0
Original Article |

Incidence of Social Anxiety Disorder and the Consistent Risk for Secondary Depression in the First Three Decades of Life FREE

Katja Beesdo, PhD; Antje Bittner, PhD; Daniel S. Pine, MD; Murray B. Stein, MD, MPH; Michael Höfler, Dipl-Stat; Roselind Lieb, PhD; Hans-Ulrich Wittchen, PhD
[+] Author Affiliations

Author Affiliations: Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany (Drs Beesdo, Bittner, and Wittchen and Mr Höfler); National Institute of Mental Health, Bethesda, Maryland (Dr Pine); Departments of Psychiatry and Family and Preventive Medicine, University of California–San Diego, La Jolla (Dr Stein); Unit of Clinical Psychology and Epidemiology, Max Planck Institute of Psychiatry, Munich, Germany (Drs Lieb and Wittchen); and Institute for Psychology, Epidemiology, and Health Psychology, University of Basel, Basel, Switzerland (Dr Lieb).


Arch Gen Psychiatry. 2007;64(8):903-912. doi:10.1001/archpsyc.64.8.903.
Text Size: A A A
Published online

Context  Epidemiological findings demonstrating an increased risk for individuals with social anxiety disorder (SAD) to develop depression have been challenged by discrepant findings from prospective longitudinal examinations in childhood and early adolescence.

Objectives  To examine patterns of SAD incidence, the consistency of associations of SAD with subsequent depression, and distal and proximal predictors for subsequent depression.

Design  Face-to-face, 10-year prospective longitudinal and family study of up to 4 waves. The DSM-IV Munich–Composite International Diagnostic Interview was administered by clinically trained interviewers.

Setting  Community sample in Munich.

Participants  Three thousand twenty-one individuals aged 14 to 24 years at baseline and 21 to 34 years at follow-up.

Main Outcome Measures  Cumulative incidence of SAD and depression (major depressive episode or dysthymia).

Results  Cumulative incidence for SAD was 11.0%; for depression, 27.0%. Standardized person-years of incidence for SAD were highest for those aged 10 to 19 years (0.72%) and were low before (0.20%) and after (0.19%) that age range. Depression incidence was different, characterized by delayed and continued high rates. Social anxiety disorder was consistently associated with subsequent depression, independent of age at onset for SAD (relative risk range, 1.49-1.85, controlling for age and sex). Crude Cox regressions showed significant distal (eg, parental anxiety or depression, behavioral inhibition) and proximal SAD characteristics (eg, severity measures, persistence) as predictors. Most associations were attenuated in multiple models, leaving behavioral inhibition (hazard ratio, 1.30 [95% confidence interval, 1.04-1.62; P = .02]) and, less consistently, panic (hazard ratio, 1.85 [95% confidence interval, 1.08-3.18; P = .03]) as the remaining significant predictors.

Conclusions  Social anxiety disorder is an early, adolescent-onset disorder related to a substantially and consistently increased risk for subsequent depression. The demonstration of proximal and particularly distal predictors for increased depression risks requires further exploration to identify their moderator or mediator role. Along with previous evidence that comorbid SAD is associated with a more malignant course and character of depression, these results call for targeted prevention with the aim of reducing the burden of SAD and its consequences.

Figures in this Article

Large-scale epidemiological studies worldwide have provided relatively convergent prevalence estimates of DSM-IV social anxiety disorder (SAD) and its correlates and associations with other mental disorders, particularly depression, in the general population (eg, the National Comorbidity Survey [NCS],13 Mental Health Stratified subsample of the Supplement to the Ontario Residents of Households Health Survey [MHS-OHS],4 the Netherlands Mental Health Survey and Incidence Study [NEMESIS],5,6 Early Developmental Stages of Psychopathology [EDSP] Study,79 German Health Interview and Examination Survey [NHS],10,11 Australian Mental Health Survey [ANMHS],12 European Study of the Epidemiology of Mental Disorders [ESEMeD],13,14 National Institute on Alcohol Abuse and Alcoholism National Epidemiological Survey on Alcohol and Related Conditions [NIAAA-NESARC],15 and National Comorbidity Survey Replication [NCS-R]16,17). Owing to the retrospective nature of these mostly cross-sectional studies and the wide age range (16 to ≥ 65 years), however, it remains unclear whether SAD actually predicts the onset of subsequent depression. Moreover, patterns of incidence for SAD remain understudied, particularly with regard to the period that has been suggested in retrospective studies as the peak risk phase, ie, the first 3 decades of life.18,19 A better description of the incidence patterns of SAD in its early developmental stages is important for a better understanding of the etiologic factors involved in the first onset of SAD and in particular the temporal patterns and potential causal mechanisms involved in the onset of subsequent depression. Furthermore, such data are essential to early intervention and the prevention of more severe stages of SAD and its complications as the onset of subsequent depression.

Several reports from clinical20,21 and nonclinical studies3,8,9,2225 suggest that SAD predicts an increased risk for depression. However, few studies use prospective designs in epidemiological samples, and most of those that do focus on adults. Because SAD may start as early as childhood, studies examining the longitudinal association between SAD and depression should ideally begin at least in early adolescence and must ensure a sufficient observation period into adulthood to examine the risk of depression. To our knowledge, only 2 prospective epidemiological studies have examined the association between childhood or adolescent SAD and adult depression risk. Pine et al26 found no association between the 2 conditions in an upstate New York sample, but the adult follow-up only extended into the middle 20s. Because onset of depression might also occur later, that study may have underestimated the strength of the relationship. Stein et al8 and Bittner et al22 used 4 to 5 years of prospective longitudinal data in 14- to 24-year-old individuals from the EDSP Study and demonstrated, using different methods, that SAD is prospectively associated with an increased risk for incident depression. However, Stein et al8 also analyzed separate cohorts (aged 14-17 and 18-24 years at baseline) and found that this association seems to be restricted to the older cohort of individuals aged 18 to 24 years at baseline. As with Pine et al,26 it has been speculated that the absence of the SAD-depression association for the younger cohort (aged 14-17 years at baseline) may be attributed to the fact that, owing to the relatively short follow-up, these SAD cases had not yet passed through the peak period for first onset of depression.

The present study reexamines these issues by using 10 years of recently available prospective data from the EDSP Study, thus extending the examination by Stein et al8 by an additional 5 years of observation. We further provide for the first time a more complete description of incidence patterns of SAD and depression from the early adolescent period to 34 years of age and will examine the consistency of the association between SAD and adult depression for different SAD age-at-onset groups. In addition, several distal risk factors and proximal SAD characteristics will be explored in their ability to predict onset of subsequent depression.

