Dr. Grossi's Blog


Dr. Philip Grossi
Tuesday, 06 November 2012

In the September 2012 issue of the American Journal of Psychiatry Karen Ersche, PhD, et al. published an article entitled "Cognitive Dysfunction and Anxious-Impulsive Personality Traits Are Endophenotypes for Drug Dependence". Most readers are probably not familiar with the term endophenotype. The authors are saying that the behavior, addiction, is related to an underlying phenotype, anxious-impulsive personality traits, which in turn have a genetic connection. Another common example is colonic polyps which if left alone for long periods tend to become cancerous.

This article assumes that addiction disorders depend on antecedent behavior or features or traits which may be inherited. So, substance abuse which is highly prevalent in anxiety, affective, and impulse control disorders may be a manifestation of an underlying neural dysregulation of motivation, arousal, impulsivity, reward sensitivity or impaired executive function.

In the Ersche study, 45 of the 50 stimulant dependent probands were using during the study thus avoiding any confounds arising from withdrawal. The authors were then measuring the characteristics likely to indicate genetic risk for the condition. They measured environmental, behavioral, cognitive, and social factors and focused on similar features shared by drug dependent subjects and their unaffected siblings that were not shared by healthy comparitors.

The important findings include the following. Stimulant dependence is strongly related to impulsivity and especially impaired response inhibition. The results also showed greater impulsive and anxious personality traits in probands.  They also demonstrated a strong positive correlation between impulsivity and anxiety which may be related to dysregulation of arousal. A type of impulsivity associated with negative or stressful emotion results in responses which may contribute to suicidal behavior which is a risk in substance use disorders.

The investigators also examined the impact of early environmental stressors and chaotic family life. They found that stressful events and stimulants interact to produce a reinforcing pattern leading to increased stimulant usage. This may be the mechanism that leads from sporadic usage to addictive use and further suggests that susceptibility to substance use disorder may lie in susceptibility to the behavioral sensitization.  Conversely, it suggests that siblings may be resistant if they do not have this susceptibility even though they share the same environment.

A cautionary note should be sounded, however. The subjects of this study do not possess the genome they were born with but one that has been modified epigenetically by stress and stimulant usage in the probands. The differences between the probands and their siblings could either be accounted for by inheritance or epigenetic consequences of stimulant usage. Interestingly, this study does not address the issue of resilience which was the topic of the prior blog.