تفاوت های جنسیتی در مواجهه واکنش پذیری محرک و پیامد 9 ماه

Abstract Gender differences have been shown to be related to the course of cocaine dependence and treatment. While previous research has shown cue exposure procedures to be somewhat effective at reducing reactivity of substance dependent individuals to drug related stimuli, the few studies that have examined gender differences in craving and cue-reactivity have yielded equivocal results. We have recently demonstrated that an active cue-exposure procedure that featured cocaine-dependent individuals receiving immediate feedback about their level of physiological arousal following videotaped exposure to cocaine-related stimuli was capable of positively influencing in-treatment (helplessness, abstinence efficacy) as well as 9-month followup outcome (i.e., urinalysis) indices (Sterling, R., Gottheil, E., Murphy, J., & Weinstein, S. (2001). Cue exposure and abstinence efficacy. College on Problems of Drug Dependence, Phoenix, AZ, June 17, 2001). The purpose of the present study was to determine whether differential in-treatment or 9-month followup outcomes were obtained for male and female study participants. Subjects in this study were 81 individuals (47 male/34 female) who met DSM-IV criteria for cocaine dependence and who had consented to be randomly assigned to either the active cue-exposure or control conditions. Participants were compared along a myriad of pre-treatment, in-treatment, and 9-month followup measures. Other than males reporting more recent employment, there was no obvious systematic pattern of differences on pre-treatment indices. No gender differences in treatment retention were observed. With respect to 9-month followup, no gender differences on measures of addiction severity, psychological functioning, or urinalyses were noted. However males were more “cue-reactive” and more successful at establishing control over their reactivity to the cocaine stimuli. Additional research is needed to determine whether these differences in reactivity can be more clearly defined and utilized positively in a treatment setting.

Introduction Research studies on the treatment of addiction have indicated that outcomes may be improved by targeting treatment strategies to specific sub-populations of treatment-seeking substance-abusing individuals Grissom, 1997, McLellan et al., 1997 and Project Match Research Group, 1997. For example, patient gender has been implicated as a factor that influences both the course and treatment of cocaine dependence Fiorentine & Hillhouse, 1999, Griffin et al., 1989, Lundy et al., 1995, McCance-Katz et al., 1999 and Weiss et al., 1997. McCance-Katz et al. (1999)demonstrated that women tended to favor a more addictive route of drug administration and, as a consequence, experienced a more rapid deterioration in the quality of their lives and addictive behaviors. Similarly, other studies Griffin et al., 1989 and Weiss et al., 1993have reported evidence of more drug-related difficulties and psychopathology in cocaine dependent females. In contrast, others have not demonstrated the clinical significance of gender as a factor in the addictive process Denier et al., 1991, Dudish & Hatsukami, 1996, Erikson & Murray, 1989 and Lundy et al., 1995. A recent promising approach to the treatment of cocaine addiction has involved progressive cue-exposure in which patients' subjective and objective responses to drug related stimuli are extinguished Childress et al., 1987 and O'Brien et al., 1990. In a series of recent studies, researchers have begun to quantify the degree to which gender is a factor in classical conditioning paradigms and the extinction of reactivity to drug related cues/triggers Avants et al., 1995 and Robbins et al., 1999. For example, Elman, Karlsgodt, and Gastfriend (2001)examined differences in craving between 10 women and 11 men participating in an imaging study of the effects of cocaine on brain activity. Their results indicated that on a series of measures women both significantly craved cocaine more than men and were more reactive to drug related stimuli. Robbins et al. (1999)examined the physiological reactivity of a sample of DSM-III-R (American Psychiatric Association, 1987)diagnosed cocaine dependent individuals to drug-related stimuli, and found little difference in both subjective and objective reactivity to cocaine related stimuli presented via multiple methods (i.e., audio, video, and in-vivo). Similarly, results from Avants et al. (1995)indicated that methadone-maintained cocaine dependent women were no more likely to be responsive to cocaine related stimuli than a sample of male counterparts matched for addiction severity. The purpose of the current study was to further research gender-based differences in cue reactivity and outcome. Using a variant of the cue-exposure procedure employed by Robbins et al. (1999), we examined whether male and female participants in a cue-exposure study that included providing direct feedback about arousal levels differed in both levels of physiological reactivity and their ability to establish control over reactivity to drug-related stimuli. In addition, we examined whether there were gender-related differences on measures of addiction severity and psychological well being (i.e., helplessness, abstinence efficacy), as well as 9-month followup outcomes (i.e., urinalysis, addiction severity indices).

