Tumor-Associated Retinal Pigmentation in Choroidal Melanoma.

PURPOSE: To report a previously unrecognized choroidal melanoma clinical feature termed tumor-associated retinal pigmentation (TARP) and determine any correlation with tumor biology. DESIGN: Imaging and histologic analysis of a retrospective cohort of patients. PARTICIPANTS: Patients with choroidal melanoma identified as having TARP on funduscopy at the Liverpool Ocular Oncology Centre (LOOC), United Kingdom, from January 2020 through January 2023. METHODS: Clinical and imaging characteristics of patients diagnosed with choroidal melanoma and exhibiting TARP on fundoscopy were documented. Details of these choroidal melanomas were collated and correlated with histopathology and molecular genetic reports. The chromosome 3 status of each tumor was assessed. In enucleated samples, immunostaining was undertaken to determine the nature of the TARP using specific markers (CD68 and MelanA). MAIN OUTCOME MEASURES: Features of TARP on widefield fundus color imaging, fundus autofluorescence (FAF), and OCT were described. Tumor chromosome 3 status and the immunoprofile of the TARP also were collated. RESULTS: Tumor-associated retinal pigmentation had a prevalence rate of 7.47 per 100 cases of choroidal melanoma at the LOOC. Twenty-three eyes with TARP were analyzed, with a mean age of 71.4 years (range, 51-88 years). The median largest basal diameter was 16.10 mm (range, 9.17-21.32 mm), and the mean tumor thickness was 8.04 mm (range, 1.40-13.80 mm). Tumor-associated retinal pigmentation was observed on widefield color fundus imaging, with hypofluorescence on FAF images and represented hyperreflective foci located in intraretinal and subretinal spaces on OCT scans. Seventeen patients (73.9%) underwent enucleation, and 6 patients (26.1%) underwent globe-sparing treatment. Molecular genetic analysis of 20 choroidal melanomas (after enucleation or radiotherapy biopsy) revealed monosomy 3 in 18 tumors (90%). Immunostaining of the TARP in enucleated eyes showed CD68+ melanophages in all 17 patients appearing as scattered cells and aggregates; MelanA findings were negative. CONCLUSIONS: Tumor-associated retinal pigmentation represents tumor-associated macrophages, not melanocytes, within intraretinal and subretinal spaces of larger choroidal melanomas. Radiation treatments need not involve this area in the treatment plan, minimizing radiation-related complications. This novel clinical sign seems to be linked to tumors of high metastatic-risk clinical and genetic characteristics, with a preponderance having monosomy 3 anomalies. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Cannabis Use and Brain Volume in Adolescent and Young Adult Cannabis Users: Effects Moderated by Sex and Aerobic Fitness.

OBJECTIVES: Studies examining the impact of adolescent and young adult cannabis use on structural outcomes have been heterogeneous. One already-identified moderator is sex, while a novel potential moderator is extent of aerobic fitness. Here, we sought to investigate the associations of cannabis use, sex, and aerobic fitness levels on brain volume. Second, we explored brain-behavior relationships to interpret these findings. METHODS: Seventy-four adolescents and young adults (36 cannabis users and 38 controls) underwent 3 weeks of monitored cannabis abstinence, aerobic fitness testing, structural neuroimaging, and neuropsychological testing. Linear regressions examined cannabis use and its interaction with sex and aerobic fitness on whole-brain cortical volume and subcortical regions of interests. RESULTS: No main-effect differences between cannabis users and nonusers were observed; however, cannabis-by-sex interactions identified differences in frontal, temporal, and paracentral volumes. Female cannabis users generally exhibited greater volume while male users exhibited less volume compared to same-sex controls. Positive associations between aerobic fitness and frontal, parietal, cerebellum, and caudate volumes were observed. Cannabis-by-fitness interaction was linked with left superior temporal volume. Preliminary brain-behavior correlations revealed that abnormal volumes were not advantageous in either male or female cannabis users. CONCLUSIONS: Aerobic fitness was linked with greater brain volume and sex moderated the effect of cannabis use on volume; preliminary brain-behavior correlations revealed that differences in cannabis users were not linked with advantageous cognitive performance. Implications of sex-specific subtleties and mechanisms of aerobic fitness require large-scale investigation. Furthermore, present findings and prior literature on aerobic exercise warrant examinations of aerobic fitness interventions that aimed at improving neurocognitive health in substance-using youth.

