Kenneth Blum

Bio: Kenneth Blum is an academic researcher from University of Florida. The author has contributed to research in topics: Addiction & Dopaminergic. The author has an hindex of 56, co-authored 313 publications receiving 13450 citations. Previous affiliations of Kenneth Blum include University of Texas Health Science Center at San Antonio & University of North Texas.

Allelic association of human dopamine D2 receptor gene in alcoholism.

Abstract: In a blinded experiment, we report the first allelic association of the dopamine D2receptor gene in alcoholism. From 70 brain samples of alcoholics and nonalcoholics, DNA was digested with restriction endonucleases and probed with a clone that contained the entire 3' coding exon, the polyadenylation signal, and approximately 16.4 kilobases of noncoding 3' sequence of the human dopamine D2receptor gene (λhD2G1). In the present samples, the presence of A1 allele of the dopamine D2receptor gene correctly classified 77% of alcoholics, and its absence classified 72% of nonalcoholics. The polymorphic pattern of this receptor gene suggests that a gene that confers susceptibility to at least one form of alcoholism is located on the q22-q23 region of chromosome 11. (JAMA. 1990;263:2055-2060)

Reward deficiency syndrome: a biogenetic model for the diagnosis and treatment of impulsive, addictive, and compulsive behaviors.

Abstract: The dopaminergic system, and in particular the dopamine D2 receptor, has been implicated in reward mechanisms. The net effect of neurotransmitter interaction at the mesolimbic brain region induces “reward” when dopamine (DA) is released from the neuron at the nucleus accumbens and interacts with a dopamine D2 receptor. “The reward cascade” involves the release of serotonin, which in turn at the hypothalmus stimulates enkephalin, which in turn inhibits GABA at the substania nigra, which in turn fine tunes the amount of DA released at the nucleus accumbens or “reward site.” It is well known that under normal conditions in the reward site DA works to maintain our normal drives. In fact, DA has become to be known as the “pleasure molecule” and/or the “antistress molecule.” When DA is released into the synapse, it stimulates a number a DA receptors (D1-D5) which results in increased feelings of well-being and stress reduction. A consensus of the literature suggests that when there is a dysfunction in ...

Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism.

Abstract: • The allelic association of the human D2dopamine receptor gene with the binding characteristics of the D2dopamine receptor was determined in 66 brains of alcoholic and nonalcoholic subjects. In a blinded experiment, DNA from the cerebral cortex was treated with the restriction endonuclease Taql and probed with a 1.5-kilobase (kb) digest of a clone (XhD2G1) of the human D2dopamine receptor gene. The binding characteristics (Kd[binding affinity] and Bmax[number of binding sites]) of the D2dopamine receptor were determined in the caudate nuclei of these brains using tritiated spiperone as the ligand. The adjusted Kdwas significantly lower in alcoholic than in nonalcoholic subjects. In subjects with the A1 allele, in whom a high association with alcoholism was found, the Bmaxwas significantly reduced compared with the Bmaxof subjects with the A2 allele. Moreover, a progressively reduced Bmaxwas found in subjects with A2/A2, A1/A2, and A1/A1 alleles, with subjects with A2/A2 having the highest mean values, and subjects with A1/A1, the lowest. The polymorphic pattern of the D2dopamine receptor gene and its differential expression of receptors suggests the involvement of the dopaminergic system in conferring susceptibility to at least one subtype of severe alcoholism.

Reward deficiency syndrome: genetic aspects of behavioral disorders.

Abstract: The dopaminergic and opioidergic reward pathways of the brain are critical for survival since they provide the pleasure drives for eating, love and reproduction; these are called 'natural rewards' and involve the release of dopamine in the nucleus accumbens and frontal lobes. However, the same release of dopamine and production of sensations of pleasure can be produced by 'unnatural rewards' such as alcohol, cocaine, methamphetamine, heroin, nicotine, marijuana, and other drugs, and by compulsive activities such as gambling, eating, and sex, and by risk taking behaviors. Since only a minority of individuals become addicted to these compounds or behaviors, it is reasonable to ask what factors distinguish those who do become addicted from those who do not. It has usually been assumed that these behaviors are entirely voluntary and that environmental factors play the major role; however, since all of these behaviors have a significant genetic component, the presence of one or more variant genes presumably act as risk factors for these behaviors. Since the primary neurotransmitter of the reward pathway is dopamine, genes for dopamine synthesis, degradation, receptors, and transporters are reasonable candidates. However, serotonin, norepinephrine, GABA, opioid, and cannabinoid neurons all modify dopamine metabolism and dopamine neurons. We have proposed that defects in various combinations of the genes for these neurotransmitters result in a Reward Deficiency Syndrome (RDS) and that such individuals are at risk for abuse of the unnatural rewards. Because of its importance, the gene for the [figure: see text] dopamine D2 receptor was a major candidate gene. Studies in the past decade have shown that in various subject groups the Taq I A1 allele of the DRD2 gene is associated with alcoholism, drug abuse, smoking, obesity, compulsive gambling, and several personality traits. A range of other dopamine, opioid, cannabinoid, norepinephrine, and related genes have since been added to the list. Like other behavioral disorders, these are polygenically inherited and each gene accounts for only a small per cent of the variance. Techniques such as the Multivariate Analysis of Associations, which simultaneously examine the contribution of multiple genes, hold promise for understanding the genetic make up of polygenic disorders.

Risk and protective factors for alcohol and other drug problems in adolescence and early adulthood: Implications for substance abuse prevention.

Abstract: The authors suggest that the most promising route to effective strategies for the prevention of adolescent alcohol and other drug problems is through a risk-focused approach. This approach requires the identification of risk factors for drug abuse, identification of methods by which risk factors have been effectively addressed, and application of these methods to appropriate high-risk and general population samples in controlled studies. The authors review risk and protective factors for drug abuse, assess a number of approaches for drug abuse prevention potential with high-risk groups, and make recommendations for research and practice.

Genetic dissection of complex traits

Abstract: Medical genetics was revolutionized during the 1980s by the application of genetic mapping to locate the genes responsible for simple Mendelian diseases. Most diseases and traits, however, do not follow simple inheritance patterns. Genetics have thus begun taking up the even greater challenge of the genetic dissection of complex traits. Four major approaches have been developed: linkage analysis, allele-sharing methods, association studies, and polygenic analysis of experimental crosses. This article synthesizes the current state of the genetic dissection of complex traits--describing the methods, limitations, and recent applications to biological problems.

The Adolescent Brain

Abstract: Adolescence is a developmental period characterized by suboptimal decisions and actions that are associated with an increased incidence of unintentional injuries, violence, substance abuse, unintended pregnancy, and sexually transmitted diseases. Traditional neurobiological and cognitive explanations for adolescent behavior have failed to account for the nonlinear changes in behavior observed during adolescence, relative to both childhood and adulthood. This review provides a biologically plausible model of the neural mechanisms underlying these nonlinear changes in behavior. We provide evidence from recent human brain imaging and animal studies that there is a heightened responsiveness to incentives and socioemotional contexts during this time, when impulse control is still relatively immature. These findings suggest differential development of bottom-up limbic systems, implicated in incentive and emotional processing, to top-down control systems during adolescence as compared to childhood and adulthood. This developmental pattern may be exacerbated in those adolescents prone to emotional reactivity, increasing the likelihood of poor outcomes.