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Temporal relationship between the age of onset of phobic disorders and development of substance dependence in adolescent psychiatric patients
Drug and Alcohol Dependence 75 (2004) 327–330
Short communication
Temporal relationship between the age of onset of phobic disorders and development of substance dependence in adolescent psychiatric patients Risto Ilomäki a,∗ , Helinä Hakko a,b , Markku Timonen a,c , Jaakko Lappalainen d , Taru Mäkikyrö a,b , Pirkko Räsänen b a
Department of Psychiatry, University of Oulu, BOX 5000, 90014 Oulu, Finland Department of Psychiatry, Oulu University Hospital, BOX 26, 90029 OYS, Finland c Oulu Health Centre, Box 8, FIN-90015 City of Oulu, Oulu Finland Yale University School of Medicine, Department of Psychiatry, New Haven, CT, USA
b d
Received 19 September 2003; received in revised form 2 March 2004; accepted 30 March 2004
Abstract Aims: To investigate the age of onset of phobic disorders in relation to later development of substance dependence in a sample of adolescent psychiatric patients. Design, setting and participants: Clinical sample of 238 adolescents (age 12–17) admitted to psychiatric inpatient hospitalization between April 2001 and July 2003. Measurements: Psychiatric diagnoses and onset ages obtained from the schedule for affective disorders and schizophrenia for school aged children-present and lifetime (K-SADS-PL). Findings: Logistic regression analyses revealed that adolescents with phobic disorders had a 4.9-fold risk for comorbid substance dependence compared to those without phobia. The mean onset age was 11.4 and 14.4 years for phobias and comorbid substance dependence, respectively. Boys (13.7 years) had a statistically significantly lower onset age for substance dependence than girls (15.4 years). Over one-half of the adolescents with phobic disorders had developed substance dependence within three years after the onset of phobia. Conclusions: We found that phobias might influence the development of secondary substance dependence within a few years from the onset of phobia already in adolescence. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Adolescent; Phobia; Dependence; Comorbidity; Age of onset; Temporality
1. Introduction Phobic disorders are under-diagnosed, under-treated and common in the western world. In previous studies, the lifetime prevalence of social phobia has been found to vary from 2 to 16% in adults (den Boer, 1997; Nelson et al., 2000) and from 4 to 15% in adolescents (Verhulst et al., 1997; Last et al., 1992). Lifetime prevalences of agoraphobia and simple phobia have been reported to vary from 3 to 7% and from 6 to 22%, respectively (Curtis et al., 1998; Magee et al., 1996). The majority of studies have found the onset age of phobic disorders to be between 11 and 16. Because of the considerably earlier occurrence of phobias as compared to other ∗
Corresponding author. Tel.: +358-8-315-6910; fax: +358-8-333-167. E-mail address: [email protected] (R. Ilomäki).
psychiatric disorders they may influence the development of later psychopathology (Compton et al., 2000; Magee et al., 1996). The comorbidity of phobic disorders with other psychopathology, including drug and alcohol disorders, has been noted in adult samples, and phobias are found mainly primary to common comorbidity including depression, other anxiety disorders and substance dependence (Compton et al., 2000; Magee et al., 1996). Though phobias are found mainly primary in the cascade of comorbidity, the mean times between the onset ages has not been assessed and it has remained unclear how rapidly secondary dependence develops after onset of phobia. In an adolescent sample of female twins, the presence of social phobia increased the risk for alcohol dependence two-fold and that for major depressive disorder three-fold (Nelson et al., 2000). However, the association of phobic
0376-8716/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.drugalcdep.2004.03.014
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disorders with other types of substance dependence was not assessed and the sample was limited to females. Also, Clark et al. (1995) found a high prevalence of anxiety disorders, including social phobia, among adolescents hospitalized for treatment of alcohol disorders. On the other hand, Brook et al. (1998) found no prospective evidence of this putative association between phobic disorders and substance use in adolescence. Despite the overall high prevalence, the early onset of phobic disorders in adolescence and the comorbidity to substance dependence later in adulthood, there are only few studies concerning comorbidity of phobic disorders and alcohol/drug dependence in clinical samples of adolescents. Furthermore, some of the previous results are somewhat contradictory (Nelson et al., 2000; Brook et al., 1998; Clark et al., 1995). The aim of this study was to investigate the putative phobia—substance dependence comorbidity among adolescents under 18 years of age. Secondly, for the first time we studied the temporal relationship between the onset ages of these disorders among adolescents. Our population-based clinical sample allowed us to study these questions by using DSM-IV diagnoses based on established semi-structured interviews.
