Clouding Up Cognition? Secondhand Cannabis and Tobacco Exposure Related to Cognitive Functioning in Youth.

Background: Increasing legalization of cannabis, in addition to longstanding rates of tobacco use, raises concerns for possible cognitive decrements from secondhand smoke or environmental exposure, although little research exists. We investigate the relation between cognition and secondhand and environmental cannabis and tobacco exposure in youth. Methods: The Adolescent Brain Cognitive Development (ABCD) Study year 2 follow-up (N = 5580; 48% female) cognitive performance and secondhand or environmental cannabis or tobacco exposure data were used. Principal components analysis identified a global cognition factor. Linear mixed-effects models assessed global cognition and individual cognitive task performance by cannabis and/or tobacco environmental exposure. Sociodemographics and other potential confounds were examined. p values were adjusted using the false discovery rate method. Results: Global cognition was not related to any exposure group after testing corrections and considering confounds. Beyond covariates and family- and site-level factors, secondhand tobacco was related to poorer visual memory (p = .02), and environmental tobacco was associated with poorer visuospatial (p = .02) and language (p = .008) skills. Secondhand cannabis was related to cognition, but not after controlling for potential confounders (p > .05). Environmental cannabis was related to better oral reading (p = .01). Including covariates attenuated effect sizes. Conclusions: Secondhand tobacco exposure was associated with poorer visual memory, while environmental tobacco exposure was related to poorer language and visuospatial skills. Secondhand cannabis was not related to cognition after controlling for sociodemographic factors, but environmental cannabis exposure was related to better reading. Because, to our knowledge, this is the first known study of its kind and thus preliminary, secondhand cannabis should continue to be investigated to confirm results.

Preliminary Evidence for Cannabis and Nicotine Urinary Metabolites as Predictors of Verbal Memory Performance and Learning Among Young Adults.

OBJECTIVE: Verbal memory deficits are linked to cannabis use. However, self-reported episodic use does not allow for assessment of variance from other factors (e.g., cannabis potency, route of consumption) that are important for assessing brain-behavior relationships. Further, co-occurring nicotine use may moderate the influence of cannabis on cognition. Here we utilized objective urinary measurements to assess the relationship between metabolites of cannabis, 11-nor-9-carboxy-∆9-tetrahydrocannabinol (THCCOOH), and nicotine (cotinine) on verbal memory in young adults. METHOD: Adolescents and young adults (n = 103) aged 16-22 completed urinary drug testing and verbal memory assessment (RAVLT). Linear regressions examined the influence of THCCOOH and cotinine quantitative concentrations, and their interaction, on RAVLT scores, controlling for demographics and alcohol. Cannabis intake frequency was also investigated. Secondary analyses examined whether past month or recency of use related to performance, while controlling for THCCOOH and cotinine concentrations. RESULTS: THCCOOH concentration related to both poorer total learning and long delay recall. Cotinine concentration related to poorer short delay recall. Higher frequency cannabis use status was associated with poorer initial learning and poorer short delay. When comparing to self-report, THCCOOH and cotinine concentrations were negatively related to learning and memory performance, while self-report was not. CONCLUSIONS: Results confirm the negative relationship between verbal memory and cannabis use, extending findings with objective urinary THCCOOH, and cotinine concentration measurements. No moderating relationship with nicotine was found, though cotinine concentration independently associated with negative short delay performance. Findings support the use of both urinary and self-report metrics as complementary methods in substance use research.

Child reward neurocircuitry and parental substance use history: Findings from the Adolescent Brain Cognitive Development Study.

