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PubMed2006

Genetics of dopamine and its contribution to cocaine addiction.

Cocaine addiction is a major health and social problem for which there are presently no effective pharmacotherapies. Many of the most promising medications target dopamine based on the large literature that supports its role in addiction. Recent studies show that genetic factors are also important. Rodent models and gene knock-out technology have helped elucidate the involvement of specific genes in the function of the dopamine reward system and intracellular cascades that lead to neuronal changes in this system. Human epidemiological, linkage, and association studies have identified allelic variants (polymorphisms) that give rise to altered metabolism of dopamine and its functional consequences. Individuals with these polymorphisms respond differently to psychostimulants and possibly to pharmacotherapies. Here we review the literature on genetic variations that affect dopamine neurotransmission, responses to psychostimulants and potential treatments for cocaine addiction. Behavioral responses to psychostimulants in animals with different or modified genetics in dopamine signaling are discussed. We also review polymorphisms in humans that affect dopaminergic neurotransmission and alter the subjective effects of psychostimulants. Pharmacotherapies may have increased efficacy when targeted to individuals possessing specific genetic polymophisms in dopamine's metabolic and intracellular messenger systems.

Animals↗
PubMed2001

Reducing resistance and denial by exercising ambivalence during the treatment of addiction.

Stage change models and motivational enhancement therapies have significantly influenced the therapeutic tactics clinicians employ in the treatment of addictive behaviors. While motivational enhancement strategies have addressed client ambivalence to increase motivation to change, this article suggests that focusing on ambivalence during treatment has even wider clinical utility than previously thought. Resistance reduction concentrates on exercising ambivalence without an investment in clients changing, thereby strengthening client tolerance for ambivalent thoughts and feelings. Exercising ambivalence reduces resistance to treatment and change by validating a wide array of possible outcomes through detailed exploration of how a behavior pattern works for a client. Since resistance reduction does not require clients to want to change for therapy to progress, exploring the decision-making process becomes paramount. A general discussion of the resistance reduction model, ambivalence, and how clients present for treatment precedes clinical case examples.

Adult↗
PubMed2000

Women's steps of change and entry into drug abuse treatment. A multidimensional stages of change model.

The Transtheoretical, or Stages of Change Model, has been applied to the investigation of help-seeking related to a number of addictive behaviors. Overall, the model has shown to be very important in understanding the process of help-seeking. However, substance abuse rarely exists in isolation from other health, mental health, and social problems. The present work extends the original Stages of Change Model by proposing "Steps of Change" as they relate to entry into substance abuse treatment programs for women. Readiness to make life changes in four domains-domestic violence, HIV sexual risk behavior, substance abuse, and mental health-is examined in relation to entry into four substance abuse treatment modalities (12-step, detoxification, outpatient, and residential). The Steps of Change Model hypothesizes that help-seeking behavior of substance-abusing women may reflect a hierarchy of readiness based on the immediacy, or time urgency, of their treatment issues. For example, women in battering relationships may be ready to make changes to reduce their exposure to violence before admitting readiness to seek substance abuse treatment. The Steps of Change Model was examined in a sample of 451 women contacted through a substance abuse treatment-readiness program in Los Angeles, California. A series of logistic regression analyses predict entry into four separate treatment modalities that vary. Results suggest a multidimensional Stages of Change Model that may extend to other populations and to other types of help-seeking behaviors.

Adolescent↗
PubMed2001

Sociopsychiatric characteristics of adolescents who use computers to excess.

OBJECTIVE: This study attempted to investigate current computer use by Korean adolescents, consequences of its excessive use and its relationship to psychiatric symptoms. METHOD: Questions for computer use, Computer-Related Addictive Behavior Inventory (CRABI), computer-induced behavioral alterations and Symptom Checklist-90-Revision (SCL-90-R) were assessed in 1296 students (12-19 years). RESULTS: Students were divided into three group users: minimal users (63.4%), moderate users (30.5%) and excessive users (6.1%). Computer-induced behavioral alterations occurred most frequently to excessive users and it was significantly correlated with total CRABI score. Average score on nine symptom dimensions and three global indexes of SCL-90-R were able to discriminate four decreasing orders of subjective psychiatric complaints: most frequent in excessive users and then moderate, non- and mild users, in order. CONCLUSION: Those adolescents with excessive computer use were found to show serious sociopsychiatric problems.

Adolescent↗
PubMed2005

Effects of dopamine D2 receptor (DRD2) and transporter (SLC6A3) polymorphisms on smoking cue-induced cigarette craving among African-American smokers.