2. Methods The study sample consisted of psychiatric inpatients aged 12–17 years admitted to Oulu University Hospital between April 2001 and July 2003. Of the total of 302 adolescents admitted, 16 were excluded (because of mental retardation, organic brain disorder and age over 18 years). Of the 286 patients, 83% (n = 238, boys 104) gave a written informed consent and were enrolled in the study. The study protocol was approved by the Ethics Committee of the Faculty of Medicine, University of Oulu. The subjects were interviewed by the patient’s treating physician, using the schedule for affective disorder and schizophrenia for school-age children present and lifetime (K-SADS-PL) to obtain DSM-IV diagnoses. Data regarding the onset age of disorders and the type of substance dependence were obtained from the K-SADS-PL (Kaufman et al., 1997). Data is described elsewhere in detail (Mäkikyrö et al., 2003). Phobic disorders included simple phobias, agoraphobia and social phobia (DSM-IV-codes 300.29, 300.21, 300.23). Alcohol (303.90) and drug (3 0 4) dependencies, excluding nicotine dependence (304.70), were combined into a substance dependence group. The other diagnoses were grouped as follows: (1) depressive (296.2-3, 300.4, 311) (n = 103, 43.3%), (2) bipolar (296.4-8, 301.13), (n = 8, 3.4%), (3) conduct and oppositional defiant (312.8-9, 313.81, 314) (n = 103, 43.3%), (4) Anxiety—other than phobia (300.00–300.20, 300.3, 308.3, 309.81) (n = 71, 29.8%), (5) psychotic (295, 296.0, 296.4-9, 297.1-3, 298.8-9, 301.13,
301.22) (n = 27, 11.3%) and (6). Other psychiatric disorders (n = 21, 8.8%). The onset ages of disorders were based on patients’ information gathered in the K-SADS-PL diagnostic interview. In statistical analyses differences between groups in categorical variables were analyzed with Pearson’s χ2 - or Fisher’s exact test. Group differences in continuous variables were investigated with Student’s t-test or Mann–Whitney U-test. The association between phobic disorders and dependence was assessed with logistic regression model after adjusting for adolescent’s sex, age and other psychiatric disorders. Kaplan–Meier’s method was used to study the temporal association between phobic disorders and substance/alcohol dependence.
