Review articleDecision-making ability in current and past users of opiates: A meta-analysis
Introduction
Long term opiate use is associated with a range of problems in everyday life, including poor physical and mental health, impaired social functioning, and high unemployment rates (De Maeyer et al., 2010, De Maeyer et al., 2011, Meulenbeek, 2000). These difficulties may be linked to deficits in cognitive functioning, with a number of cognitive processes including attention, verbal memory, and executive functions shown to be impaired in both heroin and prescribed opiate users (see Baldacchino et al., 2012; and Wang et al., 2013 for reviews). Of the cognitive processes negatively impacted by opiate use, decision-making ability appears to be one of the most consistently and severely affected (Baldacchino et al., 2012).
While it is relatively well-established that decision-making is compromised in opiate users (Baldacchino et al., 2012), little is known about which individuals within this heterogeneous population are most at risk. Similarly, the trajectory of the decision-making impairment following treatment is currently unclear. In particular, it is not known whether decision-making deficits abate during periods of abstinence. Such information has the potential to improve understanding of the difficulties that opiate users face and to assist policy makers and service providers to develop effective support services.
A more detailed understanding of the relationship between opiate use and decision-making ability has been limited by the fact that most available studies in this field have relatively small sample sizes, and findings have been inconsistent, making it difficult to draw reliable conclusions. Therefore, the current study used a meta-analysis to pool and re-examine available data to investigate the temporal trajectory of decision-making deficits in opiate users, and examine the potential influence of individual factors on the severity of these deficits.
In the current context, effective decision-making refers to the ability to avoid making choices that result only in small or short-term benefits, and/or choices that carry a high risk of adverse outcomes. Studies of decision-making have shown that, compared to non-drug-using controls, opiate users tend to select options with short-terms gains but long term losses (e.g., Lemenager et al., 2011, Mintzer et al., 2005, Mintzer and Stitzer, 2002, Verdejo-Garcia et al., 2007, Verdejo-Garcia and Perez-Garcia, 2007) as well as smaller immediate rewards over larger delayed rewards (i.e. delay discounting, Kirby and Petry, 2004, Kirby et al., 1999). In addition, opiate users generally choose riskier options, such as choosing a large but unlikely reward, over a smaller, but likely reward (Brand et al., 2008, Ersche et al., 2006, Ersche et al., 2005b). The magnitude of these decision-making difficulties is substantial, with medium to large effect sizes (Cohen’s d = 0.70) reported in studies that compare opiate users to non-drug-using controls (Baldacchino et al., 2012). These decision making difficulties have the potential to impact on real life choices about money, housing, and health related behaviours (e.g. Wilson and Vassileva, 2016).
Compromised decision-making ability in this population is not surprising given that opiate use is associated with abnormalities in the orbitofrontal cortex (OFC) and associated neural networks. The OFC supports the integration of sensory and emotional inputs when calculating the value of rewards (Elliott et al., 2000, Krawczyk, 2002, Rolls, 2000, Wallis, 2007). The OFC is also part of a larger neural network involving the dorsolateral prefrontal cortex (dlPFC) and nucleus accumbens (Cohen et al., 2005, Ernst and Paulus, 2005, Krawczyk, 2002) which is particularly important for planning behaviour that leads to distant, as opposed to immediate, rewards (Bechara, 2004, Bechara, 2005, Bechara et al., 2000a, Bechara et al., 2000b, Gläscher et al., 2012, Wallis, 2007). Opiate users show evidence of reduced OFC and dlPFC grey matter density (Lyoo et al., 2006, Yuan et al., 2010) and damage to white matter (Li et al., 2016, Liu et al., 2008, Lyoo et al., 2004, Qiu et al., 2013). Abnormal functional connectivity in OFC networks has also been found in opiate users (Cheng et al., 2013, Liu et al., 2009, Ma et al., 2010), and this has been linked to poorer decision-making performance (Qiu et al., 2011). In addition, in comparison to controls, users of different types of opiates have demonstrated either hyper- or hypo-activation of the OFC while making risky decisions during a gambling task (Ersche et al., 2006). Furthermore, reductions in dopamine and serotonin transmission systems are also evident amongst opiate users (Liu et al., 2013, Shi et al., 2008, Yeh et al., 2012, Zaaijer et al., 2015). Although the relationship between neurotransmitters and decision-making has not been specifically investigated in opiate users, abnormalities, for example in dopamine transmission, have been linked to reduced performance in other aspects of cognitive functioning in opiate users (Liang et al., 2016). Taken together, the research reveals that there are abnormalities in relation to OFC and dlPFC structure, function, and neurotransmission in opiate users that might underpin, at least to some extent, their impaired decision-making ability. Although it should be noted that the extent to which neural pathology precedes opiate use is currently unclear, a recent longitudinal brain imaging study by Li et al. (2016) showed that opiate use was associated with white matter degeneration over the period of one year. This research has confirmed that at least some measurable degeneration occurs over a period of active opiate use.
If neural pathology does contribute to the decision-making deficit in opiate users, it may be anticipated that people with a longer history of opiate use will display more severe decision-making impairments, given that structural brain changes have been shown to be greater in people who have used opiates for longer periods of time (Yuan et al., 2010, Yuan et al., 2009). However, findings from the five available studies directly addressing this relationship have been mixed. Some have reported a negative association between duration of opiate use and decision-making ability (Cheng et al., 2012, Yan et al., 2014), whereas others failed to detect such a relationship (Brand et al., 2008, Clark et al., 2006, Lemenager et al., 2011). The limited number of these studies however, makes it difficult to make firm conclusions regarding the relationship between decision-making and duration of opiate use. It is nevertheless possible to investigate this issue further by considering other studies of decision-making in opiate users that do not directly investigate this relationship. More specifically, because the mean duration of opiate use across such studies varies, we were able to collate the data from these studies in the current meta-analysis and use meta-regression to further examine whether the size of the decision-making deficit varies as a function of the duration of opiate use.