Prevalence of Barrett's esophagus in obese patients undergoing pre-bariatric surgery evaluation: a systematic review and meta-analysis.

INTRODUCTION: Obesity is a known risk factor for gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC). Obese patients routinely undergo preoperative esophagogastroduodenoscopy (EGD) before bariatric procedures. We aimed to assess the prevalence of BE in this patient population. METHODS: We conducted a comprehensive literature search ending in March 2019. Search results were imported into covidence.org and screened by two independent reviewers. Heterogeneity was assessed using I 2 and Q statistics and publication bias using funnel plots and the Orwin fail-safe test. Random-effects modeling was used in all analyses. RESULTS : Of 4087 citations, 77 were reviewed in full text and 29 were included in the final analysis based on our predetermined inclusion/exclusion criteria. A total of 13 434 patients underwent pre-bariatric surgery EGD. The pooled prevalence of BE using random-effects modeling was 0.9 % (95 % confidence interval [CI] 0.7 % - 1.3 %); P < 0.001; I 2 = 58 %, Q = 67). In meta-regression analyses, controlling for sex and GERD, we found a positive association between mean body mass index (BMI) and the prevalence of BE (ß = 0.15 [95 %CI 0.02 - 0.28]; P = 0.03). A linear relationship between the prevalence of BE and the prevalence of GERD was also noted (ß = 3.9 [95 %CI 0.4 - 7.5]; P = 0.03). CONCLUSIONS : Obesity has been postulated as a major risk factor for BE, yet we found that the prevalence of BE in morbidly obese patients undergoing preoperative EGD was very low. Therefore, obesity alone may not be a major risk factor for BE.

Impact of 2 Weeks of Monitored Abstinence on Cognition in Adolescent and Young Adult Cannabis Users.

OBJECTIVES: Previous research suggests recovery from cannabis-related deficits in verbal learning and memory functioning after periods of cannabis abstinence in adolescents. Here, we examine how cannabis cessation affects cognitive performance over 2 weeks of monitored abstinence compared to controls in adolescents and young adults. METHODS: Seventy-four participants (35 cannabis users) aged 16-26 ceased all cannabis, alcohol, and other illicit substance consumption for a 2-week period; abstinence was monitored via weekly urinalysis, breath, and sweat patch testing. Starting at baseline, participants completed weekly abbreviated neuropsychological batteries. Measures included tests of attention, inhibition, verbal working memory, and learning. Repeated measures assessed within and between subject effects for time and group status, while controlling for past year alcohol and nicotine use. RESULTS: Cannabis users showed increased performance compared to controls on sustained attention tasks after 2 weeks of cannabis use. CONCLUSIONS: Deficits in attention, but not verbal learning and memory, recovered after 2 weeks of monitored abstinence. This differs from previous literature, suggesting that other cognitive domains may show signs of recovery after periods of cannabis cessation in adolescents and young adults.

Objective aerobic fitness level and neuropsychological functioning in healthy adolescents and emerging adults: Unique sex effects.

Objective: Research suggests positive relationships between aerobic fitness and cognition in older adults; however, limited research has adequately investigated the relationship between objectively measured aerobic fitness and broad cognitive functioning in healthy adolescents and young adults without psychiatric or physical health disorders. Further, studies to date have disproportionately examined males and failed to examine sex differences. Here we examine the relationship between aerobic fitness and neuropsychological functioning in physically healthy youth and whether sex moderates these findings. Design: Sixty-four healthy emerging adults (16-25 years-old; 32 female) underwent measurement of objective aerobic fitness (VO2 max) and neuropsychological assessment. Exclusion criteria included: left-handedness, prenatal medical issues or alcohol/illicit drug exposure, Axis-I psychiatric disorders, major medical disorders including metabolic conditions such as diabetes, hypertension, hyperlipidemia, major neurologic disorders, LOS greater than 2 min, intellectual disability or learning disability, regular substance use (e.g., greater than biweekly use of cannabis) or positive drug toxicology testing. Method: Multiple regressions examined VO2 max, sex, sex*VO2interaction in relation to neurocognition, controlling for objectively measured body fat percentage. Results: Prior to including body fat percentage, higher VO2 max related to improved working memory (Letter-Number Sequencing; p = .03) and selective attention (CPT-II hit response time standard error; p = .03). Aerobic fitness significantly interacted with sex, as higher-fit males had better performance on two sustained attention tasks while females did not demonstrate this pattern (CPT-II variability standard error, p = .047; Ruff 2&7 Total Speed, p = .02). Body fat percentage was positively slower cognitive flexibility (D-KEFS color-word switching/inhibition, p = .046). Conclusions: VO2 independently predicted better working memory and selective attention. Increased aerobic fitness level related to increased performance on sustained attention tasks in males but not females. Therefore, aerobic fitness may be positively related to better cognitive functioning in physically healthy adolescents and emerging adults without metabolic conditions. Further research into factors (e.g., intensity or type of activity) that may relate to beneficial outcomes by sex are needed.