3. Results Of all the adolescents, 18.1% (n = 43) were suffering from phobic disorders and 28.6% (n = 68) from substance dependence. Of adolescents with phobic disorders, 48.8% (n = 21) had comorbid substance dependence (χ2 = 10.56, d.f. = 1, P-value = 0.001). After adjusting for age, sex and other major psychiatric disorders, the logistic models revealed that phobic disorders (OR = 4.85 95%CI 2.04-11.51, P-value < 0.001) and conduct and oppositional defiant disorders (OR = 3.46 95%CI 1.64-7.33, P-value = 0.001) were associated with substance dependence (Table 1). The risk of substance dependence increased with age. The likelihood for drug dependence with or without alcohol dependence (adjusted OR 5.64 95%CI 1.83-17.41, p-value = 0.003) was more prevalent than that for alcohol dependence without drug dependence (adjusted OR 4.47 95%CI 1.63-12.29, P-value = 0.004). The prevalence of phobia was more common among adolescents with alcohol (28.9%) or drug dependence (31.1%) than among those without any dependence (13.1%) (χ2 = 9.60, d.f. = 2, P-value = 0.008). Seventy percent of the drug-dependence diagnosed individuals with phobic disorders had developed dependence for hard drugs (opioids or amphetamine). In 90.5% of adolescents, the phobic disorder preceded substance dependence or began at the same time. For adolescents with both disorders, the mean onset age of phobia was 11.4 years (S.D. 3.65), being 11.5 years (S.D. 3.29) for boys and 11.2 years (S.D. 4.29) for girls (no gender difference). The corresponding onset age of substance dependence was 14.4 years (S.D. 1.48), for boys 13.7 years (S.D. 1.42) and for girls 15.4 (S.D. 0.93) (gender difference: t = −3.08, d.f. = 19, P = 0.006). Fig. 1 shows the Kaplan–Meier estimates for the time (years) from the onset of phobia to the onset of substance dependence in boys and girls (log-rank = 02.99, d.f. = 1, P-value = 0.084). The mean difference between the onset ages of the comorbid disorders was 3.7 years (S.D. = 3.3) for boys and 4.4 years (S.D. = 3.6) for girls (no gender
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Table 1 Factors associated with likelihood of substance dependence in a clinical sample of adolescents aged 17 or less Factor
Phobic disorders Depressive disorders Bipolar disorders Conduct and oppositional defiant disorders Anxiety disorders—other than phobia Psychoses Age (years) Sex, female
Prevalence of subjects with substance dependence
Likelihood of substance dependence∗
n (%)
OR
(95% CI)
P-value∗∗
21 28 0 41 25 3 – 35
4.85 0.73 Not est. 3.46 1.49 0.24 2.27 0.91
(2.04–11.51) (0.36–1.51)
<0.001 ns
(1.64–7.33) (0.71–3.13) (0.06–0.96) (1.66–3.11) (0.45–1.85)
0.001 ns 0.044 <0.001 ns
(48.8) (27.2) (0) (39.8) (35.2) (11.1) (26.1)
Phobic disorders included social phobia (n = 31, 13.0%), simple phobia (n = 9, 3.8%) and agoraphobia (n = 13, 5.5%). ∗ Determined with multivariate logistic regression analysis (method = enter) after adjusting for all other variables in the table. Odds ratios >1 indicate higher likelihood; odds ratios <1 indicate lower likelihood of drug/alcohol dependence. ∗∗ ns: Not statistically significant (P-value > 0.05), not est.: not estimable.
Fig. 1. Kaplan–Meier estimates for time (years) elapsed from age at onset of phobia to age at onset of substance/alcohol dependence among boys and girls suffering from phobic disorders (simple phobia, agoraphobia or social phobia) in a clinical sample of inpatients aged 17 or less.
difference). Over one half (57.9%) of the adolescents with phobic disorders had developed substance dependence within 3 years from the onset of phobia.
4. Discussions Our main finding was that among adolescents, preceding phobic disorder increased the risk for subsequent substance dependence up to 4.9-fold compared to adolescents without phobic disorders. The corresponding risk was 4.5-fold for alcohol dependence and 5.6-fold for drug dependence. Previous epidemiological studies have reported parallel results, yet lower rates of comorbidity compared to our results. (Nelson et al., 2000; Magee et al., 1996). One proba-
ble explanation for this discrepancy might be that our study population consists of the most severe, early-onset manifestations of these disorders. In the majority of adolescents, the onset of phobic disorder occurred mainly 3 years prior to the onset of substance dependence. The phenomenon that phobic disorders are primary to comorbid substance dependence has previously been demonstrated in adult sample studies (Compton et al., 2000). The time interval between the onset ages of phobias and substance dependence is poorly researched. Our study adds important evidence to the earlier literature by showing these time-intervals. The onset age of phobic disorders was 11 years for both sexes. The gender difference between the onset ages for secondary substance dependence indicated that boys with a