SAMPLE

The EDSP Study is a prospective longitudinal study designed to collect data on the prevalence, incidence, comorbidity, risk factors, and course of mental and substance use disorders in a representative sample that originally included 3021 adolescents and young adults aged 14 to 24 years at baseline (T0). The study also includes 3 follow-up surveys (T1, T2, and T3), a family history component, and direct information from the parents assessed at T1.7,27,28

The baseline sample was drawn in 1994 from government registries in the greater Munich area of registrants expected to be aged 14 to 24 years at the T0 interview in 1995. Because the study emphasized early developmental stages of psychopathology, individuals aged 14 to 15 years were sampled at twice the probability of those aged 16 to 21 years, and individuals aged 22 to 24 years were sampled at half the probability of those aged 16 to 21 years.

Most interviews throughout the study took place in the respondents' homes or, in some instances, at another location preferred by the respondent. Approximately one-third of the sample received a financial incentive ($10-$20) to participate. Participants provided informed consent; parental consent was provided for respondents 18 years or younger.

The baseline sample (N = 3021) is representative of the greater Munich population aged 14 to 24 years; baseline response rate was 70.8%. Refusal to participate in the survey (18.2%) was by far the most frequent reason for nonresponse, followed by a reported lack of time (3.3%), failure to contact anyone in the identified household (3.1%), and failure to contact the sampled individual in the household (3.0%) (1.6% were lost owing to other reasons). The first follow-up survey (T1) was conducted only for individuals aged 14 to 17 years at baseline, whereas the second (T2) and third (T3) follow-up surveys were conducted for all individuals. At T1 (median interval since baseline, 1.6 years; interval range, 1.2-2.1 years), 1228 interviews were completed (response rate, 88.0%). A total of 2548 of the original 3021 individuals (response rate, 84.3%) took part in T2 (median interval since baseline, 3.5 years; interval range, 2.8-4.1 years). In all, 2210 individuals participated in T3 (response rate, 73.2%; median interval since baseline, 8.2 years; interval range, 7.3-10.6 years). A more detailed description of the study and the demographic characteristics of the sampled population and the respondents has been reported elsewhere.7,27,28

DIAGNOSTIC ASSESSMENT

Individuals were interviewed with the computer-assisted Munich–Composite International Diagnostic Interview (DIA-X/M-CIDI)29,30 and its embedded assessment modules.7,27,28 The DIA-X/M-CIDI allows for the assessment of symptoms and syndromes and for the diagnosis of 48 mental disorders, along with information about onset, duration, severity, and psychosocial impairment. Trained clinical interviewers (ie, clinical psychologists) performed the 2- to 3-hour face-to face interviews. Diagnoses of mental disorders were obtained by using the M-CIDI DSM-IV algorithms. The DIA-X/M-CIDI is supplemented by a separate respondent's booklet that includes disorder-specific questionnaires as well as symptom lists and cognitive aids to assist the respondent in dating symptom onset and recency, answering complicated symptom questions, and identifying course patterns. Test-retest reliability and validity for the full DIA-X/M-CIDI have been reported elsewhere,3032 along with descriptions of the DIA-X/M-CIDI format and coding conventions.

At baseline, the lifetime version of the DIA-X/M-CIDI was used. At each of the follow-up assessments, we applied the DIA-X/M-CIDI interval version, which refers to the period between the last and the current assessment. Findings presented herein are based on the aggregation of all available information for each participant from baseline to T3 (for individuals aged 14-17 years at baseline, T0, T1, T2, and T3; for individuals aged 18-24 years at baseline, T0, T2, and T3).

The diagnosis of SAD was assigned according to the DSM-IV DIA-X/M-CIDI diagnostic algorithms.9Depressive disorder was defined as meeting DSM-IV criteria for 1 or more episodes of major depression (MDE) or dysthymia (without using the exclusion criteria). The test-retest reliability of diagnostic categories ranged from κ values of 0.68 for major depression to 0.72 for SAD.30 The validity of these DIA-X/M-CIDI diagnoses compared with independent clinical consensus diagnoses by treating physicians was estimated with κ values of 0.54 for dysthymia, 0.80 for SAD, and 0.96 for MDE.31

All SAD characteristics reported herein were also derived from the DIA-X/M-CIDI SAD section.9 Age-at-onset information was based on the lowest age at onset reported by the respondent at any of the assessment waves.33 This definition of age at onset agreed well (> 90%) with other age-at-onset aggregation methods (ie, first and mean age at onset over the 4 EDSP assessments); ie, the absolute value of differences were at most 1 year for both SAD and depression, besides that lower agreement rates (about 70%) were found for depression when the mean method was used. Duration of SAD was calculated as the number of years between age at onset of SAD and the highest reported age at recency. Degree of avoidance refers to the frequency at which social situations were avoided owing to anxiety (never, rarely, frequently, or always; mean across all completed waves). If respondents reported no avoidance, they were further asked whether they had always tolerated such situations. A negative response was used as an indicator of rare avoidance. The SAD severity indicators included the following:

  1. The number of social situations refers to the number of reported social situations in the M-CIDI avoided or endured with anxiety by the respondent (range, 1-7).

  2. The number of anxiety cognitions refers to the reported count of having 1 or more of the following M-CIDI cognitions: (1) something embarrassing or shameful could happen; (2) being regarded as dumb or weak; (3) being regarded as crazy; (4) to experience an anxiety (panic) attack; (5) to be confused; (6) to be ashamed; (7) to throw up; (8) to lose control over intestinal organs; or (9) to turn red whenever one was in a social situation, thought about it, or was about to enter such a situation.

Degree of impairment reflects how much the anxiety of social situations or avoidance interfered with life and daily activities (not at all, a little, much, or very much). For each of these indicators, a total mean score across all completed waves was generated. Persistence of SAD is based on an index constituting the following elements: (1) degree of SAD expression at each wave (0 indicates none; 1, symptomatic; 2, subthreshold; and 3, threshold); (2) persistence of anxiety or avoidance of social situations for months or years (1 indicates no persistence; 2, persistence); (3) degree of avoidance (1 indicates partial; 2, complete avoidance); and (4) frequency of anxiety and avoidance (1 indicates none; 2, rarely; 3, sometimes; and 4, always). The persistence index was calculated by multiplying the mean scores of the 4 components; the resulting overall persistence score ranged from 0.75 to 24.00.

