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May 19, 2007 - 12:00am to May 24, 2007 - 12:00am
San Diego, California

Invited Lectures

The Neurobiology of Free Will in Addictive Disorders

Nora D. Volkow, M.D.
National Institute on Drug Abuse

Addiction is a disorder that involves complex interactions between a wide array of biological, environmental, and developmental variables. Studies employing neuroimaging technology paired with sophisticated behavioral measurement paradigms have led to extraordinary progress in elucidating many of the neurochemical and functional changes that occur in the brains of people who are addicted to drugs. Although large and rapid increases in dopamine have been linked with the rewarding properties of drugs, the addicted state, in striking contrast, is marked by significant decreases in brain dopamine function. Such decreases are associated with dysfunction of prefrontal regions including the orbitofrontal cortex and cingulate gyrus. In addiction, disturbances in salience attribution result in enhanced value given to drugs and drug-related stimuli at the expense of other reinforcers. Dysfunction in inhibitory control systems, by decreasing the addicted person’s ability to refrain from seeking and consuming drugs, ultimately results in the compulsive drug intake that characterizes the disease. Discovery of such disruptions in the fine balance that normally exists between brain circuits underlying reward, motivation, memory, and cognitive control have important implications for designing multi-pronged therapies for treating addictive disorders.

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The Evolving Climate for Neuroscience and Society

Alan Leshner, Ph.D.
Chief Executive Officer
American Association for the Advancement of Science

The relationship between science and society is critical to the way in which science is perceived and the way that scientific findings are used. For science to prosper, the science–society relationship has to be a strong one. The problem is that we have never experienced a period with quite the amount of tension that now exists between science and society. The overall relationship is beginning to erode and has tremendous consequences for the way scientists can do their job and the way that science can prosper. Advances in science are coming at a tremendous pace and neuroimaging is responsible for quantum jumps in understanding the way we study mental health and addiction disorders.

However, other areas of science are not doing as well. It’s important not to underestimate the aggregative consequences of the sporadic incidents that occur within science. Internally, scientific misconduct, human subject concerns, animal welfare issues, and conflict of interest negatively affect the broader societal context for science. Externally, people respect science but don’t understand what it is. Tension between scientific findings and political or economic concerns and core human values has increased with stem cell research, sex and gender studies, and genetics of behavior. The public is uncomfortable with neuroscience’s ability to look into the human brain and watch it in action. This has led to an emergence of neuroethics as a new field. The overlay of societal values has consequences for science in that society wants to influence science and not the other way around.

Education alone will not work to improve this relationship. We need to adopt a more assertive strategy and engage the public on issues to try to find common ground. We need to change from communicating to the public to communicating with the public by asking what questions need to be answered. The field of genetics has taken this approach; now neuroscience needs to follow their lead.

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Substance Abuse in Your Patients: Beyond What is Taught in Your Residency

Chair: Nora D. Volkow, M.D.
National Institute on Drug Abuse


According to the most recent National Survey on Drug Use and Health, an estimated 19.7 million Americans or 8.1% of the population aged 12 or older were current (past month) illicit drug users and nearly 8 million are in need of treatment. Drug abuse has far-reaching consequences for individuals, families, communities, and society at large. Research has demonstrated that addiction is a disease that can be successfully treated, but not if the symptoms are undetected and the problem undiagnosed. This Forum brings together leading experts in the treatment of drug abuse and addiction to discuss how to recognize drug abuse problems as well as introduce participants to the most recent discoveries about the neurobiology of addiction and how those discoveries are contributing to the development of new, effective addiction treatments.

What They Didn’t Teach You in Residency About Diagnosing & Treating Prescription Opioid Abuse

Herbert D. Kleber, M.D.

Although prescription opioid abuse is one of the fastest growing drug problems, most psychiatric residents have little exposure to its diagnosis and treatment. Between 1994 and 2001, narcotic analgesic abuse more than doubled. Schedule III products (e.g., Vicodin) are readily available without prescription via the Internet. Schedule II opioids (e.g., Oxycontin) are mainly obtained from prescriptions, doctor shopping, theft from medicine cabinets, and street sales. The greater availability is significantly related to concerns about inadequate treatment of pain and, therefore, increased prescribing during the 1990s, which has continued to the present. Although there is a relatively high prevalence of comorbid chronic pain and substance abuse, most individuals treated for pain with these agents do not become addicted.

Treatment options include: Detoxification to antagonist maintenance (naltrexone, nalmefene, and depot naltrexone), residential therapeutic communities, and abstinence-oriented programs (counseling, and 12 step programs), and maintenance with methadone or buprenorphine.

For individuals who have been addicted for more than a year, detoxification, unless followed by continual treatment such as a narcotic antagonist or residential therapeutic community, is associated with a high relapse rate. These patients are usually better served by maintenance on buprenorphine.