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phobic disorder had significantly earlier onset age for substance dependence (13.7 years) than girls (15.4 years). We recommend further studies on the putative gender difference of the temporal relationship between these disorders. Conduct and oppositional defiant disorders were also associated with increased likelihood of comorbid substance dependence. These results on disruptive disorders support the previously reported comorbidity with substance use disorders (Disney et al., 1999). In our study, mood disorders were not associated with substance dependence. Our results differ from previous adult (Compton et al., 2000) and adolescent (Brook et al., 1998) studies and could be explained by the temporality of the disorders (Swendsen et al., 1998; Räsänen et al., 1998). Several possible biological mechanisms could contribute to the association between phobic disorders and substance dependence. Serotonergic metabolism, striatal dopamine and other neurotransmitter systems, such as gamma aminobutyric acidergic and noradrenergic systems, have been linked to both phobic and substance-related disorders (Nutt et al., 1998; Stein, 1998; Ratsma et al., 2002; Ameringen et al., 2000), and more studies are needed to solve the biological aspects behind the complex relationship of these disorders. Psychosocial explanations are also possible. The use of alcohol and drugs alleviates social anxiety, and may give an opportunity for those with phobic disorders to unite with others of the same age group. Phobic youngsters may consider self-medicating effects of alcohol more important than the possible “side-effects,” such as alcoholism. Our main limitation was the small number of phobic cases, which does not allow separate feasible statistical analyses according to different types of phobias. The information of the onset ages of disorders was self-reported and retrospective. However, the use of semi-structured K-SADS-Pl minimizes this recall bias. Our sample consisted of hospitalized adolescents, which limits the generalization of our findings. In sum, phobias might influence the development of secondary substance dependence within a few years from the onset of phobia already in adolescence. This emphasizes the importance of early diagnosis and treatment of phobias in order to improve both the life quality of individuals with phobic disorders and to prevent development of comorbid substance use disorders. Acknowledgements This study received support from Ethel F. Donaghue Women’s Health Investigator Program at Yale, Alcoholic Beverage Medical Research Foundation (ABMRF) and from the Päivikki and Sakari Sohlberg Foundation. We thank the staff of the adolescent unit 70 of the Oulu University
Hospital for data collection, and all the adolescents who participated in this study.
References Ameringen, M.V., Mancini, C., Farvolden, P., Oakman, J., 2000. Drugs in development for social anxiety disorder: more to social anxiety than meets the SSRI. Expert Opin. Invest. Drugs 9 (10), 2215–2231. den Boer, J.A., 1997. Social phobia: epidemiology, recognition, and treatment. BMJ 315 (7111), 796–800. Brook, J.S., Cohen, P., Brook, D.W., 1998. Longitudinal study of co-occurring psychiatric disorders and substance use. J. Am. Acad. Child Adolescent Psychiatr. 37 (3), 322–330. Clark, D.B., Bukstein, O.G., Smith, M.G., Kaczynski, N.A., Mezzich, A.C., Donovan, J.E., 1995. Identifying anxiety disorders in adolescents hospitalized for alcohol abuse or dependence. Psychiat. Services 46 (6), 618–620. Compton 3rd, W.M., Cottler, L.B., Phelps, D.L., Ben Abdallah, A., Spitznagel, E.L., 2000. Psychiatric disorders among drug dependent subjects: are they primary or secondary? Am. J. Addict. 9 (2), 126– 134. Curtis, G.C., Magee, W.J., Eaton, W.W., Wittchen, H.U., Kessler, R.C., 1998. Specific fears and phobias. Epidemiology and classification. Br. J. Psychiatry 173, 212–217. Disney, E.R., Elkins, I.J., McGue, M., Iacono, W.G., 1999. Effects of ADHD, conduct disorder, and gender on substance use and abuse in adolescence. Am. J. Psychiatry 156 (10), 1515–1521. Kaufman, J., Birmaher, B., Brent, D., Rao, U., Flynn, C., Moreci, P., Williamson, D., Ryan, N., 1997. Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): initial reliability and validity data. J. Am. Acad. Child Adolescent Psychiatr. 