From the DIA-X/M-CIDI response booklet, the following scales were selected to examine risk factors and SAD-related characteristics in greater detail. The German version of the Retrospective Self-Report of Inhibition34 (assessed at baseline) is composed of a set of 30 questions about specific childhood behaviors reflecting behavioral inhibition (BI), defined as consistent restraint in response to both social and nonsocial situations (sympathetic nervous system activity, fear of things, etc). The total mean BI score was chosen because the 2-dimensional scores did not reveal notably different findings. Internal consistency of the Retrospective Self-Report of Inhibition was found to be acceptable in clinical and nonclinical samples with the Cronbach coefficient α for the 30 questions of 0.77 or greater and median item-to-total correlations of r ≥ 0.31. Validity was high as reflected by a strong agreement between individuals (self-reports) and their parents (observer reports) regarding the individual's inhibited behaviors as a child, a positive relation of retrospective self-report and contemporary measures of inhibition, and accounts for variance in general and specific measures of mental health.34 The self-reported Liebowitz Social Anxiety Scale,35 a reliable and valid measure of SAD in patient samples,36 was used at T2 to assess the degree of anxiety in (0 indicates none; 1, mild; 2, moderate; and 3, severe) and the frequency of avoidance of (0 indicates never; 1, occasionally; 2, often; and 3, always) 23 social situations. For each of these scales, a sum score was generated (theoretical range, 0-69). The German version37 of the Symptom Checklist-90–Revised was used at baseline to assess the presence of a broad range of psychological problems and symptoms of psychopathology referring to the past 7 days. In the present report, the phobic-anxiety subscale is used for the characterization of SAD individuals. The 1-week retest reliability of the subscales was found to be satisfactory to good (student sample; N = 80; rtt, 0.69-0.92). Internal consistencies (Cronbach coefficient α) for the subscales ranged in nonclinical samples from 0.51 to 0.83.

For the present article, the scores from these questionnaires were standardized, resulting in a mean of 0 (SD, 1) in the weighted total sample; the reported associations thus indicate the change in outcome (or transformed outcome, respectively, eg, ln[odds] [the natural logarithm of the odds] in logistic regressions) per increase by 1 SD.

As previously reported,38parental mental disorders assessment was based on direct DIA-X/M-CIDI interviews with parents (n = 1053) as part of the T1 family assessments or on family history information as obtained in the family history module at T2 and T3 with the respondent as informant. Family history items were designed to take the family history research diagnostic criteria39 as a basic model. Diagnostic information about parental mental disorders was aggregated, with predominance given to direct information from the interviewed parent (T1) over indirect family history information (T2/T3); ie, whenever direct information was available, indirect information was ignored. Only the presence of any parental DSM-IV anxiety or depressive disorder was used herein.

STATISTICAL ANALYSIS

Data are weighted by age, sex, and geographic location at baseline to match the distribution of the sampling frame; frequencies are reported unweighted. The Stata software package, version 9.0,40 was used to compute robust variances, 95% confidence intervals (CIs), and P values (by applying the Huber-White sandwich matrix), which are required when analyses are based on weighted data.41

Our analyses are based on a total sample of 3021 individuals and a subsample of 319 individuals who met the SAD criteria at any assessment wave. Two individuals with missing age-at-onset data were excluded. Associations between the cumulative SAD and depression occurrences were assessed with odds ratios (ORs) from logistic regressions while adjusting for sex and age. The association between SAD and subsequent depression was assessed with risk ratios from risk ratio regressions (procedure BINREG in Stata software40,42) and risk differences derived from logistic regressions (procedures LOGISTIC and Mfx in Stata software40,43). Referring to Greenland,44 we prefer risk differences as a more appropriate measure than ORs or risk ratios when assessing interactions. Age-specific cumulative lifetime incidence rates were estimated with the Kaplan-Meier method. Cox regressions with hazard ratios (HRs) were used to assess factors of the transition from SAD and risk of subsequent depressive disorders. Our analyses on factors for the transition from SAD to depression are based on the time-dependent covariate SAD(t) in the person-year data file, defined as 1 if SAD had ever been present before the age of t (assessed with age-at-onset data) and 0 otherwise. For the overall sample, the person-year data file included 36 753 units of observation; for the subsample with SAD(t), 1427 units were available. For some predictors, this number decreases slightly (by ≤ 5%) owing to missing information on the predictor. All Cox regressions were conducted using the strata variables age cohort and sex to adjust for effects of these variables.45 We also calculated standardized incidence rates per person-year, defined as 100 times the number of incident cases in the risk period divided by the total number of person-years under risk.46

CUMULATIVE INCIDENCE

The overall cumulative incidence for SAD up to T3 was 11.0% for the total sample (weighted; unweighted number, 319 of 3021), 8.0% for males (weighted; unweighted number, 120 of 1533), and 14.0% for females (weighted; unweighted number, 199 of 1488). The estimated age-dependent cumulative incidence rate for SAD at 33 years of age was 11.6%, and 8.2% and 14.9% for men and women, respectively (Figure). The incidence of SAD increased steeply after 9 years of age and then gradually decreased, with the inflection point occurring around 17 years of age in boys and 19 years of age in girls. The standardized incidence rates per person-year were highest (0.72%) from 10 to 19 years of age (0.50% for males and 0.95% for females); considerably lower rates were found below (≤ 9 years, 0.20%) and above (20-34 years, 0.19%) this age range.

Place holder to copy figure label and caption
Figure.

Overall age-dependent cumulative lifetime incidence of social anxiety disorder (SAD) and of depression (major depressive episode or dysthymia) in cases with or without the presence of SAD to age 33 years (based on a total of 3021 subjects [A], including 1533 males [B] and 1488 females [C] in up to 4 waves).

