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The glutamate decarboxylase 1 gene may play a pivotal role in developing alcoholism
October 25, 2006GAD1 may also play a significant role in the outcome of alcohol withdrawal
- Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain.
- An enzyme called glutamate decarboxylase (GAD) is involved in the synthesis of GABA.
- Results indicate that the GAD1 gene may play a role in the development of alcoholism as well as the outcome of alcohol withdrawal.
Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain. GABA has been implicated in the development of alcoholism, although the mechanisms through which this occurs are unclear. A recent "association" study has found that an enzyme called glutamate decarboxylase (GAD) - which is involved in the synthesis of GABA - may play a significant role.
Results are published in the November issue of Alcoholism: Clinical & Experimental Research.
"GABA's main function is to inhibit excitatory neuro-activities so that the brain can remain stable," said Andrew T.A. Cheng, Distinguished Research Fellow and professor at Academia Sinica in Taipei. "When one consumes alcohol, GABA levels rise in the brain, providing sedative effects. When one drinks regularly, a counter mechanism is set up until gradually, the ability to raise GABA is reduced. Defects in GABA synthesis may push one to drink more alcohol in order to treat abnormal physiology caused by low GABA Furthermore, individuals who release GABA slowly during alcohol consumption may consume more alcohol to reach its sedative effects, exposing themselves to a higher risk of alcohol dependence." Cheng is also the corresponding author for the study.
"This study takes a so-called candidate gene approach to explore the possible role of GABA in the development of alcoholism," observed Wei-Jen Chen, director of the Institute of Epidemiology at the National Taiwan University Hospital. "GAD has two forms, encoded by the GAD1 and GAD2 genes that are located in different chromosomes, and is involved in the production of GABA from glutamate. This knowledge is mainly derived from studies on mice, whereas human studies so far point to the potential role of GAD in schizophrenia."
Researchers examined two groups of Han Taiwanese men recruited from community and clinical settings: 140 who met Diagnostic and Statistical Manual-III-R criteria for alcohol dependence (22 to 69 years of age); and 146 individuals without alcohol dependence (41 to 84 years of age).
"This is the first study reporting a significant association of the GAD1 gene with the development of alcoholism," said Cheng. "Because GAD1 is the major enzyme in the synthesis of GABA, GAD1 may act as a common factor in the development of common diseases across populations, including alcoholism."
"Although statistical analyses seem to indicate that certain genetic variants of the GAD1 gene were associated with alcohol dependence," added Chen, "the meaning of this association remains to be clarified. For example, one may guess that these genetic variants are probably merely markers that are closely located to a 'real' susceptibility gene for alcohol dependence and hence form 'linkage disequilibrium' with it. Nonetheless, this study does remind researchers that GAD might be involved in maintenance of GABA levels. People with a lower GABA level that is attributed to a less active form of GAD may have a greater chance to drink alcohol to help augment the effects of the inhibitory neurotransmission exerted by GABA. This may also help explain co-occurring anxiety disorders in people with alcohol dependence."
For example, said Chen, patients with schizophrenia are known to have an increased co-occurrence of substance use disorders. Given that the GAD gene has been implicated in genetic susceptibility to schizophrenia too "it might be that the GAD gene confers a common liability to both alcohol dependence and schizophrenia," he said, "probably via the dysfunction of the GABA-related neurotransmission."
Nonetheless, said Cheng, "in order to become an alcoholic, one must be exposed to alcohol first. An individual's genetic background may play a role in pushing someone to become an alcoholic by creating physical and psychological memories that lead to a further demand for alcohol. Our findings may provide a scientific basis to further explore GABA involvement in the development of alcoholism. Advances in this field are likely to create new treatment strategies in alcoholism, either by modern molecular intervention, traditional chemical therapeutics, or psychological approaches based on a GABA-deficit theory."
Alcoholism: Clinical & Experimental Research
- Results indicate that the GAD1 gene may play a role in the development of alcoholism as well as the outcome of alcohol withdrawal.
Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain. GABA has been implicated in the development of alcoholism, although the mechanisms through which this occurs are unclear. A recent "association" study has found that an enzyme called glutamate decarboxylase (GAD) - which is involved in the synthesis of GABA - may play a significant role.
Results are published in the November issue of Alcoholism: Clinical & Experimental Research.
"GABA's main function is to inhibit excitatory neuro-activities so that the brain can remain stable," said Andrew T.A. Cheng, Distinguished Research Fellow and professor at Academia Sinica in Taipei. "When one consumes alcohol, GABA levels rise in the brain, providing sedative effects. When one drinks regularly, a counter mechanism is set up until gradually, the ability to raise GABA is reduced. Defects in GABA synthesis may push one to drink more alcohol in order to treat abnormal physiology caused by low GABA Furthermore, individuals who release GABA slowly during alcohol consumption may consume more alcohol to reach its sedative effects, exposing themselves to a higher risk of alcohol dependence." Cheng is also the corresponding author for the study.
