ویژگی اختلال اضطراب اجتماعی به عنوان یک عامل خطر برای مصرف الکل و وابستگی به حشیش

Abstract Social anxiety disorder (SAD) is highly comorbid with alcohol use disorders (AUDs) and cannabis dependence. However, the temporal sequencing of these disorders has not been extensively studied to determine whether SAD serves as a specific risk factor for problematic substance use. The present study examined these relationships after controlling for theoretically-relevant variables (e.g., gender, other Axis I pathology) in a longitudinal cohort over approximately 14 years. The sample was drawn from participants in the Oregon Adolescent Depression Project. After excluding those with substance use disorders at baseline, SAD at study entry was associated with 6.5 greater odds of cannabis dependence (but not abuse) and 4.5 greater odds of alcohol dependence (but not abuse) at follow-up after controlling for relevant variables (e.g., gender, depression, conduct disorder). The relationship between SAD and alcohol and cannabis dependence remained even after controlling for other anxiety disorders. Other anxiety disorders and mood disorders were not associated with subsequent cannabis or alcohol use disorder after controlling for relevant variables. Among the internalizing disorders, SAD appears to serve as a unique risk factor for the subsequent onset of cannabis and alcohol dependence.

Introduction Social anxiety disorder (SAD) is frequently comorbid with both alcohol abuse and dependence (Davidson et al., 1993, Grant et al., 2005 and Kessler et al., 1997) as well as cannabis dependence (Agosti et al., 2002 and Lynskey et al., 2002). For instance, 48% of individuals with a lifetime diagnosis of SAD also meet criteria for a lifetime diagnosis of an AUD (Grant et al., 2005). The 12-month prevalence of AUDs among individuals with SAD is 13.1% (Grant et al., 2005) compared to only 8.5% among the general population (Grant et al., 2004 and Grant et al., 2004). Similarly, findings from the National Comorbidity Study (NCS) indicate that there is a 4.2% lifetime prevalence rate for cannabis dependence in the general population, whereas among individuals with SAD, the prevalence rate of cannabis dependence is elevated to 29.0% (Agosti et al., 2002). Yet, little is known about the specificity or temporal sequencing of the relationships between SAD and these substance use disorders. Elucidation of these relationships could have important implications for the prevention and treatment of these conditions among socially anxious individuals (Heimberg and Becker, 2002). The high rates of comorbidity between SAD and AUD and cannabis dependence are cause for concern because misuse of alcohol or cannabis tends to compound the already significant problems of patients with SAD. For example, SAD patients with AUD report more severe impairment than patients with SAD without AUD (Schneier et al., 1989) and alcoholics with SAD demonstrate more severe symptoms of alcohol dependence and display more depressive symptomatology than alcoholics without SAD (Thomas et al., 1999b). Cannabis dependence among individuals with SAD is problematic because smoking cannabis has a larger effect on respiratory function than smoking tobacco (Bloom et al., 1987 and Sherrill et al., 1991), including cellular changes that may serve as a risk factor for cancer (Fligiel et al., 1997 and Sarafian et al., 1999). Long-term cannabis use is associated with legal problems and increased alcohol and tobacco use (Patton et al., 2002 and Reilly et al., 1998) and driving under the influence of cannabis leads to increased automobile crash risk (Ramaekers et al., 2004). Among the anxiety disorders, SAD appears to show a particularly problematic risk profile for comorbid AUD and CUD. For example, SAD is associated with higher rates of AUD relative to most other anxiety disorders (Kessler et al., 1997). SAD is also correlated with cannabis dependence at rates more than twice that of any other anxiety disorder (Agosti et al., 2002). On the matter of sequencing, evaluation of typical age of onset of SAD and AUD suggests that SAD serves as a risk factor for subsequent AUD (Kessler et al., 1997, Randall et al., 2001a, Randall et al., 2001b and Schneier et al., 