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.

Age-related parieto-occipital and other gray matter changes in borderline personality disorder: A meta-analysis of cortical and subcortical structures.

Previous research suggests that core borderline personality disorder (BPD) symptoms vary in severity with advancing age. While structural neuroimaging studies show smaller limbic and prefrontal gray matter volumes (GMV) in primarily adult and adolescent BPD patients, respectively, findings are inconsistent. Using the effect-size signed differential mapping (ES-SDM) meta-analytic method, we investigated the relationship between advancing age and GMV abnormalities in BPD patients. A total of nine voxel-based morphometry (VBM) studies comparing regional GMV of 256 BPD patients and 272 healthy control subjects were included. Meta-analysis identified lower GMV in the right superior/middle temporal gyri and higher GMV in the right supplementary motor area of BPD patients. Meta-regression showed that increasing age was significantly associated with increased GMV in the left superior parieto-occipital gyri, with younger-aged patients starting at lower GMV compared to controls. In contrast, increasing age was associated with decreased GMV in the right amygdala. These findings suggest that while GMV deficits in limbic structures may become pronounced with advancing age in the course of BPD, parieto-occipital rather than frontal GMV deficits could be especially prominent in younger-aged BPD patients.

Gray matter abnormalities in cocaine versus methamphetamine-dependent patients: a neuroimaging meta-analysis.

BACKGROUND: Voxel-based morphometry has been used to explore gray matter alterations in cocaine and methamphetamine dependence. However, the results of this research are inconsistent. OBJECTIVES: The current study meta-analytically examined neuroimaging findings of all studies published before 2014 using the Anisotropic Effect-Size Signed Differential Mapping (ES-SDM). METHODS: Independent investigators searched four major databases for relevant neuroimaging studies involving cocaine and methamphetamine dependence. Nine cocaine and four methamphetamine studies met inclusion criteria. RESULTS: Results indicated that cocaine- and methamphetamine-dependent patients share overlapping regional gray matter abnormalities compared to healthy controls. However, subgroup analysis showed some regional differences; with methamphetamine showing more prominent reductions in the left superior temporal gyrus and the right inferior parietal lobe. Reductions in the right insula and the left superior frontal gyrus were more prominent in cocaine dependence. Moderator analyses indicated that with longer use, cocaine is associated with reductions in the right hippocampus, right middle temporal gyrus, and right inferior frontal gyrus, while methamphetamine is associated with reductions in the left precentral gyrus and the right supramarginal gyrus. CONCLUSION: These findings indicate that cocaine and methamphetamine dependence are significantly and differentially associated with gray matter abnormalities. Results also point to possible gray matter recovery after abstinence from methamphetamine. Although the sample size was adequate, these findings should be considered preliminary and analyses should be revisited with additional primary research focusing on long or short-term duration of use, as well as the length of abstinence.

White matter abnormalities in long-term heroin users: a preliminary neuroimaging meta-analysis.

BACKGROUND: Diffusion tensor imaging has been used to explore white matter changes in heroin-dependent patients; however, results have been inconsistent. OBJECTIVES: The current study meta-analytically examines the neuroimaging findings of all studies published before 2014 using the novel technique of Effect Size Signed Differential Mapping (ES-SDM). METHODS: Two independent investigators searched three databases for whole-brain voxel-based fractional anisotropy morphometric studies involving heroin use without comorbid polysubstance abuse. Of 59 initial primary studies, four met stringent inclusion criteria. RESULTS: RESULTS from this preliminary analysis indicate that heroin abusers may have significant reductions in fractional anisotropy in the bilateral frontal sub-gyral regions extending from the limbic structures to the prefrontal association cortices, implicating damage to the cingulum and superior longitudinal fasciculus. Exploratory moderator analyses indicate that the potential damage in the left cingulate gyrus may increase with longer use and decrease after long-term abstinence. CONCLUSION: These preliminary findings suggest that heroin abuse is significantly associated with damage to white matter integrity. These results are considered preliminary and analyses should be revisited with more primary studies focusing on either long- or short-term abuse as well as abstinence.