36 (7), 980–988. Last, C.G., Perrin, S., Hersen, M., Kazdin, A.E., 1992. DSM-III-R anxiety disorders in children: sociodemographic and clinical characteristics. J. Am. Acad. Child Adolescent Psychiatr. 31 (6), 1070–1076. Magee, W.J., Eaton, W.W., Wittchen, H.U., McGonagle, K.A., Kessler, R.C., 1996. Agoraphobia, simple phobia, and social phobia in the National Comorbidity Survey. Arch. Gen. Psychiatry 53 (2), 159–168. Mäkikyrö, T., Hakko, H., Timonen, J., Lappalainen, J., Ilomäki, R., Marttunen, M., Läksy, K., Räsänen, P., 2003. Smoking and suicidality among adolescent psychiatric patients. J. Adolescent Health 4 (3), 250–253. Nelson, E.C., Grant, J.D., Bucholz, K.K., Glowinski, A., Madden, P.A.F., Reich, W., Heath, A.C., 2000. Social phobia in a population-based female adolescent twin sample: co-morbidity and associated suicide-related symptoms. Psychol. Med. 30 (4), 797–804. Nutt, D.J., Bell, C.J., Malizia, A.L., 1998. Brain mechanisms of social anxiety disorder. J. Clin. Psychiat. 59 (Suppl. 17), 4–11. Räsänen, P., Tiihonen, J., Hakko, H., 1998. The incidence and onset-age of hospitalized bipolar affective disorder in Finland. J. Affective Disorders 48 (1), 63–68. Stein, M.B., 1998. Neurobiological perspectives on social phobia: from affiliation to zoology. Biol. Psychiatry 44 (12), 1277–1285. Swendsen, J.D., Merikangas, K.R., Canino, G.J., Kessler, R.C., Rubio-Stipec, M., Angst, J., 1998. The comorbidity of alcoholism with anxiety and depressive disorders in four geographic communities. Comprehensive Psychiatry 39 (4), 176–184. Ratsma, J.E., Van Der Stelt, O., Ganning, W.B., 2002. Neurochemical markers of alcoholism vulnerability in humans. Alcohol Alcohol. 37 (6), 522–533. Verhulst, F.C., van der Ende, J., Ferdinand, R.F., Kasius, M.C., 1997. The prevalence of DSM-III-R diagnoses in a national sample of Dutch adolescents. Arch. Gen. Psychiatry 54 (4), 329–336.
Short communication
Temporal relationship between the age of onset of phobic disorders and development of substance dependence in adolescent psychiatric patients Risto Ilomäki a,∗ , Helinä Hakko a,b , Markku Timonen a,c , Jaakko Lappalainen d , Taru Mäkikyrö a,b , Pirkko Räsänen b a
Department of Psychiatry, University of Oulu, BOX 5000, 90014 Oulu, Finland Department of Psychiatry, Oulu University Hospital, BOX 26, 90029 OYS, Finland c Oulu Health Centre, Box 8, FIN-90015 City of Oulu, Oulu Finland Yale University School of Medicine, Department of Psychiatry, New Haven, CT, USA
b d
Received 19 September 2003; received in revised form 2 March 2004; accepted 30 March 2004
Abstract Aims: To investigate the age of onset of phobic disorders in relation to later development of substance dependence in a sample of adolescent psychiatric patients. Design, setting and participants: Clinical sample of 238 adolescents (age 12–17) admitted to psychiatric inpatient hospitalization between April 2001 and July 2003. Measurements: Psychiatric diagnoses and onset ages obtained from the schedule for affective disorders and schizophrenia for school aged children-present and lifetime (K-SADS-PL). Findings: Logistic regression analyses revealed that adolescents with phobic disorders had a 4.9-fold risk for comorbid substance dependence compared to those without phobia. The mean onset age was 11.4 and 14.4 years for phobias and comorbid substance dependence, respectively. Boys (13.7 years) had a statistically significantly lower onset age for substance dependence than girls (15.4 years). Over one-half of the adolescents with phobic disorders had developed substance dependence within three years after the onset of phobia. Conclusions: We found that phobias might influence the development of secondary substance dependence within a few years from the onset of phobia already in adolescence. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Adolescent; Phobia; Dependence; Comorbidity; Age of onset; Temporality
1. Introduction Phobic disorders are under-diagnosed, under-treated and common in the western world. In previous studies, the lifetime prevalence of social phobia has been found to vary from 2 to 16% in adults (den Boer, 1997; Nelson et al., 2000) and from 4 to 15% in adolescents (Verhulst et al., 1997; Last et al., 1992). Lifetime prevalences of agoraphobia and simple phobia have been reported to vary from 3 to 7% and from 6 to 22%, respectively (Curtis et al., 1998; Magee et al., 1996). The majority of studies have found the onset age of phobic disorders to be between 11 and 16. Because of the considerably earlier occurrence of phobias as compared to other ∗
Corresponding author. Tel.: +358-8-315-6910; fax: +358-8-333-167. E-mail address: [email protected] (R. Ilomäki).
