Neuropsychological functioning in opioid use disorder: A research synthesis and meta-analysis.

BACKGROUND: Research has demonstrated that patients with opioid use disorders (OUD; including both opioid abuse and/or dependence) have poorer neuropsychological functioning compared to healthy controls; however, the pattern and robustness of the findings remain unknown. OBJECTIVES: This study meta-analyzed the results from previous research examining the neuropsychological deficits associated with opioids across 14 neurocognitive domains. METHOD: Articles comparing patients with OUD to healthy controls were selected based on detailed inclusion/exclusion criteria and variables of interest were coded. In total, 61 studies were selected for the analyses. These consisted of 2580 patients with OUD and 2102 healthy control participants (15.9% female). Drug-related variables were analyzed as potential moderators. RESULTS: The largest effect size difference in neuropsychological performance was observed in complex psychomotor ability. With the exception of the motor and processing speed domains, which showed no group differences, small-to-medium effect sizes were associated with all neurocognitive domains examined. Meta-regression revealed that increases in the length of abstinence were associated with decreases in effect sizes of the complex psychomotor domain. Additionally, attentional ability predicted effect size differences in executive functioning as well as verbal memory ability. Although the majority of meta-analyzed studies demonstrated significant differences between patients with OUD and controls, the average raw scores for patients with OUD in these studies typically fell within the normal range. CONCLUSION: The pattern of neuropsychological performance among patients with OUD appears to reflect mild generalized cognitive dysfunction, with a large effect in complex psychomotor abilities.

Neuropsychological comparisons of cocaine versus methamphetamine users: A research synthesis and meta-analysis.

BACKGROUND: Previous meta-analytical research examining cocaine and methamphetamine separately suggests potentially different neuropsychological profiles associated with each drug. In addition, neuroimaging studies point to distinct structural changes that might underlie differences in neuropsychological functioning. OBJECTIVES: This meta-analysis compared the effect sizes identified in cocaine versus methamphetamine studies across 15 neuropsychological domains. METHOD: Investigators searched and coded the literature examining the neuropsychological deficits associated with a history of either cocaine or methamphetamine use. A total of 54 cocaine and 41 methamphetamine studies were selected, yielding sample sizes of 1,718 and 1,297, respectively. Moderator analyses were conducted to compare the two drugs across each cognitive domain. RESULTS: Data revealed significant differences between the two drugs. Specifically, studies of cocaine showed significantly larger effect-size estimates (i.e., poorer performance) in verbal working memory when compared to methamphetamine. Further, when compared to cocaine, methamphetamine studies demonstrated significantly larger effect sizes in delayed contextual verbal memory and delayed visual memory. CONCLUSION: Overall, cocaine and methamphetamine users share similar neuropsychological profiles. However, cocaine appears to be more associated with working memory impairments, which are typically frontally mediated, while methamphetamine appears to be more associated with memory impairments that are linked with temporal and parietal lobe dysfunction.

Gray matter abnormalities in opioid-dependent patients: A neuroimaging meta-analysis.

BACKGROUND: Prior research utilizing whole-brain neuroimaging techniques has identified structural differences in gray matter in opioid-dependent individuals. However, the results have been inconsistent. OBJECTIVES: The current study meta-analytically examines the neuroimaging findings of studies published before 2016 comparing opioid-dependent individuals to drug-naïve controls. METHOD: Exhaustive search of five databases yielded 12 studies that met inclusion criteria. Anisotropic Effect-Size Seed-Based d Mapping (AES-SDM) was used to analyze the data extracted by three independent researchers. Voxel-based AES-SDM distinguishes increases and decreases in brain matter significant at the whole-brain level. RESULTS: AES-SDM identified the fronto-temporal region, bilaterally, as being the primary site of gray matter deficits associated with opioid use. Moderator analysis revealed that length of opioid use was negatively associated with gray matter in the left cerebellar vermis and the right Rolandic operculum, including the insula. Meta-regression revealed no remaining significant areas of gray matter reductions, except in the precuneus, following longer abstinence from opioids. CONCLUSIONS: Opioid-dependent individuals had significantly less gray matter in several regions that play a key role in cognitive and affective processing. The findings provide evidence that opioid dependence may result in the breakdown of two distinct yet highly overlapping structural and functional systems. These are the fronto-cerebellar system that might be more responsible for impulsivity, compulsive behaviors, and affective disturbances and the fronto-insular system that might account more for the cognitive and decision-making impairments.

