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.

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.

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.

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.

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.

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.

Hypertension and neurofibromatosis. Case report.

A 14-year-old girl with neurofibromatosis presented with severe hypertension. She was subsequently found to have a cerebellar glioblastoma multiforme and vascular lesions producing coarctation of the abdominal aorta and 50% and 95% stenosis of the left and right renal arteries respectively. No evidence of pheochromocytoma was found. After removal of the cerebellar tumor, marked amelioration of the hypertension suggested that the tumor had a major role in the pronounced elevation of her blood pressure. Patients who have both neurofibromatosis and hypertension should be carefully evaluated for these several potential lesions.

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.

The assessment and treatment of performance anxiety in musicians.

OBJECTIVE: Performance anxiety in musicians may be severe enough to require intervention but has been the subject of relatively little clinical research. The authors' objectives were to describe the results of a comprehensive clinical and laboratory assessment and to perform a double-blind, placebo-controlled study comparing buspirone, cognitive-behavior therapy, and the combination of these treatments for performance anxiety. METHOD: Ninety-four subjects were recruited by mass media announcements and were seen in a university-based outpatient psychiatric clinic. Assessments were 1) questionnaires for all 94 subjects, 2) diagnostic interview of 50 subjects, and 3) laboratory performance of 34 subjects. Treatment conditions were 1) 6 weeks of buspirone, 2) 6 weeks of placebo, 3) a five-session, group cognitive-behavior therapy program with buspirone, or 4) the cognitive-behavior therapy program with placebo. Treatment outcome measures included subjective anxiety ratings and heart rate measures during a laboratory performance, a questionnaire measure of performance confidence, and a blind rating of musical performance quality. RESULTS: All subjects fulfilled criteria for DSM-III-R social phobia. Of the 15 full-time professional musicians, ten had tried propranolol and three had stopped performing. Most of the subjects had substantial anxiety and heart rate increases during laboratory speech and musical performances. Cognitive-behavior therapy resulted in statistically significant reductions in subjective anxiety, improved quality of musical performance, and improved performance confidence. Buspirone was not an effective treatment. CONCLUSIONS: Cognitive-behavior therapy is a viable treatment approach for performance anxiety in musicians.

Panic in otolaryngology patients presenting with dizziness or hearing loss.

This study compared 50 patients presenting to an otolaryngology clinic with a complaint of dizziness and 50 patients presenting with hearing loss on questionnaire measures of panic, phobic avoidance, generalized anxiety, and depression. Clinical and laboratory evaluations of vestibular and audiological complaints were also completed. Twenty percent of the group with dizziness and none of the group with hearing loss reported symptoms that met DSM-III-R criteria for panic disorder. Patients with dizziness and peripheral vestibulopathy had more symptoms of phobic avoidance, generalized anxiety, and depression than patients with confirmed hearing loss.

Surreptitious drug use by patients in a panic disorder study.

In a double-blind, placebo-controlled trial comparing alprazolam and imipramine for panic disorder, serum analysis revealed that a substantial proportion of the patients took explicitly prohibited anxiolytic medication. Excluding these patients changed the results.

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.

Twins with Alzheimer's disease.

Twins of identical appearance were both affected by Alzheimer's senile dementia. In one, dementia began in her late 60s. She died at age 74. In the other, onset was at age 83. She died of ovarian carcinoma at age 85. The histopathologic findings of Alzheimer's disease were confirmed in both twin sisters.

Spinal cord infarction due to minor trauma in children.

In two children, ages 22 months and 4 years, after slight trauma, flaccid weakness of both arms developed, followed by flaccid quadriplegia with sphincter involvement. No vertebral fracture or dislocation was found, myelograms were negative, and diagnosis was made only after the full clinical syndrome developed. Pathologic studies revealed ischemic infarction involving the cervical cord and low medulla in one patient, and central gray matter of low cervical cord in the other, without hematomyelia or external compressive lesions. The pattern of infarction may be related to spasm of distal branches of the central sulcal arteries in a terminal arterial bed.

Iodine-123 HIPDM brain imaging findings in subacute spongiform encephalopathy (Creutzfeldt-Jakob disease).

Decreased perfusion of the left frontal and left temporoparietal cortex has been shown in [123I] HIPDM planar and single photon emission computed tomographic images of a patient with Creutzfeldt-Jakob disease (CJD) that was proven by brain biopsy and subsequent autopsy. An EEG showed diffuse, periodic discharges most prominent to the left hemisphere. Concurrent head computed tomography (CT), nuclear magnetic resonance (NMR), and cerebral angiographic studies were negative. Abnormalities demonstrated by [123I]HPDM imaging and by EEG may represent changes in neurophysiological and neurochemical status while cerebral angiography, CT, and possibly NMR register only anatomic or structural lesions. Premortem diagnosis of CJD depends on brain biopsy; the availability of the [123I] HIPDM study may provide regional cerebral neurochemical and neurophysiological information, guiding or avoiding brain biopsy in the appropriate clinical setting.

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.

Reliability and validity of the Hamilton Anxiety Rating Scale in an adolescent sample.

OBJECTIVE: Although generalized anxiety is an important clinical problem among adolescents, there are no interview procedures to provide a global anxiety rating that have demonstrated reliability and validity for this population. The Hamilton Anxiety Rating Scale (HARS) is a general measure of anxiety that was developed for adults. The purpose of this study was to determine the reliability and validity of the HARS when used with adolescents. METHOD: The sample consisted of 257 adolescents aged 12 to 18 years from both clinical and community sources. The HARS interviews and ratings were conducted as part of an extensive psychiatric and medical assessment. Psychiatric diagnoses were determined by structured interview. Other questionnaire measures of anxiety were also obtained. RESULTS: The interrater reliability and internal consistency of the HARS were acceptable in this adolescent sample and were comparable to results reported for adults. The HARS exhibited good construct validity, showing statistically significant relationships with independent self-report measures of generalized anxiety and other anxiety variables. The factor structure of the HARS also was found to be similar to that found earlier with adults. CONCLUSIONS: These results demonstrate that the HARS is a reliable and valid measure for the assessment of global anxiety in the adolescent population.

Traumas and other adverse life events in adolescents with alcohol abuse and dependence.

OBJECTIVE: Clinical observation suggests that adolescents with alcohol use disorders often have complex histories that include childhood maltreatment and other traumas. The aim of this study was to determine the relationships among adolescent alcohol use disorders and a broad range of traumas and adverse life events. METHOD: The subjects were 132 adolescents with alcohol dependence, 51 adolescents with alcohol abuse, and 73 adolescents recruited from the community as a control group. Trauma history was assessed by a semistructured interview and other adverse life events by questionnaire. RESULTS: Traumatic events reflecting interpersonal violence had occurred in many of the adolescents with alcohol dependence and abuse and few of the control adolescents. Adolescents with alcohol abuse or dependence, compared with control subjects, were 6 to 12 times more likely to have a physical abuse history and 18 to 21 times more likely to have a sexual abuse history. Sexual abuse was more common in females, and victimization by other violent acts was more common in males. Many other adverse life events were also significantly more common in the alcohol use disorder groups than in the control group, including having a close friend die, arguments within the family, and legal difficulties. CONCLUSIONS: These results demonstrate that trauma and other adverse life events are strongly associated with alcohol use disorders in adolescents. Clinical screening of adolescents with alcohol use disorders for a range of traumatic events is recommended.