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Pharmacotherapy: From Antabuse to Zenova-vax

Thomas Kosten, M.D.

Two new concepts are evolving in our pharmacotherapy of substance abuse—pharmacogenetics and immunotherapy. Both are being applied to the treatment of stimulant dependence. Disulfiram, an inhibitor of dopamine beta hydroxylase (DBH), is being successfully used to treat cocaine dependence, and a specific genetic polymorphism that relates to treatment response has been identified in the promoter region of this gene. This polymorphism leads to a 10–100-fold lower level of the DBH enzyme and is relatively common in about 40 percent of individuals. In these individuals, DBH is substantially inhibited by disulfiram leading to an increase in dopamine release and a reduction in norepinephrine production and release from neurons. This effect appears to reduce cocaine craving and the priming effect of cocaine use that leads to relapse. Immunotherapy has taken the form of an anti-cocaine vaccine that can block the effects of cocaine by retaining it in the bloodstream, where it is inactivated by another enzyme in the blood—cholinesterase. In human laboratory studies and in outpatient clinical trials, this vaccine takes several injections over about 2 months to produce adequate antibodies, but then substantially blocks the effects of cocaine.

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Clinical Implications and Applications of Advances in Addiction Research to the Evaluation and Treatment of Adolescents

Paula D. Riggs, M.D.

Advances in addiction research highlight the importance of understanding neuro-developmental factors that increase adolescents’ vulnerability to substance use disorders and mental health problems.

Data from Dr. Riggs' recently completed randomized controlled trial of fluoxetine vs. placebo + CBT support the safety and efficacy of integrated, concurrent treatment of a common psychiatric comorbidity (MDD) in adolescents who have active substance use disorders. Preliminary data from this study also show that adolescents with marijuana dependence have greater pre-treatment brain activation in “reward” circuits in response to marijuana cues than to food cues, and greater post-treatment (after 16 weeks’ CBT) brain activation to the same marijuana cues in cortical/pre-frontal areas compared with food cues.

This presentation aims to help understand the key developmental risk factors that increase the risk of mental health problems, substance abuse, and other behavioral pathology in adolescents, along with the clinical implications of scientific advances in our understanding of adolescent brain development and the neuro-developmental processes underpinning addiction and commonly associated psychiatric comorbidity.

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What Should All Psychiatry Residents Know About Treating Addiction?

Charles P. O'Brien, M.D., Ph.D.

In this brief presentation the definition of addiction is discussed. An important point is that tolerance and physical dependence are normal responses to repeated use of drugs that affect the central nervous system and are not necessarily a sign of addiction. Drug abuse and addiction are essentially maladaptive memories, a disorder of the reward system, which is activated as the reinforcer of all behavior. There are a large variety of drugs that can be abused, but all have in common the activation of this reward system. In recent years, research has brought us new medication that can be used in combination with psychotherapy. A discussion of the action mechanism of some of these medications is described. The essential goal of addiction treatment is prevention of relapse. Detoxification is only the beginning of treatment but not a treatment by itself. In addition to medications, we have specific forms of psychotherapy. These have been codified in treatment manuals and can be studied in research projects just as the dose of medication can be studied quantitatively. The best treatment for addictive disorders is a combination of psychotherapy and medication. There is absolutely no evidence that medications interfere with psychotherapy or 12-step programs. In fact there is good evidence that they enhance the benefits obtained from these psychosocial interventions.

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Insights on Obesity and Drug Addiction From Brain Imaging

Co-Chairs: Nora D. Volkow, M.D.
National Institute on Drug Abuse

Joseph Frascella, Ph.D.
National Institute on Drug Abuse


Drug addiction and obesity represent major health problems in the United States. Despite a number of different etiologies (e.g., social, environmental, psychological, biological, and behavioral) for both drug addiction and obesity, each can often be characterized as a complex biobehavioral disorder resulting from a loss of control with compulsive or excessive behaviors. Both eating and drug abuse directly involve brain reward pathways; both obesity and drug addiction are chronic, relapsing disorders that represent unique treatment challenges. This symposium explores the commonalities (and differences) between drug addiction and obesity through shared neurobiological processes and brain systems, particularly drawing on insights gained from human brain imaging studies.

Modulators of Orbitofrontal Activation in Response to Food Stimuli

Deborah Yurgelum-Todd, Ph.D.

It has been hypothesized that addictive drugs activate the same brain reward mechanisms involved in the control of normal appetitive behavior. The orbitofrontal cortex consistently emerges as a critical convergence zone for the stream of afferent sensory information related to rewarding stimuli, particularly for primary reinforcers such as food. Functional magnetic resonance imaging (fMRI) techniques provide a method for characterizing orbitofrontal response. To clarify the neurobiological mechanisms by which body weight, mood, and age may influence appetitive response, we presented healthy, normal-weight adolescent and adult females with color photographs of foods differing in fat-content/calorie-density (e.g., high-reward or low-reward) while they underwent blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI).