psychiatric disorders they may influence the development of later psychopathology (Compton et al., 2000; Magee et al., 1996). The comorbidity of phobic disorders with other psychopathology, including drug and alcohol disorders, has been noted in adult samples, and phobias are found mainly primary to common comorbidity including depression, other anxiety disorders and substance dependence (Compton et al., 2000; Magee et al., 1996). Though phobias are found mainly primary in the cascade of comorbidity, the mean times between the onset ages has not been assessed and it has remained unclear how rapidly secondary dependence develops after onset of phobia. In an adolescent sample of female twins, the presence of social phobia increased the risk for alcohol dependence two-fold and that for major depressive disorder three-fold (Nelson et al., 2000). However, the association of phobic
0376-8716/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.drugalcdep.2004.03.014
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disorders with other types of substance dependence was not assessed and the sample was limited to females. Also, Clark et al. (1995) found a high prevalence of anxiety disorders, including social phobia, among adolescents hospitalized for treatment of alcohol disorders. On the other hand, Brook et al. (1998) found no prospective evidence of this putative association between phobic disorders and substance use in adolescence. Despite the overall high prevalence, the early onset of phobic disorders in adolescence and the comorbidity to substance dependence later in adulthood, there are only few studies concerning comorbidity of phobic disorders and alcohol/drug dependence in clinical samples of adolescents. Furthermore, some of the previous results are somewhat contradictory (Nelson et al., 2000; Brook et al., 1998; Clark et al., 1995). The aim of this study was to investigate the putative phobia—substance dependence comorbidity among adolescents under 18 years of age. Secondly, for the first time we studied the temporal relationship between the onset ages of these disorders among adolescents. Our population-based clinical sample allowed us to study these questions by using DSM-IV diagnoses based on established semi-structured interviews.
2. Methods The study sample consisted of psychiatric inpatients aged 12–17 years admitted to Oulu University Hospital between April 2001 and July 2003. Of the total of 302 adolescents admitted, 16 were excluded (because of mental retardation, organic brain disorder and age over 18 years). Of the 286 patients, 83% (n = 238, boys 104) gave a written informed consent and were enrolled in the study. The study protocol was approved by the Ethics Committee of the Faculty of Medicine, University of Oulu. The subjects were interviewed by the patient’s treating physician, using the schedule for affective disorder and schizophrenia for school-age children present and lifetime (K-SADS-PL) to obtain DSM-IV diagnoses. Data regarding the onset age of disorders and the type of substance dependence were obtained from the K-SADS-PL (Kaufman et al., 1997). Data is described elsewhere in detail (Mäkikyrö et al., 2003). Phobic disorders included simple phobias, agoraphobia and social phobia (DSM-IV-codes 300.29, 300.21, 300.23). Alcohol (303.90) and drug (3 0 4) dependencies, excluding nicotine dependence (304.70), were combined into a substance dependence group. The other diagnoses were grouped as follows: (1) depressive (296.2-3, 300.4, 311) (n = 103, 43.3%), (2) bipolar (296.4-8, 301.13), (n = 8, 3.4%), (3) conduct and oppositional defiant (312.8-9, 313.81, 314) (n = 103, 43.3%), (4) Anxiety—other than phobia (300.00–300.20, 300.3, 308.3, 309.81) (n = 71, 29.8%), (5) psychotic (295, 296.0, 296.4-9, 297.1-3, 298.8-9, 301.13,
301.22) (n = 27, 11.3%) and (6). Other psychiatric disorders (n = 21, 8.8%). The onset ages of disorders were based on patients’ information gathered in the K-SADS-PL diagnostic interview. In statistical analyses differences between groups in categorical variables were analyzed with Pearson’s χ2 - or Fisher’s exact test. Group differences in continuous variables were investigated with Student’s t-test or Mann–Whitney U-test. The association between phobic disorders and dependence was assessed with logistic regression model after adjusting for adolescent’s sex, age and other psychiatric disorders. Kaplan–Meier’s method was used to study the temporal association between phobic disorders and substance/alcohol dependence.
