Showing papers by "Edythe D. London published in 2021"

Mapping cortical and subcortical asymmetries in substance dependence: Findings from the ENIGMA Addiction Working Group

Abstract: Brain asymmetry reflects left-right hemispheric differentiation, which is a quantitative brain phenotype that develops with age and can vary with psychiatric diagnoses. Previous studies have shown that substance dependence is associated with altered brain structure and function. However, it is unknown whether structural brain asymmetries are different in individuals with substance dependence compared with nondependent participants. Here, a mega-analysis was performed using a collection of 22 structural brain MRI datasets from the ENIGMA Addiction Working Group. Structural asymmetries of cortical and subcortical regions were compared between individuals who were dependent on alcohol, nicotine, cocaine, methamphetamine, or cannabis (n = 1,796) and nondependent participants (n = 996). Substance-general and substance-specific effects on structural asymmetry were examined using separate models. We found that substance dependence was significantly associated with differences in volume asymmetry of the nucleus accumbens (NAcc; less rightward; Cohen's d = 0.15). This effect was driven by differences from controls in individuals with alcohol dependence (less rightward; Cohen's d = 0.10) and nicotine dependence (less rightward; Cohen's d = 0.11). These findings suggest that disrupted structural asymmetry in the NAcc may be a characteristic of substance dependence.

Sex Differences in the Association of Cigarette Craving With Insula Structure.

Abstract: BACKGROUND Cigarette craving, which can negatively impact smoking cessation, is reportedly stronger in women than in men when they initiate abstinence from smoking Identifying approaches to counteract craving in people of different sexes may facilitate the development of personalized treatments for Tobacco Use Disorder, which disproportionately affects women Because cigarette craving is associated with nicotine dependence and structure of the insula, this study addressed whether a person's sex influences these associations METHODS The research participants (n = 99, 48 women) reported daily cigarette smoking and provided self-reports of nicotine dependence After overnight abstinence from smoking, they underwent structural magnetic resonance imaging scanning to determine cortical thickness of the left and right anterior circular insular sulcus, and self-rated their cigarette craving before and after their first cigarette of the day RESULTS Women reported stronger craving than men irrespective of smoking condition (ie, pre- and post-smoking) (P = 048), and smoking reduced craving irrespective of sex (P < 001) A 3-way interaction of sex, smoking condition, and right anterior circular insular sulcus thickness on craving (P = 033) reflected a negative association of cortical thickness with pre-smoking craving in women only (P = 012) No effects of cortical thickness in the left anterior circular insular sulcus were detected Nicotine dependence was positively associated with craving (P < 001) across groups and sessions, with no sex differences in this association CONCLUSIONS A negative association of right anterior insula thickness with craving in women only suggests that this region may be a relevant therapeutic target for brain-based smoking cessation interventions in women

Effects of oral contraceptive pills on mood and magnetic resonance imaging measures of prefrontal cortical thickness.

Abstract: Gonadal hormones influence neuronal organization and plasticity. Yet the consequences of altering their concentrations by administering contraceptive agents, which are used by most reproductive-age women in the United States, are unclear. Cross-sectional studies have found both larger and smaller cortical regions alongside a variety of mood alterations in women who use oral contraceptive pills (OCPs) compared to naturally-cycling women. The goal of this study, therefore, was to determine whether there is an effect of OCPs on MRI measures of prefrontal cortical brain structure that may influence regulation of mood. We performed a double-blind, placebo-controlled, randomized crossover study comparing effects of OCPs (0.15 mg levonorgestrel + 0.30 μg ethinyl estradiol) vs placebo (N = 26) on MRI measures of prefrontal cortical thickness and on mood, as indicated by self-report on the Daily Record of Severity of Problems, which also includes one item related to somatic symptoms. MRI measures that reflect cortical thickness were smaller bilaterally in the pars triangularis and in the pars opercularis and frontal pole of the right hemisphere during the OCP arm vs. placebo. Only the effect in the right pars triangularis survived multiple comparisons correction. Right pars triangularis MRI measures of cortical thickness were not related to mood symptoms, but negatively correlated across conditions with severity of somatic symptoms on the DSRP. The somatic symptoms and MRI measures may be independently related to the actions of steroid hormones in OCPs, with OCPs simultaneously inducing both more effects on MRI measures of cortical thickness and somatic symptoms.

The relationship between duration of abstinence and gray-matter brain structure in chronic methamphetamine users.

Abstract: Background: Brain structural findings in chronic methamphetamine users have been inconsistent. Identifying contributing influences (e.g., sex, abstinence duration) can help clarify the clinical cou...

Striatal dopamine D2-type receptor availability and peripheral 17β-estradiol.

Abstract: Research using rodent models has established a relationship between the steroid hormone estrogen and dopamine function, by revealing changes throughout the estrous cycle and by directly manipulating neuroendocrine signaling through ovariectomy and administration of estrogen. However, a direct link between estrogen levels and dopamine signaling had not been established in humans. The goal of this study, therefore, was to assess the relationship between circulating 17β-estradiol and dopamine signaling in the human brain by testing for a relationship between two proxies for these variables: peripheral 17β-estradiol and striatal dopamine D2-type receptor availability, measured with [18F]fallypride and positron emission tomography (PET). Sixteen (23-45 years of age) women were tested on 2 days of the menstrual cycle estimated prospectively to occur during (a) the early follicular phase, when estrogen levels are near their nadir, and (b) the periovulatory phase, when estrogen levels peak. PET scans with [18F]fallypride were performed on these 2 days, and serum 17β-estradiol was measured using radioimmunoassay. Dopamine D2-type receptor availability did not differ significantly in the whole striatum or the caudate, putamen, or accumbens subregions during the high-estrogen vs. the low-estrogen phases of the menstrual cycle. We conclude that circulating estrogen levels do not affect dopamine D2-type receptor availability in the human striatum although other indices of dopaminergic function may be affected.