1989). Additionally, in a 13-year longitudinal investigation (Crum and Pratt, 2001), individuals with subclinical symptoms of SAD showed a greater risk for AUD relative to individuals without subclinical SAD symptomatology. Unexpectedly, individuals diagnosed with SAD using DSM-III standards did not show an increased risk of subsequent AUD, but changes in diagnostic criteria for SAD from DSM-III to DSM-IV-TR complicate interpretation of these findings in relation to contemporary diagnostic definitions. In particular, DSM-III criteria included avoidance as a necessary symptom for social phobia and avoidance is no longer a necessary criterion for SAD. This change is not trivial because it may very well be those individuals with SAD who do not avoid social situations who are most vulnerable to problematic alcohol use, especially if they use alcohol in social situations in an attempt to attenuate anxiety reactions. Similarly, among German adolescents, SAD is associated with subsequent regular and hazardous alcohol use but not DSM-IV alcohol abuse or dependence at 4-year follow-up ( Zimmermann et al., 2003). That study, however, did not follow participants very far into the typical period of onset of alcohol dependence, thereby limiting its interpretability. Although there are no known longitudinal investigations of the relationship between SAD and cannabis abuse and/or dependence, given that marijuana users report they use to marijuana to cope with stress and anxiety ( Hathaway, 2003 and Ogborne et al., 2000), it follows that a similar temporal relationship would occur between SAD and cannabis dependence. The limited literature in this area makes it difficult to draw firm conclusions regarding the risk for alcohol and cannabis use disorders among those with SAD. Importantly, it is unknown whether the development of AUD or CUD is unique to SAD versus other forms of anxiety. The question of specificity is critical because SAD is highly comorbid with other anxiety disorders (Davidson et al., 1993 and Merikangas and Angst, 1995) and other anxiety conditions are associated with increased rates of AUD (Kushner et al., 1990) and cannabis dependence (Zvolensky et al., 2006). When all anxiety disorder diagnoses were combined, anxiety disorders preceded AUD in the Oregon Adolescent Project (Rohde et al., 1996). However this study did not investigate the temporal relations among specific anxiety disorders. The few studies that have examined specific anxiety conditions and their temporal associations with AUD and CUD suggest that other anxiety disorders were more likely to be sequelae of alcohol and cannabis use, whereas SAD may serve as a risk factor for subsequent AUD and CUD. For instance, among individuals with co-occurring panic and AUD, panic onset tends to follow AUD (Kushner et al., 1990). Age of onset of panic is also later than that of CUD among individuals with both conditions (Zvolensky et al., 2006). Similarly, age of onset of substance use disorder is earlier than that of generalized anxiety disorder (GAD) among individuals with both disorders (Kessler et al., 2002). It is also unclear whether SAD and/or other anxiety conditions demonstrate specific relationships to AUD or cannabis dependence after accounting for other types of psychopathology related to these substance use disorders. Considering that SAD is highly comorbid with mood disorders (Stein and Kean, 2000) and that depression is related to both alcohol and cannabis use problems (Buckner et al., in press), often preceding the onset of alcohol use (King et al., 2004) and cannabis use (Paton et al., 1977), it may be that the high rates of alcohol and cannabis dependence among individuals with SAD are due to co-occurring mood pathology. Likewise, externalizing disorders, particularly conduct disorder, are highly comorbid with anxiety disorders (Russo and Beidel, 1994 and Zoccolillo, 1992) and predict later AUDs and CUDs (Myers et al., 1995), so they must be controlled in analyses of connections between anxiety and substance use disorders. And, of course, alcohol and cannabis use are themselves highly comorbid (Agosti et al., 2002), making it is necessary to examine the effects of one substance after controlling for effects of