Severity of childhood trauma is predictive of cocaine relapse outcomes in women but not men

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Abstract

We prospectively examined the gender-specific effects of childhood trauma on cocaine relapse outcomes in an inpatient sample of treatment engaged cocaine dependent adults. Cocaine dependent men (n = 70) and women (n = 54) participating in inpatient treatment for cocaine dependence were assessed on severity of childhood trauma and followed for 90 days after discharge from treatment. Greater severity of childhood emotional abuse was associated with an increased risk of relapse in women. Severity of emotional abuse, sexual abuse, and overall childhood trauma was associated with the number of days cocaine was used during follow-up in women, as was the association of severity of physical abuse and overall childhood trauma with the average amount of cocaine used per occasion. No associations between childhood trauma and cocaine relapse outcomes were found in men. These findings demonstrate that childhood trauma increases the likelihood of cocaine relapse and drug use escalation after initial relapse in women but not in men. Comprehensive assessments of childhood trauma and specialized treatments that address trauma-related pathophysiology could be of benefit in improving cocaine treatment outcomes in women.

Introduction

Childhood trauma places individuals at risk for disturbances in biological and psychological development (Cicchetti and Toth, 2005) and can lead to the manifestation of psychiatric and substance use disorders (Kendler et al., 2000, MacMillan et al., 2001, Wexler et al., 1997). However, men and women may differ with respect to the nature and consequences of childhood trauma with gender playing a role in determining the types of trauma to which children are exposed and their pathological reactions to specific traumatic events. For instance, while both boys and girls are exposed to various types of childhood trauma, girls are more likely to experience childhood sexual abuse (Ullman and Filipas, 2005, Walker et al., 2004), whereas rates of childhood physical abuse have been reported higher in boys (Thompson et al., 2004). Furthermore, although men and women are both adversely affected by specific types of childhood trauma, the association between childhood trauma and the risk of developing psychiatric and substance use disorders is generally stronger in women (MacMillan et al., 2001, Simpson and Miller, 2002, Sinha and Rounsaville, 2002, Thompson et al., 2004, Widom and Hiller-Sturmhofel, 2001, Widom and White, 1997). For example, childhood trauma is a risk factor in the development of anxiety and mood disorders, both of which are more likely to occur in women (Breslau, 2002, MacMillan et al., 2001, Sinha and Rounsaville, 2002, Thompson et al., 2004, Weiss et al., 1999). Post-traumatic Stress Disorder (PTSD), which is frequently diagnosed in childhood trauma survivors (Rodriguez et al., 1996, Widom, 1999), is more likely to develop following childhood sexual abuse in females as compared to males (Walker et al., 2004). Moreover, while substance use disorders are more prevalent in men, the association between childhood trauma and the development of substance use disorders is generally stronger in women (Hyman et al., 2006, MacMillan et al., 2001, Simpson and Miller, 2002, Sinha and Rounsaville, 2002).

These findings indicate that there are gender-specific interactions between childhood trauma and the development of psychiatric and substance use disorders. In contrast, the effects of childhood trauma on substance use relapse and the subsequent clinical course of substance use disorders has received less attention. If research indicates that childhood trauma has enduring gender-specific effects on the clinical course of these disorders, it could have significant implications for the treatment of substance use problems.

There is growing evidence of gender differences in the development and course of substance use disorders including cocaine dependence. Although men are twice as likely to be cocaine dependent than women, women exhibit a more rapid progression of the illness with greater negative consequences compared to men (McCance-Katz et al., 1999, Sinha and Rounsaville, 2002). Cocaine dependent women also report fewer years of regular cocaine use, spend less money on cocaine, have less extensive treatment histories, and are more likely to test positive for cocaine at treatment intake than men (Wong et al., 2002).

Furthermore, preclinical evidence indicates that female rats are more sensitive to the behavioral effects of psychostimulants and self-administer cocaine more rapidly than male rats (Lynch et al., 2002). Recent evidence has also shown that female rats self-administer more cocaine, binge for longer time periods, and display a loss of circadian control over intake as compared to male rats, effects that appear to be estrogen dependent (Lynch and Taylor, 2004, Lynch and Taylor, 2005). Indeed, animal models appear to demonstrate a greater vulnerability to the compulsive aspects of cocaine abuse in females, findings that when extrapolated to humans would suggest a gender-specific vulnerability to a more severe course of the disorder in women as compared to men.

