A theoretical argument for inherited thiamine insensitivity as one possible biological cause of familial alcoholism.

Thiamine deficiency has been specifically linked to the development of Wernicke-Korsakoff syndrome (WK)--a degenerative brain disorder that is typically associated with alcoholic drinking. Alcoholism-related thiamine deficiency is a major cause of WK. However, an inherited abnormality in thiamine utilization has been identified in some WK patients that may predispose heavy drinkers to this severe neurological syndrome. Individuals who possess this variant require more thiamine throughout their lives to prevent them from experiencing thiamine deficiency. Recent prospective studies have implicated early childhood nutritional and environmental influences in the etiology of alcoholism in adults. These studies have suggested that developmental abnormalities involving brain white matter growth might precipitate the later development of alcoholism possibly by altering the emerging reward-related brain systems. Brain white matter growth is highly sensitive to nutritional deficiency (including thiamine deficiency) and oxidative injury, especially during the perinatal period. The proposed model of familial alcoholism hypothesizes that an inherited insensitivity to thiamine can precipitate brain abnormalities very early in life that will greatly increase the risk of developing alcoholism in adulthood. This paper offers a heuristic model of a possible mechanism by which both inherited and environmental factors related to thiamine utilization might coaggregate to cause alcoholism.