Sex, ADHD symptoms, and smoking outcomes: an integrative model

Abstract

Both females and individuals with Attention-Deficit/Hyperactivity Disorder (ADHD) have been found to be at increased risk for a range of smoking outcomes, and recent empirical findings have suggested that women with ADHD may be particularly vulnerable to nicotine dependence. On a neurobiological level, the dopamine reward processing system may be implicated in the potentially unique interaction of nicotine with sex and with ADHD status. Specifically, nicotine appears to mitigate core ADHD symptoms through interaction with the dopamine reward processing system, and ovarian hormones have been found to interact with nicotine within the dopamine reward processing system to affect neurotransmitter release and functioning. This article synthesizes data from research examining smoking in women and in individuals with ADHD to build an integrative model through which unique risk for cigarette smoking in women with ADHD can be systematically explored. Based upon this model, the following hypotheses are proposed at the intersection of each of the three variables of sex, ADHD, and smoking: (1) individuals with ADHD have altered functioning of the dopamine reward system, which diminishes their ability to efficiently form conditioned associations based on environmental contingencies; these deficits are partially ameliorated by nicotine; (2) nicotine interacts with estrogen and the dopamine reward system to increase the positive and negative reinforcement value of smoking in female smokers; (3) in adult females with ADHD, ovarian hormones interact with the dopamine reward system to exacerbate ADHD-related deficits in the capacity to form conditioned associations; and (4) during different phases of the menstrual cycle, nicotine and ovarian hormones may interact differentially with the dopamine reward processing system to affect the type and value of reinforcement smoking provides for women with ADHD. Understanding the bio-behavioral mechanisms underlying cigarette addiction in specific populations will be critical to developing effectively tailored smoking prevention and cessation programs for these groups. Overall, the goal of this paper is to examine the interaction of sex, smoking, and ADHD status within the context of the dopamine reward processing system not only to elucidate potential mechanisms specific to female smokers with ADHD, but also to stimulate consideration of how the examination of such individual differences can inform our understanding of smoking more broadly.

Figure 1. Positive and Negative Reinforcement of Smoking During the Menstrual Cycle

During the follicular phase, increasing estrogen levels facilitate dopamine-mediated positive reinforcement. During this stage, it is predicted that female smokers with ADHD will report the greatest positive reinforcement from smoking. During the late luteal/pre-menstrual phase, the effects of estrogen on positive reinforcement are dampened by progesterone, and withdrawal symptoms are difficult to distinguish from ADHD and premenstrual symptoms. During this stage, it is predicted that female smokers with ADHD will report the greatest negative reinforcement from smoking.

Figure 2

Summary of the interaction of ADHD, Female Sex, and Nicotine