Body mass was observed to be negatively correlated with activity of the orbitofrontal cortex when adult females viewed images of highly rewarding food, suggesting a relationship between weight status and rewarding effects of the food images. In addition, activation of the orbitofrontal cortex was shown to be significantly related to mood ratings. Positive affect was associated with decreased medial orbitofrontal activity during the viewing of high-fat food, whereas negative affect was associated with increased activation of this region during the viewing of high-reward, high-calorie food. These associations suggest that mood may play an important role in moderating the approach to foods that differ in reward salience. In a complementary study, a significant positive correlation was observed between age and activation of the orbitofrontal cortex in adolescent females viewing high-calorie images. Taken together these results indicate that mood state, body mass, and development of the brain circuitry may moderate the reinforcing capacity of rewarding stimuli. These findings have important implications for clarifying models underlying reward response and for the development of more effective therapies of eating disorders and drug addiction.

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Hunger as an Addiction

Alain Dagher, M.D.

Drug addiction is an interesting model to try to understand cognitive control. The addict, attempting to abstain from drugs, is under the influence of two contradictory phenomena: a compulsion to use the drug, and a desire to quit. These two thought processes are likely mediated by different, but interacting, brain regions, all of which are innervated by dopamine. It is also instructive to view obesity from the standpoint of addiction neuroscience. There are obvious parallels between attempting to lose weight and abstaining from a drug.

Drugs of abuse are thought to target the same neural systems as natural rewards. The most likely candidate brain region is the mesolimbic and mesostriatal dopamine system. In animals, dopamine is released in the striatum in response to food, sexual mates, and to almost all drugs of abuse. Different theories propose that dopamine acts by mediating the hedonic impact of a reinforcing stimulus, promoting associative learning about the stimulus, or by serving as an incentive to the consumption of the stimulus. Moreover, it has been suggested that the magnitude of the dopamine response to drugs and stressors may be a marker of vulnerability to addiction.

The research described here uses two techniques: functional MRI to measure neural activity during craving induced by drug or food cues, and positron emission tomography to measure dopamine release in human volunteers using [11C] raclopride, a D2 receptor ligand. We have used these techniques to study the brain response to abused drugs (e.g., alcohol, amphetamine, and nicotine) and natural rewards such as food and money.

We review some of the factors that favor the expression of abstinence or relapse in addicts, and the similarities and differences between drugs of abuse and natural rewards such as food.

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Neuroimaging Studies of Obesity and Drug Addiction

Gene-Jack Wang, M.D.

The cerebral mechanisms underlying the behaviors that result in pathological overeating and obesity are poorly understood. The regulation of food intake is a complex balance between excitatory and inhibitory processes. Excitatory processes arise from the body’s needs for nutrients and calories. Studies using positron emission tomography (PET) implicate the involvement of brain dopamine (DA) in non-hedonic motivational properties of food intake in humans. We also found reductions of striatal DA D2 receptors in pathologically-obese subjects, which were similar to those in drug-addicted subjects. We postulated that decreased levels of DA receptors predisposed subjects to search for reinforcers—in the case of drug-addicted subjects, for the drug, and in the case of the obese subjects, for food—as a means to temporarily compensate for a decreased sensitivity of DA-regulated reward circuit. The inhibitory processes arise from satiety signals (e.g., electrical and chemical) after food consumption. We used PET to measure the brain metabolic responses in obese subjects who had an implantable gastric stimulator, which induces stomach expansion via electrical stimulation of the vagus nerve in order to identify the brain circuits responsible for its effects in decreasing food intake. These findings corroborated the role of the vagus nerve in regulating hippocampal activity as well as the importance of the hippocampus in modulating eating behaviors linked to emotional eating and lack of control. The brain regions (orbitofrontal cortex, hippocampus, cerebellum, and striatum) activated by gastric stimulation overlap with those reported during craving responses in addicted subjects, supporting the commonalities in the neurocircuitry that underlie compulsive food intake and compulsive drug intake.

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What is the Directionality of the Onset of Comorbid Substance Use and Other Psychiatric Disorders?

