by Monique Ernst, MD, PhD, and Eric Moolchan, MD
[Spring 1999; Vol.26 No. 1]
The National Institute on Drug Abuse (NIDA) has long recognized the critical adverse consequences of substance abuse on the psychological, physical, academic and social development of teenagers, and on the severity of substance abuse in adulthood. Recently, the NIDA Intramural Research Program (IRP) initiated a research program devoted to substance abuse in adolescents. The Adolescent Program is currently addressing two major questions: 1) cognitive and neurobiological vulnerabilities to the development of substance abuse, and 2) treatment of nicotine dependence. Identifying causal factors before the onset of substance abuse should lead to the development of rational and focused preventive interventions. In addition, past findings of cognitive and neurobiological abnormalities in adults with substance abuse, based largely on retrospective and cross-sectional studies, need to be contrasted with prospective findings in adolescents to be interpreted as either causal to or effects of substance abuse.
Dr. Monique Ernst of the Neuroimaging Branch (headed by Dr. Edythe London) is conducting two longitudinal studies that will follow a large cohort of 12 to 14 years-old adolescents until they reach 19 years of age. This cohort includes children at risk for later substance abuse, and healthy controls. The children at risk are those with diagnoses of attention-deficit/hyperactivity disorder (ADHD) or conduct disorder. Prospective epidemiological studies indicate that, compared to their healthy peers, children with ADHD carry a 1.5-fold greater risk of developing substance abuse, those with conduct disorder a 7-fold greater risk, and those with both ADHD and conduct disorder an 8- to 9-fold greater risk.
The first study examines cognitive performance and the second study cerebral function as measured by cerebral metabolic rates of glucose (CMRglc) using positron emission tomography (PET). The cognitive deficits that are expected to convey vulnerability for substance abuse are impairment in working memory and in judgment of consequences (e.g., balance between long-term negative consequences and short-term positive consequences). These cognitive functions have been shown to be altered in adults with substance abuse. Hypothesized neurobiological markers predictive of the development of substance abuse include abnormal neural activity in the orbitofrontal cortex (a brain region which plays a role in motivation), in the dorsolateral prefrontal cortex (which subserves cognitive executive function), and in dopaminergic structures, particularly within the mesolimbic pathway (associated with reward functions). Brain imaging studies in adults with histories of substance abuse have reported structural and functional abnormalities in these brain areas. Functional neuroimaging methodologies comprise magnetic resonance imaging, and nuclear medicine techniques, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT). The NIDA IRP has its own PET center. PET permits the mapping of brain function, using various radiolabeled tracers that target different neurochemical systems. For example, PET scanning with the tracer 18F-fluorodeoxyglucose measures cerebral metabolic rates of glucose (CRMglc). Studies using this technique have identified both global and localized alterations of cerebral metabolic activity in various psychiatric disorders, including substance abuse. The predictive power of both specific cognitive deficits and localized cerebral dysfunction will be evaluated by analyses of association between measures collected at study entry, before the development of substance abuse, and subjects' diagnostic status 5-7 years later, at age 19 years.
The treatment component of the NIDA adolescent program currently focuses on the treatment of nicotine dependence. Recent epidemiological data on cigarette smoking in adolescents underscore the need for both preventive and therapeutic interventions. Despite public health campaigns, the prevalence of current cigarette smoking among U.S. high school students increased from 27.5% in 1991 to 36.4% in 1997. In national surveys, 10% of eighth graders, 18% of tenth graders, and 22% of twelfth graders say they smoke every day. By high school graduation, 28 % of students are smoking cigarettes. Their peers who have dropped out of high school have smoking rates approaching 70%. Furthermore, adolescents try to quit on their own and often fail. As a result, many are interested in treatment, which unfortunately is not readily available.
Dr. Eric Moolchan of the NIDA Clinical Pharmacology Branch and Office of the Clinical Director (headed by Dr. Jean Lud Cadet) leads this project, which will assess the safety and therapeutic efficacy of pharmacological and psychological interventions for tobacco dependence in adolescents. Research in adult cigarette smokers indicates that both nicotine replacement therapy and psychological interventions (e.g., group counseling and cognitive-behavioral therapy) can be effective for smoking cessation. There is also evidence that the combination of pharmacological and psychological treatment can be more effective than either alone. However, there has been very little systematic evaluation of these treatments in adolescent tobacco users.
The initial study will focus on adolescents 13 to 17 years of age who smoke at least 11 cigarettes per day and are motivated to quit. Two forms of nicotine replacement therapy, skin patch and gum, will be evaluated, along with weekly supportive group counseling for 12 weeks. This will allow evaluation of the safety and efficacy of pharmacological treatment, as well as its interaction with psychological support in a developmentally appropriate setting. Careful attention is paid to the special aspects of conducting clinical research with adolescents, such as obtaining their assent and parental consent without coercion and protecting confidentiality vis-à-vis their parents and school. These studies, like most NIDA clinical studies, are conducted under a federal Certificate of Confidentiality, which allows the researchers to keep all research data completely confidential unless requested to release it by the research subject.
Adolescents who participate in any of these research studies will receive free medical, psychiatric, psychological and psychoeducational assessment. Those who participate in the non-treatment studies will be financially compensated for their time and effort. Their parents will also be compensated for their time spent in helping the research project. Anyone wishing to refer families for participation in any of these protocols (identification of risk factors for substance abuse or treatment of nicotine dependence) can contact Dr. Miquin Robinson at (410) 550-1858.
Dr. Monique Ernst, board certified in general psychiatry and in child and adolescent psychiatry, is Associate Director of the NIDA IRP Brain Imaging Center, and assistant professor of Child and Adolescent Psychiatry, Johns Hopkins University.
Dr. Eric Moolchan, board-certified in pediatrics and internal medicine, is a staff fellow in the Clinical Pharmacology Branch, NIDA IRP.