The Effects of Ultrasound on the Electro-Oxidation of Sulfate Solutions at Low pH.

The electro-oxidation of sulfate solutions is a well-established route for the generation of powerful oxidants such as persulfate. Despite this, the effects of simultaneous ultrasound irradiation during this process has attracted little attention. Herein, we investigate the effects of a low-intensity ultrasonic field on the generation of solution-phase oxidants during the electro-oxidation of sulfate solutions. Our results show that at high current densities and high sulfate concentrations, ultrasound has little effect on the Faradaic and absolute yields of solution-phase oxidants. However, at lower current densities and sulfate concentrations, the amount of these oxidants in solution appears to decrease under ultrasonic irradiation. A mechanism explaining these results is proposed (and validated), whereby anodically-generated sulfate and hydroxyl radicals are more effectively transported into bulk solution (where they are quenched) during sonication, whereas in the absence of an ultrasonic field these radicals combine with one another to form more persistent species (such as persulfate) that can be detected by iodometry.

Aerobic Fitness Level Moderates the Association Between Cannabis Use and Executive Functioning and Psychomotor Speed Following Abstinence in Adolescents and Young Adults.

OBJECTIVES: The high rate of cannabis (CAN) use in emerging adults is concerning given prior research suggesting neurocognitive deficits associated with CAN use in youth. Regular CAN use downregulates endocannabinoid activity, while aerobic exercise upregulates cannabinoid receptor 1 activity and releases endocannabinoids. Here we investigate the influence of regular CAN use on neuropsychological performance, and whether aerobic fitness moderates these effects. METHODS: Seventy-nine young adults (37 CAN users) aged 16-26 participated. Groups were balanced for aerobic fitness level. Exclusion criteria included: left-handedness, past-year independent Axis-I disorders, major medical/neurologic disorders, prenatal issues, or prenatal alcohol/illicit drug exposure. After 3 weeks of abstinence, participants completed a neuropsychological battery and a maximal oxygen consumption test (VO2 max). Multiple regressions tested whether past-year CAN use, VO2 max, and CAN*VO2 max interaction predicted neuropsychological performance, controlling for past-year alcohol use, cotinine, gender, and depression symptoms. RESULTS: Increased CAN use was associated with decreased performance on working memory and psychomotor tasks. High aerobic fitness level was related to better performance on visual memory, verbal fluency, and sequencing ability. CAN*VO2 max predicted performance of psychomotor speed, visual memory, and sequencing ability. CONCLUSIONS: Following monitored abstinence, increased CAN use was associated with poorer performance in working memory and psychomotor speed. Higher aerobic fitness level moderated the impact of CAN on visual memory, executive function and psychomotor speed, as more aerobically fit CAN users demonstrated better performance relative to low-fit users. Therefore, aerobic fitness may present an affordable and efficacious method to improve cognitive functioning in CAN users. (JINS, 2019, 25, 134-145).

The Atomic, Molecular and Optical Science instrument at the Linac Coherent Light Source.

The Atomic, Molecular and Optical Science (AMO) instrument at the Linac Coherent Light Source (LCLS) provides a tight soft X-ray focus into one of three experimental endstations. The flexible instrument design is optimized for studying a wide variety of phenomena requiring peak intensity. There is a suite of spectrometers and two photon area detectors available. An optional mirror-based split-and-delay unit can be used for X-ray pump-probe experiments. Recent scientific highlights illustrate the imaging, time-resolved spectroscopy and high-power density capabilities of the AMO instrument.

Amygdala Volume and Depression Symptoms in Young Adolescents Who Use Cannabis.