Results 3.1. Demographics and intake measures Gender differences on study entry measures were examined using t-tests for the continuous and chi-square for the categorical variables. No meaningful pattern of differences on most admission demographic measures were observed between the male (n=47) and female (n=34) participants. For example, there were no statistically significant differences in age at admission, years of cocaine use, race, marital status, and grade. While the proportion of male and female participants reporting employment at study entry did not significantly differ, male participants reported significantly more months employed in the 2 years prior to study entry (M=8.42 and 3.32 for male and female participants, respectively), t=3.08, p=.003. In general, composite and severity scores on the ASI did not differ between male and females. The only significant differences indicated that female participants scored higher on the Legal scale of the ASI (M=.04 and .11 for males and females, respectively), t=2.28, p=.026. No other pre-study differences in either indices of addiction severity (i.e., years of use, number of prior treatment episodes, days of cocaine use in the last month, and days of abstinence prior to treatment) or psychological functioning (SCL-90-R, BDI, LHS, SCQ, SEI, ASQ) were noted with the exception that women scored higher on the Somatization scale of the SCL-90, t=2.01, p=.048. 3.2. Gender and cocaine cue reactivity/craving Forty individuals were randomly assigned to the ACE condition. Results indicated a non-significant trend for male participants (n=24) to attend more of these sessions (M=5.46±4.97 and 3.00±3.85 for male and female subjects, respectively), t(38)=1.67, p=.10, experience more cocaine cue-induced arousals (M=7.42±8.23 and 3.81±5.55 for males and females, respectively), t(38)=1.53, p>.05, and in absolute numbers, exhibit more success at establishing control over their cue-induced arousals (M=6.38±7.94 and 2.69±4.08 for males and females, respectively), t(38)=1.89, p=.08. To account for gender differences in the absolute number of sessions attended, we created a success ratio by dividing the absolute number of success trials by the total number of arousals. Results indicated that male participants successfully reduced their arousal to a greater proportion of cocaine stimuli to which they became aroused than did females (M=.61±.53 and .31±.40 for male and female subjects, respectively), t(39)=1.93, p=.06. A 2×2×2 repeated measures analysis of variance crossing gender and study condition (i.e., control vs. active cue exposure) and using craving measures at study entry and study end as the repeated measure allowed us both to conduct a more complete test of the gender effects noted and to determine whether the gender differences in cue reactivity generalized to measures of cocaine craving. Introducing the control condition into this analysis allowed us to better tease apart the effects of gender, recognizing that the effects on reactivity noted may have been an effect of a general tendency on the behalf of males to be more responsive to drug-related stimuli. While some study entry to study-end changes in craving were observed (see Table 1), the 3-way interaction term which would have indicated differential gender effects did not begin to approach conventional levels of significance, F(1, 56)=.39, p=ns. Two-way interaction terms were also non-significant. Thus, it appears that while exposure to the ACE procedure yielded differential male and female response on objective measures, similar effects were not observed on indices of subjective appetitive response (i.e., cocaine-craving). Table 1. Changes in Cocaine-Craving: Study entry to study end* Control Active Cue-Exposure Male Female Male Female Pre-craving 1.80 .68 1.52 1.87 Post-craving 1.75 1.03 1.28 1.55 * 7-point Likert scale where higher values indicate greater craving. Table options Urinalyses were conducted each week of study participation. Two-way analysis of variance crossing study condition and gender yielded a borderline significant interaction, F(1, 55)=3.10, p=.08. These results while not statistically significant were consistent with the findings regarding cue reactivity, and indicated that the females assigned to ACE provided relative to the other participants the smallest proportion of cocaine free urines. 3.3. Nine-month followup Fifty-nine cases (73%) across both study conditions were followed. Followup data included ASI composite scores, number of self-reported days of cocaine use in the month prior to interview, and patient reports of helplessness (LHS), self-esteem (SEI) and efficacy to remain abstinent (SCQ). Three-way repeated measures analyses of variance crossing study condition, participant gender and time (i.e., study entry/followup) were used to look for differential gender followup effects amongst those assigned to active cue-exposure. As can be seen in Table 2, main effects of time demonstrating significant reductions in ASI drug and alcohol composite scores from intake to followup were observed. A significant main effect of time indicating a decrease in the self-reported number of days of cocaine use from intake (8.16±9.69) to followup (4.52±7.87) was also observed. A two-way interaction of gender and time for the Medical composite score was also observed. This interaction, which suggests that males grew worse in ASI assessed medical difficulties from intake to followup while females improved, is not immediately explicable. Regarding the additional psychological measures, main effects of time indicating positive changes in self-esteem and learned helplessness were obtained. Table 2. Nine-month followup effects Variable Intake Followup Sig Male Female Male Female Addiction severity ASI Composite Scores Medical .10 .24 .27 .14 B Legal .03 .15 .02 .03 A Alcohol .18 .24 .13 .07 A Drug .19 .18 .14 .11 A Family .16 .20 .25 .22 ns Employment .86 .92 .68 .83 A Psych .23 .30 .28 .41 ns Days Cocaine Use Last Mo. 8.9 7.1 4.2 5.0 A Study related psychological measures Coopersmith 49.63 52.21 57.19 58.95 A SCQ 68.72 69.06 70.71 69.79 ns LHS 43.96 47.45 41.48 43.60 A A=Time p< .05. B=Gender * Time p< .05.