BACKGROUND: Substance use research has focused on family history of alcohol use disorders but less on other addictions in biological family members. We examined how parental substance use history relates to reward system functioning, specifically nucleus accumbens (NAcc) and putamen activation at age 9-10 in the Adolescent Brain Cognitive Development (ABCD) Study. This research hopes to address limitations in prior literature by focusing analyses on a large, substance-naïve sample. METHOD: We included ABCD participants with valid Monetary Incentive Delay task fMRI Baseline data and parent substance use history at project baseline from Data Release 2.0 (N = 10,622). Parent-history-positive (PH+) participants had one or both biological parents with a history of two+problems with alcohol (n = 741; PH+A) and/or other drugs (n = 638; PH+D). Of participants who were parent-history-negative (PH-) for alcohol and/or drugs, a stratified random sample based on six sociodemographic variables was created and matched to the PH+group (PH-A n = 699; PH-D n = 615). The contrast of interest was anticipation of a large reward vs. neutral response. RESULTS: PH+A youth had more activation in the right NAcc during large reward anticipation than PH-A. PH+D youth showed enhanced left putamen activation during large reward anticipation than PH-D youth. Bayesian hypothesis testing showed moderate evidence (BF > 3) in favor of the null hypothesis. CONCLUSION: These findings suggest that pre-adolescents whose biological parents had a history of substance-related problems show small differences in reward processing compared to their PH- peers.

Risk factors associated with curiosity about alcohol use in the ABCD cohort.

Curiosity and intent to use alcohol in pre-adolescence is a risk factor for later experimentation and use, yet we know little of how curiosity about use develops. Here, we examine factors that may influence curiosity about alcohol use, as it may be an important predictor of later drinking behavior. Cross-sectional data on youth ages 10-11 from the ongoing Adolescent Brain Cognitive Development℠ (ABCD) Study Year 1 follow-up were used (n = 2,334; NDA 2.0.1). All participants were substance-naïve at time of assessment. Group factor analysis identified latent factors across common indicators of risk for early substance use (i.e., psychopathology and trait characteristics; substance use attitudes/behaviors; neurocognition; family and environment). Logistic mixed-effect models tested associations between latent factors of risk for early substance use and curiosity about alcohol use, controlling for demographics and study site. Two multidimensional factors were significantly inversely and positively associated with greater curiosity about alcohol use, respectively: 1) low internalizing and externalizing symptomatology coupled with low impulsivity, perceived neighborhood safety, negative parental history of alcohol use problems, and fewer adverse life experiences and family conflict; and 2) low perceived risk of alcohol use coupled with lack of peer disapproval of use. When assessing all risk factors in an overall regression, lack of perceived harm from trying alcohol once or twice was associated with greater likelihood of alcohol curiosity. Taken together, perceptions that alcohol use causes little harm and having peers with similar beliefs is related to curiosity about alcohol use among substance-naïve 10-11-year-olds. General mental health and environmental risk factors similarly increase the odds of curiosity for alcohol. Identification of multidimensional risk factors for early alcohol use may point to novel prevention and early intervention targets. Future longitudinal investigations in the ABCD cohort will determine the extent to which these factors and curiosity predict alcohol use among youth.

Cross-Sectional Analysis of Spatial Working Memory Development in Children with Histories of Heavy Prenatal Alcohol Exposure.

BACKGROUND: In children with prenatal alcohol exposure, spatial working memory is affected and brain regions important for spatial working memory performance exhibit atypical neurodevelopment. We therefore hypothesized that children with prenatal alcohol exposure may also have atypical development of spatial working memory ability. METHODS: We examined the relation between spatial working memory and age using a cross-sectional developmental trajectory approach in youth with and without histories of heavy prenatal alcohol exposure. The Cambridge Neuropsychological Test Automated Battery Spatial Working Memory subtest was administered to children 5.0 to 16.9 years old. RESULTS: While the controls and children with prenatal alcohol exposure showed similar performance at younger ages, larger group differences were observed in older children. This effect was replicated in a separate sample. CONCLUSIONS: The atypical brain development that has previously been reported in children with heavy prenatal alcohol exposure may have clinically relevant implications for cognitive development; however, longitudinal cognitive analyses are needed.

Correspondence Between Perceived Pubertal Development and Hormone Levels in 9-10 Year-Olds From the Adolescent Brain Cognitive Development Study.

