly; one study (Munafo et al, 2005) because it was investigating social 'drinkers' rather than alcohol-dependent or abusing subjects; one study (Rasmussen et al, 2009) because it investigated alcohol and cigarette consumption rather than dependence or abuse; three studies (Budde et al, 2010;Mingione et al, 2012;Thompson et al, 2010) because no matched control data were described; and two studies Hallikainen et al, 1999;Hammoumi et al, 1999;Hill et al, 2002;Ishiguro et al, 1999;Johann et al, 2003;Kohnke et al, 2006;Konishi et al, 2004;Kranzler et al, 2002;Lee et al, 2009;Lichtermann et al, 2000;Marques et al, 2006;Matsushita et al, 2001;Mokrovic et al, 2008;Namkoong et al, 2008;Nellissery et al, 2003;Parsian and Cloninger, 2001;Philibert et al, 2008;Preuss et al, 2001;Reese et al, 2010;Saiz et al, 2009;Samochowiec et al, 2006;Sander et al, 1998;Sander et al, 1997;Shin et al, 2009;Stoltenberg et al, 2002;Thompson et al, 2000;Wang et al, 2012;Wang et al, 2011b;Wu et al, 2008) investigated alcohol dependence or abuse. Among them...…”

Section: Resultsmentioning

confidence: 99%

Multi-Cultural Association of the Serotonin Transporter Gene (SLC6A4) with Substance Use Disorder

Cao

Hudziak

2013

Neuropsychopharmacol

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A number of studies have reported associations between the serotonin transporter gene (SLC6A4) and alcohol, heroin, cocaine, or methamphetamine abuse. Other studies have yielded contrary results. There are a number of reasons for non-replication, including inadequate statistical power, population stratification, and poor phenotype definition. This study was to test the association using a meta-analytic approach across a variety of racial and ethnic populations. Using the genotype data of 55 studies (7999 cases, 8264 controls, and 676 families or parent-offspring trios) published in the past 15 years, we have conducted comprehensive meta-analyses to examine the associations of the 5-HTTLPR and STin2 polymorphisms with substance use disorder. The meta-analyses support the associations of 5-HTTLPR with alcohol, heroin, cocaine, and methamphetamine dependence and abuse (eg, the smallest P-values were 0.0058 with odds ratio (OR) ¼ 0.54 (0.35, 0.84); 0.0024 with OR ¼ 0.77 (0.66, 0.91); 0.018 with OR ¼ 1.38 (1.06, 1.81); and 0.028 with OR ¼ 0.46 (0.23, 0.92) for alcohol, heroin, cocaine, and methamphetamine dependence/abuse, respectively). When all the phenotypes are combined, the P-value was 0.0006 with OR ¼ 0.86 (0.78, 0.94) in the combined European, Asian, and Mexican populations and P-value was 0.0028 with OR ¼ 1.41 (1.13, 1.78) in the African populations. Evidence of significant associations was also identified in other subgroup analyses regarding differently combined substance and populations. The effect sizes of 5-HTTLPR were comparable among the European, Asian, and Mexican populations, however, the risk allele was more frequent in Asians than in Europeans and Mexicans. The opposite directions of risk allele in African population might be driven by the opposite directions of risk allele in cocaine dependence. This meta-analysis supports that the association of the SLC6A4 gene with substance use disorder varies depending on substances with different risk allele frequencies in the multi-cultural populations. Further studies using larger sample size are warranted.

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Family-based and case-control study of DRD2, DAT, 5HTT, COMT genes polymorphisms in alcohol dependence

Cited by 81 publications

References 41 publications

Can serotonin transporter genotype predict serotonergic function, chronicity, and severity of drinking?

Can serotonin transporter genotype predict serotonergic function, chronicity, and severity of drinking?

Immediate Reward Bias in Humans: Fronto-Parietal Networks and a Role for the Catechol-O-Methyltransferase 158^Val/ValGenotype

Multi-Cultural Association of the Serotonin Transporter Gene (SLC6A4) with Substance Use Disorder

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Family-based and case-control study of DRD2, DAT, 5HTT, COMT genes polymorphisms in alcohol dependence

Cited by 81 publications

References 41 publications

Can serotonin transporter genotype predict serotonergic function, chronicity, and severity of drinking?

Can serotonin transporter genotype predict serotonergic function, chronicity, and severity of drinking?

Immediate Reward Bias in Humans: Fronto-Parietal Networks and a Role for the Catechol-O-Methyltransferase 158Val/ValGenotype

Multi-Cultural Association of the Serotonin Transporter Gene (SLC6A4) with Substance Use Disorder

Contact Info

Product

Resources

About

Immediate Reward Bias in Humans: Fronto-Parietal Networks and a Role for the Catechol-O-Methyltransferase 158^Val/ValGenotype