Graphic Jump Location

The overall cumulative incidence for depression (dysthymia and MDE) was 27.0% for the total sample (weighted; unweighted number, 782 of 3021), 20.8% for males (weighted; unweighted number, 302 of 1533), and 33.0% for females (weighted; unweighted number, 480 of 1488). The age-dependent cumulative incidence for depressive disorders at 33 years of age was 31.9%, and 25.2% and 38.5% for men and women, respectively. The Figure shows a considerably different—namely, delayed— age-dependent incidence function for depression among both individuals with and individuals without SAD as compared with the incidence function of SAD. Incidence rates for depression were increasing across the age spectrum considered in both sexes. Besides the overall higher cumulative incidence, the incidence curve for depression differed among lifetime SAD and non-SAD cases. Although there were continuing high incidences of depression among non-SAD cases, depression incidence decreased after 25 years of age in men and after 26 years of age in women. By 21 years of age in women and 26 years of age in men, the cumulative incidence of depression among SAD cases had reached about 50% of the cumulative incidence of SAD; a further increase of this proportion at higher ages was observed for women only (about 65% at 33 years of age).

SAD AND RISK FOR DEPRESSION

Overall, 50.2% (weighted; unweighted number, 152 of 319) of respondents with SAD also had a depressive disorder during the observation period. The overall association between SAD and depression was substantial (OR, 3.18 [95% CI, 2.45-4.14]) and decreased only slightly when controlling for age (OR, 3.12 [95% CI, 2.40-4.06]), sex (OR, 2.98 [95% CI, 2.28-3.89]), or age and sex (OR, 2.92 [95% CI, 2.23-3.81]; for all, P < .001). Social anxiety disorder was found to be the temporal primary disorder in most of the cases (59.3% [weighted; unweighted number, 89 of 150]); 11.7% (weighted; unweighted number, 18) reported an onset in the same year, and 28.4% (weighted; unweighted number, 43) reported an onset of depression before SAD. There were no significant differences between SAD cases with prior, same-year, or subsequent onset of depression on sociodemographic and clinical characteristics. As shown by Cox regressions, the risk for subsequent depression was 2-fold in individuals with SAD compared with respondents with no SAD (HR, 2.02 [95% CI, 1.59-2.57]) and almost 3-fold in individuals with SAD compared with respondents with no anxiety disorder (HR, 2.60 [95% CI, 2.03-3.34; for both, P < .001]). (Note: The conditional risk for depression by SAD status is not displayed in the Figure; the Figure shows the overall cumulative lifetime incidence of SAD and depression.) This increase in depression risk was found for both the generalized (HR for the comparison with no SAD, 2.64 [95% CI, 1.84-3.79]; HR for the comparison with no anxiety disorder, 3.39 [95% CI, 2.35-4.88]) and the nongeneralized subtype of SAD (HR for the comparison with no SAD, 1.76 [95% CI, 1.31-2.38]; HR for the comparison with no anxiety disorder, 2.27 [95% CI, 1.67-3.08; for all, P < .001]). The difference in depression risk between individuals with generalized compared with the nongeneralized subtype of SAD was not significant (HR, 1.47 [95% CI, 0.93-2.34; P = .10]).

ROLE OF AGE AT ONSET OF SAD FOR SUBSEQUENT DEPRESSION RISK

To examine whether the occurrence of SAD in different developmental stages is associated with a different probability for subsequent depression, we examined the proportion of depression occurrences (overall, n = 782) in individuals who had or did not have SAD up to a certain age (Table 1). Because almost all SAD onsets occurred before the age of 20 years, only ages younger than 11 years to ages younger than 20 years were considered. Table 1 shows that the eligible SAD cases in each age-at-onset row had a significantly higher risk for onset of subsequent depression compared with cases without SAD. Although this difference occurred irrespective of the age at onset of SAD, it was most pronounced for onsets from younger than 11 years to younger than 16 years.

Table Graphic Jump LocationTable 1. Risk for Subsequent Depression Among Individuals With or Without SAD by Onset of SAD Before a Specific Age

Recent prospective studies with a shorter follow-up period extending only to the mid 20s8,26 did not find an association between SAD and incident depression among younger adolescents but did find one among older adolescents and young adults. Using our 10-year follow-up data extending up to the mid 30s, we examined interactions for the older birth cohort (aged 18-24 years at baseline) vs the younger birth cohort (aged 14-17 years at baseline) in the prediction of subsequent depression among cases with SAD onset to a certain age. No interactions were found for birth cohort (a table is available from the authors on request). Both younger and older participants at the outset of the study who had developed SAD up to any of the defined ages had an increased risk for subsequent depression.

PREDICTORS OF THE PROGRESSION FROM SAD TO SUBSEQUENT DEPRESSION

To explore to what degree distal and proximal characteristics play a role in promoting the secondary depression risk in SAD, we first examined the crude associations between several putative distal risk factors and more proximal characteristics of SAD with onset of subsequent depression using Cox regressions (first column in Table 2). Among the distal factors, parental anxiety disorder and/or MDE, female sex, BI in childhood, and having multiple (≥ 3) other preceding anxiety disorders were found to be associated with increased risk for subsequent depression. Among the disorder characteristics, avoidance and duration of SAD were not associated with the risk of depression. Degree of impairment, persistence, and several indicators of greater severity of SAD were associated; a higher number of social anxiety situations and anxiety cognitions, occurrence of panic attacks, the fear of an anxiety attack in social situations, and a higher Symptom Checklist-90–Revised phobic-anxiety subscale score were all associated with secondary depression among SAD cases. Although the DSM-IV distinction of generalized (defined as ≥ 3 anxiety situations) vs nongeneralized subtype of SAD (defined as 1-2 anxiety situations) did not show a significant association with subsequent depression risk (HR, 1.47 [95% CI, 0.93-2.34]), the number of feared social situations as a dimensional variable was significant (the change in hazard rate per increase by 1 anxiety situation was 1.37 [95% CI, 1.09-1.72]).

Table Graphic Jump LocationTable 2. Variables Predicting the Onset of Depression Among Those Who Have Ever Had SAD Before the Respective Age (Cox Regression With Time-Dependent Covariate)

Subsequently, a series of multiple regression models were computed with all (second column in Table 2) and separate (third column in Table 2) groups of variables. Behavioral inhibition was the only variable that remained significant in the overall model for predicting subsequent depression among SAD cases (HR, 1.34 [95% CI, 1.02-1.76]). In the separate model for distal and proximal factors, BI (HR, 1.30 [95% CI, 1.04-1.62]) and the occurrence of panic attack in SAD (HR, 1.85 [95% CI, 1.08-3.18]) remained significant in the prediction of subsequent depression.

To our knowledge, this is the first report to describe and compare the patterns of incidence for DSM-IV SAD and depression among community individuals during the first 3 decades of life considered to cover the whole high-risk age period for first onset of SAD. The report is also a considerable extension of previous contributions from our group8,22 because it covers a 10-year observation period rather than a 4-year span and demonstrates that SAD is associated with a consistently increased risk for incident depression in all ages considered.