Aim: To examine individual variability between perceived physical features and hormones of pubertal maturation in 9-10-year-old children as a function of sociodemographic characteristics. Methods: Cross-sectional metrics of puberty were utilized from the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) Study-a multi-site sample of 9-10 year-olds (n = 11,875)-and included perceived physical features via the pubertal development scale (PDS) and child salivary hormone levels (dehydroepiandrosterone and testosterone in all, and estradiol in females). Multi-level models examined the relationships among sociodemographic measures, physical features, and hormone levels. A group factor analysis (GFA) was implemented to extract latent variables of pubertal maturation that integrated both measures of perceived physical features and hormone levels. Results: PDS summary scores indicated more males (70%) than females (31%) were prepubertal. Perceived physical features and hormone levels were significantly associated with child's weight status and income, such that more mature scores were observed among children that were overweight/obese or from households with low-income. Results from the GFA identified two latent factors that described individual differences in pubertal maturation among both females and males, with factor 1 driven by higher hormone levels, and factor 2 driven by perceived physical maturation. The correspondence between latent factor 1 scores (hormones) and latent factor 2 scores (perceived physical maturation) revealed synchronous and asynchronous relationships between hormones and concomitant physical features in this large young adolescent sample. Conclusions: Sociodemographic measures were associated with both objective hormone and self-report physical measures of pubertal maturation in a large, diverse sample of 9-10 year-olds. The latent variables of pubertal maturation described a complex interplay between perceived physical changes and hormone levels that hallmark sexual maturation, which future studies can examine in relation to trajectories of brain maturation, risk/resilience to substance use, and other mental health outcomes.

Neuropsychological Trajectories Associated with Adolescent Alcohol and Cannabis Use: A Prospective 14-Year Study.

OBJECTIVES: Alcohol and cannabis remain the substances most widely used by adolescents. Better understanding of the dynamic relationship between trajectories of substance use in relation to neuropsychological functioning is needed. The aim of this study was to examine the different impacts of within- and between-person changes in alcohol and cannabis use on neuropsychological functioning over multiple time points. METHODS: Hierarchical linear modeling examined the effects of alcohol and cannabis use on neuropsychological functioning over the course of 14 years in a sample of 175 adolescents (aged 12-15 years at baseline). RESULTS: Time-specific fluctuations in alcohol use (within-person effect) predicted worse performance across time on the Wechsler Abbreviated Scale of Intelligence Block Design subtest (B = -.05, SE = .02, p = .01). Greater mean levels of percent days of cannabis use across time (between-person effect) were associated with an increased contrast score between Delis-Kaplan Executive Function System Color Word Inhibition and Color Naming conditions (B = .52, SE = .14, p < .0001) and poorer performance over time on Block Design (B = -.08, SE = .04, p = .03). Neither alcohol and/nor cannabis use over time was associated with performance in the verbal memory and processing speed domains. CONCLUSIONS: Greater cumulative cannabis use over adolescence may be linked to poorer inhibitory control and visuospatial functioning performance, whereas more proximal increases in alcohol consumption during adolescence may drive alcohol-related performance decrements in visuospatial functioning. Results from this prospective study add to the growing body of literature on the impact of alcohol and cannabis use on cognition from adolescent to young adulthood.

Shared gray matter reductions across alcohol use disorder and posttraumatic stress disorder in the anterior cingulate cortex: A dual meta-analysis.

The considerable comorbidity of posttraumatic stress disorder (PTSD) and alcohol use disorders (AUD) poses a greater public health burden than either condition alone. Although there is a substantial body of evidence linking the direct neurotoxic effect of heavy drinking to gray matter (GM) deficits, as well as a growing body of literature supporting a strong association between PTSD and GM alterations, there is scant research interrogating the direct interaction of the two disorders. In order to generate data-driven, specific hypotheses regarding the overlapping neural substrates of PTSD and AUD, we conducted a meta-analysis of GM volumes in each disorder relative to healthy control subjects. We found shared GM deficits in the anterior cingulate cortex (ACC) across both disorders relative to healthy control participants. These findings suggest that reduced volumes of the ACC across PTSD and AUD may have implications for the development, expression, or treatment of symptoms linked to these frequently co-existing disorders. Recommendations are made for future work aimed at delineating the specific and shared effects of traumatic stress and alcoholism on neural integrity.