INTRODUCTION: Both cannabis use and depressive symptomology increase in prevalence throughout adolescence. Concurrently, the brain is undergoing neurodevelopment in important limbic regions, such as the amygdala. Prior research indicates the amygdala may also be related to cannabis use and depressive symptoms. We aimed to investigate the effects of adolescent cannabis use on amygdala volumes as well as the interaction of cannabis use and amygdala morphometry on depressive symptoms in youth. METHOD: Two-hundred-twenty-four participants (ages 12-15), balanced by sex assigned at birth, were selected from a sub-sample of the Adolescent Brain Cognitive Development (ABCD) Study based on hair toxicology and self-report measures of cannabis use. Participants positive for cannabinoids in hair and/or self-reported cannabis use were demographically matched to youth with no self-reported or confirmed cannabis use. The guardians of these youth reported depression symptoms on the Child Behavioral Checklist. Linear mixed effect models were run investigating cannabis use group on amygdala volumes bilaterally, controlling for whole brain volume and random effects of scanner type. Additional analyses examined cannabis group status and bilateral amygdala volume on depression symptoms. RESULTS: Cannabis use was not significantly associated with amygdala volume but was associated with increased depressive symptoms (p<0.01). Cannabis group interacted with amygdala volume, such that individuals with smaller volumes had increased depressive symptoms within the cannabis group (p's<0.01-0.02). CONCLUSION: Aberrations in amygdala volume based on cannabis use were not found in early adolescence; however, more depressive symptoms were related to cannabis group. Youth who use cannabis and have smaller amygdala volumes were at increased risk for depressive symptomology, suggesting potential neurovulnerabilities to cannabis use.

New forceps free injection technique for delivering descemet membrane endothelial keratoplasty preloaded endothelium-in grafts.

PURPOSE: To describe a new method for delivering DMEK grafts into the recipient's eye with endothelium inward configuration using a no-forceps injection technique. METHODS: We retrospectively review 11 patients that underwent DMEK surgery at our institution using a no-forceps injection technique. The graft was preloaded into an intraocular lens (IOL) cartridge and connected to an anterior chamber maintainer (ACM). A 5 ml non luer lock syringe was inserted into the other end of the ACM to create a one-flow system. The cartridge was inserted into the posterior end of an injector, and the graft was successfully delivered into the recipient's eye. RESULT: Twelve eyes of 11 patients were included. Mean follow-up was 9.16 ± 1.3 months. At baseline, mean best corrected visual acuity (BCVA) was 0.76 ± 0.13 logMAr and mean endothelial cell density (ECD) was 2619.00 ± 115.89 cells/mm2. At follow-up, BCVA significantly improved to 0.22 ± 0.05 logMAR (p = 0.003). Although we observed a significant reduction in ECD at follow-up (1688 ± 182.20, p = 0.002), our patients lost only 35.69 ± 6.36% of endothelial cells. CONCLUSION: Our technique can help surgeons safely deliver an endothelium-in graft into the recipient's eye. The method doesn't require the use of a forceps, minimizing the risk of endothelial cell loss or graft damage.

Performance outcomes from a DMEK peeling and preparation wet lab.

OBJECTIVE: To evaluate the Descemet membrane endothelial keratoplasty (DMEK) preparation performance of trainee surgeons in an ex vivo human donor cornea DMEK wet lab simulation setting. METHODS: Human donor corneoscleral rims unsuitable for transplantation were obtained from Moorfields Lions Eye Bank. At the wet lab, graft stripping was performed by scoring the peripheral endothelium. The trypan blue positive cells (TBPC) and cell density (cells/mm2-reticule count) were counted manually before and after stripping. The procedural time, peripheral and central tears and complete peel-off were also recorded and analysed. RESULTS: Eight trainee surgeons attended the wet lab each attempting three DMEKs. Between the first and last attempts a significant decrease was seen in the procedural time (17.6 min vs 10.6 min (p<0.05)) and the TBPC % (12.9% vs 3.8% (p<0.05)). The percentage of tears peripherally and centrally also reduced between the first and the last trials (50% vs 13% (p=0.2226) and 38% vs 0% (p=0.1327)). A significant correlation was found between longer peeling times and higher TBPC % (p<0.001) with a 0.7% endothelial mortality increase for each additional minute required to complete the peel. CONCLUSIONS: DMEK wet labs provide a controlled risk-free learning opportunity for trainee surgeons to improve confidence and competence. Wet labs improve the success rate of DMEK graft preparation as well as flatten the learning curve. This emphasises the importance of continued support for the expansion of this valuable learning resource, promoting wider uptake of DMEK surgery.