The incidence patterns clearly support the notion of SAD as an early, adolescent-onset disorder; new-onset cases in the third decade of life, especially after 25 years of age, are rare. Although we also confirm the higher prevalence and incidence of SAD among females,18 there is no notable sex difference in the onset distributions, with the exception of a more pronounced decrease of incidence after 20 years of age in men compared with women. For depression, a markedly different incidence function was found compared with SAD, characterized by a considerably later onset and depression incidences extending into the third and fourth decades of life. This observation is consistent with previous findings from cross-sectional retrospective studies covering a broader age range of respondents that yielded later median ages at onset in depression (20s and 30s24,47) compared with SAD (10s17,24) and similar prevalence and onset patterns.10,48 However, according to our findings, the incidence curve of depression among cases without SAD showed continuous, high incidence rates from adolescence to the end of our observation period at 34 years of age, whereas the depression-onset curve among cases with SAD gradually plateaued after 25 years of age. This decrease in depression incidence was delayed but parallel to the decrease of SAD incidence after 21 years of age. Based on descriptive observational data, this might suggest an important role for SAD in a substantial proportion of early-onset depressions.

Our prospective analyses further provide strong support for the notion that SAD substantially increases the risk for subsequent depression. The overall effect is similar to the one reported in our previous publications8,22 that covered only a 4-year follow-up. Because Stein et al8 raised concerns about the nature of this relationship owing to the observation that the association between SAD and incident depression during the 4-year follow-up was found only in the older but not in the younger study cohort, we have now demonstrated with 10 years of prospective data that the risk for subsequent depression among individuals with SAD exists independent of the age at onset of SAD, as well as independent of the age of respondents. This suggests that the failure to show an association between SAD and subsequent depression in the previous reports8,26 was most likely a result of the fact that individuals had not gone through the entire period of high risk for SAD and, particularly, depression.

The theoretical implications of this finding are that (1) the most vulnerable period for onset of SAD is limited to the adolescent years and that (2) SAD in adolescence yields a negative prognosis in terms of depression risk at any time during this period. This also lends strong support to the notion that early identification and intervention with socially anxious adolescents might therefore reduce risk for depressive disorders in adolescence and young adulthood, even more so because of previous demonstrations that SAD-comorbid depression is strongly associated with a more malignant course of depressive illness in terms of more suicidal ideation and suicide attempts, more depressive symptoms during episodes, more frequent and/or more protracted depressive episodes,8 and poorer depression outcomes.49 However, prevention of depression is hampered by the fact that few individuals with SAD receive adequate treatment, despite overall increased health care utilization.9,50

Thus, to what degree is this association mediated and/or moderated by other factors? Although this issue is beyond the scope of the present report, our exploratory multivariate regression analysis, in which a BI temperament, assessed with the Retrospective Self-report of Inhibition of Reznick et al,34 was retained as the only significant predictor for secondary depression among all other distal and proximal variables, suggests that the depression risk seems to be particularly enhanced among vulnerable individuals with increased childhood BI. Along with Kagan's hypotheses51 and indications that a BI temperament is also a vulnerability factor for SAD,5254 this finding suggests that high levels of BI might be used for defining high-risk target groups for primary prevention of SAD in childhood and adolescence and for secondary prevention of depression among individuals with SAD during adolescence and the transition to adulthood. However, this attractive speculation is tempered by data from the Dunedin Study.55 That study did not find associations between BI and subsequent anxiety disorders, despite an association with later depression. However, other data, albeit in studies of younger subjects, suggest that BI is a risk factor for anxiety but not major depressive disorder.54 This finding indicates that this question needs a more comprehensive analysis to identify the relevant interactions between vulnerability and risk factors in an attempt to identify the moderating and mediating role of a wider range of possible variables.

Furthermore, the partial failure to demonstrate a dose-response relationship between SAD severity characteristics and the risk of subsequent depression was unexpected. It seems counterintuitive, from a clinical perspective, that SAD characteristics such as severity, impairment, and persistence were not confirmed in the explorative multivariate analyses as significant predictors for subsequent depression. Only the occurrence of severe paniclike anxiety reactions remained significant in the separate multiple regression model. The core role of panic attacks is consistent with the DSM-IV and previous findings22,5658 that panic attacks are a sensible indicator for emerging severe psychopathology and depression in particular. Nevertheless, this finding needs replication and closer consideration in future studies. If this finding holds, however, it might be of substantial relevance. Given that most individuals with SAD do not get treated1,9 on the one hand, but that the treatment of panic attacks may reduce the risk for developing major depressive disorder59 and that approximately 10% of mood disorders may be prevented by successful early intervention in SAD3 on the other hand, our results strongly suggest that we study the effects of early intervention programs in adolescent SAD, most importantly when panic attacks or high levels of BI co-occur.

These findings must be viewed in light of some limitations of our study. First, we did not include a psychopathological comparison group (ie, subjects with other anxiety disorders), and therefore it remains to be shown in a direct comparison whether the increased risk for subsequent depression is unique to SAD or whether the magnitude of the association is specifically pronounced in SAD—the most common form of anxiety comorbidity among depressed patients.60,61 Previous findings suggest that the associations might not be specific to SAD.22,26 However, it was shown that SAD without other comorbid anxiety disorders is predictive for depression onset, even when previous other disorders are controlled for.22 Second, no causal inferences can be drawn from our observational data.62,63 Third, we did not explore a more comprehensive range of risk factors, and in particular we did not examine whether the risk factors for subsequent depression among SAD cases are moderators or mediators of this association64; this will be dealt with in a followup report. Although we cannot rule out nonparticipation of most severely disturbed individuals, we did not find selective attrition for persons with SAD during the assessment waves. A final, more general notion of caution concerns the retrospective nature of diagnoses and age-at-onset information, despite the overall prospective-longitudinal design of our study.

To summarize, SAD is an early, adolescent-onset disorder related to a substantially and consistently increased risk for subsequent depression. Along with previous evidence that comorbid SAD is associated with a more malignant course and character of depression, these results call for testing prevention and early-intervention programs aimed at reducing the burden of SAD and its consequences. In doing so, BI and panic appear to be important indicators for targeting such programs; however, further exploration is necessary to identify their moderator or mediator role.

Correspondence: Katja Beesdo, PhD, Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Chemnitzer Strasse 46, 01187 Dresden, Germany.