Co-Chairs: Kevin P. Conway, Ph.D.
National Institute on Drug Abuse

Iván D. Montoya, M.D., M.P.H.
National Institute on Drug Abuse


Epidemiological and clinical studies routinely demonstrate extensive comorbidity between specific substance use and other psychiatric disorders. However, the directionality of their onset is not clear. Is it that substance use disorders trigger the onset of other psychiatric disorders? Or do individuals use drugs because of their mental disorder? Results from recent epidemiological, genetic and neurodevelopmental studies may be shedding light about the directionality of the onset of these disorders. Epidemiological studies are providing information about the age of onset and incidence of disorders. Genetic studies have shown common genetic predispositions to subsets of comorbid disorders and in some instances to specific combinations of comorbid conditions. Neurodevelopmental studies have shown the presence of abnormalities in neurobiological pathways that seem to antecede the development of comorbid conditions. Unfortunately, some of those studies still have methodological limitations including the reliability of data evaluating the onset and duration of the disorders, age of the subject, and period of time used to estimate disorder prevalence. Obtaining clear answers to the questions posed above is important in understanding the etiology of the disorders and planning treatment. Clinicians often try to identify the first condition to determine the most effective treatment approach. The purpose of this symposium is to discuss the directionality between substance use disorders and other psychiatric disorders, and their clinical implications.

Evidence of Directionality in Epidemiological Studies of Adults

Ronald Kessler, Ph.D.

The National Comorbidity Survey Follow-up (NCS-2) re-interviewed a probability sub-sample of respondents from the National Comorbidity Survey (NCS) a decade after the baseline NCS data collection. In order to study the extent to which temporally primary mental disorders predict the subsequent onset and progression of substance use disorders, the NCS-2 panel was used to study baseline (NCS) predictors of the first onset and progression of tobacco, alcohol, and illegal drug use, abuse, and dependence. A wide range of baseline (NCS) mental disorders significantly predicted increased risk of the subsequent (NCS-2) onset and persistence of nicotine use and dependence, while impulse-control disorders and, to a lesser extent, anxiety disorders predicted onset and progression of alcohol use disorders and illegal drug disorders. Further analysis is needed to study specification of these patterns as a function of multivariate profiles of mental disorders and age of onset of substance disorders.

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Genetic Factors and the Directionality of Comorbid Disorders

Michael Vanyukov, Ph.D.

The directionality of relationships between substance use disorders (SUD) and comorbid conditions is often unclear. Arbitrariness and heterogeneity of diagnoses lead to changes in the definition and position of the diagnostic thresholds and in the relative timing of the landmarks of natural histories of the disorders. Genetic studies show that despite the diversity of addictive substances, genetic variation in the risks for disorders related to them is largely nonspecific and shared with other comorbid behavioral disorders. This suggests that mechanisms other than those involved in pharmacologic action may play a significant role. Attention is drawn to the psychological traits developmentally predating drug abuse, including liabilities to childhood behavioral disorders. Genetic overlap between some of these indicators of psychological regulation and liability to SUD points to common factors that are likely involved in neurotransmission, neuromaturation, and physiological maturation. Studies longitudinally tracking genetic relationships of behavioral development and providing information on their mediators at biochemical and physiological levels (including neuroimaging), combined with structured environmental data, may be able to disambiguate comorbidities and elucidate the individual trajectory to SUD.

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Developmental Model to explain onset and directionality of comorbid disorders

Monique Ernst, Ph.D.

Directionality of onset of psychiatric disorders raises much interest because it can inform causality, and thus mechanisms underlying pathology. Here, a neurodevelopmental model of vulnerability to psychiatric disorders that are characterized by core deficits in reward systems is presented. We review findings from neuroimaging studies that address structural and functional patterns of neural circuitry engaged in reward-related processes, across both development and psychopathology. These findings concur to suggest that vulnerability to substance use and other psychiatric disorders could be conferred by the different timelines in maturation of neural circuits controlling behavior. Schematically, these circuits comprise the amygdala that promotes avoidance behavior, the ventral striatum that promotes approach behavior, and the medial prefrontal cortex that supervises these subcortical systems. Different maturational trajectories are proposed to result in states of imbalance relative to the normative adult coordination of motivated behavior. For example, risk taking behaviors peak in adolescence, and account for the sharp and paradoxical rise in morbidity and mortality during this period of life. The proposed model assumes a relative delay in maturation of the supervisory structures, in a context where the approach-related neural system is prominent relative to the avoidance behavior system. Although reductionistic, this model has the merit to be testable and to provide direction for the study of comorbid disorders.

At the conclusion of this presentation, the participant should be able to recognize the importance of the role of neurodevelopment in shaping deviant behavior as well as conferring risk for pathology emerging later in life. Designing environmental support that could help mitigate the consequences of a transient normative imbalance in the maturation of brain circuits that coordinate motivated behavior could be one way to avoid long-term health consequences. The participant should become sensitive to this issue that promotes the implementation of preventive measures early in life, particularly during adolescence.

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Treatment Implications of Determining the Directionality of Comorbid Disorders

Edward V. Nunes, M.D.

