Review articleImpact of general cognition and executive function deficits on addiction treatment outcomes: Systematic review and discussion of neurocognitive pathways
Introduction
Addiction has been defined as a brain disorder, which reflects a shift from impulsivity to compulsivity and becomes chronic and relapsing along its course (Koob and Volkow, 2010). The unprecedented progress of neuroscience approaches has allowed neuropsychological models, which integrate neurobiological evidence with psychological and psychosocial consequences of neuroplasticity, to provide better explanations of addictive behaviors (Volkow et al., 2016). These integrated models include the Impaired Response Inhibition and Salience Attribution framework (I-RISA; Goldstein and Volkow, 2002), the Vulnerabilities in Decision-Making model (Redish et al., 2008) and the Somatic Marker theory (Verdejo-García and Bechara, 2009), among others. All these models assume that addiction is associated with poorer top-down cognitive control of behavior (executive functions), which ultimately impact on key stages of the addictive cycle, and psychosocial and treatment outcomes.
Systematic reviews and meta-analyses have established the link between drug use and cognitive deficits. Spronk et al. (2013) demonstrated that long-term cocaine use is associated with cognitive impairments in most cognitive domains, with the strongest evidence in executive functions such as sustained attention, response inhibition, working memory and decision-making. Consistent deficits in executive functions have also been shown in users of opiates, methamphetamine or alcohol (Baldacchino et al., 2012, Dean et al., 2013, Stavro et al., 2013). Executive functions are higher-order processes critical for successful goal-directed behavior, including the skills needed to succeed in addiction treatment (Blume and Marlatt, 2009, Loughead et al., 2015). Thus, from both basic and clinical standpoints, it is crucial to determine if executive deficits have a meaningful impact on addiction treatment.
In recent years, growing studies have examined the relationship between cognitive measures of executive functions and treatment outcomes. A previous review on this topic analyzed the impact of cognitive impulsivity (one of the domains of executive functions), and found evidence of moderate associations between this construct and treatment outcomes (Stevens et al., 2014). However, this review did not analyze other components of executive function linked to drug use (e.g., reasoning, working memory, flexibility). Moreover, the authors detected significant heterogeneity among existing studies, and raised the need to conduct a more systematic methodological approach to facilitate interpretation of the mounting evidence (Stevens et al., 2014). Specifically, previous studies have not systematically analyzed differences between cognitive predictors of treatment adherence versus drug relapse. Treatment adherence is a measure of treatment progress and a well-established proxy of treatment success (Jackson, 2002, NIDA, 2002). Drug relapse is a direct measure of post-treatment outcomes, linked to remission and long-term recovery (Donovan, 2012). Although adherence and abstinence are meaningfully intertwined in the context of addiction treatment, they are also dissociable from the clinical standpoint: a substantial proportion of patients can achieve abstinence without adhering to treatment (Klingemann and Roserberg, 2009), and many patients adhere to treatment without intending to achieve abstinence (i.e., their goal is to reduce drug use or to ameliorate quality of life). This dissociation has been recently acknowledged by expert consensus statements on selection of appropriate outcomes for addiction treatment studies (Donovan, 2012, Tiffany et al., 2012). The utility of identifying a variable that predicts treatment adherence (but not abstinence) relates to the possibility of improving treatment outcomes other than drug use, such as mood or quality of life (Tiffany et al., 2012). The utility of identifying a variable that predicts abstinence (but not treatment adherence) relates to the possibility of developing self-change interventions, or brief interventions that can rapidly target the identified variable without requiring adherence to intensive treatment regimens. Logically, different cognitive-executive functions would be more relevant to each of these separate outcomes, but this notion needs to be systematically tested.
The overarching aim of this review is to systematically examine the relationship between executive functions and clinically meaningful treatment outcomes. Specific aims are: i) to review existing evidence on the link between executive deficits and treatment outcomes, focusing on methodological aspects among studies; ii) to unravel the differential relationship between executive functions and therapeutic adherence versus drug relapse; iii) to discuss the resulting findings, drawing on integrated neuropsychological models of addiction.
Section snippets
Literature search & study selection
A systematic search was conducted to identify studies using neuropsychological measures of executive functions in patients with substance use disorders, for the purpose of predicting relapse or therapeutic adherence.
The databases queried were PubMed and PsycInfo. Table 1 shows the keywords employed and their combination. The search was done in the ‘title’ and ‘abstract’ fields. The time criterion set was 15 years (2000–2015). Only empirical studies published in English-language scientific
Description of studies
Table 3 shows descriptive information of the studies selected for this review. 50% were carried out in the United States (23 studies) and 15.2% in the United Kingdom. Studies from other European countries (Belgium, Netherlands, Spain, Austria and Germany) are included. Japan, China and Australia add one study each. Most of the studies included patients with cocaine (39.1%) or alcohol (26.1%) use. Four studies had been conducted on poly-drug users. Opiates, cannabis and methamphetamines were
Discussion
Neurocognitive evidence has established the importance of neuropsychological deficits, and specifically deficits in cognitive-executive functions, for understanding addiction. Nevertheless, the impact of these deficits on treatment progress and recovery is still under investigation. This review has examined emerging evidence of links between deficits in cognitive-executive functions and therapeutic adherence and drug relapse. We found substantial variability among studies, depending mostly on
Conclusion
Methodological differences were observed across studies, resulting in substantial variability in the findings. Nevertheless, notwithstanding this variance, we have found suggestive evidence of associations, of moderate effect size, between general cognition and treatment adherence, and reward-based decision-making and alcohol and drug relapse. The methodological issues should be addressed in future studies in this area. The tentative findings on general cognition and decision-making can inform
Conflict of interest
The authors of the present manuscript declare no conflict of interest.
Acknowledgements
This work has been supported by funds of the program grant RETICS from the Institute of Health Carlos III, Spanish of Ministry of Health, co-funded by FEDER funds of the European Union – a way to build Europe – (RD12/0028/0017) to AVG and OML.
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2023, Neuroscience and Biobehavioral ReviewsCitation Excerpt :Against the background of these substance-specific effects, it seems logical to assume that the noradrenergic system, which is targeted by AMPH, METH and MDMA, should be similarly affected (i.e., down-regulated) by any kind of chronic ATS use. Yet, these changes have so far not been sufficiently investigated in human subjects, but evidence from animal models provides valuable support for this assumption, given that both chronically METH- and MDMA-treated animals demonstrated noradrenaline depletion (Clemens et al., 2007; Du et al., 2022; Seiden et al., 1976). The primary mechanisms of acute use and the (often opposing) chronic tolerance effects of the three most popular ATS on the monoaminergic system are specified in Table 1.