Investigating sex differences and age of onset in emotion regulation, executive functioning, and cannabis use in adolescents and young adults.

BACKGROUND: Young adults have historically high levels of cannabis use at a time which coincides with emotional and cognitive development. Age of regular onset of cannabis use and sex at birth are hypothesized to influence the relationship between cannabis use and cognition. Here we investigated past 6-month cannabis use in relation to emotional and executive functioning. We further considered age of onset and sex in subgroup analyses. METHOD: Young adults (N = 225; ages 16-22) completed a substance use interview and cognitive battery, including the Emotional Word-Emotional Face Stroop and NIH toolbox executive functioning tasks. Linear regressions examined relationships between past 6-month cannabis use episodes and performance. Subgroup analyses investigated whether age of onset or sex impacted relationships. RESULTS: After correcting for multiple comparisons, greater past 6-month cannabis use episodes were related to poorer Emotional Stroop Congruent Accuracy (p = .0004, FDR-p = .002) and List Sorting Working Memory (p = .02, FDR-p = .10) performance. Younger age of regular use onset marginally related to lower Emotional Stroop Congruent Accuracy performance (p = .03, FDR-p = .13). There were no cannabis use by sex interactions on cognition. CONCLUSIONS: Consistent with prior findings, results suggest small reductions in cannabis-related performance in processing speed during emotional Stroop and working memory tasks. Age of onset was modestly related to Stroop performance, but not sex. Longitudinal studies which detail patterns of cannabis and other substance use are needed to better assess brain-behavior relationships and other factors (e.g., age of onset of regular use, sex) which could influence cannabis-related impairments in cognitive functioning.

Commercial Cannabidiol for Community-Based Young Adolescents: Predicting Medicinal Use.

Objectives: Cannabidiol (CBD) is rising in popularity, including as a potential medicinal product. Yet data on use of commercial CBD for medicinal or health reasons in adolescents are lacking. In this study we aim to detail characteristics of adolescents given commercial CBD for health reasons (health CBD [hCBD]) and to investigate predictors of use. Materials and Methods: The Adolescent Brain Cognitive Development (ABCD) Study is a population-based cohort study following U.S. healthy, community-based adolescents annually, with data from 2018 to 2022 (11- to 15-year-olds; N=11,189). Participants and caregivers completed questionnaires, including whether adolescents were given CBD with parent or doctor's permission. Participants reported past-month pain, attention problems, externalizing symptoms, internalizing symptoms, and total mental health problems. Caregivers reported youth sociodemographics, sleep problems, whether the youth had mental health treatment or sought medical treatment, and rules about recreational cannabis use. We describe youth given hCBD, and run generalized estimating equations predicting odd ratios (ORs) and 95% confidence intervals of adolescents given hCBD by mental health, physical health, or sociodemographics of factors. Results: Of the 11,189 participants across up to three waves of data, 48% were female. Mean age across waves was 12.8 years old (SD=1). In total, 307 (2.8%) were given hCBD. Common administration methods were oil (42%), topical (31%), and edibles (29%). Increased hCBD odds were associated with being older (OR=1.32 [1.17-1.49]), White (relative to Black, OR=05.97 [2.81-12.65] or Hispanic, OR=1.82 [1.17-2.82]), parents with some college (relative to no high school diploma, OR=3.55 [1.09-11.6]), internalizing symptoms (OR=1.81 [1.13-2.91]), mental health treatment (OR=1.76 [1.3-2.38]), pain (OR=1.38 [1.09-1.76]), medical treatment (OR=1.39 [1.08-1.79]), and sleep problems (OR=1.69 [1.27-2.25]). Rules against recreational cannabis decreased odds of hCBD (OR=1.75 [1.30-2.36]). Conclusions: Findings indicate some healthy adolescents are given hCBD, and predictors of use include mental and physical health concerns, being White, older, and parents with some college education. Providers should ask if their youth patients are being given CBD medicinally, and transparently discuss potential benefits, consequences, and unknowns of CBD.

Cannabis use and neurocognitive performance at 13-14 Years-Old: Optimizing assessment with hair toxicology in the Adolescent brain cognitive development (ABCD) study.

