Adolescent Binge Drinking Is Associated With Accelerated Decline of Gray Matter Volume.

The age- and time-dependent effects of binge drinking on adolescent brain development have not been well characterized even though binge drinking is a health crisis among adolescents. The impact of binge drinking on gray matter volume (GMV) development was examined using 5 waves of longitudinal data from the National Consortium on Alcohol and NeuroDevelopment in Adolescence study. Binge drinkers (n = 166) were compared with non-binge drinkers (n = 82 after matching on potential confounders). Number of binge drinking episodes in the past year was linked to decreased GMVs in bilateral Desikan-Killiany cortical parcellations (26 of 34 with P < 0.05/34) with the strongest effects observed in frontal regions. Interactions of binge drinking episodes and baseline age demonstrated stronger effects in younger participants. Statistical models sensitive to number of binge episodes and their temporal proximity to brain volumes provided the best fits. Consistent with prior research, results of this study highlight the negative effects of binge drinking on the developing brain. Our results present novel findings that cortical GMV decreases were greater in closer proximity to binge drinking episodes in a dose-response manner. This relation suggests a causal effect and raises the possibility that normal growth trajectories may be reinstated with alcohol abstinence.

Substance use patterns in 9-10 year olds: Baseline findings from the adolescent brain cognitive development (ABCD) study.

BACKGROUND: The Adolescent Brain Cognitive Development ™ Study (ABCD Study®) is an open-science, multi-site, prospective, longitudinal study following over 11,800 9- and 10-year-old youth into early adulthood. The ABCD Study aims to prospectively examine the impact of substance use (SU) on neurocognitive and health outcomes. Although SU initiation typically occurs during teen years, relatively little is known about patterns of SU in children younger than 12. METHODS: This study aims to report the detailed ABCD Study® SU patterns at baseline (n = 11,875) in order to inform the greater scientific community about cohort's early SU. Along with a detailed description of SU, we ran mixed effects regression models to examine the association between early caffeine and alcohol sipping with demographic factors, externalizing symptoms and parental history of alcohol and substance use disorders (AUD/SUD). PRIMARY RESULTS: At baseline, the majority of youth had used caffeine (67.6 %) and 22.5 % reported sipping alcohol (22.5 %). There was little to no reported use of other drug categories (0.2 % full alcohol drink, 0.7 % used nicotine, <0.1 % used any other drug of abuse). Analyses revealed that total caffeine use and early alcohol sipping were associated with demographic variables (p's<.05), externalizing symptoms (caffeine p = 0002; sipping p = .0003), and parental history of AUD (sipping p = .03). CONCLUSIONS: ABCD Study participants aged 9-10 years old reported caffeine use and alcohol sipping experimentation, but very rare other SU. Variables linked with early childhood alcohol sipping and caffeine use should be examined as contributing factors in future longitudinal analyses examining escalating trajectories of SU in the ABCD Study cohort.

Baseline brain function in the preadolescents of the ABCD Study.

The Adolescent Brain Cognitive Development (ABCD) Study® is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N = 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N = 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N = 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development.

Design and interpretation of clinical research studies in oral medicine: a brief review.

The objective of this short review is to help researchers improve the designs of their clinical studies. Also included is a discussion of the level of evidence provided by the various clinical research study designs.

Charting a Course for Implementation Research in Oral Health.

Knowledge Transfer Statement: This article provides an overview of implementation science and outlines NIDCR's interest and commitment to research that decreases time from development through implementation of evidence-based oral health interventions.

Disruptive behavior disorders and indicators of disinhibition in adolescents: The BRIEF-SR, anti-saccade task, and D-KEFS color-word interference test.

