Untangling the matrix of risk factors for alcoholism

Exactly how a serotonergic dysfunction relates to BD and NA is the realm of great speculation," commented Robert O. Pihl, professor of psychology and psychiatry at McGill University. "Because serotonergic dysfunction seems related to an exceedingly wide range of behaviors, a likely explanation is that of a regulatory role for many biochemical systems in the brain. A speculative analogy has serotonin acting much like the maestro of an orchestra, able to meld disparate sections in order to produce music rather than cacophonous noise. Thus, without appropriate modulation - which we assume is supplied by serotonin - individuals will overreact to emotional stimuli."

Knowing of the strong association between serotonergic dysfunction and behavioral disorders such as alcoholism, aggressiveness and depression, researchers wanted to further examine genetic variations in the serotonin transporter gene (5-HTTLPR). Genetic variation in 5-HTTLPR is related to efficiency in 5-HT reuptake, one aspect of 5-HT functioning. The long (LL) variation or genotype has been associated with an increased number and function of 5-HT transporters (the 5-HT structure that recycles synaptic 5-HT back into the pre-synaptic neuron) when compared to the short (SS) or the short/long (SL) genotypes. An increased functionality of the 5-HT transporter has the effect of reducing the amount of 5-HT available in the synapse. Decreased synaptic 5-HT has the effect of decreasing overall 5-HT functioning.

Some psychiatric genetic studies had previously documented a relationship between the SS variant of 5-HTTLPR and alcohol dependence, depression, anxiety, and the personality trait neuroticism (which is also a marker of NA).

Some studies of alcoholics, however, have found a relationship between the LL variant of 5-HTTLPR and low levels of response to alcohol, alcohol dependence, and antisocial alcoholism. For the current study, researchers examined 47 families classified by th

Contact: Geoffrey R. Twitchell, Ph.D.
Alcoholism: Clinical & Experimental Research

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