Meta-analyses of clinical neuropsychological tests of executive dysfunction and impulsivity in alcohol use disorder.

BACKGROUND: Promising models for cognitive rehabilitation in alcohol treatment rest on a more nuanced understanding of the associated impairments in the multifaceted domains of executive functioning (EF) and impulsivity. OBJECTIVES: This meta-analysis examined the effects of alcohol on the individual subcomponents of EF and impulsivity in recently detoxified participants, including 1) Inhibition & Self-Regulation, 2) Flexibility & Set Shifting, 3) Planning & Problem Solving, 4) Reasoning & Abstraction, and 5) Verbal Fluency. Impulsivity was further examined through an analysis of motor, cognitive, and decisional subcategories. METHOD: Investigators searched, coded, and calculated effect sizes of impairments demonstrated in a broad range of neuropsychological tests for EF. A total of 77 studies were selected covering 48 years of research with a sample size of 5140. RESULTS: Findings ranged from a Hedges' g effect size of 0.803 for Inhibition to a Hedges' g of 0.359 for Verbal Fluency. Results also varied for the individual subcategories of Inhibition, including a large effect size for decisional impulsivity (g = 0.817) and cognitive impulsivity (0.860), and a moderate effect size for motor impulsivity (g = 0.529). The Hayling Test, Wisconsin Card Sorting Test, and Iowa Gambling Task were the measures most sensitive for alcohol effects. CONCLUSION: Planning, problem solving, and inhibitory abilities are significantly affected by alcohol abuse, with decisional and cognitive forms of impulsivity most impacted. Cognitive remediation targeting these deficits might increase the related functions that mediate the ability to moderate or abstain from alcohol, and so lead to improved treatment results.

Callosal white matter microstructural recovery in abstinent alcoholics: a longitudinal diffusion tensor imaging study.

BACKGROUND: Previous neuroimaging studies of recently detoxified alcohol-dependent patients (RDA) have found significant loss of white matter integrity associated with the shrinkage of the frontal lobes and thinning of the corpus callosum, especially the genu. The current study hypothesized that, in addition to exhibiting the most microstructural white matter disruption in RDA, the genu will also evidence the most recovery after abstinence. This microstructural recovery will be associated with improvements in executive functioning measures. METHODS: Fifteen RDA were examined approximately 2 weeks after abstinence and again after 1 year of abstinence and compared to 15 age- and education-matched nonalcoholic controls using diffusion tensor imaging (DTI). The effects of group, time, and their interactions on fractional anisotropy, radial diffusivity, and axial diffusivity were evaluated with repeated measures MANOVA; in addition, 2 × 2 ANOVA was used to test changes in measures of executive functioning in the 2 groups. RESULTS: At 2 weeks of abstinence, DTI of RDA showed significantly lower fractional anisotropy and greater radial diffusivity compared to controls in the genu and body of the corpus callosum. Reexamination after 1 year showed significant time by group interaction with fractional anisotropy increasing and radial diffusivity decreasing in RDA but not controls in these 2 regions. A smaller relapsed group did not show improvements between the 2 time points. Abstinent RDA also showed improvement on Digit Span Backward, a measure of working memory, but did not benefit from practice effects on the Halstead Category Test compared to controls. CONCLUSIONS: The results suggest susceptibility of the genu and body of the corpus callosum to the effects of alcohol, and the potential for recovery of both these regions after abstinence, perhaps via mechanisms involving myelin reconstitution.