Disinhibition contributes to the development of disruptive behavior disorders (DBD) in adolescents. Self-reports and behavioral tasks are commonly used to assess disinhibition, each with their unique strengths and limitations. Accordingly, it is important to identify which measure, or combination thereof, is the most effective in predicting DBD symptoms. This study assessed the relationship between DBD (symptoms of ADHD/ODD/CD) and two behavioral disinhibition tasks: the anti-saccade task and the D-KEFS color-word interference test, as well as a self-report measure (the BRIEF-SR). The results indicated that the BRIEF-Inhibit scale accounted for the majority of the variance in the DBD sum score. The anti-saccade task and color-word interference test were also significantly associated with an increase in the number of DBD symptoms endorsed. These behavioral tasks accounted for 9% additional variance than the self-report alone. Therefore, combining self-report measures with behavioral disinhibition tasks may provide the most thorough assessment of adolescent DBD.

Neuroimaging methods for adolescent substance use disorder prevention science.

Magnetic resonance imaging (MRI) methods safely provide in vivo indicators of cerebral macrostructure, microstructure, and activation that can be examined in relation to substance use disorder (SUD) risks and effects. This article will provide an overview of MRI approaches, including volumetric measures, diffusion tensor imaging, and functional MRI, that have been applied to studies of adolescent neuromaturation in relationship to risk phenotypes and adolescent SUD. To illustrate these applications, examples of research findings will be presented. MRI indicators have demonstrated that neurobiological maturation continues throughout adolescence. MRI research has suggested that variations in neurobiological maturation may contribute to SUD risk, and that substance use adversely influences adolescent brain development. Directly measured neurobiological variables may be viable preventive intervention targets and outcome indicators. Further research is needed to provide definitive findings on neurodevelopmental immaturity as an SUD risk and to determine the directions such observations suggest for advancing prevention science.

Tropical rain forest tree growth and atmospheric carbon dynamics linked to interannual temperature variation during 1984-2000.

During 1984-2000, canopy tree growth in old-growth tropical rain forest at La Selva, Costa Rica, varied >2-fold among years. The trees' annual diameter increments in this 16-yr period were negatively correlated with annual means of daily minimum temperatures. The tree growth variations also negatively covaried with the net carbon exchange of the terrestrial tropics as a whole, as inferred from nearly pole-to-pole measurements of atmospheric carbon dioxide (CO(2)) interpreted by an inverse tracer-transport model. Strong reductions in tree growth and large inferred tropical releases of CO(2) to the atmosphere occurred during the record-hot 1997-1998 El Niño. These and other recent findings are consistent with decreased net primary production in tropical forests in the warmer years of the last two decades. As has been projected by recent process model studies, such a sensitivity of tropical forest productivity to on-going climate change would accelerate the rate of atmospheric CO(2) accumulation.

Health problems in adolescents with alcohol use disorders: self-report, liver injury, and physical examination findings and correlates.

BACKGROUND: Although adolescent alcohol consumption has been found to be positively correlated with self-reported health problems, few studies have examined other health indicators. This study compared adolescents with alcohol use disorders (AUDs) and a community reference group on self-reported health problems, serum liver enzymes, and physical examination findings. The relevance of negative emotionality to understanding these health problems was also investigated. METHODS: The subjects were adolescents with AUDs recruited from clinical programs and classified as having DSM-IV alcohol dependence (n = 71) or alcohol abuse (n = 57) and reference adolescents without AUDs recruited from community sources (n = 131). The assessment of health status included self-reported health problems in 15 areas; serum liver enzyme assays, including gamma-glutamyl transpeptidase, alanine aminotransferase, and aspartate aminotransferase; and physical examination findings. Negative emotionality was determined by systematically combining scores from the Hamilton Anxiety Rating Scale, the Beck Depression Inventory, the Child Behavior Checklist, and the Multidimensional Personality Questionnaire. RESULTS: Adolescent AUDs were associated with more self-reported health problems, higher gamma-glutamyl transpeptidase and alanine aminotransferase levels, and more physical examination abnormalities. Negative emotionality was highly correlated with self-reported health problems, mediated the relationship between AUDs and self-reported health problems, and was not correlated with serum liver enzyme levels or physical examination abnormalities. CONCLUSIONS: These results indicated that AUDs during adolescence were associated with health problems, including modest but demonstrable liver injury. Self-reported health problems were probably best understood, in this context, as a negative emotionality manifestation.

Alcohol use disorders and risk factor interactions for adolescent suicidal ideation and attempts.

