Dynamic and Systems-Based Models for Evaluating Hypotheses Related to Predicting Treatment Response

Introduction

Approaches to treating alcohol dependence are heterogeneous, ranging from group therapy in 12-step programs to pharmacotherapy. Such treatment heterogeneity is a reflection of client heterogeneity that results from the complex biopsychosocial architecture underlying multiple alcoholism types with different developmental trajectories.

Although each treatment approach is successful in reducing the number of drinking episodes and the amount of alcohol consumed per episode, no single treatment approach is superior to the others in all cases. One size does not fit all when it comes to treatment for alcohol dependence. If no single alcoholism treatment is equally effective for all individuals who seek treatment, is there some way to identify those who will respond best to a particular treatment? In other words, is there some way to personalize treatment for alcohol dependence? Although the relevant individual differences among treatment seekers have not been fully elucidated, it is likely that at least some of those relevant individual differences result from genetic variation in mechanisms crucial to etiology or to treatment response. In this sense, alcoholism treatment providers are in the same situation as much of the medical profession in the quest for personalized medicine. In addition, although there is much to anticipate about developments in the area of personalized medicine, progress has not kept pace with the clamor. As interest intensifies in personalized medicine, it seems prudent to consider the ways in which investigators will endeavor to make sense of often conflicting empirical results in an effort to understand complex biological systems across levels of analysis from gene to physiological systems to treatment outcome. In this chapter, an approach is presented that focuses on genetic variation in neurotransmitter systems and utilizes dynamic systems modeling to better understand the contribution of genetic variation to pharmacological treatment for alcohol dependence.

The goals of this chapter are to: (1) discuss personalized treatment and pharmacogenetics as it applies to alcoholism, (2) describe the Johnson Model of individual differences in response to pharmacological treatment for alcoholism, (3) discuss a dynamic control system model developed to examine the Johnson Model, and (4) discuss the potential for the use of control systems modeling to test hypotheses regarding the pharmacogenetics of alcoholism.