OBJECTIVE: Cannabis is widely used, including in early adolescence, with prevalence rates varying by measurement method (e.g., toxicology vs. self-report). Critical neurocognitive development occurs throughout adolescence. Given conflicting prior brain-behavior results in cannabis research, improved measurement of cannabis use in younger adolescents is needed. METHODS: Data from the Adolescent Brain Cognitive Development (ABCD) Study Year 4 follow-up (participant age: 13-14 years-old) included hair samples assessed by LC-MS/MS and GC-MS/MS, quantifying THCCOOH (THC metabolite), THC, and cannabidiol concentrations, and the NIH Toolbox Cognitive Battery. Youth whose hair was positive for cannabinoids or reported past-year cannabis use were included in a Cannabis Use (CU) group (n = 123) and matched with non-using Controls on sociodemographics (n = 123). Standard and nested ANCOVAs assessed group status predicting cognitive performance, controlling for family relationships. Follow-up correlations assessed cannabinoid hair concentration, self-reported cannabis use, and neurocognition. RESULTS: CU scored lower on Picture Memory (p = .03) than Controls. Within the CU group, THCCOOH negatively correlated with Picture Vocabulary (r = -0.20, p = .03) and Flanker Inhibitory Control and Attention (r = -0.19, p = .04), and past-year cannabis use was negatively associated with List Sorting Working Memory (r = -0.33, p = .0002) and Picture Sequence Memory (r = -0.19, p = .04) performances. CONCLUSIONS: Youth who had used cannabis showed lower scores on an episodic memory task, and more cannabis use was linked to poorer performances on verbal, inhibitory, working memory, and episodic memory tasks. Combining hair toxicology with self-report revealed more brain-behavior relationships than self-report data alone. These youth will be followed to determine long-term substance use and neurocognition trajectories.

A preliminary investigation of physical and mental health features of cannabis & nicotine co-use among adolescents and young adults by sex.

INTRODUCTION: Cannabis and nicotine/tobacco products (NTP) are commonly co-used in adolescence and young adulthood; however, limited research has been done on predictive health behaviors to co-use. The current study is a preliminary investigation into the relationships of modifiable health behaviors on cannabis and NTP co-use in adolescents and young adults. METHOD: 221 participants (ages 16-22) were characterized into cannabis use only (N = 55), NTP use only (N = 20), cannabis and NTP co-use (used cannabis and NTP; N = 96) and control (no use; N = 50) groups based on past 30-day use. Self-report measures for physical activity, sleep quality, mental health, and reward responsivity were utilized. Participants were given a comprehensive neurocognitive battery. Logistic regressions of self-report measures and fluid intelligence composite scores on substance use group status were run stratified by sex. RESULTS: Higher approach reward sensitivity traits were associated with increased likelihood of cannabis use only (Odds Ratio (OR) = 1.15, p = .036) in female participants. Increased aerobic activity was associated with decreased likelihood of cannabis use only (OR = 0.91, p = .047) and cannabis and NTP co-use (OR = 0.88, p = .007) in female participants. Higher anxiety was associated with increased likelihood of cannabis NTP co-use (OR = 1.51, p = 0.025) in male participants. DISCUSSION: Several health behaviors were linked with cannabis use and cannabis and NTP co-use in both females and male adolescents and young adults. Health markers differed by sex suggesting differing mechanisms of substance co-use. This study informs targetable health behaviors for prevention and intervention efforts.

Childhood adversity is associated with reduced BOLD response in inhibitory control regions amongst preadolescents from the ABCD study.

Adolescence is characterized by dynamic neurodevelopment, which poses opportunities for risk and resilience. Adverse childhood experiences (ACEs) confer additional risk to the developing brain, where ACEs have been associated with alterations in functional magnetic resonance imaging (fMRI) BOLD signaling in brain regions underlying inhibitory control. Socioenvironmental factors like the family environment may amplify or buffer against the neurodevelopmental risks associated with ACEs. Using baseline to Year 2 follow-up data from the Adolescent Brain Cognitive Development (ABCD) Study, the current study examined how ACEs relate to fMRI BOLD signaling during successful inhibition on the Stop Signal Task in regions associated with inhibitory control and examined whether family conflict levels moderated that relationship. Results showed that greater ACEs were associated with reduced BOLD response in the right opercular region of the inferior frontal gyrus and bilaterally in the pre-supplementary motor area, which are key regions underlying inhibitory control. Further, greater BOLD response was correlated with less impulsivity behaviorally, suggesting reduced activation may not be behaviorally adaptive at this age. No significant two or three-way interactions with family conflict levels or time were found. Findings highlight the continued utility of examining the relationship between ACEs and neurodevelopmental outcomes and the importance of intervention/prevention of ACES.