Cue-induced craving for addictive substances has long been known to contribute to the problem of persistent addiction in humans. Research in animals over the past decade has solidly established the central role of dopamine in cue-induced craving for addictive substances, including nicotine. Analogous studies in humans, however, are lacking, especially among African-American smokers, who have lower quit rates than Caucasian smokers. Based on the animal literature, the study's objective was to test the hypothesis that smokers carrying specific variants in dopamine-related genes previously associated with risk for addictive behaviors would exhibit heightened levels of cigarette craving following laboratory exposure to cues. To this end, cigarette craving was induced in healthy African-American smokers (n=88) through laboratory exposure to smoking cues. Smokers carrying either the DRD2 (D2 dopamine receptor gene) TaqI A1 RFLP or the SLC6A3 (dopamine transporter gene) 9-repeat VNTR polymorphisms had stronger cue-induced cravings than noncarriers (Ps <0.05 and 0.01, respectively). Consistent with the separate biological pathways involved (receptor, transporter), carriers of both polymorphisms had markedly higher craving responses compared to those with neither (P<0.0006), reflecting additive effects. Findings provide support for the role of dopamine in cue-induced craving in humans, and suggest a possible genetic risk factor for persistent smoking behavior in African-American smokers.

Adult↗
PubMed2000

Clinical perspectives for the study of craving and relapse in animal models.

Several major clinical models of alcoholism in which craving plays a role are summarized and key questions are raised regarding the course of craving in the emergence of alcoholism, how it varies in different stages of the disorder (e.g. active alcoholic, withdrawal, protracted abstinence) and what craving may contribute to major signs and symptoms of alcoholism. Turning to animal models, a plea is made for development of a standardized definition of human craving that can be represented and operationalized in animal models. Until there is scientific consensus on such a definition, four ways are elucidated in which animal model research can contribute to advances in our knowledge of human craving and the role it plays in addictive behavior: (1) engaging both basic and clinical researchers to identify parallel constructs of craving and predictors of craving for adoption in comparative human and animal model studies; (2) conducting exploratory research on craving in animal models using relapse to drinking as the dependent measure; (3) identifying mechanisms that underlie clinical signs and symptoms of alcoholism in animal models; and (4) identifying genetic models in basic research that account for variations in response to alcohol that may also occur in humans. This latter point is made in a discussion of the genetic contribution to voluntary alcohol consumption, the alcohol deprivation effect, tolerance and dependence, as illustrated by differences between alcohol-preferring (P) rats and -nonpreferring (NP) rats. The review concludes with four questions and issues that need to be among those that guide future research on craving.

Alcohol-Related Disorders↗
PubMed1992

Drug abuse, dependence, and addiction in chronic pain patients.

It is claimed that a significant percentage of chronic pain patients suffer from drug/alcohol abuse/dependency/addiction. To address this question, 24 articles alluding to chronic pain patient drug/alcohol dependence/addiction were reviewed according to the following criteria: method for drug misuse diagnosis, which drug misuse diagnosis used (abuse, dependence, or addiction), and percentage of patients within each diagnostic category of drug misuse. The result of the review indicated that only seven studies utilized acceptable diagnostic criteria and/or definitions for the drug misuse diagnoses and gave percentages of drug misuse. Within these seven studies, the prevalence percentages for the diagnoses for drug abuse, drug dependence, and drug addiction were in the range of 3.2-18.9%. It is concluded that these diagnoses occur in a significant percentage of chronic pain patients. However, there is little evidence in these studies that addictive behaviors are common within the chronic pain population.

Behavior, Addictive↗
PubMed2000

Helping patients with Crohn's disease quit smoking.

Smoking is not only a risk factor for Crohn's disease, but ongoing smoking is associated with a poorer disease course. Therefore, smoking cessation should be an important treatment strategy for Crohn's disease patients who smoke tobacco. Recent improvements in understanding how people quit smoking and the development of pharmacological interventions, such as nicotine patches and bupropion, have improved cessation rates. In this article, we first briefly review the evidence supporting the adverse effects of smoking on the disease course. We next review the current understanding of how people change addictive behaviors, such as smoking. We then describe how the gastroenterologist can aid the patient with Crohn's disease to quit smoking, including appropriate and brief counseling strategies and the use of adjunctive treatments. Given the improvements in smoking cessation strategies, all patients with Crohn's disease should be strongly advised to quit smoking and be aided in doing so.

Administration, Cutaneous↗
PubMed1998

Obsessive-compulsive disorder and ventromedial frontal lesions: clinical and neuropsychological findings.