Submitted for Publication: November 14, 2006; final revision received January 19, 2007; accepted January 22, 2007.

Author Contributions: Principal investigators of the EDSP Study are Drs Lieb and Wittchen, who take responsibility for the integrity of the study data. All authors and coauthors had full access to all study data. Data analysis and manuscript preparation were completed by the authors and coauthors of this article, who take responsibility for its accuracy and content. Study concept and design: Beesdo, Bittner, Lieb, and Wittchen. Acquisition of data: Bittner, Lieb, and Wittchen. Analysis and interpretation of data: Beesdo, Pine, Stein, Höfler, Lieb, and Wittchen. Drafting of the manuscript: Beesdo, Pine, Höfler, and Wittchen. Critical revision of the manuscript for important intellectual content: Beesdo, Bittner, Pine, Stein, Höfler, Lieb, and Wittchen. Statistical analysis: Beesdo, Bittner, Höfler, and Wittchen. Obtained funding: Lieb and Wittchen. Administrative, technical, and material support: Pine and Lieb. Study supervision: Pine, Höfler, Lieb, and Wittchen.

Financial Disclosure: Dr Beesdo has received speaking honoraria from Pfizer. Dr Stein has received research support from Eli Lilly and Company, Forest Laboratories, Novartis, GlaxoSmithKline, and UCB Pharma; and has served as a consultant for AstraZeneca, Avera Pharmaceuticals, Bristol-Myers Squibb, Cephalon, Eli Lilly and Company, Forest Laboratories, GlaxoSmithKline Pharmaceuticals, Hoffmann-La Roche Pharmaceuticals, Jazz Pharmaceuticals, Johnson & Johnson, Pfizer, UCB Pharma, and Wyeth. Dr Lieb has received speaking honoraria from Wyeth. Dr Wittchen has received research support from Eli Lilly and Company, Novartis, Pfizer, and Schering-Plough; has served as a consultant for Eli Lilly, GlaxoSmithKline Pharmaceuticals, Hoffmann-La Roche Pharmaceuticals, Novartis, Pfizer, and Wyeth; and has received speaking honoraria from Novartis, Schering-Plough, Pfizer, and Wyeth.

Funding/Support: As part of the EDSP Study, the present study was supported by projects 01EB9405/6, 01EB 9901/6, EB01016200, 01EB0140, and 01EB0440 from the German Federal Ministry of Education and Research; and by projects LA1148/1-1, WI2246/1-1, WI 709/7-1, and WI 709/8-1 from the Deutsche Forschungsgemeinschaft (field work and analyses).

Additional Contributions: Andrew T. Gloster, PhD, provided helpful comments and suggestions on earlier drafts of this article. Kirsten von Sydow, PhD, Gabriele Lachner, MD, Axel Perkonigg, PhD, Peter Schuster, PhD, Holger Sonntag, Dipl-Psych, Tanja Brückl, PhD, Elzbieta Garczynski, Dipl-Psych, Barbara Isensee, PhD, Agnes Nocon, Dipl-Psych, Chris Nelson, PhD, Hildegard Pfister, Dipl-Inf, Victoria Reed, PhD, Barbara Spiegel, Dipl-Soz, Andrea Schreier, PhD, Ursula Wunderlich, PhD, and Petra Zimmermann, PhD, are current or past core staff members of the EDSP group and managed field and data work. Jules Angst, MD (Zurich, Switzerland), Jürgen Margraf, PhD (Basel), Günther Esser, PhD (Potsdam, Germany), Kathleen Merikangas, PhD (Bethesda), Ron Kessler, PhD (Boston, Massachusetts), and Jim van Os, PhD (Maastricht, the Netherlands), provided scientific advice on the design of the EDSP Study.