Cocaine dependence is a chronic relapsing disorder despite the availability of efficacious treatments (Carroll et al., 2004, Higgins et al., 1994, Kang et al., 1991, O’Brien et al., 1998). Stress-related factors contribute to the chronic, relapsing nature of the disorder (O’Brien et al., 1998, Sinha, 2001, Sinha et al., 2006), and clinical surveys indicate that women may be more likely to relapse in the context of stress and negative affect whereas men are more susceptible to drug cue-related relapse precipitants (McKay et al., 1996). Cocaine dependent men and women also differ in the biological markers of stress that could be affected by the extent and severity of childhood traumatic experiences (Fox et al., 2006, Heim et al., 2000).

Although some previous research supports a positive association between childhood trauma and treatment outcome following inpatient alcohol treatment, no gender differences were found and the association was no longer significant when current disorders and specific demographic variables (e.g., education level and marital status) were included in multivariate analyses (Greenfield et al., 2002). Thus, a comprehensive examination of the various forms of childhood trauma and the influence of gender on relapse to cocaine in individuals with primary cocaine dependence has not been conducted thus far. On the basis of the aforementioned preclinical and human data on gender differences in the effects of childhood trauma on risk of developing substance use disorders, in the clinical course of cocaine dependence, and in stress responses, we hypothesized that the effects of childhood trauma on relapse susceptibility and the course of cocaine dependence will be gender-specific and observed more strongly in women than men. This hypothesis was tested in a sample of cocaine dependent men and women engaged in inpatient treatment for cocaine dependence. All participants were administered a childhood trauma measure upon admission and prospectively followed for 90 days after discharge from inpatient treatment. The primary outcomes were time to cocaine relapse and escalation of cocaine use as measured by number of days of cocaine use and amount of cocaine used per occasion during the follow-up period.

Section snippets

Participants and procedures

Men and women, between the ages of 19–50 (mean age: 37.1, S.D. = 6.4), seeking inpatient treatment for primary cocaine dependence were evaluated for participation in a comprehensive research program evaluating the effects of childhood and recent life stressors, laboratory-induced stress responses, and their effects on cocaine relapse outcomes (see Sinha et al., 2003, Sinha et al., 2006 for additional information on study procedures). One hundred and thirty two individuals (75 men and 57 women)

Data analysis

Men and women were compared on demographic variables (age, ethnicity, employment status, educational background), age of first alcohol and cocaine use, lifetime and current prevalence of mood disorders, anxiety disorders including PTSD, substance abuse disorders, and baseline cocaine use (frequency and amount) using chi-square tests for categorical variables and Wilcoxon rank sum tests for continuous variables. These variables were also examined for their association with cocaine relapse

Relapse rates

On the basis of urine toxicology screens and self-report data, 90 (72.6%) participants [49 (70.0%) men and 41 (75.9%) women] of the 124 individuals that were successfully followed had returned to cocaine use during the 90-day follow-up period.

Demographics and sample characteristics

Demographic variables, baseline drug use measures, and lifetime and current prevalence rates of psychiatric and substance use disorders are presented by gender in Table 1. Please note that as individuals who were on psychiatric medications were excluded,

Discussion

The present findings indicate that childhood trauma increases the likelihood of cocaine relapse and cocaine use escalation after initial relapse in women but not in men. This association remained significant even after accounting for the contribution of baseline cocaine use and PTSD on the escalation of cocaine use. Interestingly, associations differed depending upon the form of childhood trauma experienced. Only greater severity of emotional abuse was associated with increased risk of cocaine

Conflict of interest

All authors declare that they have no conflicts of interest.

Acknowledgements

We acknowledge the contributions of staff at the Yale Research Program on Stress, Addiction and Psychopathology, Women's Health Research at Yale, Clinical Neuroscience Research Unit and the Substance Abuse Treatment Unit of the Connecticut Mental Health Center, Yale University School of Medicine. We also thank Dr. Benjamin Toll for his editorial comments and Julie Hansen for assisting the preparation of this manuscript.

Contributors. All authors contributed to and have approved the final

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    This research was supported by the National Institutes of Health (NIH) grants R01-DA11077 (RS), P50-DA16556 (RS) and K02-DA17232 (RS) and the NIH Office of Research on Women's Health. The NIH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.

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