3. Results Of all the adolescents, 18.1% (n = 43) were suffering from phobic disorders and 28.6% (n = 68) from substance dependence. Of adolescents with phobic disorders, 48.8% (n = 21) had comorbid substance dependence (χ2 = 10.56, d.f. = 1, P-value = 0.001). After adjusting for age, sex and other major psychiatric disorders, the logistic models revealed that phobic disorders (OR = 4.85 95%CI 2.04-11.51, P-value < 0.001) and conduct and oppositional defiant disorders (OR = 3.46 95%CI 1.64-7.33, P-value = 0.001) were associated with substance dependence (Table 1). The risk of substance dependence increased with age. The likelihood for drug dependence with or without alcohol dependence (adjusted OR 5.64 95%CI 1.83-17.41, p-value = 0.003) was more prevalent than that for alcohol dependence without drug dependence (adjusted OR 4.47 95%CI 1.63-12.29, P-value = 0.004). The prevalence of phobia was more common among adolescents with alcohol (28.9%) or drug dependence (31.1%) than among those without any dependence (13.1%) (χ2 = 9.60, d.f. = 2, P-value = 0.008). Seventy percent of the drug-dependence diagnosed individuals with phobic disorders had developed dependence for hard drugs (opioids or amphetamine). In 90.5% of adolescents, the phobic disorder preceded substance dependence or began at the same time. For adolescents with both disorders, the mean onset age of phobia was 11.4 years (S.D. 3.65), being 11.5 years (S.D. 3.29) for boys and 11.2 years (S.D. 4.29) for girls (no gender difference). The corresponding onset age of substance dependence was 14.4 years (S.D. 1.48), for boys 13.7 years (S.D. 1.42) and for girls 15.4 (S.D. 0.93) (gender difference: t = −3.08, d.f. = 19, P = 0.006). Fig. 1 shows the Kaplan–Meier estimates for the time (years) from the onset of phobia to the onset of substance dependence in boys and girls (log-rank = 02.99, d.f. = 1, P-value = 0.084). The mean difference between the onset ages of the comorbid disorders was 3.7 years (S.D. = 3.3) for boys and 4.4 years (S.D. = 3.6) for girls (no gender
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Table 1 Factors associated with likelihood of substance dependence in a clinical sample of adolescents aged 17 or less Factor
Phobic disorders Depressive disorders Bipolar disorders Conduct and oppositional defiant disorders Anxiety disorders—other than phobia Psychoses Age (years) Sex, female
Prevalence of subjects with substance dependence
Likelihood of substance dependence∗
n (%)
OR
(95% CI)
P-value∗∗
21 28 0 41 25 3 – 35
4.85 0.73 Not est. 3.46 1.49 0.24 2.27 0.91
(2.04–11.51) (0.36–1.51)
<0.001 ns
(1.64–7.33) (0.71–3.13) (0.06–0.96) (1.66–3.11) (0.45–1.85)
0.001 ns 0.044 <0.001 ns
(48.8) (27.2) (0) (39.8) (35.2) (11.1) (26.1)
Phobic disorders included social phobia (n = 31, 13.0%), simple phobia (n = 9, 3.8%) and agoraphobia (n = 13, 5.5%). ∗ Determined with multivariate logistic regression analysis (method = enter) after adjusting for all other variables in the table. Odds ratios >1 indicate higher likelihood; odds ratios <1 indicate lower likelihood of drug/alcohol dependence. ∗∗ ns: Not statistically significant (P-value > 0.05), not est.: not estimable.