Adolescent Brain Surface Area Pre- and Post-Cannabis and Alcohol Initiation.

OBJECTIVE: Changes in gray matter volume and thickness are associated with adolescent alcohol and cannabis use, but the impact of these substances on surface area remains unclear. The present study expands on previous findings to examine the impact of alcohol and cannabis on surface area before and after use initiation. METHOD: Scans for 69 demographically similar youth were obtained at baseline (ages 12-14 years; before substance use) and at 6-year follow-up (ages 17-21 years). Participants were classified into three groups based on substance use: alcohol use initiators (ALC, n = 23), alcohol and cannabis use initiators (ALC+CU, n = 23), and individuals with minimal substance use (<3 lifetime alcohol and 0 marijuana use episodes; CON, n = 23). For each hemisphere, group differences in surface area across time (pre- and post-substance use initiation) and significant group-by-time interactions were examined individually for 34 cortical regions using repeated measures analysis of covariance. A vertex-wise analysis assessed group differences in surface area percent change. RESULTS: A significant group-by-time interaction was found in three regions, bilateral medial orbitofrontal cortices and right insula. Although all regions showed decreases in surface area over time (ps < .05), a more substantial decrease was identified in the ALC group. Of note, the right medial orbitofrontal cortex survived the conservative vertex-wise analyses (p < .001), as a more substantial decrease was found in the ALC compared to the ALC+CU group in this region. CONCLUSIONS: Surface area in the medial orbitofrontal cortex may be a useful intermediate phenotype for exploring the mechanisms underlying the effects of substance use on brain development.

Altered functional connectivity during spatial working memory in children with heavy prenatal alcohol exposure.

Individuals prenatally exposed to alcohol often have impaired spatial working memory (SWM). This study examines functional connections of frontal and parietal regions that support SWM in children with and without prenatal alcohol exposure. Children ages 10 to 16 with histories of heavy prenatal alcohol exposure (AE group; n = 18) and controls (CON group; n = 19) underwent functional magnetic resonance imaging (fMRI) while performing a SWM task. Whole brain task-related functional connectivity of bilateral dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC) seed regions were estimated for each participant using a psychophysiological interaction approach. Children in the AE group were less accurate than children in the CON group when performing the SWM task (p = 0.008). Positive coupling between bilateral DLPFC seeds and regions within the fronto-parietal network was observed in the CON group, whereas the AE group showed negative connectivity. In contrast to the CON group, the AE group showed positive connectivity between PPC seeds and frontal lobe regions. Across seeds, decreased negative coupling with regions outside the fronto-parietal network (e.g., left middle occipital gyrus) were observed in the AE group relative to the CON group. Functional data clusters were considered significant at p < 0.05. Overall findings suggest that localized alterations in neural activity, aberrant fronto-parietal network synchrony, and poor coordination of neural responses with regions outside of this network may help explain SWM deficits in individuals with a history of heavy prenatal alcohol exposure.

Pituitary lacks sexual dimorphism and displays reduced signal intensity on T1-weighted MRI in adolescents with histories of heavy prenatal alcohol exposure.

Prenatal alcohol exposure can interfere with endocrine function and have sex-specific effects on behavior. Disrupted development of the pituitary gland, which has been observed in rodent studies, may account for some of these effects. To determine if gestational exposure to alcohol produces measureable changes in the pituitary in human adolescents, we manually traced the pituitary in T1-weighted structural magnetic resonance images (MRI) from adolescents with (15 males, 11 females) and without (16 males, 11 females) heavy prenatal alcohol exposure. Pituitary gland volume and maximum signal intensity were examined for group differences. Control female adolescents presented with significantly greater pituitary volume compared to males, as has been previously reported. However, this sexual dimorphism was absent in adolescents with histories of prenatal alcohol exposure. Alcohol-exposed adolescents, regardless of sex, demonstrated reduced pituitary maximum signal intensity compared to controls. The lack of a sex difference in pituitary volumes within the alcohol-exposed group suggests such exposure may interfere with adolescent typical sexual dimorphism of the pituitary. Signal intensity in the posterior pituitary may reflect vasopressin storage. Our findings suggest vasopressin activity should be evaluated in alcohol-exposed adolescents.

