کمک افسردگی و اجرای اختلال عملکرد به اختلال فراحافظه در میان افراد مبتلا به اختلالات استفاده از مت آمفتامین

Objective: Chronic methamphetamine (MA) use is associated with moderate deficits in learning and memory, but the extend to which MA users are aware of such memory deficits (i.e., metamemory) is not known. Methods: In the current study, 195 participants with lifetime MA use diagnoses (MA +) and 195 non-MA-using comparison subjects (MA -) underwent comprehensive neuropsychiatry research assessments, including performance-based and self-report measures of episodic memory. Results: MA use disorders, major depressive disorder (MDD), and their interaction were uniquely associated with metamemory functioning, such that MDD increased the likelihood of a metamemory deficit among MA + participants. Within the MA group, individuals who over-estimated their memory abilities demonstrated greater executive dysfunction and lower cognitive reserve. Conclusions: Chronic MA use is associated with reduced awareness of objective deficits in memory acquisition and recall, which is particularly exacerbated by the presence of major depression. Efforts to enhance metamemory accuracy and deployment of compensatory mnemonic strategies may benefit substance abuse treatment outcomes.

Methamphetamine (MA) has a preferential neurotoxic effect on the frontostriatal systems (Earnst, Chang, Leonido-Yee, et al., 2000) that contributes to both emotion dysregulation (London, Simon, Berman, et al., 2004) and neurocognitive impairment (Scott, Woods, Matt, et al., 2007). MA-related neurocognitive deficits most commonly include episodic memory and executive functions (Woods, Rippeth, Conover, et al., 2005) and are associated with poorer functioning in daily activities (Henry, Minassian, & Perry, 2010), including unemployment (Weber, Blackstone, Iudicello, et al., 2012). One mechanism by which such MA-related neurocognitive deficits may impact daily functioning is via poor awareness of the nature and extent of one's impairment. For example, a MA dependent individual who is unaware of a memory deficit would be much less likely to use a compensatory strategy during daily tasks (e.g., using a calendar or alarm to help them remember to take a medication), and is therefore more vulnerable to experience critical memory failures in real life (e.g., medication nonadherence). According to Nelson and Narens (1990), awareness of memory abilities (i.e., metamemory) may be disrupted at several time points during the acquisition, retention, and/or retrieval of new information. Specifically, the overall correspondence between an individual's perceived memory abilities and his actual memory capacity is postulated to be influenced by how well the material has been learned (e.g., do I need to continue studying?), initiation and termination of recall search strategies, and recall selection choices (e.g., how confident am I that this is the memory I am searching for?); all of which require internal self-regulation. Such processes utilize prefrontal systems, and the combination of executive and memory dysfunction appears to confer greater metamemory inaccuracy (Pannu & Kaszniak, 2005). These same systems are commonly disrupted among MA users suggesting a potential vulnerability to metamemory dysfunction in this population (Ersche, Williams, Robbins, et al., 2013). Yet only two studies to date have examined metacognition in chronic MA users; Cattie, Woods, Iudicello, et al. (2012) found that self-reported symptoms of executive dysfunction in daily life were not related to objective laboratory measures of executive dysfunction among individuals with MA dependence, while Kirkpatrick, Metcalfe, Greene, et al. (2008) illustrated that increasing doses of intranasal methamphetamine administration among MA users disrupted accuracy of metacognitive judgments. Given the prefrontal and striatal predilection of MA-associated neural disruption, it is not surprising that mood dysregulation, such as major depression, is a highly comorbid (Conway, Compton, Stinson, et al., 2006) and functionally impactful condition among chronic MA users (Glasner-Edwards, Marinelli-Casey, Hillhouse, et al., 2009). As postulated in the Nelson and Narens model of metamemory (1990), an individual's belief regarding the difficulty level of the information to be learned (i.e., self-efficacy) in combination with his motivation to learn directly influences his memory behaviors (e.g., to study the information or not). Given that depressive symptoms directly impact self-efficacy and motivation and are related to increased prevalence of memory symptoms in the general population (Ponds & Jolles, 1996), major depressive disorder (MDD) may moderate metamemory accuracy by lowering self-perceived memory abilities and motivation to learn. Therefore, it may not be surprising that memory self-efficacy is consistently a stronger indicator of memory complaints than actual memory test performance (Dellefield and McDougall, 1996 and Ponds and Jolles, 1996). In fact, depression has been consistently associated with inaccurate under-estimation of actual memory abilities in the general population (Kalska, Punamaki, Makinen-Pelli, et al., 1999). For example, depression demonstrated a stronger relationship with reported memory symptoms than memory test performance among a cohort of older healthy adults (Bolla, Lindgren, Bonaccorsy, & Bleecker, 1991), and increasing levels of depression are consistently associated with greater number of memory symptoms among both younger and older adults, regardless of actual memory capacities (Bolla et al., 1991, Kalska et al., 1999 and Niederehe and Yoder, 1989). Considering the frontostriatal systems that are disrupted in MA use and depression and the role of such systems in metamemory, MA + individuals may be particularly susceptible to inaccurate perceptions of their memory abilities; yet, no studies to date have examined this construct among substance users. Therefore, we aim to determine the independent and additive impact of MA use and MDD on metamemory, as well as explore other factors that may affect metamemory processes within the MA + cohort (e.g., executive dysfunction).

Demographic and medical disease characteristics are represented in Table 1. Significant (ps < 0.01) multivariable linear regression models indicated that MA + participants demonstrated lower scores on objective measures of learning (i.e., BVMT-R and HVLT-R learning; F(8,381) = 27.6, p = 0.011) and recall (BVMT-R and HVLT-R delayed recall; F(8,381) = 24.3, p = 0.028) and higher scores on perceived memory symptoms (PAOFI; F(8,381) = 13.2, p < 0.001) than MA− participants. As detailed in the methods, metamemory was operationalized as a four-level variable across all study subjects: under-estimate memory abilities, over-estimate memory abilities, accurately estimate impaired memory, or accurately estimate normal memory. In a multivariable logistic regression model similarly controlling for demographics and those variables that differed between the MA groups, we found independent main effects for MA status (χ2 = 10.0, p = 0.02) and lifetime MDD (χ2 = 8.3, p = 0.04), as well as an interaction between these two variables (MA × lifetime MDD: χ2 = 11.7, p = 0.008; overall model: χ2 = 107.8, p < 0.001). At the univariate level, the MA × lifetime MDD interaction demonstrated a stair step effect such that each risk factor contributed to increasingly greater proportions of inaccurate metamemory (i.e., increased over-estimators and under-estimators), with the highest prevalence of both inaccurate under- and over-estimators observed in MA + participants with a history of MDD (χ2 = 42.2, p < 0.001). These data are displayed in Fig. 1. Examining the main effect of MA use on metamemory abilities demonstrated that up to 56% of MA + users exhibited some sort of metamemory inaccuracy (44% under- and 12% over-estimating), compared to only 37% inaccuracy rate among the MA− comparison participants (30% under- and 7% over-estimating).