the other. Further, the majority of studies in this area tend to combine alcohol abuse and alcohol dependence diagnoses (Crum and Pratt, 2001 and Schneier et al., 1989), making it difficult to demarcate whether individuals with SAD are at increased risk for alcohol abuse, dependence or both. This distinction is important because alcohol dependence is a more debilitating disorder (American Psychiatric Association, 1980) and it appears that individuals with SAD are particularly vulnerable to this more severe condition. For example, epidemiological studies using DSM-IV criteria suggest SAD is more likely to be associated with increased risk of alcohol dependence than alcohol abuse (Grant et al., 2005 and Kessler et al., 1997). Further, among individuals seeking treatment for alcohol-related problems, 23–39% meet diagnostic criteria for SAD (Kushner et al., 1990, Schneier et al., 1989, Smail et al., 1984 and Thomas et al., 1999a). Individuals with higher levels of alcohol-related problems also experience significantly higher levels of social anxiety (Buckner et al., 2006c and Lewis and O’Neill, 2000). In regards to cannabis, greater SAD symptoms are associated with greater number of CUD symptoms (Buckner et al., 2006a and Buckner et al., 2006b) and the NCS data indicate that SAD is associated with increased rates of cannabis dependence but not abuse (Agosti et al., 2002). Given the ambiguities described above, the present investigation contributes to the elucidation of the relations of anxiety disorders with AUDs and CUDs in several ways. First, the comorbidity of specific anxiety disorders and AUDs and CUDs was evaluated. Second, longitudinal analyses examined whether particular anxiety disorders serve as risk factors for subsequent AUDs or CUDs. Third, relevant variables (e.g., depression, conduct disorder) served as covariates to ensure that observed effects were not better accounted for by these conditions. Fourth, the relationships between SAD and specific AUDs and CUDs were examined after also controlling for other anxiety disorders to ensure observed relationships were not due to comorbidity of anxiety pathology. Last, analyses clarified whether observed relations applied to substance abuse, dependence, or both. Given the data suggesting that SAD is particularly associated with alcohol and cannabis dependence, we hypothesized that, after controlling for theoretically relevant variables, SAD would be significantly associated with alcohol and cannabis dependence, but not abuse. Additionally, given other theoretical and empirical work suggesting that other anxiety disorders appear to be a sequelae of substance use (Kessler et al., 2002 and Zvolensky et al., 2006), it was hypothesized that SAD, but not other anxiety disorders, would be associated with the onset of subsequent alcohol and cannabis dependence, thereby demonstrating explanatory specificity.

3. Results 3.1. Descriptive information Table 1 summarizes demographic characteristics of the sample. Diagnostic frequencies, odds ratios, and confidence intervals were computed to examine the relations between T1 predictor variables and T4 criterion variables (alcohol abuse, alcohol dependence, cannabis abuse, cannabis dependence) (Table 2). Additionally, 84 (4.9%) reported a T1 lifetime history of AUD and 92 (5.4%) participants reported a T1 lifetime history of CUD. Table 1. Demographic information for entire sample and by social anxiety diagnosis Variable Entire sample No social anxiety diagnosis Social anxiety diagnosis n % M SD n % M SD n % M SD Age (years) 16.56 1.19 16.56 1.19 28.76 10.91 Gender (female) 891 52.1 870 51.7 21 84.0 Race/ethnicity (Caucasian) 1557 91.1 1535 91.2 22 88.0 Annual income $0–14,999 373 21.9 365 21.6 8 32.0 $15,000–29,999 312 18.3 305 18.1 7 28.0 $30,000+ 248 14.5 246 14.6 2 8 Table options Table 2. Associations between T1 anxiety disorders and T4 criterion variables Predictor variable T4 alcohol abuse T4 alcohol dependence T4 cannabis abuse T4 cannabis dependence Frequency (% total sample) T1 SAD 0.48 (0.11–2.11) 3.98 (1.51–10.47)⁎⁎ 1.01 (0.23–4.50) 4.89 (1.82–13.15)⁎⁎ 25 (1.5%) T1 PD 0.52 (0.06–4.23) 5.82 (1.38–24.57)⁎ 1.09 (0.13–8.92) 4.06 (0.96–17.25) 12 (0.7%) T1 OCD 2.44 (0.41–14.72) 5.18 (0.86–31.26) 1.91 (0.21–17.24) 4.48 (0.74–27.14) 8 (0.5%) T1 OD 0.28 (0.04–2.12) 1.37 (0.43–4.43) 0.58 (0.08–4.48) 0.51 (0.07–3.90) 22 (1.3%) T1 SP 0.78 (0.22–2.73) 1.89 (0.69–5.18) 1.65 (0.46–5.84) 0.41 (0.05–3.11) 34 (2.0%) T1 separation anxiety disorder 0.56 (0.23–1.35) 0.87 (0.41–1.85) 0.35 (0.08–1.46) 1.51 (0.68–3.34) 72 (4.2%) Frequency (% total sample) 176 (10.3%) 185 (10.8%) 95 (5.6%) 107 (6.3%) Note. Values are expressed as odds ratios (95% confidence interval). T1 and T4 diagnoses reflect lifetime history. Abbreviations: social anxiety disorder (SAD), panic disorder (PD), obsessive compulsive disorder (OCD), overanxious disorder (OD), specific phobia (SP). ⁎ p < 0.05. ⁎⁎ p < 0.01. Table options First, relations between T1 anxiety disorders and criterion variables were examined. As predicted, T4 alcohol dependence was significantly associated with T1 SAD and T1 PD. T4 cannabis dependence was associated only with T1 SAD. T4 alcohol and cannabis abuse were not significantly associated with increased odds for any T1 anxiety disorder. Third, relations between criterion variables and T1 covariates were examined (Table 3). T4 alcohol abuse was related to male gender, T1 conduct disorder, and T1 cannabis abuse. T4 cannabis abuse was related to T1 conduct disorder and T1 alcohol abuse. T4 alcohol and cannabis dependence were both related to all T1 covariates. Table 3. Associations between T1 covariates and T4 criterion variables Predictor variable T4 alcohol abuse T4 alcohol dependence T4 cannabis abuse T4 cannabis dependence Frequency (% total sample) Gender 1.73 (1.23–2.42)⁎⁎ 1.91 (1.38–2.66)⁎⁎ 1.46 (0.95–2.25) 1.68 (1.12–2.53)⁎ 52.0% female T1 mood disorder 0.72 (0.49–1.06) 1.57 (1.11–2.22)⁎ 1.00 (0.63–1.62) 1.78 (1.17–2.71)⁎⁎ 347 (20.3%) T1 conduct disorder 3.86 (1.81–8.27)⁎⁎ 6.69 (3.03–14.77)⁎⁎ 3.22 (1.38–7.54)⁎⁎ 16.79 (7.37–38.26)⁎⁎ 56 (3.3%) T1 alcohol abuse – 7.92 (2.71–23.08)⁎⁎ 18.75 (6.36–55.28)⁎⁎ 12.08 (4.29–33.98)⁎⁎ 32 (1.9%) T1 alcohol dependence 0.91 (0.36–2.25) – 1.55 (0.58–4.14) 10.13 (4.75–21.51)⁎⁎ 53 (3.1%) T1 cannabis abuse 3.40 (1.36–8.49)⁎⁎ 2.55 (1.01–6.43)⁎ – 5.13 (2.01–13.06)⁎⁎ 31 (1.8%) T1 cannabis dependence 1.88 (0.92–3.84) 7.69 (3.76–15.71)⁎⁎ 1.90 (0.81–4.46) – 61 (3.6%) Frequency (% total sample) 176 (10.3%) 185 (10.8%) 95 (5.6%) 107 (6.3%) Note. Values are expressed as odds ratios (95% confidence interval). T1 and T4 diagnoses reflect lifetime history. ⁎ p < 0.05. ⁎⁎ p < 0.01. Table options 3.2. Prediction of lifetime history of cannabis and alcohol use disorders using anxiety disorder diagnoses in adolescence Hierarchical logistic regression analyses were performed with each criterion variable, controlling for theoretically relevant variables. Only those T1 affective disorders found to be associated with T4 criterion variables (i.e., SAD, PD, mood disorders) served as predictor variables. Consistent with expectation, T1 SAD was the only anxiety condition to significantly predict T4 AUD or CUD after controlling for theoretically relevant variables. Specifically, T1 SAD was associated with increased odds of T4 alcohol dependence (OR = 4.47, 95% CI = 1.48–13.45, p < 0.01) but not T4 alcohol abuse (OR = 0.39, 95% CI = 0.05–3.07, p > 0.05). Further, T1 SAD was associated with increased odds of T4 cannabis dependence (OR = 6.58, 95% CI = 1.94–22.34, p < 0.01) but not T4 cannabis abuse (OR = 0.99, 95% CI = 0.13–7.79, p > 0.05). Given that T1 PD was associated with significantly increased odds of T4 alcohol dependence, hierarchical logistic regression analyses were performed to determine whether T1 PD was significantly associated with increased odds alcohol dependence above and beyond the covariates. After controlling for T1 AUD, T1 mood disorder, T1 conduct disorder, and gender, T1 PD was not significantly associated with T4 alcohol dependence (OR = 2.36, 95% CI = 0.25–21.96, p > 0.05). Similarly, because T1 mood disorder was also associated with significantly increased odds of T4 alcohol and cannabis dependence, hierarchical logistic regression analyses were performed with each relevant criterion variable for T1 mood disorder. After controlling for T1 AUD, T1 conduct disorder, and gender, T1 mood disorder was not significantly associated with T4 alcohol dependence (OR = 1.49, 95% CI = 1.0–2.28, p > 0.05) or T4 cannabis dependence (OR = 0.86, 95% CI = 0.45–1.64, p > 0.05). 