Fig. 1. Kaplan–Meier estimates for time (years) elapsed from age at onset of phobia to age at onset of substance/alcohol dependence among boys and girls suffering from phobic disorders (simple phobia, agoraphobia or social phobia) in a clinical sample of inpatients aged 17 or less.
difference). Over one half (57.9%) of the adolescents with phobic disorders had developed substance dependence within 3 years from the onset of phobia.
4. Discussions Our main finding was that among adolescents, preceding phobic disorder increased the risk for subsequent substance dependence up to 4.9-fold compared to adolescents without phobic disorders. The corresponding risk was 4.5-fold for alcohol dependence and 5.6-fold for drug dependence. Previous epidemiological studies have reported parallel results, yet lower rates of comorbidity compared to our results. (Nelson et al., 2000; Magee et al., 1996). One proba-
ble explanation for this discrepancy might be that our study population consists of the most severe, early-onset manifestations of these disorders. In the majority of adolescents, the onset of phobic disorder occurred mainly 3 years prior to the onset of substance dependence. The phenomenon that phobic disorders are primary to comorbid substance dependence has previously been demonstrated in adult sample studies (Compton et al., 2000). The time interval between the onset ages of phobias and substance dependence is poorly researched. Our study adds important evidence to the earlier literature by showing these time-intervals. The onset age of phobic disorders was 11 years for both sexes. The gender difference between the onset ages for secondary substance dependence indicated that boys with a
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phobic disorder had significantly earlier onset age for substance dependence (13.7 years) than girls (15.4 years). We recommend further studies on the putative gender difference of the temporal relationship between these disorders. Conduct and oppositional defiant disorders were also associated with increased likelihood of comorbid substance dependence. These results on disruptive disorders support the previously reported comorbidity with substance use disorders (Disney et al., 1999). In our study, mood disorders were not associated with substance dependence. Our results differ from previous adult (Compton et al., 2000) and adolescent (Brook et al., 1998) studies and could be explained by the temporality of the disorders (Swendsen et al., 1998; Räsänen et al., 1998). Several possible biological mechanisms could contribute to the association between phobic disorders and substance dependence. Serotonergic metabolism, striatal dopamine and other neurotransmitter systems, such as gamma aminobutyric acidergic and noradrenergic systems, have been linked to both phobic and substance-related disorders (Nutt et al., 1998; Stein, 1998; Ratsma et al., 2002; Ameringen et al., 2000), and more studies are needed to solve the biological aspects behind the complex relationship of these disorders. Psychosocial explanations are also possible. The use of alcohol and drugs alleviates social anxiety, and may give an opportunity for those with phobic disorders to unite with others of the same age group. Phobic youngsters may consider self-medicating effects of alcohol more important than the possible “side-effects,” such as alcoholism. Our main limitation was the small number of phobic cases, which does not allow separate feasible statistical analyses according to different types of phobias. The information of the onset ages of disorders was self-reported and retrospective. However, the use of semi-structured K-SADS-Pl minimizes this recall bias. Our sample consisted of hospitalized adolescents, which limits the generalization of our findings. In sum, phobias might influence the development of secondary substance dependence within a few years from the onset of phobia already in adolescence. This emphasizes the importance of early diagnosis and treatment of phobias in order to improve both the life quality of individuals with phobic disorders and to prevent development of comorbid substance use disorders. Acknowledgements This study received support from Ethel F. Donaghue Women’s Health Investigator Program at Yale, Alcoholic Beverage Medical Research Foundation (ABMRF) and from the Päivikki and Sakari Sohlberg Foundation. We thank the staff of the adolescent unit 70 of the Oulu University
Hospital for data collection, and all the adolescents who participated in this study.
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