Co-occurring psychiatric disorders are associated with poor treatment outcome in substance-dependent patients, suggesting the hypothesis that specific treatment of co-occurring disorders should improve substance use outcome. However, accurate diagnosis of co-occurring disorders (e.g., depression) has been a challenge, since substance abuse may induce psychiatric symptoms. We review naturalistic studies on the impact of comorbidity on treatment outcomes of substance use disorders, and placebo-controlled trials of antidepressant medications in depressed, substance-dependent patients. The findings suggest that a careful diagnosis that takes account of the order of onset and offset of depression in relation to substance use is important in identifying depressive syndromes that affect prognosis and response to treatment. This supports the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) definition of independent depression, as opposed to substance-induced depression, although more research is needed to directly test the treatment implications of these diagnostic categories. This presentation explains the problems inherent in diagnosing psychiatric disorders among substance dependent patients; the DSM-IV categories of primary (independent) and substance-induced depression; and the data from clinical trials supporting the effectiveness of antidepressant treatment among depressed substance dependent patients, and the importance of diagnosis.

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Drug Abuse Treatment Within the Criminal Justice System: Addressing Our Nation's Public Health Needs

Co-Chairs: Timothy P. Condon, Ph.D.
National Institute on Drug Abuse

Redonna K. Chandler, Ph.D.
National Institute on Drug Abuse


An estimated 6.7 million people are involved with some aspect of the criminal justice system; nearly 2.1 million are in prison or jail and 4.8 million are participating in community-based supervision. The drug abuse, mental health, and HIV treatment needs of this population are tremendous. Among individuals incarcerated in State and Federal prisons, 69% were involved in drug or alcohol related offenses, and 56% reported using illicit drugs in the month prior to committing the offense for which they were incarcerated. In addition, a recent survey found that within jails, 52% of the women and 44% of the men met diagnostic criteria for alcohol and/or drug dependence.

Epidemiological studies have found high rates of mental health disorders and co-occurring mental health and drug abuse disorders among individuals in the criminal justice system. A survey of individuals entering the Washington State prison system found that 84% of the men met criteria for Axis I or Axis II mental health disorders and substance use disorders. Similarly, researchers found that 80% of probationers sentenced to participate in substance abuse treatment had serious mental health problems.

Finally, those involved in the criminal justice system are far more likely than the general public to have infectious diseases including HIV, AIDS, hepatitis C, and tuberculosis. In 1997, individuals passing through correctional facilities constituted 20-26 percent of people living with HIV in the United States, 29-43 percent of those infected with hepatitis C, and 40 percent of those with tuberculosis. Effectively reducing HIV and hepatitis C infection and providing treatment and services to individuals struggling with these serious health conditions are critical areas of intervention.

Research is currently underway to address the complex medical, psychosocial, and behavioral needs of individuals involved in the criminal justice system. This symposium examines the current state of scientific knowledge and findings from studies seeking to develop interventions and services to effectively address drug abuse, mental health disorders, and HIV among this population.

Findings From a National Survey of Correctional Agencies on Substance Abuse Treatment and Health Services: Who Can Get Served?

Faye S. Taxman, Ph.D.

The National Criminal Justice Treatment Practices Survey (NCJTPS) is designed as the first national survey to systematically describe the prevalence of substance abuse treatment programs across all correctional settings—prisons, jails, probation and parole offices, and other local community correctional agencies—for juvenile and adult offenders. The survey provides a picture of the substance abuse treatment programs that exist for different types of offenders and how these programs operate.

While our national strategy includes drug treatment as a method to control crime and to reduce the demand for drugs, the survey findings illustrate that substance abuse treatment services are not widely available for offenders in all phases of the correctional system (prisons, jails, and community correctional programs), and that the available services are not likely to change behavior. The survey found overall that:

  • Access to treatment services within correctional settings is minimal—less than 10 percent of adult offenders and about 20 percent of juvenile offenders across all settings receive the treatment that they need;
  • Less than half of the administrators report using a standardized tool to screen for substance abuse disorders;
  • Less than half of the correctional administrators report using an actuarial-based risk tool, despite the fact that research supports that high-risk offenders should be placed in more structured programs;
  • Inadequate numbers of treatment staff, and types of training for the staff, makes effective implementation of programs and services difficult;
  • Substance abuse treatment services are reported to be offered in 65 percent of the adult correctional programs (e.g., work release, intensive supervision, etc.), but the most frequently provided services are educationally oriented or low-intensive group therapy (less than four hours a week), which are unlikely to facilitate behavior change;
  • Most of the substance abuse services are less than the 90 days recommended by the literature; and
  • Treatment providers report using some of the consensus-driven, evidence-based practices, but in general, correctional administrators are unaware of these practices occurring in the programs offered to offenders.