Executive Function and Contingency Management in Methamphetamine Use Disorder.

Abstract: Objectives: Contingency management is a promising intervention for Methamphetamine Use Disorder (MUD).Impaired executive function may decrease adherence to such treatment, but there are few data on whether impairment in executive function predicts treatment outcomes. We therefore evaluated whether baseline performance on tests of executive function predicted treatment response in a trial of contingency management for MUD. Methods: Thirty participants with MUD and 23 healthy controls performed the Connors Continuous Performance Task (CPT) and the Trail Making Task. MUD participants then entered an 8-week contingency management trial. Participants were categorized as responders (n=17; no methamphetamine-positive urine tests) or non-responders (n=13; >1 positive test). The Kruskal-Wallis test was used to compare scores in participants with MUD and healthy controls, and in responders versus non-responders. Results: Participants withMUD performed worse than controls on the CPT (d-prime) (p=0.012); non-responders performed worse than responders (p = 0.034). Performance of MUD participants did not differ significantly from controls on the Trail Making Task B (time to completion), but variation was high with non-responders performing worse than responders (p=0.013). Conclusion: These findings suggest that tests of executive function at baseline may be useful in predicting treatment response in MUD. Future work in larger samples may ultimately allow a more personalized treatment approach to methamphetamine use disorder.

Age Influences Loss Aversion Through Effects on Posterior Cingulate Cortical Thickness.

Abstract: Decision-making strategies shift during normal aging and can profoundly affect wellbeing. Although overweighing losses compared to gains, termed "loss aversion," plays an important role in choice selection, the age trajectory of this effect and how it may be influenced by associated changes in brain structure remain unclear. We therefore investigated the relationship between age and loss aversion, and tested for its mediation by cortical thinning in brain regions that are susceptible to age-related declines and are implicated in loss aversion - the insular, orbitofrontal, and anterior and posterior cingulate cortices. Healthy participants (n = 106, 17-54 years) performed the Loss Aversion Task. A subgroup (n = 78) provided structural magnetic resonance imaging scans. Loss aversion followed a curvilinear trajectory, declining in young adulthood and increasing in middle-age, and thinning of the posterior cingulate cortex mediated this trajectory. The findings suggest that beyond a threshold in middle adulthood, atrophy of the posterior cingulate cortex influences loss aversion.

CYP2D6 genotype may moderate measures of brain structure in methamphetamine users

Abstract: Chronic methamphetamine use is linked to abnormalities in brain structure, which may reflect neurotoxicity related to metabolism of the drug. As the cytochrome P450 2D6 (CYP2D6) enzyme is central to the metabolism of methamphetamine, genotypic variation in its activity may moderate effects of methamphetamine on brain structure and function. This study explored the relationship between CYP2D6 genotype and measures of brain structure and cognition in methamphetamine users. Based on the function of genetic variants, a CYP2D6 activity score was determined in 82 methamphetamine-dependent (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV] criteria) and 79 healthy-control participants who completed tests of cognitive function (i.e., attention, memory, and executive function); most were also evaluated with structural magnetic resonance imaging (MRI) (66 methamphetamine-dependent and 52 controls). The relationship between CYP2D6 activity score and whole brain cortical thickness differed by group (interaction p = 0.024), as increasing CYP2D6 activity was associated with thinner cortical thickness in the methamphetamine users (β = -0.254; p = 0.035), but not in control subjects (β = 0.095; p = 0.52). Interactions between CYP2D6 activity and group were nonsignificant for hippocampal volume (ps > 0.05), but both hippocampi showed trends similar to those observed for cortical thickness (negative relationships in methamphetamine users [ps 0.50]). Methamphetamine users had lower cognitive scores than control subjects (p = 0.007), but there was no interaction between CYP2D6 activity score and group on cognition (p > 0.05). Results suggest that CYP2D6 genotypes linked to higher enzymatic activity may confer risk for methamphetamine-induced deficits in brain structure. The behavioral consequences of these effects are unclear and warrant additional investigation.

Nicotine dependence and functional connectivity of insular cortex subregions

Abstract: The insular cortex has been identified as a promising target in brain-based therapies for Tobacco Use Disorder, and has three major sub-regions (ventral anterior, dorsal anterior, and posterior) that serve distinct functional networks. How these subregions and associated networks contribute to nicotine dependence has not been well understood, and therefore was the subject of this study. Forty-seven individuals (24 women; 18-45 years old) who smoked cigarettes daily rated their dependence using the Fagerstrom Test for Nicotine Dependence (FTND), abstained from smoking overnight (~12 h), and underwent resting-state functional MRI. Correlations between dependence and resting-state functional connectivity (RSFC) of the major insular sub-regions were evaluated using whole-brain-corrected voxel-wise analyses and post-hoc region-of-interest (ROI) analyses. Dependence was analyzed both as a unitary (FTND total score) and bivariate construct - two FTND factors ("morning smoking" and "daytime smoking"). Dependence was negatively correlated with connectivity of both the right dorsal and left ventral anterior insula with the left precuneus, and with connectivity of the left posterior insula to the left putamen. In post-hoc analyses, dependence correlated negatively with connectivity between all anterior insula subregions and the left precuneus, and with bilateral posterior insula connectivity with the left posterior putamen. The latter finding was driven by "daytime smoking". These results suggest an anterior-posterior distinction in functional insular networks associated with different dimensions of nicotine dependence, with greater dependence linked to weaker connectivity. They may inform therapeutic approaches involving brain stimulation that may elicit differential clinical outcomes depending on the insular subnetwork targeted.