Four hundred eighty-two adolescents who were diagnosed with at least one mental disorder were studied to determine the predictors of suicidal ideation and suicide attempts. Major depression was predictive of suicidal ideation and suicide attempts for both genders. Chronic stress was found predictive of male suicidal ideation, while low self-esteem and high family dysfunction were found to be predictive of suicidal ideation in females. Statistical trends suggest that females with comorbid alcohol use/conduct disorder were approximately three times more likely to have attempted suicide than those with only one of these conditions. Clinicians working with adolescents should be aware that, while depression remains the number one clinical risk forsuicidal behavior, risk factors for suicidal ideation may be different than those for attempted suicide and may vary by gender.

Treating the substance-abusing suicidal patient.

Studies concerning the treatment of substance-abusing suicidal patients are scarce despite the frequent presence of suicidal behavior among this population. Indeed, suicidality (ideation or behavior) is generally an exclusion criterion for participation in treatment studies of subjects with alcohol or drug abuse. Consequently, to date, little is known about the optimal treatment of this population. The first study involving substance-abusing suicidal patients was an open-label trial conducted in the early 1990s. This study involved 12 patients, all of whom demonstrated recent suicidal ideations and had made a lifetime suicide attempt. The results of that open-label study demonstrated significant within-group improvement in both depressive symptoms (including suicidal ideations) and level of drinking. However, substantial residual depressive symptoms and drinking persisted at the end of the trial. Also, because no placebo control group was utilized, the authors of that study could not rule out the possibility that the apparent therapeutic effect from fluoxetine was the result of the placebo effect. To date, only one double-blind, placebo-controlled study of subjects with alcohol or substance abuse has included substantial numbers of suicidal patients. The study involved 51 subjects, of whom 20 (39%) had made a suicide attempt in the current depressive episode, 31 (61%) had made a suicide attempt in their lifetime, and 46 (90%) had reported suicidal ideations in the week before hospitalization. The results of that double-blind, placebo-controlled study suggest that fluoxetine was effective in decreasing but not eliminating both the depressive symptoms (including suicidal ideations) and the level of alcohol consumption among a study group of subjects with comorbid major depressive disorder and alcohol dependence, many of whom displayed suicidal ideations. A secondary data analysis from that study suggested that cigarette smoking is also significantly decreased by fluoxetine, but the magnitude of the decrease is limited and few of these patients totally quit smoking with fluoxetine treatment alone. Another secondary data analysis from that study suggested that marijuana smoking was also significantly decreased in a subgroup of subjects who demonstrated cannabis abuse and that the magnitude of this improvement was robust. A third secondary data analysis from that study suggested that cocaine abuse acts as a predictor of poor outcome for both depressive symptoms (including suicidality) and level of alcohol use in this population. The results of a 1-year naturalistic follow-up study involving the patients from that study suggest that the benefits of fluoxetine in decreasing depressive symptoms and level of drinking persist 1 year after entering the treatment program. To date, no other double-blind, placebo-controlled studies involving substantial numbers of substance-abusing suicidal patients have been reported to either confirm or refute these findings. Further studies are clearly warranted to evaluate the efficacy of various pharmacotherapeutic agents and various psychotherapies in the treatment of substance-abusing suicidal patients.

Clinical correlates of heavy tobacco use among adolescents.

The primary aim of this study was to determine the clinical factors differentiating adolescents with heavy smoking (> or = 10 cigarettes/day) from adolescents with light smoking. This study involved a study group of 812 adolescents recruited from adolescent alcoholism treatment centers and from the community. Logistic regression analyses demonstrated that adolescents with heavy smoking, compared with adolescents with light smoking, were significantly more likely to demonstrate Caucasian American ethnicity, drug-use disorders, alcohol-use disorders, and conduct disorder. Our findings suggest that the clinical correlates of heavy smoking among adolescents are generally similar to those for smoking at any level (vs. nonsmokers), except that heavy smoking is more strongly associated with Caucasian American ethnicity. Also, depressive disorders were associated with smoking at any level in our sample, but depressive disorders were not associated with heavy smoking.