As the first national survey of its kind, these findings raise question regarding the capability of the adult and juvenile correctional system to address effectively the drug use and criminal behavior of offenders—far too few programs and services exist and those that do exist are only offered to a small percentage of offenders and often do not incorporate the core principles of effective programs. The number and capacity of the services available indicates that access to needed services is a significant concern across all categories of adult and juvenile offender programs. Many of the services that are available are education-based substance abuse programs, which are useful, but are not a substitute for clinical services that can guide offenders through the behavior change process. Unless drug-dependent offenders or sufficient numbers of offenders are participating in substance abuse treatment programs, then it is unlikely that States will realize the reductions in recidivism that are desired and are often demanded to justify sustained funding for programs. The survey findings can be used strategically to improve services for offenders.

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The Long-Term Effectiveness of Corrections-Based Treatment for Drug-Involved Offenders

James A. Inciardi, Ph.D.

With growing numbers of drug-involved offenders coming to the attention of the criminal justice system, substance abuse treatment has become a critical part of the overall correctional process. The therapeutic community appears to be a treatment modality especially well suited for correctional clients because its intensive nature addresses their long-term treatment needs. A multistage therapeutic community treatment system has been implemented in the Delaware correctional system. The centerpiece of the treatment process occurs during work release—the transitional stage between prison and the free community. When evaluating this program, 690 individuals in four research groups were followed: treatment graduates with and without aftercare, treatment dropouts, and a “no treatment” comparison group. At 5 years after release, treatment graduates, with or without aftercare, had significantly greater probabilities of remaining both arrest-free and drug-free than did those without treatment. Treatment dropouts were slightly, though not significantly, less likely to be arrested on a new charge as those without treatment, but were significantly more likely to be drug free. These outcome data suggest that the widespread implementation of such treatment programs would bring about significant reductions in both drug use and drug-related crime.

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Mental Health and Co-Occurring Treatment Needs of Individuals in the Criminal Justice System

Roger H. Peters, Ph.D.

In this presentation, I review the mental health and co-occurring treatment needs of individuals in the criminal justice system. There are a number of challenges in providing services for this population, including the high risk for relapse, deficits related to educational and job skills, scarce prevention and treatment resources, and stigma related to co-occurring disorders and offender status. The prevalence of mental and substance use disorders are higher (approximately 15 percent) in criminal justice settings than in the general population. Unique areas that need to be addressed among this population include ingrained criminal belief systems and related behaviors, the interrelated nature of mental and substance use disorders, and managing the transition from institutional to community settings. Key features of evidence-based offender treatment programs include use of a highly structured approach, focus on symptom management vs. cure, basic life management and problem-solving skills, and “criminal thinking” groups. These programs feature isolated treatment units often situated within therapeutic communities, and provide several phases of treatment that include orientation/assessment, intensive treatment, and relapse prevention/reentry.

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Meeting the Medical Needs of Offenders

Peter D. Friedmann, M.D.

The jail and prison populations are drawn from underserved communities, to which the great majority will return. The high prevalence of medical conditions in the correctional population stems from current or past risk behaviors, including parental drug use; tattoos and unsafe sex; direct toxic effects of illicit drugs or adulterants; impoverished living conditions; and poor access to routine medical care in the community. Combined with high turnover rates in jails and prisons, the constitutional right to medical care for inmates provides an opportunity to improve public health through prevention and treatment of drug abuse and overdose; infectious diseases, including HIV/AIDS, hepatitis C, and hepatitis B; homicide; mental illness and suicide; motor vehicle accidents; cardiovascular disease and cancer.

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Pharmacotherapy in Correctional Settings for Addictive and Other Mental Disorders

Robert P. Schwartz, M.D.

Medication therapy for psychiatric and addictive disorders is part of the standard of care in community settings and should be a part of such care in correctional settings as well. The lack of access to medications for the treatment of psychiatric disorders has been the subject of class action litigation. There are several unique aspects of providing psychopharmacologic treatment in correctional institutions. These include avoiding the use of medication as a form of restraint, dealing with formulary restrictions, avoiding neuroleptic malignant syndrome, and attending to discharge planning. Opioid agonist therapy, with methadone or buprenrophine, is the most widely used and effective treatment in the community for heroin addiction. It has been used widely outside of the United States in correctional institutions but has been rarely available to U.S. inmates. This lack of access to treatment exists, despite evidence of methadone treatment’s efficacy obtained in a study of pre-release jail inmates in New York City conducted nearly 40 years ago, and despite more than 20 years of clinical experience in that jail with providing methadone detoxification from heroin addiction, initiating methadone maintenance, and continuing methadone maintenance for individuals enrolled in treatment at the time of arrest. An ongoing randomized clinical trial of methadone as a pre-release strategy for addressing heroin addiction, and a recently completed pilot study of buprenorphine in a pre-release prison in San Juan, show the ability of opioid agonist treatment to increase treatment enrollment and reduce heroin use after release from prison.