Magee  WJEaton  WWWittchen  H-UMcGonagle  KAKessler  RC Agoraphobia, simple phobia, and social phobia in the National Comorbidity Survey. Arch Gen Psychiatry 1996;53 (2) 159- 168
PubMed
Kessler  RCMcGonagle  KAZhao  SNelson  CBHughes  MEshleman  SWittchen  H-UKendler  KS Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: results from the National Comorbidity Survey. Arch Gen Psychiatry 1994;51 (1) 8- 19
PubMed
Kessler  RCStang  PWittchen  H-UStein  MBWalters  EE Lifetime comorbidities between social phobia and mood disorders in the US National Comorbidity Survey. Psychol Med 1999;29 (3) 555- 567
PubMed
Offord  DRBoyle  MHCampbell  DGoering  PLin  EWong  MRacine  YA One-year prevalence of psychiatric disorder in Ontarians 15 to 64 years of age. Can J Psychiatry 1996;41 (9) 559- 563
PubMed
Bijl  RVde Graaf  RRavelli  ASmit  FVollebergh  WAM Gender and age-specific first incidence of DSM-III-R psychiatric disorders in the general population. Soc Psychiatry Psychiatr Epidemiol 2002;37 (8) 372- 379
PubMed
Bijl  RVRavelli  AVan Zessen  G Prevalence of psychiatric disorder in the general population: results of the Netherlands Mental Health Survey and Incidence Study (NEMESIS). Soc Psychiatry Psychiatr Epidemiol 1998;33 (12) 587- 595
PubMed
Wittchen  H-UNelson  CBLachner  G Prevalence of mental disorders and psychosocial impairments in adolescents and young adults. Psychol Med 1998;28 (1) 109- 126
PubMed
Stein  MBFuetsch  MMüller  NHöfler  MLieb  RWittchen  H-U Social anxiety disorder and the risk of depression: a prospective community study of adolescents and young adults. Arch Gen Psychiatry 2001;58 (3) 251- 256
PubMed
Wittchen  H-UStein  MBKessler  RC Social fears and social phobia in a community sample of adolescents and young adults: prevalence, risk factors and comorbidity. Psychol Med 1999;29 (2) 309- 323
PubMed
Jacobi  FWittchen  H-UHölting  CHöfler  MPfister  HMüller  NLieb  R Prevalence, comorbidity and correlates of mental disorders in the general population: results from the German Health Interview and Examination Survey (GHS). Psychol Med 2004;34 (4) 597- 611
PubMed
Wittchen  H-UJacobi  F Size and burden of mental disorders in Europe: a critical review and appraisal of 27 studies. Eur Neuropsychopharmacol 2005;15 (4) 357- 367
PubMed
Andrews  GHenderson  SHall  W Prevalence, comorbidity, disability and service utilisation: overview of the Australian Mental Health Survey. Br J Psychiatry 2001;178145- 153
PubMed
Alonso  JAngermeyer  MCBernert  SBruffaerts  RBrugha  TSBryson  Hde Girolamo  Gde Graaf  RDemyttenaere  KGasquet  IHaro  JMKatz  SJKessler  RCKovess  VLepine  JPOrmel  JPolidori  GRusso  LJVilagut  GAlmansa  JArbabzadeh-Bouchez  SAutonell  JBernal  MBuist-Bouwman  MACodony  MDomingo-Salvani  AFerrer  MJoo  SSMartinez-Alonso  MMatschinger  HMazzi  FMorgan  ZMorosini  PPalacin  CRomera  BTaub  NVollebergh  WAMESEMeD/MHEDEA 2000 Investigators, European Study of the Epidemiology of Mental Disorders, (ESEMeD) Project. Prevalence of mental disorders in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project. Acta Psychiatr Scand Suppl 2004; (420) 21- 27
PubMed
Alonso  JAngermeyer  MCBernert  SBruffaerts  RBrugha  TSBryson  Hde Girolamo  Gde Graaf  RDemyttenaere  KGasquet  IHaro  JMKatz  SJKessler  RCKovess  VLepine  JPOrmel  JPolidori  GRusso  LJVilagut  GAlmansa  JArbabzadeh-Bouchez  SAutonell  JBernal  MBuist-Bouwman  MACodony  MDomingo-Salvani  AFerrer  MJoo  SSMartinez-Alonso  MMatschinger  HMazzi  FMorgan  ZMorosini  PPalacin  CRomera  BTaub  NVollebergh  WAMESEMeD/MHEDEA 2000 Investigators, European Study of the Epidemiology of Mental Disorders, (ESEMeD) Project. 12-Month comorbidity patterns and associated factors in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project. Acta Psychiatr Scand Suppl 2004; (420) 28- 37
PubMed
Grant  BFStinson  FSDawson  DAChou  SPDufour  MCCompton  WPickering  RPKaplan  K Prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry 2004;61 (8) 807- 816
PubMed
Kessler  RCChiu  WTDemler  OWalters  EE Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication [published correction appears in Arch Gen Psychiatry. 2005;62(7):709]. Arch Gen Psychiatry 2005;62 (6) 617- 627
PubMed
Kessler  RCBerglund  PDemler  OJin  RMerikangas  KRWalters  EE Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication [published correction appears in Arch Gen Psychiatry. 2005;62(7):768]. Arch Gen Psychiatry 2005;62 (6) 593- 602
PubMed
Wittchen  HUFehm  L Epidemiology and natural course of social fears and social phobia. Acta Psychiatr Scand Suppl 2003; (417) 4- 18
PubMed
Heimberg  RGStein  MBHiripi  EKessler  RC Trends in the prevalence of social phobia in the United States: a synthetic cohort analysis of changes over four decades. Eur Psychiatry 2000;15 (1) 29- 37
PubMed
Van Ameringen  MMancini  CStyan  GDonison  D Relationship of social phobia with other psychiatric illness. J Affect Disord 1991;21 (2) 93- 99
PubMed
Lépine  J-PWittchen  HUEssau  CA Lifetime and current comorbidity of anxiety and affective disorders: results from the International WHO/ADAMHA CIDI field trials. Int J Methods Psychiatr Res 1993;3 (2) 67- 77
Bittner  AGoodwin  RDWittchen  H-UBeesdo  KHöfler  MLieb  R What characteristics of primary anxiety disorders predict subsequent major depressive disorder? J Clin Psychiatry 2004;65 (5) 618- 626
PubMed
Essau  CAConradt  JPetermann  F Frequency and comorbidity of social phobia and social fears in adolescents. Behav Res Ther 1999;37 (9) 831- 843
PubMed
de Graaf  RBijl  RSpijker  JBeekman  ATFVollebergh  WAM Temporal sequencing of lifetime mood disorders in relation to comorbid anxiety and substance use disorders. Soc Psychiatry Psychiatr Epidemiol 2003;38 (1) 1- 11
PubMed
Schneier  FRJohnson  JHornig  CDLiebowitz  MRWeissman  MM Social phobia: comorbidity and morbidity in an epidemiologic sample. Arch Gen Psychiatry 1992;49 (4) 282- 288
PubMed
Pine  DSCohen  PGurley  DBrook  JMa  Y The risk for early-adulthood anxiety and depressive disorders in adolescents with anxiety and depressive disorders. Arch Gen Psychiatry 1998;55 (1) 56- 64
PubMed
Wittchen  H-UPerkonigg  ALachner  GNelson  CB Early Developmental Stages of Psychopathology Study (EDSP): objectives and design. Eur Addict Res 1998;4 (1-2) 18- 27
PubMed
Lieb  RIsensee  Bvon Sydow  KWittchen  H-U The Early Developmental Stages of Psychopathology Study (EDSP): a methodological update. Eur Addict Res 2000;6 (4) 170- 182