OBJECTIVE: The authors sought to determine the long-term outcome of subjects with severe and refractory obsessive-compulsive disorder (OCD) who had undergone ventromedial frontal leukotomy during the 1970s. Special emphasis was given to the analysis of specific lesion sites. METHOD: Sixteen OCD subjects who had undergone ventromedial frontal leukotomy were evaluated clinically and neuropsychologically and compared to seven well comparison OCD subjects without leukotomy. The 16 leukotomized subjects were divided into three groups according to the main lesion sites as determined by current magnetic resonance imaging scans. RESULTS: The leukotomized OCD subjects showed significant improvement of obsessive-compulsive symptoms; subjects with frontostriatal lesions tended to have improved most. The subjects with combined diagnoses of OCD and obsessive personality disorder (N = 3) had improved significantly less. Of 11 subjects with lesions of the ventral striatum, eight had developed substance dependence postoperatively. Intellectual functions were largely preserved in subjects with ventromedial frontal lesions only or frontostriatal lesions. However, all subjects showed subnormal performance on the Wisconsin Card Sorting Test. Subjects with lesions of the dorsolateral frontal convexity also showed memory problems, attentional slowing, and lower performance IQ. CONCLUSIONS: Restricted ventromedial frontal leukotomy should be discussed as a last-resort treatment for severe and refractory OCD but not obsessive personality disorder. Lesions of the ventral striatum were significantly related to the occurrence of substance dependence, suggesting a role of this area in human addictive behavior.

Behavior, Addictive↗
PubMed1996

Psychology of computer use: XL. Addictive use of the Internet: a case that breaks the stereotype.

This case involves a homemaker 43 years of age who is addicted to using the Internet. This case was selected as it demonstrates that a nontechnologically oriented woman with a reportedly content home life and no prior addiction or psychiatric history abused the Internet which resulted in significant impairment to her family life. This paper defines addictive use of the Internet, outlines the subject's progression of addictive on-line use, and discusses the implications of such addictive behavior on the new market of Internet consumers.

Adult↗
PubMed1999

The subjective experience of craving: an exploratory analysis.

Craving is a motivational state associated with a variety of addictive behaviors. To date no studies have systematically asked substance misusers to describe their subjective experience of craving. The aim of the present study was to examine the common themes found in descriptions of craving and the situations that give rise to the experience of craving in a sample of substance misusers (N = 23). Analyses of the interview text revealed that the subjective experience of craving is heterogeneous. Eight dimensions were found to be associated with the subjective experience of craving: specificity, strength, positive outcomes, behavioral intention, thoughts, physical symptoms, affect, and cues. Individual differences in the extent to which each of these dimensions is experienced across substance misusers was evident in the interview text. Implications of these results for the development of a multivariate theory of craving are discussed.

Adult↗
PubMed1998

Stress and low birth weight: a structural modeling approach using real life stressors.

This study presents a structural equation model describing the influence of stressful life experiences on low birth weight. Data were gathered prospectively in two waves from 5295 inner-city women as part of a city-wide preterm birth prevention project. Using interviews and the medical record, over 200 measures were gathered on each mother and her infant, where each measure was included because of its relevance documented in the risk factor literature. Seventeen of these measures reflected real life stressful experiences and through measurement modeling, eleven of these measures were chosen to represent three underlying measures of stress: economic stress, family stress, and the lack of social support. This study incorporates these psychosocial stressors into a full structural equation model to show their influence on addictive behavior and low birth weight. The full model emerged from tests of alternative causal conceptualizations of how these stressors influence each other and low birth weight--whether their influence on low birth weight in simple and direct, or whether their influence is mediated by addictive behaviors. The model was tested on the first wave, a sample of 3205, and cross-validated on the second wave, a sample of 2090. The model shows that economic stress influences both social support and family stress, but has no direct influence on low birth weight: that social support, or its absence, influences addictive behavior, but has no direct influence on low birth weight, and that family stress influences addictive behavior, and consistent with 30 years of research on humans, has no direct influence on low birth weight. Finally, the mother's history of medical risks shows an independent influence on low birth weight, while her age does not. Age, however, shows a strong influence on addictive behavior. The study demonstrates how structural equation modeling can be used to create and test alternative conceptualizations of how stress affects low birth weight. There are strong implications for planners of prenatal care programs.

Female↗
PubMed1998

Addiction: a new paradigm.