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A Picture of the Development of the Adolescent Brain: A Structural and Functional Assessment

Co-Chairs:Laurence Stanford, Ph.D.
National Institute on Drug Abuse

David Shurtleff, Ph.D.
National Institute on Drug Abuse


Maturation of the human brain is a complex, protracted process that is being extensively studied across several levels of analysis using neuroimaging, as well as cognitive and behavioral techniques. There is now considerable evidence that points to the adolescent period as a time during which critical neurobiological and cognitive capacities undergo maturation. Speakers will describe research looking at cortical and subcortical brain and cognitive changes in adolescence using magnetic resonance imaging, taking advantage of the capabilities of MRI for demonstrating structural, chemical, connectional, and functional patterns. Structural, chemical, and cognitive changes observed in healthy children, will be contrasted with developmental alterations related to early onset substance use disorder (SUD) and attention deficit hyperactivity disorder (ADHD) among others. Research on the development of basic cognitive control processes will describe how the maturation of cognitive processes can be related to the development and differential activation of frontostriatal brain regions. This symposium provides an overview of the changes in brain development and cognition associated with normal development and early onset behavioral and psychiatric disorders.

Mapping Adolescent Brain Maturation With Structural Magnetic Resonance Imaging

Elizabeth R. Sowell, Ph.D.

This talk highlights our recent work evaluating maturational change in brain structure during the childhood and adolescent years and how these structural changes relate to changing cognitive abilities and brain activation. The primary focus of this talk is on recent studies using cortical pattern matching (CPM) techniques to assess age-related changes in gray matter distribution and brain growth during the childhood and adolescent years. Specifically, we have found cortical thinning over large regions of the dorsal, frontal, and parietal lobes, and increased cortical thickness in primary language cortices in three independent samples of normal individuals studied both cross-sectionally and longitudinally. The spatial and temporal pattern of results, with incomplete development of frontal cortices during adolescence, is consistent with observations of increased risk taking behaviors during this period. We have also used CPM methods to assess relationships between cortical thickness and cognitive function on tests of general verbal intellectual functioning and have recently found cortical dissociations between improved phonological processing and motor skills within children studied longitudinally. Finally, we discuss findings of relationships between cortical thickness and brain activation on tests of language and executive function in normally developing children and adolescents with combined functional and structural MRI. An integration of these findings highlights the great variability in brain structure and function that occur during normative adolescent development and how brain structure may be a better predictor of cognitive function and brain activation than chronological age.

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Magnetic Resonance Spectroscopy Studies of Human Brain Development

Perry F. Renshaw, M.D., Ph.D. and Young-Hoon Sung, M.D.

Magnetic Resonance Spectroscopy (MRS) provides a unique in vivo assessment of the chemistry of the human brain. In addition, the role of MRS as a tool for characterizing human brain development has become more significant due to recent technical advances. Proton (1H) and phosphorus (31P) MRS detectable metabolites provide information with respect to neuronal viability from N-acetyl aspartate (NAA); membrane metabolism from choline containing compounds (Cho); phospholipid metabolism from anabolites (phosphomonoesters; PME) and catabolites (phosphodiesters; PDE); and bioenergetics from high-energy phosphate metabolites.

A MEDLINE literature search was done from 1989 to 2006 and initially 54 articles relevant to human brain development were identified. A much smaller number of these articles described changes occurring during adolescence.

White matter NAA levels, which reflect axonal development and myelination, increase steeply throughout the first decade of life and reach a peak around adolescence. Gray matter NAA levels decrease in adolescence relative to childhood, perhaps due to synaptic/neuronal pruning that mainly occurs in adolescence.

The Cho resonance shows a decreasing concentration with age early in life, but not during adolescence. Cho serves as an intermediate for cell membrane formation. PME and PDE levels generally reflect anabolic and catabolic states of freely mobile membrane phospholipids, respectively. Several study results suggest increasing PME levels or phospholipid turnover in adolescent brain white matter. This finding may reflect both increased glial and neuronal membrane synthesis.

MRS is a useful tool for exploring the maturational process and provides valuable in vivo information for further investigating the developmental and diseased human brain. Knowledge of dynamic metabolite changes with age using MRS, especially during the adolescent period, is important for monitoring and evaluating normal brain maturation.

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Risk Taking and the Adolescent Brain: Who is at Risk?

B.J. Casey, Ph.D.

