Substance use disorders (SUDs) are chronic relapsing illnesses with devastating psychosocial, health and societal consequences. Differential susceptibility to SUDs in men and women is well known. Historically, prevalence of disorders such as cocaine abuse is higher in men than women, but emerging evidence indicates that adolescents girls are as likely or slightly more likely to use and abuse substances, such as cocaine, than adolescent boys. Stress is a major factor increasing the vulnerability to develop SUDs in girls and in women. Our current SCOR findings indicate that females are more vulnerable to the addictive properties of abusive drugs and that stress markers such as early trauma and altered stress neurobiology plays a pivotal role in the continued drug use and relapse cycle in women.
Cocaine addiction is a chronic relapsing disorder with devastating psychosocial, health and societal consequences. Although women are more likely to abuse nicotine and prescribed medications, a growing number of the illicit drug-using population, an estimated 4.7 million, are women and an ever-growing subgroup of those abusing drugs like cocaine are women. Such data underscore the need for studying sex-specific factors in cocaine dependence.
Substantial clinical data also exist to show a strong correlation between stress and drug abuse. Recent evidence suggests a role of stress in cocaine reinforcement, cocaine craving and in relapse. Stress has also been identified as one of the key factors in increasing the vulnerability to develop cocaine dependence in women. Women report stress and negative mood as playing a pivotal role in the continued drug use and relapse cycle. While there have been attempts to understand the mechanisms underlying the association between stress and cocaine addiction, systematic research on sex-specific factors that contribute to this association has been rare.
Using interdisciplinary approaches, the work of the SCOR will include examination of the effects of early life stress, sex hormones and stress hormones on cocaine reinforcement and the risk of developing cocaine dependence; as well as the contribution of sex-based factors in the association between stress and cocaine relapse. A better understanding of these sex-specific mechanisms will contribute to the development of new treatments and prevention strategies. Interdisciplinary studies will address the following three scientific goals:
These goals will be accomplished by means of basic science and clinical studies conducted in animals and in humans. A greater understanding of these interactions will directly affect the development of sex-specific prevention and treatment approaches that will enhance the health of addicted women and their families.
The following specific aims will be achieved by the SCOR:
Researchers in the Department of Psychiatry and affiliated with Women's Health Research at Yale will examine sex-specific factors in the association between stress and cocaine addiction with help from a new five-year, $5.8 million grant. The grant is funded by the National Institute on Drug Abuse and the National Institutes of Health's Office of Research on Women's Health. It will help establish a specialized center of research (SCOR) to study how women differ from men in response to stress and cocaine addiction.
Rajita Sinha, associate professor of psychiatry and director of addiction services at the Connecticut Mental Health Center, is the principal investigator and director of the SCOR. Carolyn Mazure, professor of psychiatry and director of Women's Health Research at Yale, and Bruce Rounsaville, M.D., professor of psychiatry, are co-directors of the SCOR. Other key investigators associated with the SCOR at Yale include Jane Taylor, associate professor of psychiatry; Marina Picciotto, associate professor of psychiatry, pharmacology and neurobiology; and Thomas Kosten, M.D., professor of psychiatry. Investigators interested in participating in the SCOR may send e-mail to rajita.sinha@ yale.edu for more information.
PROJECT 1: Sex and Stress Mechanisms of Vulnerability to Addiction (PI: Jane Taylor, Ph.D./Co-PI: Peter Olausson, Ph.D.).
PROJECT 2: Sex Differences in Stress Arousal in Cocaine-exposed Youth At-risk for Addiction (PI: Linda Mayes, MD).
PROJECT 3: Sex Differences in fMRI of Stress in Cocaine-Exposed Youth At-Risk for Addiction (PI: Marc Potenza, M.D., Ph.D.).
PROJECT 4: Sex Differences in Progesterone’s Effects on Responses to Stress and Drug Cues (PI: Rajita Sinha, Ph.D./Co-PI: Mehmet Sofuoglu, M.D., Ph.D.).