Correlates of mental health service utilization and unmet need among a sample of male adolescents.

The authors sought to identify the correlates of mental health services utilization and unmet need for these services among a sample of adolescent males. We hypothesized that our findings would replicate and extend those of the recent Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) study, which found that parental factors play a major role in their children's unmet mental health care needs. Our study involved an evaluation of mental health service utilization and unmet need during the prior 2 years, as reported by the subjects at a follow-up assessment at age 16. Four factors were found to predict increased mental health services utilization, including attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) among the adolescent males, the father's alcohol use disorder, and the mother's amphetamine use disorder. One factor was found to predict decreased utilization, the father's cannabis use disorder. Four factors significantly predicted unmet treatment need, including conduct disorder, the mother's amphetamine use disorder, a higher number of siblings, and a parental history of having had a childhood anxiety disorder. The results of this study suggest that parental psychopathology, parental substance abuse, the presence of conduct disorder, and an increased number of siblings act as barriers to adequate mental health treatment among adolescents. These findings confirm the crucial role that parental factors play in the treatment utilization and the unmet treatment need of their children, and also suggest that an increased number of siblings can also be associated with unmet treatment need.

Developmental sources of variation in liability to adolescent substance use disorders.

This review provides a synthesis of the literature on the complex sequence of maturational, psychosocial, and neuroadaptive processes that lead to substance use disorders (SUD) in adolescence. A brief overview introduces the concepts of liability to SUD and epigenesis. A theory is presented explaining how affective, cognitive, and behavioral dysregulation in late childhood is exacerbated during early and middle adolescence by family and peer factors, as well as puberty, leading to substance use. Continued exacerbation of the three components of dysregulation by drug and non-drug stressors during late adolescence is posited to result in neuroadaptations that increase the likelihood of developing SUD, particularly in high-risk individuals. Implications for etiologic research as well as clinical and preventive interventions are discussed.

Comparative efficacy of 24-hour and 16-hour transdermal nicotine patches for relief of morning craving.

AIMS: To compare a transdermal nicotine patch designed for 24-hour wear with one designed for 16-hour wear for relief of craving and withdrawal, particularly in the morning hours. DESIGN: Smokers were randomly assigned to use one of two common patch regimens: NicoDerm/NiQuitin (24-hour wear, 21 mg nicotine) or Nicotrol/Nicorette (16-hour wear, 15 mg). In a double-dummy design, participants wore two patches during the day, one active, one placebo and one patch while sleeping. SETTING: A smoking cessation research clinic. PARTICIPANTS: Two hundred and forty-four smokers who suffered morning cravings. INTERVENTION: Two patch formulations approved and marketed for over-the-counter use in the US--NicoDerm CQ (labeled as 21 mg over 24 hours) and Nicotrol (labeled as 15 mg over 16 hours)--were each used according to its instructions. Smokers also received behavioral counseling. MEASUREMENTS: For a week of baseline and 2 weeks after quitting, smokers used palm-top computers to assess craving and withdrawal symptoms several times each day. FINDINGS: The 21 mg/24-hour patch yielded consistently better control of craving, not only during the morning hours, but throughout the day, and over the 2-week period of abstinence. Additionally, the 21 mg/24-hour patch yielded greater reductions in anxiety, irritability and restlessness. Smokers using the 21 mg/24-hour dosing regimen also experienced longer abstinence than those using the 15 mg/16-hour patch. CONCLUSIONS: These findings demonstrate that 24-hour dosing with a 21 mg patch affords superior relief of craving and withdrawal during the first 2 weeks of abstinence, when symptoms are at their peak, and when relapse is most likely. They confirm the importance of dosing parameters in nicotine replacement products.

Gender differences and similarities in the personality correlates of adolescent alcohol problems.