Adolescence is a developmental period characterized by suboptimal decisions and actions that give rise to an increased incidence of unintentional injuries and violence, alcohol and drug abuse, unintended pregnancy, and sexually transmitted diseases. Traditional neurobiological and cognitive explanations for adolescent behavior have failed to account for the nonlinear changes in behavior observed during adolescence, relative to childhood and adulthood. This presentation provides a biologically plausible conceptualization of the neural mechanisms underlying these nonlinear changes in behavior as a heightened responsiveness to incentives and emotional reactivity, while impulse control is still relatively immature during this period. Recent human imaging and animal studies provide a biological basis for this view, suggesting differential development of limbic systems relative to top-down control systems during adolescence, compared to childhood and adulthood. This developmental pattern may be exacerbated in those adolescents with a predisposition toward risk taking, increasing the risk for poor outcomes.

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Prenatal Nicotine Exposure: How Does it Relate to Developmental Vulnerabilities?

Co-Chairs: Nicolette Borek, Ph.D.
National Institute on Drug Abuse

Allison Chausmer, Ph.D.
National Institute on Drug Abuse


Impressive advances have been made in examining relationships between prenatal nicotine exposure and developmental vulnerabilities among the exposed offspring. For example, a strong association has been reported between maternal smoking during pregnancy and disruptive behavior disorders in childhood. This symposium: (1) examines associations between prenatal nicotine exposure and neurobiological and behavioral vulnerabilities in the developmental period from birth into adolescence, (2) considers possible mechanisms underlying these relationships, and (3) examines implications of the research for clinical practice. Using focused presentations and interactions between the speakers and the attendees, the symposium addresses multiple developmental outcome areas, reflects findings from clinical and preclinical studies, and includes neurobiological, behavioral, and neuroimaging data. This symposium is intended for individuals with clinical and/or research interest in the effects of prenatal risk factors on the development of clinical disorders.

Neuroimaging Evidence of Altered Medial Temporal Lobe Function in Adolescent Tobacco Smokers With Prenatal Exposure to Maternal Smoking

Leslie K. Jacobsen, M.D.

Prenatal exposure to active maternal tobacco smoking elevates risk of cognitive and auditory processing deficits, and of smoking in offspring. Recent preclinical work has demonstrated a gender-specific pattern of reduction in cortical cholinergic markers following prenatal, adolescent, or combined prenatal and adolescent exposure to nicotine, the primary psychoactive component of tobacco smoke. Given the importance of cortical cholinergic neurotransmission to attentional function, we examined auditory and visual selective and divided attention in 181 male and female adolescent smokers and nonsmokers with and without prenatal exposure to maternal smoking. Groups did not differ in age, educational attainment, symptoms of inattention, or years of parent education. A subset of 63 subjects also underwent functional magnetic resonance imaging while performing an auditory and visual selective and divided attention task. Among females, exposure to tobacco smoke during prenatal or adolescent development was associated with reductions in auditory and visual attention performance accuracy that were greatest in female smokers with prenatal exposure (combined exposure). Among males, combined exposure was associated with marked deficits in auditory attention, suggesting greater vulnerability of neurocircuitry supporting auditory attention to insult stemming from developmental exposure to tobacco smoke in males. Activation of brain regions that support auditory attention was greater in adolescents with prenatal or adolescent exposure to tobacco smoke relative to adolescents with neither prenatal nor adolescent exposure to tobacco smoke. These findings extend prior preclinical work and suggest that, in humans, prenatal and adolescent exposure to nicotine exerts gender-specific deleterious effects on auditory and visual attention, with concomitant alterations in the efficiency of neurocircuitry supporting auditory attention.

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Prenatal Nicotine Exposure Induces Sex-Dependent Changes in Dopamine Pathways in Adolescent Brain

Frances Leslie, Ph.D.

Central dopamine systems serve numerous integrative neural functions and critically regulate action, emotion, motivation, and cognition. Dysregulation of these systems has been implicated in numerous disease states, particularly those in which there are cognitive, emotional, and/or motor deficits. Numerous clinical studies have shown that smoking during pregnancy can lead to long-standing neurobehavioral deficits in the offspring, many of which may result from central dopamine dysfunction, including attention deficit hyperactivity disorder, conduct disorder, cognitive deficits, and substance abuse. Using rats as a model, we have demonstrated that nicotine, the major psychoactive component of tobacco, targets dopamine systems in fetal brain. Chronic prenatal nicotine (PN) exposure, via an osmotic minipump, produces long-lasting changes in the properties of central dopamine neurons. In particular, sex-dependent changes in regional levels of dopamine and dopamine transporter (DAT) are observed in adolescent brains. Cocaine, which mediates many of its effects through blockade of DAT, also exhibits substantial behavioral differences in PN-treated rats, including alterations in drug self-administration, locomotion, and stereotypy. These findings suggest that not only smoking, but also the use of nicotine patch during pregnancy may substantially disrupt brain development. Thus, the safety of nicotine replacement therapy as a therapeutic regimen during pregnancy and adolescence must be evaluated more thoroughly.

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