Neurite Orientation Dispersion and Density Imaging (NODDI) of Brain Microstructure in Adolescent Cannabis and Nicotine Use.

INTRODUCTION: Despite evidence suggesting deleterious effects of cannabis and nicotine tobacco product (NTP) use on white matter integrity, there have been limited studies examining white matter integrity among users of both cannabis and nicotine. Further, updated white matter methodology provides opportunities to investigate use patterns on neurite orientation dispersion and density (NODDI) indices and subtle tissue changes related to the intra- and extra-neurite compartment. We aimed to investigate how cannabis and NTP use among adolescents and young adults interacts to impact the white matter integrity microstructure. MATERIALS AND METHODS: A total of 221 participants between the ages of 16 and 22 completed the Customary Drinking and Drug Use Record (CDDR) to measure substance use, and underwent a magnetic resonance imaging (MRI) session. Participants were divided into NTP-control and NTP groupings and cannabis-control and cannabis groupings (≥26 NTP/cannabis uses in past 6 months). Tract-Based Spatial Statistics (TBSS) and two-way between-subjects ANOVA investigated the effects of NTP use group, cannabis use group, and their interaction on fractional anisotropy (FA) and NODDI indices while controlling for age and biological sex. RESULTS: NTP use was associated with decreased FA values and increased orientation dispersion in the left anterior capsule. There were no significant effects of cannabis use or the interaction of NTP and cannabis use on white matter outcomes. DISCUSSION: NTP use was associated with altered white matter integrity in an adolescent and young adult sample. Findings suggest that NTP-associated alterations may be linked to altered fiber tract geometry and dispersed neurite structures versus myelination, as well as differential effects of NTP and cannabis use on white matter structure. Future work is needed to investigate how altered white matter is related to downstream behavioral effects from NTP use.

The Combined Effects of Nicotine and Cannabis on Cortical Thickness Estimates in Adolescents and Emerging Adults.

Early life substance use, including cannabis and nicotine, may result in deleterious effects on the maturation of brain tissue and gray matter cortical development. The current study employed linear regression models to investigate the main and interactive effects of past-year nicotine and cannabis use on gray matter cortical thickness estimates in 11 bilateral independent frontal cortical regions in 223 16-22-year-olds. As the frontal cortex develops throughout late adolescence and young adulthood, this period becomes crucial for studying the impact of substance use on brain structure. The distinct effects of nicotine and cannabis use status on cortical thickness were found bilaterally, as cannabis and nicotine users both had thinner cortices than non-users. Interactions between nicotine and cannabis were also observed, in which cannabis use was associated with thicker cortices for those with a history of nicotine and tobacco product (NTP) use in three left frontal regions. This study sheds light on the intricate relationship between substance use and brain structure, suggesting a potential modulation of cannabis' impact on cortical thickness by nicotine exposure, and emphasizing the need for further longitudinal research to characterize these interactions and their implications for brain health and development.

Hispanic/Latinx ethnic differences in the relationships between behavioral inhibition, anxiety, and substance use in youth from the ABCD cohort.

Introduction: Elevated levels of behavioral inhibition (BI) may connote risk for both anxiety and substance use disorders. BI has consistently been shown to be associated with increased levels of anxiety, while the association between BI and substance use has been mixed. It is possible that the relationship between BI and substance use varies by individual difference factors. Hispanic/Latinx (H/L) youth in particular may have stronger relationships between BI, anxiety, and substance use. Methods: The present study therefore evaluated (1) the prospective relationships between BI [assessed via self-reported behavioral inhibition system (BIS) scale scores], anxiety, and substance use in youth (n = 11,876) across baseline, 1-, and 2-year follow-ups of the Adolescent Brain Cognitive Development (ABCD) Study (ages 9-12) and (2) whether these relationships differed by H/L ethnicity while covarying for average behavioral approach system scores, race, sex, age, highest parental income, highest parental education, and past-year substance use (for analyses involving substance use outcomes). Results: Baseline levels of BIS scores predicted increased anxiety symptoms at both 1- and 2-year follow-ups and did not differ by H/L ethnicity. Baseline levels of BIS scores also prospectively predicted increased likelihood of substance use at 2-year follow-up, but only for H/L youth and not at 1-year follow-up. Discussion: High scores on the BIS scale contribute risk to anxiety across ethnicities and may uniquely contribute to risk for substance use in H/L youth.