Working memory deficits affect risky decision-making in methamphetamine users with attention-deficit/hyperactivity disorder
Introduction
Risky decision-making is common in individuals with substance use disorders, who often continue to use alcohol and drugs despite the high probability of it having adverse long-term consequences on their social (e.g., interpersonal relationships; Gardner and Steinberg, 2005), emotional (e.g., depression; Bechara and Damasio, 2002) and physical (e.g., infectious disease; Hardy et al., 2006) health. Methamphetamine (MA) users are therefore ostensively at risk for deficits in decision-making in the laboratory and in their everyday lives. Chronic MA use is associated with a disruption of the dopamine-rich prefrontostriatal circuits (Volkow et al., 2001) that are essential to a number of different cognitive and motor processes, including decision-making (Rogers et al., 1999; van Gaalen et al., 2006). Indeed, several lines of research now suggest that MA-associated prefrontostriatal pathophysiology may underlie aspects of risky decision-making among some chronic MA users (Rogers et al., 1999; Volkow et al., 2001). Bechara and colleagues (2001) first reported evidence of laboratory-based decision-making deficits in MA users on the Iowa Gambling Task (IGT; Bechara, 2007). Specifically, MA users were significantly more likely to select cards from “disadvantageous” (i.e., high immediate value cards, but with greater risk of long-term penalties) versus “advantageous” (i.e., lower immediate value cards, but with reduced risk of long-term penalties) decks on the IGT than healthy adults (Bechara et al., 2001). Moreover, MA users tend to perform worse on laboratory measures of decision-making compared with users of alcohol (Gonzalez et al., 2007) and other illicit substances, such as cocaine (Simon et al., 2002) and opiates (Rogers et al., 1999). Functional neuroimaging studies of MA dependent individuals show decreased prefrontal and parietal activation during tasks of decision-making (Paulus et al., 2001, Paulus et al., 2003). Speaking to the real-world implications of such deficits, altered prefrontal and parietal brain response to decision-making tasks predicts relapse in MA dependent individuals (Paulus et al., 2005).
MA misuse co-occurs with a variety of psychiatric disorders that are characterized by frontostriatal systems alterations and therefore might impact decision-making, including Attention-Deficit/Hyperactivity Disorder (ADHD). Approximately 40% of adult MA users report a lifetime history of ADHD (Jaffe et al., 2005), as compared to prevalence rates of 3–5% in the general population (Kessler et al., 2006). Elevated rates of lifetime ADHD diagnoses among adult MA users may reflect a self-medicating attempt to ameliorate their symptoms, most notably inattention (Sim et al., 2001), although the literature is not entirely consistent in this regard (Wilens et al., 2003). ADHD is associated with structural and functional abnormalities in frontostriatal neural circuitry (Faraone and Biederman, 1998), including prefrontal cortical thinning (Almeida et al., 2010; Castellanos and Proal, 2009; Makris et al., 2007) and reduced caudate volumes (Hesslinger et al., 2002; Castellanos et al., 1996; Makris et al., 2010; Seidman et al., 2006). ADHD is also associated with prefrontal and subcortical gray matter reductions in adults who have been diagnosed with ADHD in childhood, regardless of whether the diagnosis persists into adulthood (Proal et al., 2011). The neuropsychological profile of ADHD in adults includes deficits in multiple aspects of attention (e.g., sustained) and executive functions (Woods et al., 2002). At the behavioral level, ADHD adults show increased impulsivity and engagement in high risk behaviors, including gambling (e.g., Breyer et al., 2009) and reckless automobile driving (e.g., Thompson et al., 2007). To this end, adults with ADHD also demonstrate impaired performance on tasks that mimic real-life decision-making (e.g., Malloy-Dinz et al., 2007; Mantyla et al., 2010). Mantyla et al. (2010), for example, found that adults with ADHD exhibit impairment (i.e., opting for choices that produce disadvantageous outcomes) on laboratory tasks of decision-making compared to healthy adults, which imaging studies suggest may be associated with decreased activation in the ventromedial prefrontal cortex in this population (Ernst et al., 2003).
Despite the elevated rates of ADHD among MA users and their overlapping cognitive and neural substrates, only two prior studies have examined the neuropsychological functioning of MA users with comorbid ADHD. Sim et al. (2001) found that MA users with ADHD symptomatology showed incremental deficits on neurocognitive tasks of executive functions and working memory compared to MA users without ADHD symptoms. Jaffe and colleagues (2005) found no effect of childhood symptoms of ADHD on the baseline neurocognitive performance of MA dependent individuals; however, MA dependent participants who endorsed ADHD symptomatology failed to show improvements on tests of attention and working memory at one-month follow-up from treatment of MA. Although these two prior studies suggest that comorbid ADHD may exacerbate the cognitive deficits observed in MA users, especially in the domains of executive function and working memory (Sim et al., 2001; Jaffe et al., 2005), we aimed to extend this research by specifically examining the effects of comorbid ADHD and MA on risky decision-making. We hypothesized that MA dependent individuals with comorbid ADHD would demonstrate an increased propensity for risky decision-making (i.e., making choices that produce disadvantageous outcomes) on a well-validated laboratory task (i.e., the IGT) as compared to MA dependent individuals without ADHD and healthy adults.