3.3. Evaluation of the unique contribution of social anxiety disorder relative to other axis I anxiety disorders in predicting the development of alcohol and cannabis use disorders Hierarchical logistic regression analyses were performed to examine whether the relation between T1 SAD and T4 criterion variables occurred above and beyond the associations between SAD and other anxiety disorders. After controlling for all theoretically relevant variables (including other anxiety disorder diagnoses and relevant T1 SUDs), T1 lifetime history of SAD continued to be significantly related to T4 lifetime history of alcohol dependence (OR = 3.72, 95% CI = 1.23–11.29, p < 0.05) but not T4 alcohol abuse (OR = 0.36, 95% CI = 0.05–2.78, p > 0.05). Similarly, T1 lifetime history of SAD continued to be significantly related to T4 lifetime history of cannabis dependence (OR = 4.88, 95% CI = 1.43–16.64, p < 0.05) but not T4 cannabis abuse (OR = 1.07, 95% CI = 0.14–8.56, p > 0.05). 3.4. Survival curve analyses of social anxiety disorder in predicting the development of alcohol dependence Based on cumulative sample survival probabilities from the Kaplan–Meier models, 26% of T1 participants with a SAD diagnosis developed alcohol dependence by age 24 with the steepest onset slope occurring between 18 and 19 years old. In comparison, only 8.5% of T1 participants without a SAD diagnosis developed alcohol dependence by age 24 with total cumulative onset through the T4 assessment of only 11% (see Fig. 1). After covarying out the effects of participant sex and T1 anxiety, conduct, and mood disorders, T1 SAD significantly predicted time to onset of alcohol dependence in the Cox proportional hazard model (hazard ratio = 1.56; 95% CI = 1.06–2.31; p = 0.02) indicating that participants with a T1 SAD diagnosis were 1.56 times more likely to develop an alcohol dependence diagnosis over the period of observation than those without a T1 SAD diagnosis. Cumulative survival curve for alcohol dependence onset, excluding participants ... Fig. 1. Cumulative survival curve for alcohol dependence onset, excluding participants with T1 AUD. Figure options 3.5. Survival curve analyses of social anxiety disorder in predicting the development of cannabis dependence Of the participants with a T1 SAD diagnosis, 13% developed cannabis dependence by age 24 compared to only 4% of T1 participants without a SAD diagnosis. Total cumulative onset through the T4 assessment (roughly age 30) was 22% for T1 SAD participants and 5% for those without T1 SAD (see Fig. 2). Findings for the Cox proportional hazard model predicting onset of cannabis dependence were similar to those predicting onset of alcohol dependence. Again, participants with a T1 SAD diagnosis were significantly more likely to develop a cannabis dependence disorder over the observation period (hazard ratio = 1.94; 95% CI = 1.21–3.13; p = 0.01) than those without a T1 SAD diagnosis, after controlling for relevant T1 covariates. Cumulative survival curve for cannabis dependence onset, excluding participants ... Fig. 2. Cumulative survival curve for cannabis dependence onset, excluding participants with T1 CUD. Figure options 3.6. Evaluation of the specificity of social anxiety symptoms in predicting the development of alcohol and cannabis dependence relative to other axis I anxiety disorders To determine whether SAD uniquely predicts alcohol and cannabis dependence (but not other Axis I conditions), hierarchical logistic regression analyses were performed with each criterion variable (with gender serving as level 1 covariate). For each regression, participants with a T1 lifetime history of the T4 criterion variable were excluded from the analyses. T1 lifetime history of SAD only demonstrated significantly increased odds of T4 lifetime history of separation disorder (OR = 3.96, 95% CI = 1.06–14.79, p < 0.05) but not mood disorder (OR = 7.36, 95% CI = 0.85–63.58, p > 0.05), CD (OR = 0.00, p > 0.05), PD (OR = 1.70, 95% CI = 0.37–7.86, p > 0.05), OCD (OR = 0.00, p > 0.05), GAD (OR = 3.17, 95% CI = 0.39–25.93, p > 0.05), or SP (OR = 4.94, 95% CI = 1.03–23.76, p = 0.05).