Atypical cortical gyrification in adolescents with histories of heavy prenatal alcohol exposure.

Prenatal alcohol exposure can adversely affect brain development, although little is known about the effects of prenatal alcohol exposure on gyrification. Gyrification reflects cortical folding complexity and is a process by which the surface of the brain creates sulci and gyri. Prior studies have shown that prenatal alcohol exposure is associated with reduced gyrification in childhood, but no studies have examined adolescents. Subjects (12-16 years) comprised two age-equivalent groups: 30 adolescents with histories of heavy prenatal alcohol exposure (AE) and 19 non-exposed controls (CON). A T1-weighted image was obtained for all participants. Local gyrification index (LGI) was estimated using FreeSurfer. General linear models were used to determine between group differences in LGI controlling for age and sex. Age-by-group interactions were also investigated while controlling for sex. The AE group displayed reduced LGI relative to CON in the bilateral superior parietal region, right postcentral region, and left precentral and lateral occipital regions (ps<.001). Significant age-by-group interactions were observed in the right precentral and lateral occipital regions, and in the left pars opercularis and inferior parietal regions (ps<.01). The AE group showed age-related reductions in gyrification in all regions whereas the CON group showed increased gyrification with age in the lateral occipital region only. While cross-sectional, the age-related reduction in gyrification observed in the AE group suggests alterations in cortical development throughout adolescence and provides further insight into the pathophysiology and brain maturation of adolescents prenatally exposed to alcohol.

Anterior cingulate cortex surface area relates to behavioral inhibition in adolescents with and without heavy prenatal alcohol exposure.

Prenatal alcohol exposure is associated with behavioral disinhibition, yet the brain structure correlates of this deficit have not been determined with sufficient detail. We examined the hypothesis that the structure of the anterior cingulate cortex (ACC) relates to inhibition performance in youth with histories of heavy prenatal alcohol exposure (AE, n = 32) and non-exposed controls (CON, n = 21). Adolescents (12-17 years) underwent structural magnetic resonance imaging yielding measures of gray matter volume, surface area, and thickness across four ACC subregions. A subset of subjects were administered the NEPSY-II Inhibition subtest. MANCOVA was utilized to test for group differences in ACC and inhibition performance and multiple linear regression was used to probe ACC-inhibition relationships. ACC surface area was significantly smaller in AE, though this effect was primarily driven by reduced right caudal ACC (rcACC). AE also performed significantly worse on inhibition speed but not on inhibition accuracy. Regression analyses with the rcACC revealed a significant group × ACC interaction. A smaller rcACC surface area was associated with slower inhibition completion time for AE but was not significantly associated with inhibition in CON. After accounting for processing speed, smaller rcACC surface area was associated with worse (i.e., slower) inhibition regardless of group. Examining processing speed independently, a decrease in rcACC surface area was associated with faster processing speed for CON but not significantly associated with processing speed in AE. Results support the theory that caudal ACC may monitor reaction time in addition to inhibition and highlight the possibility of delayed ACC neurodevelopment in prenatal alcohol exposure.

Neuropsychological performance in adolescent marijuana users with co-occurring alcohol use: A three-year longitudinal study.