Over and above opiate use duration, co-morbid conditions may also affect the severity of decision-making deficits in opiate users. For example, a large proportion of people who use opiates are also dependent on other street drugs (Astals et al., 2008). In addition, many long term opiate users have experienced neurological damage, either as a result of overdose, or physical trauma (Darke et al., 2012b). To the best of our knowledge, the potential impact of poly-substance abuse and head injury on decision-making has not been examined in this group to date (Darke et al., 2000, Loeber et al., 2012). However, in opiate users, poly-substance abuse and head injury are both associated with greater levels of impairment in other cognitive domains including memory, information processing, verbal learning, and executive and general cognitive function (Darke et al., 2012b, Darke et al., 2000, Henry et al., 2012, Loeber et al., 2012). Thus, it is possible that poly-substance abuse and head injury may also detrimentally affect decision-making. In the current meta-analysis, we compared the size of the decision-making impairment reported in studies that included only opiate users who were free of co-morbid issues, to that reported in studies that included people with poly-substance abuse and head injuries.
A further issue that lacks clarity in relation to the decision-making ability of opiate users is whether deficits in this capacity abate when opiate-users enter a period of abstinence. There is evidence that there is some recovery of neurotransmitter receptor availability and function after opiate cessation (Shi et al., 2008, Yeh et al., 2012), and therefore some improvement in decision-making might be anticipated. However, abnormal neural connectivity has been observed in abstinent ex-users (Cheng et al., 2013, Liu et al., 2009), perhaps reflecting permanent opiate-related damage to dlPFC regions, or abnormalities that predated drug use. On this basis, any improvement in decision-making would be expected to be limited. No research has yet tracked a cohort of opiate users from a period of active use through to a period of abstinence. However, some group comparison studies have reported that decision-making ability in ex-users is equivalent to that of non-drug-using controls (Zeng et al., 2013, Zhang et al., 2011), implying that recovery may occur. Contrary to this, other studies have reported that decision-making ability in ex-users is poorer than controls (Ahn et al., 2014, Clark et al., 2006, Li et al., 2013, Verdejo-Garcia et al., 2007, Verdejo-Garcia and Perez-Garcia, 2007, Yan et al., 2014). In the current meta-analysis, we brought together available group comparison studies to investigate whether decision-making deficits in ex-users (relative to controls) are smaller than decision-making deficits in current users (relative to controls). Such a pattern of results would imply that some recovery of decision-making ability following abstinence does occur. In addition, we also considered the possibility that functional brain changes may occur gradually following cessation of opiate use. If this is the case, decision-making ability may not improve immediately, but may instead improve slowly over a period of time. The current meta-analysis allowed us to investigate the extent to which any recovery of decision-making ability is related to length of abstinence.
In summary, we expected that the current meta-analysis would show that (1) the magnitude of decision-making deficits (relative to controls) would be greater in studies that included opiate users with poly-substance dependence and head injury, than in studies that included only opiate users who were free from these co-morbidities; (2) the length of time using opiates would moderate the magnitude of the decision-making deficits (relative to controls), such that participants who had used opiates for longer would have more severe decision-making deficits; (3) the magnitude of the decision-making deficits (relative to controls) would be greater in current users than in ex-users; and (4) in ex-users, the length of abstinence would moderate the magnitude of the decision-making deficits (relative to controls) such that longer periods of abstinence would be associated with smaller decision-making deficits.
Section snippets
Literature search and study selection
This meta-analysis was conducted following PRISMA guidelines (Liberati et al., 2009, Moher et al., 2009). We searched for studies that measured decision-making and which compared a control group to a group that was dependent on opiates (current users) at the time of testing, and/or a group that had been dependent in the past but was now abstinent (ex-users). We used search terms related to opiate dependence, and specific decision-making measures commonly used in neuropsychological literature
Included articles
After an initial literature search, a total of 4635 articles were found, which was reduced to 3537 articles once duplicates were removed. Their titles and abstracts were screened, and 192 articles were retained. These were examined to determine whether they met the inclusion criteria for the study. From this, 38 articles were subjected to a full-text analysis. Following full-text analysis, 22 studies were deemed to meet inclusion criteria (see Fig. 1 for a summary of the screening process).
Discussion
The primary aim of this meta-analysis was to explore the influence of co-morbidities and temporal factors on the decision-making ability of opiate users. We identified 15 studies that compared the decision-making abilities of current opiate users with controls. Consistent with an earlier meta-analysis, which applied stricter inclusion criteria (Baldacchino et al., 2012), we found that the size of the deficit in decision-making in opiate users relative to non-drug-using controls was moderate to
Funding
This research was supported by an Australian Catholic University Research Program Grant.
Acknowledgements
We thank Andrew Chin for double data extraction, Samuel Beasley for data sorting and collation, and Kathryn Duncan for her assistance in refining the search strategy.
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2020, International Journal of PsychophysiologyCitation Excerpt :Problematic substance users display a global deficit in PST performance (Baker et al., 2011, 2013), which may have actually preceded drug use (Baker et al., 2019). Such abnormalities in striatal functioning may present a core susceptibility to decision-making deficits and contribute to several substance-related problems (e.g. treatment dropout, poor physical and mental health, impaired social functioning, and high unemployment rates) (Biernacki et al., 2016). Counteracting such drug-induced neurocognitive deficits thus relies on identifying non-invasive brain stimulation methods capable of modulating RPE-related activity in the aMCC and striatum.
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