The personality traits of behavioral under-control (BU) and negative emotionality (NE) are associated with alcohol problems. The authors examined gender differences in the associations of BU and NE with alcohol problems in 710 adolescents recruited from community and treatment sources. Multiple measures were used to characterize each construct, and the specified 2-factor model provided a reasonably good fit to the data. ANCOVAs were used to examine each construct by gender across four groups: never-regular drinkers, regular drinkers, and those with DSM-IV alcohol abuse and alcohol dependence. Males had significantly higher BU and lower NE than did females. BU and NE both increased with degree of alcohol problems. However, there was not a significant Gender x Alcohol Group interaction for BU or NE. Although there are gender differences in levels of BU and NE, mechanisms of alcohol involvement related to these 2 personality traits may operate similarly in adolescent males and females.

Hippocampal volume in adolescent-onset alcohol use disorders.

OBJECTIVE: Alcohol use disorders (defined as DSM-IV alcohol dependence or abuse) are prevalent and serious problems among adolescents. As adolescence is marked by progressive hippocampal development, this brain region may be particularly susceptible to the adverse effects of adolescent alcohol use disorders. This study compared the hippocampal volumes of adolescents and young adults with adolescent-onset alcohol use disorders to those of healthy matched comparison subjects. METHOD: Magnetic resonance imaging was used to measure the hippocampal volumes and volumes of comparison brain regions in 12 subjects with alcohol use disorders and 24 comparison subjects matched on age, sex, and handedness. RESULTS: Both left and right hippocampal volumes were significantly smaller in subjects with alcohol use disorders than in comparison subjects. Total hippocampal volume correlated positively with the age at onset and negatively with the duration of the alcohol use disorder. Intracranial, cerebral, and cortical gray and white matter volumes and measures of the mid-sagittal area of the corpus callosum did not differ between groups. CONCLUSIONS: In the mature brain, chronic alcohol use disorders are associated with graded global brain dysmorphology. Although the etiology, neuropsychological consequences, and permanence of these hippocampal findings need to be further examined, these findings suggest that, during adolescence, the hippocampus may be particularly susceptible to the adverse effects of alcohol.

Psychopathology and substance-related problems during early adolescence: a survival analysis.

Examined the chronological and statistical relations among onsets of psychopathology, alcohol and cannabis use, and substance-related problem psychopathology, alcohol and cannabis use, and substance-related problems from late childhood through early adolescence in boys of fathers with substance use disorder (SUD; high average risk: n = 177) and without SUD (low average risk: n = 203) using survival analysis. Proportional hazard models indicated that antisocial disorders were predicted by risk group and mediated the observed relation between risk group and substance-related problems. Negative affect disorders were predicted by risk group but did not predict substance involvement in early adolescence. Results support a model in which paternal SUD predisposes to increased antisocial and negative affect disorders in boys, and antisocial disorders lead to substance-related problems in early adolescence.

A.E. Bennett Research Award. Developmental traumatology. Part II: Brain development.

BACKGROUND: Previous investigations suggest that maltreated children with a diagnosis of posttraumatic stress disorder (PTSD) evidence alterations of biological stress systems. Increased levels of catecholaminergic neurotransmitters and steroid hormones during traumatic experiences in childhood could conceivably adversely affect brain development. METHODS: In this study, 44 maltreated children and adolescents with PTSD and 61 matched controls underwent comprehensive psychiatric and neuropsychological assessments and an anatomical magnetic resonance imaging (MRI) brain scan. RESULTS: PTSD subjects had smaller intracranial and cerebral volumes than matched controls. The total midsagittal area of corpus callosum and middle and posterior regions remained smaller; while right, left, and total lateral ventricles were proportionally larger than controls, after adjustment for intracranial volume. Brain volume robustly and positively correlated with age of onset of PTSD trauma and negatively correlated with duration of abuse. Symptoms of intrusive thoughts, avoidance, hyperarousal or dissociation correlated positively with ventricular volume, and negatively with brain volume and total corpus callosum and regional measures. Significant gender by diagnosis effect revealed greater corpus callosum area reduction in maltreated males with PTSD and a trend for greater cerebral volume reduction than maltreated females with PTSD. The predicted decrease in hippocampal volume seen in adult PTSD was not seen in these subjects. CONCLUSIONS: These data suggest that the overwhelming stress of maltreatment experiences in childhood is associated with adverse brain development.