OBJECTIVE: The effect of adolescent marijuana use on brain development remains unclear despite relaxing legal restrictions, decreased perceived harm, and increasing use rates among youth. The aim of this 3-year prospective study was to evaluate the long-term neurocognitive effects of adolescent marijuana use. METHOD: Adolescent marijuana users with concomitant alcohol use (MJ + ALC, n = 49) and control teens with limited substance use histories (CON, n = 59) were given neuropsychological and substance use assessments at project baseline, when they were ages 16-19. They were then reassessed 18 and 36 months later. Changes in neuropsychological measures were evaluated with repeated measures analysis of covariance (ANCOVA), controlling for lifetime alcohol use, and examined the effects of group, time, and group by time interactions on cognitive functioning. RESULTS: MJ + ALC users performed significantly worse than controls, across time points, in the domains of complex attention, memory, processing speed, and visuospatial functioning (ps <.05). Earlier age of marijuana use onset was associated with poorer processing speed and executive functioning by the 3-year follow-up (ps ≤.02). CONCLUSIONS: Frequent marijuana use throughout adolescence and into young adulthood appeared linked to worsened cognitive performance. Earlier age of onset appears to be associated with poorer neurocognitive outcomes that emerge by young adulthood, providing further support for the notion that the brain may be uniquely sensitive to frequent marijuana exposure during the adolescent phase of neurodevelopment. Continued follow-up of adolescent marijuana users will determine the extent of neural recovery that may occur if use abates.

Objective assessment of ADHD core symptoms in children with heavy prenatal alcohol exposure.

Attention deficits are often observed in children with prenatal alcohol exposure and attention-deficit/hyperactivity disorder (ADHD) is commonly diagnosed in this population. This study used an objective assessment tool to examine differences between alcohol-exposed and non-exposed children on core symptoms of ADHD: inattention, impulsivity, and hyperactivity. Two groups of individuals, aged 7-14years, participated in the study: alcohol-exposed children (AE, n=43), and non-exposed children (CON, n=54). Subjects were evaluated with the Quotient ADHD System, which provides objective data on ADHD core symptoms by combining an infrared motion tracking system and a computerized continuous performance task. Twelve separate ANCOVAs controlling for the effects of age and sex, were conducted on attention and motion variables. Results revealed that in comparison to the CON group, the AE group was significantly (p's<.05) less accurate, made an increased number of omission errors, had longer response latencies, and increased variability in response time. Moreover, the AE group spent less time staying still, and made an increased number of head movements, which traveled a larger distance, covered a greater area, and demonstrated a less complex movement pattern. No significant group differences were observed on the number of commission errors and temporal scaling. Our findings provide further support for the notion that inattention is a core deficit in children prenatally exposed to alcohol. Results from this study are also consistent with parent reports of increased hyperactivity. The Quotient ADHD System may be a useful objective measure of ADHD symptomatology in children with FASD.

An fMRI study of behavioral response inhibition in adolescents with and without histories of heavy prenatal alcohol exposure.

Heavy prenatal alcohol exposure results in a range of deficits, including both volumetric and functional changes in brain regions involved in response inhibition such as the prefrontal cortex and striatum. The current study examined blood oxygen level-dependent (BOLD) response during a stop signal task in adolescents (ages 13-16 y) with histories of heavy prenatal alcohol exposure (AE, n=21) and controls (CON, n=21). Task performance was measured using percent correct inhibits during three difficulty conditions: easy, medium, and hard. Group differences in BOLD response relative to baseline motor responding were examined across all inhibition trials and for each difficulty condition separately. The contrast between hard and easy trials was analyzed to determine whether increasing task difficulty affected BOLD response. Groups had similar task performance and demographic characteristics, except for full scale IQ scores (AE

Fetal Alcohol Spectrum Disorders: Recent Neuroimaging Findings.

Since the identification of Fetal Alcohol Syndrome over 40 years ago, much has been learned about the detrimental effects of prenatal alcohol exposure on the developing brain. This review highlights recent neuroimaging studies, within the context of previous work. Structural magnetic resonance imaging has described morphological differences in the brain and their relationships to cognitive deficits and measures of facial dysmorphology. Diffusion tensor imaging has elaborated on the relationship between white matter microstructure and behavior. Atypical neuromaturation across childhood and adolescence has been observed in longitudinal neuroimaging studies. Functional imaging has revealed differences in neural activation patterns underlying sensory processing, cognition and behavioral deficits. A recent functional connectivity analysis demonstrates reductions in global network efficiency. Despite this progress much remains unknown about the impact of prenatal alcohol exposure on the brain, and continued research efforts are essential.