The older view of addiction was that people became addicted because they were ignorant of the risks of addiction, they were unhappy, or they lacked healthy opportunities. Once addicted, they were hooked by physical dependence, causing them to continue use despite wanting to quit. The new paradigm of addiction focuses on reward and the powerful experience of falling in love with the feeling that addictive behaviors produce. Potential addicts seek brain reward and are heedless of the risks, of which they are seldom ignorant. Withdrawal is largely irrelevant. The problem of addiction is the power of brain reward. The new view of addiction has important implications for prevention, treatment, public policy, and medical treatment with controlled substances.

Behavior, Addictive↗
PubMed2004

Evidence for addiction-like behavior in the rat.

Although the voluntary intake of drugs of abuse is a behavior largely preserved throughout phylogeny, it is currently unclear whether pathological drug use ("addiction") can be observed in species other than humans. Here, we report that behaviors that resemble three of the essential diagnostic criteria for addiction appear over time in rats trained to self-administer cocaine. As in humans, this addiction-like behavior is present only in a small proportion of subjects using cocaine and is highly predictive of relapse after withdrawal. These findings provide a new basis for developing a true understanding and treatment of addiction.

Animals↗
PubMed2005

Addiction and its brain science.

AIMS: To illustrate how modern neurobiological approaches will help to identify the neurocircuits and genes involved in addictive behavior. BACKGROUND: The current disorder concept of addiction includes neurobiological foundations and neurobiological research assuming irreversible molecular and structural changes within the brain dopamine reinforcement system, constituting the 'molecular and structural switch' from controlled drug intake to compulsive drug abuse. However, those irreversible changes have not so far been identified and it is suggested that in addition to the mesolimbic dopamine system, other brain systems including the mesocortical and nigrostriatal pathways as well as their non-dopaminergic feedback-loops might be involved in addictive behavior. NEUROBIOLOGICAL APPROACH: A three-step neurobiological approach is described that allows in a first step via novel animal models and imaging techniques to identify the neuroanatomical sites mediating voluntary drug intake, reinstatement of drug-seeking behavior, relapse, loss of control and drug intake despite negative consequences. In a subsequent step, forward genetic approaches including quantitative trait loci (QTL)-analysis and gene expression profiling are helpful in identifying so-called candidate genes. In a final step, conditional animal mutants and selective pharmacological tools are used to functionally validate candidate genes. Following this validation process, the transfer to the human situation has to be made and candidate genes have to be verified further in well-phenotyped cohorts of addicted patients. CONCLUSION: This three-step neurobiological approach, that must involve an interdisciplinary team including experimental psychologists, geneticists, molecular biologists and finally clinical addiction researchers, will allow us to understand where and how the addicted brain goes awry.

Animals↗
PubMed1990

Spirituality: the silent dimension in addiction research. The 1990 leonard ball oration.

Researchers currently recognize and incorporate psychological, biomedical, and social determinants in the study of addictive behaviors. Yet spiritual aspects of addiction and recovery remain virtually unstudied, despite the fact that spirituality is given central importance in Alcoholics Anonymous and in the lives of many individuals. Traditional spiritual concepts have been relabelled to remove their transcendent dimension, and addiction researchers have acted as though spirituality plays no role in the lives of those they study. Consequently an entire class of potentially important variables is being overlooked. A majority of variance in addictive behaviors and treatment outcomes remains unexplained, a portion of which might be accounted for through the study of spiritual dependent, moderator, and independent variables. Behavioural scientists have begun to acknowledge the role of complex spiritual, moral, and decisional processes in the addictive behaviours. Though uncomfortable in some ways for both believers and unbelievers, the scientific study of spiritual processes may improve our understanding of the addictive behaviours, and our ability to prevent and treat these enduring problems.

Journal Article↗
PubMed2000

Gender-role stereotypes and interpersonal behavior how addicted inpatients view their ideal male and female therapist.

This study focuses on the influences of self-perceived interpersonal behavior of addicted inpatients (n = 107) on the stereotypes of their ideal male and female therapist. Based on the interpersonal model of personality patients were asked to describe their ideal male and female therapist. Perceptions of interpersonal behavior of the ideal therapist are determined by the self-perceived interpersonal behavior of the patients rather than by their gender. Ideal therapists are described as managerial-autocratic and sociable-extravert, which is in almost perfect accordance with the self-perceptions of therapists. Although most of the patients prefer a female therapist, the interpersonal behavior of a male or a female therapist does not differ significantly. The results are discussed from the viewpoint that mutual expectations and preferences between patients and therapists are thought to be of crucial importance for the outcome of therapy. In the process of matching patients and therapists, these expectations should not only be assessed, but also used to improve the final matching.

Adult↗