A secondary aim was to evaluate the possible moderating effects of working memory on MA-associated decision-making deficits. According to Bechara and Martin (2004), working memory may play a critical role in the expression of risky decision-making in substance abusers. At the level of cognitive functioning, working memory impairment likely makes it difficult to adequately maintain, monitor, and evaluate information relevant to making decisions “online.” Such online processing difficulty thus increases the likelihood of impulsive decision-making in favor of immediate, short-term rewards (Bechara and Martin, 2004). At the level of neural systems, the overlapping demands of working memory and decision-making on prefrontostriatal loops (perhaps along with the posterior parietal cortex and its connections with the striatum) may play a role in this association (Bechara and Martin, 2004). In support of this contention, Bechara and Martin found that working memory deficits were inversely correlated with performance on the IGT in a mixed group of substance abusers that included MA dependent persons (Bechara and Martin, 2004). Similarly, studies in healthy adults show that experimental manipulation of working memory load is associated with impaired performance on the IGT (e.g., Hinson et al., 2002; Jameson et al., 2004; Pecchineda et al., 2006). Hinson, Jameson, and Whitney (2002), for example, showed that conditions of high working memory load were associated with increased selections from the disadvantageous decks on a modified version of the IGT (see also Pecchineda et al., 2006). Using the same modified version of the IGT task, Jameson and colleagues (2004) found that verbal buffering alone did not interfere with IGT performance, suggesting that the executive aspects of working memory are critical to decision-making (Jameson et al., 2004). Taken together, these studies provide evidence in support of Bechara and Martin's contention that working memory plays a critical role in the expression of impaired decision-making (Bechara and Martin, 2004). Considering these conceptual factors and the neuropsychological profile of ADHD and MA, it was hypothesized that working memory deficits would interact with ADHD to amplify risky decision-making in MA users.
Section snippets
Participants
A total of 70 individuals were drawn from a larger cohort (N = 386) that was recruited as part of a National Institute on Drug Abuse (NIDA)-funded research study that examined the central nervous system effects of MA on individuals with and without human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection. Twenty-five participants who met DSM-IV diagnostic criteria for both MA dependence and ADHD (ADHD; MA+ADHD+) during their lifetime were the primary group of interest. These
Results
The primary multiple regression model predicting IGT summary score from study group status, working memory, and their interaction was significant (adjusted R2 = 0.07, p = 0.036). We observed a significant main effect of group status, such that the MA+ADHD+ group was significantly more likely to select cards from the disadvantageous decks as indicated by the IGT summary score (t-ratio = −3.62; p = 0.0006). The main effect of working memory impairment was not significant (t-ratio = −1.02; p
Discussion
Results of the present study indicate that adults with comorbid MA and ADHD demonstrate an increased propensity toward risky decision-making (i.e., making choices that produce disadvantageous outcomes) on the IGT. These findings are consistent with prior studies of stimulant abusers substances, who commonly show impaired performance on the IGT, perhaps due to dysfunction in frontostriatal pathways (e.g., Bechara et al., 2001; Bechara and Martin, 2004; Gonzalez et al., 2007; Grant et al., 2000).
Role of funding source
This research study supported by grants P01-DA12065 (Grant), P50-DA026306 (Grant), and P30-MH62512 (Grant) from the NIH. The NIH had no further role in study design; in the collection, analysis, and interpretation of the data; in the writing of the report; and in the decision to submit the paper for publication.
Contributors
Steven Paul Woods, J. Hampton Atkinson, and Igor Grant designed the study and wrote the protocol. Alexandra Rooney and Nichole A. Duarte managed the literature searches. Nichole A. Duarte undertook the statistical analysis. Nichole A. Duarte wrote the first draft of the manuscript. All authors contributed to and have approved the final manuscript.
Conflict of interest
All authors declare they have no conflicts of interest.
Acknowledgments
The Translational Methamphetamine AIDS Research Center (TMARC) is supported by Center award P50-DA026306 from the National Institute on Drug Abuse (NIDA) and is affiliated with the University of California, San Diego (UCSD) and the Sanford-Burnham Medical Research Institute. The TMARC is comprised of: Director: Igor Grant, M.D.; Co-Directors: Ronald J. Ellis, M.D., Ph.D., Cristian Achim, M.D., Ph.D., and Scott Letendre, M.D.; Center Manager: Steven Paul Woods, Psy.D.; Aaron Carr (Assistant
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