Automated cerebellar segmentation: Validation and application to detect smaller volumes in children prenatally exposed to alcohol.

OBJECTIVE: To validate an automated cerebellar segmentation method based on active shape and appearance modeling and then segment the cerebellum on images acquired from adolescents with histories of prenatal alcohol exposure (PAE) and non-exposed controls (NC). METHODS: Automated segmentations of the total cerebellum, right and left cerebellar hemispheres, and three vermal lobes (anterior, lobules I-V; superior posterior, lobules VI-VII; inferior posterior, lobules VIII-X) were compared to expert manual labelings on 20 subjects, studied twice, that were not used for model training. The method was also used to segment the cerebellum on 11 PAE and 9 NC adolescents. RESULTS: The test-retest intraclass correlation coefficients (ICCs) of the automated method were greater than 0.94 for all cerebellar volume and mid-sagittal vermal area measures, comparable or better than the test-retest ICCs for manual measurement (all ICCs > 0.92). The ICCs computed on all four cerebellar measurements (manual and automated measures on the repeat scans) to compare comparability were above 0.97 for non-vermis parcels, and above 0.89 for vermis parcels. When applied to patients, the automated method detected smaller cerebellar volumes and mid-sagittal areas in the PAE group compared to controls (p < 0.05 for all regions except the superior posterior lobe, consistent with prior studies). DISCUSSION: These results demonstrate excellent reliability and validity of automated cerebellar volume and mid-sagittal area measurements, compared to manual measurements. These data also illustrate that this new technology for automatically delineating the cerebellum leads to conclusions regarding the effects of prenatal alcohol exposure on the cerebellum consistent with prior studies that used labor intensive manual delineation, even with a very small sample.

White matter integrity pre- and post marijuana and alcohol initiation in adolescence.

Characterizing the effects of alcohol and marijuana use on adolescent brain development is important for understanding potential alterations in neurodevelopment. Several cross sectional studies have identified group differences in white matter integrity after initiation of heavy alcohol and marijuana use, however none have explored white matter trajectories in adolescents pre- and post initiation of use, particularly for marijuana users. This study followed 16 adolescents with minimal alcohol and marijuana use at ages 16-18 over three years. At follow-up, teens were 19-22 years old; half of the participants initiated heavy alcohol use and half initiated heavy alcohol and marijuana use. Repeated-measures ANOVA revealed 20 clusters in association and projection fibers tracts (p < 0.01) in which a group by time interaction was found. Most consistently, white matter integrity (i.e., fractional anisotropy) decreased for those who initiated both heavy alcohol and marijuana use over the follow-up interval. No effect of time or change in white matter integrity was seen for those who initiated alcohol use only in the majority of clusters. In most regions, at the baseline time point, teens who would later initiate both alcohol and marijuana use demonstrated white matter integrity greater than or equal to teens that initiated alcohol use only. Findings suggest poorer tissue integrity associated with combined initiation of heavy alcohol and marijuana use in late adolescence. While OPEN ACCESS pre-existing differences may also be related to likelihood of substance use, the present data suggest an effect on tissue integrity for these teens transitioning to combined alcohol and marijuana use in later adolescence.

Fetal alcohol spectrum disorders: an overview.

When fetal alcohol syndrome (FAS) was initially described, diagnosis was based upon physical parameters including facial anomalies and growth retardation, with evidence of developmental delay or mental deficiency. Forty years of research has shown that FAS lies towards the extreme end of what are now termed fetal alcohol spectrum disorders (FASD). The most profound effects of prenatal alcohol exposure are on the developing brain and the cognitive and behavioral effects that ensue. Alcohol exposure affects brain development via numerous pathways at all stages from neurogenesis to myelination. For example, the same processes that give rise to the facial characteristics of FAS also cause abnormal brain development. Behaviors as diverse as executive functioning to motor control are affected. This special issue of Neuropsychology Review addresses these changes in brain and behavior highlighting the relationship between the two. A diagnostic goal is to recognize FAS as a disorder of brain rather than one of physical characteristics.