"This study takes a so-called candidate gene approach to explore the possible role of GABA in the development of alcoholism," observed Wei-Jen Chen, director of the Institute of Epidemiology at the National Taiwan University Hospital. "GAD has two forms, encoded by the GAD1 and GAD2 genes that are located in different chromosomes, and is involved in the production of GABA from glutamate. This knowledge is mainly derived from studies on mice, whereas human studies so far point to the potential role of GAD in schizophrenia."
Researchers examined two groups of Han Taiwanese men recruited from community and clinical settings: 140 who met Diagnostic and Statistical Manual-III-R criteria for alcohol dependence (22 to 69 years of age); and 146 individuals without alcohol dependence (41 to 84 years of age).
"This is the first study reporting a significant association of the GAD1 gene with the development of alcoholism," said Cheng. "Because GAD1 is the major enzyme in the synthesis of GABA, GAD1 may act as a common factor in the development of common diseases across populations, including alcoholism."
"Although statistical analyses seem to indicate that certain genetic variants of the GAD1 gene were associated with alcohol dependence," added Chen, "the meaning of this association remains to be clarified. For example, one may guess that these genetic variants are probably merely markers that are closely located to a 'real' susceptibility gene for alcohol dependence and hence form 'linkage disequilibrium' with it. Nonetheless, this study does remind researchers that GAD might be involved in maintenance of GABA levels. People with a lower GABA level that is attributed to a less active form of GAD may have a greater chance to drink alcohol to help augment the effects of the inhibitory neurotransmission exerted by GABA. This may also help explain co-occurring anxiety disorders in people with alcohol dependence."
For example, said Chen, patients with schizophrenia are known to have an increased co-occurrence of substance use disorders. Given that the GAD gene has been implicated in genetic susceptibility to schizophrenia too "it might be that the GAD gene confers a common liability to both alcohol dependence and schizophrenia," he said, "probably via the dysfunction of the GABA-related neurotransmission."
Nonetheless, said Cheng, "in order to become an alcoholic, one must be exposed to alcohol first. An individual's genetic background may play a role in pushing someone to become an alcoholic by creating physical and psychological memories that lead to a further demand for alcohol. Our findings may provide a scientific basis to further explore GABA involvement in the development of alcoholism. Advances in this field are likely to create new treatment strategies in alcoholism, either by modern molecular intervention, traditional chemical therapeutics, or psychological approaches based on a GABA-deficit theory."
Alcoholism: Clinical & Experimental Research
Alcoholism News and Current Alcoholism Events RSSProfessional sports stadiums sell alcohol to pseudo-underage and -intoxicated buyers
Alcohol problems at sports stadiums received considerable media coverage in the early 1980s, leading to several reforms in alcohol-service and enforcement practices. But problems still exist. A recent study of alcohol use at professional sports stadiums across the United States has found that alcohol sales continue at an alarming rate to pseudo-underage and -intoxicated patrons.
Study suggests sports stadiums serve alcohol to minors and intoxicated fans
In a novel study looking at the propensity of illegal alcohol sales at sports stadiums, researchers reported that nearly one in five people posing as underage drinkers, and three out of four seemingly intoxicated "fans" were able to buy alcohol at professional sporting events. They also found that location mattered: sales were more likely if the attempt took place in the stadium stands rather than at a concession booth.
Alcohol dependence among women is linked to delayed childbearing
Alcohol use during the teen years can not only lead to subsequent alcohol problems, it can also lead to risky sexual behavior and a greater risk of early childbearing. An examination of the relationship between a lifetime history of alcohol dependence (AD) and timing of first childbirth across reproductive development has found that AD in women is associated with delayed reproduction.
Epilepsy drug may help alcoholics recover from dependence, small study suggests
It's a Catch-22 of the highest order. People with alcohol problems often use alcohol to get to sleep -- but it actually keeps them from getting good-quality sleep all night long.
Coffee and cigarette consumption are high among AA attendees
More than one million Americans currently participate in the Alcoholics Anonymous (AA) program. While AA participants are reportedly notorious for their coffee drinking and cigarette smoking, very little research has quantified their consumption of these two products.
Prenatal drinking, environmental enrichment: effects on neurotrophins are independent of each other
Prenatal alcohol exposure may be particularly destructive for neurotrophins, a family of peptides that influence the growth, development and functional plasticity of the fetal brain.
Water-diffusion technology identifies brain regions damaged by prenatal alcohol exposure
Scientists know that children with Fetal Alcohol Spectrum Disorder (FASD) often have structural brain damage. Yet little is known about how white matter connections, and deep gray matter structures that act as relay stations, are affected in children with FASD.
Loud music can make you drink more, in less time, in a bar
Commercial venues are very aware of the effects that the environment - in this case, music - can have on in-store traffic flow, sales volumes, product choices, and consumer time spent in the immediate vicinity.
Does a gene variant make women more prone to alcoholism?
A particular gene variant might make women more susceptible to alcoholism. At least, a study carried out by the Universities of Bonn and Sweden's Karolinska Institute makes this a plausible conclusion.
UNC study ties ending moderate drinking to depression
Scientific evidence has long suggested that moderate drinking offers some protection against heart disease, certain types of stroke and some forms of cancer.
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