PubMed
Wittchen  H-UPfister  H DIA-X-Interviews: Manual für Screening-Verfahren und Interview; Interviewheft Längsschnittuntersuchung (DIA-X-Lifetime); Ergänzungsheft (DIA-X-Lifetime); Interviewheft Querschnittuntersuchung (DIA-X-12 Monate); Ergänzungsheft (DIA-X-12Monate); PC-Programm zur Durchführung des Interviews (Längs- und Querschnittuntersuchung); Auswertungsprogramm.  Frankfurt, Germany Swets & Zeitlinger1997;
Wittchen  H-ULachner  GWunderlich  UPfister  H Test-retest reliability of the computerized DSM-IV version of the Munich–Composite International Diagnostic Interview (M-CIDI). Soc Psychiatry Psychiatr Epidemiol 1998;33 (11) 568- 578
PubMed
Reed  VGander  FPfister  HSteiger  ASonntag  HTrenkwalder  CSonntag  AHundt  WWittchen  H-U To what degree does the Composite International Diagnostic Interview (CIDI) correctly identify DSM-IV disorders? testing validity issues in a clinical sample. Int J Methods Psychiatr Res 1998;7 (3) 142- 155
Wittchen  H-U Reliability and validity studies of the WHO–Composite International Diagnostic Interview (CIDI): a critical review. J Psychiatr Res 1994;28 (1) 57- 84
PubMed
Wittchen  H-ULieb  RSchuster  POldehinkel  AJ When is onset? investigations into early developmental stages of anxiety and depressive disorders. Rapoport  JLedChildhood Onset of “Adult” Psychopathology: Clinical and Research Advances. Washington, DC American Psychiatric Press1999;259- 302
Reznick  JSHegeman  IMKaufman  ERWoods  SWJacobs  M Retrospective and concurrent self-report of behavioral inhibition and their relation to adult mental health. Dev Psychopathol 1992;4 (2) 301- 321
Liebowitz  MR Social phobia. Mod Probl Pharmacopsychiatry 1987;22141- 173
PubMed
Heimberg  RGHorner  KJJuster  HRSafren  SABrown  EJSchneier  FRLiebowitz  MR Psychometric properties of the Liebowitz Social Anxiety Scale. Psychol Med 1999;29 (1) 199- 212
PubMed
Franke  G Die Symptom-Checkliste von Derogatis: SCL-90-R: Deutsche Version.  Göttingen, Germany Beltz1995;
Lieb  RIsensee  BHöfler  MPfister  HWittchen  H-U Parental major depression and the risk of depressive and other mental disorders in offspring: a prospective-longitudinal community study. Arch Gen Psychiatry 2002;59 (4) 365- 374
PubMed
Andreasen  NCEndicott  JSpitzer  RLWinokur  G The family history method using diagnostic criteria: reliability and validity. Arch Gen Psychiatry 1977;34 (10) 1229- 1235
PubMed
StataCorp, Stata Statistical Software: Release 9.0.  College Station, TX StataCorp2006;
Royall  RM Model robust confidence intervals using maximum likelihood estimators. Int Stat Rev 1986;54 (2) 221- 226
Wacholder  S Binomial regression in GLIM: estimating risk ratios and risk differences. Am J Epidemiol 1986;123 (1) 174- 184
PubMed
Joffe  MMGreenland  S Standardized estimates from categorical regression models. Stat Med 1995;14 (19) 2131- 2141
PubMed
Greenland  S Basic problems in interaction assessment. Environ Health Perspect 1993;Dec;101 (Suppl 4) 59- 66
PubMed
Therneau  TMGrambsch  PM Modeling Survival Data: Extending the Cox Model.  New York, NY Springer-Verlag NY Inc2000;
Rothman  KJGreenland  S Modern Epidemiology.  Philadelphia, PA Lippincott & Lippincott1998;
Weissman  MMBland  RCCanino  GJFaravelli  CGreenwald  SHwu  H-GJoyce  PRKaram  EGLee  C-KLellouch  JLépine  J-PNewman  SCRubio-Stipec  MWells  JEWickramaratne  PJWittchen  H-UYeh  E-K Cross-national epidemiology of major depression and bipolar disorder. JAMA 1996;276 (4) 293- 299
PubMed
Andrade  LCaraveo-Anduaga  JJBerglund  PBijl  Rde Graaf  RVollebergh  WAMDragomirecká  EKohn  RKeller  MBKessler  RCKawakami  NKilic  COfford  DÜstün  TBWittchen  H-U The epidemiology of major depressive episodes: results from the International Consortium of Psychiatric Epidemiology (ICPE) Surveys. Int J Methods Psychiatr Res 2003;12 (1) 3- 21
PubMed
Gaynes  BNMagruder  KMBurns  BJWagner  HRYarnall  KSHBroadhead  WE Does a coexisting anxiety disorder predict persistence of depressive illness in primary care patients with major depression? Gen Hosp Psychiatry 1999;21 (3) 158- 167
PubMed
Lecrubier  YWittchen  H-UFaravelli  CBobes  JPatel  AKnapp  M A European perspective on social anxiety disorder. Eur Psychiatry 2000;15 (1) 5- 16
PubMed
Kagan  J Temperamental contributions to social behavior. Am Psychol 1989;44 (4) 668- 674
Schwartz  CESnidman  NKagan  J Adolescent social anxiety as an outcome of inhibited temperament in childhood. J Am Acad Child Adolesc Psychiatry 1999;38 (8) 1008- 1015
PubMed
Rosenbaum  JFBiederman  JHirshfeld  DRBolduc  EAChaloff  J Behavioral inhibition in children: a possible precursor to panic disorder or social phobia. J Clin Psychiatry 1991;52 ((suppl)) 5- 9
PubMed
Biederman  JHirshfeld-Becker  DRRosenbaum  JFHérot  CFriedman  DSnidman  NKagan  JFaraone  SV Further evidence of association between behavioral inhibition and social anxiety in children. Am J Psychiatry 2001;158 (10) 1673- 1679
PubMed
Caspi  AMoffitt  TENewman  DLSilva  PA Behavioral observations at age 3 years predict adult psychiatric disorders. Arch Gen Psychiatry 1996;53 (11) 1033- 1039
PubMed
Goodwin  RDLieb  RHöfler  MPfister  HBittner  ABeesdo  KWittchen  H-U Panic attack as a risk factor for severe psychopathology. Am J Psychiatry 2004;161 (12) 2207- 2214
PubMed
Jack  MSHeimberg  RGMennin  DS Situational panic attacks: impact on distress and impairment among patients with social phobia. Depress Anxiety 1999;10 (3) 112- 118
PubMed
Shear  MKBjelland  IBeesdo  KGloster  ATWittchen  H-U Supplementary dimensional assessment in anxiety disorders. Int J Methods Psychiatr Res 2007;16 ((suppl 1)) S52- S64
Goodwin  ROlfson  M Treatment of panic attack and risk of major depressive disorder in the community. Am J Psychiatry 2001;158 (7) 1146- 1148
PubMed
Pini  SCassano  GBSimonini  ESavino  MRusso  AMontgomery  SA Prevalence of anxiety disorders comorbidity in bipolar depression, unipolar depression and dysthymia. J Affect Disord 1997;42 (2-3) 145- 153
PubMed
Rush  AJZimmerman  MWisniewski  SRFava  MHollon  SDWarden  DBiggs  MMShores-Wilson  KShelton  RCLuther  JF Comorbid psychiatric disorders in depressed outpatients: demographic and clinical features. J Affect Disord 2005;87 (1) 43- 55
PubMed
Kraemer  HCKazdin  AEOfford  DRKessler  RCJensen  PSKupfer  DJ Coming to terms with the terms of risk. Arch Gen Psychiatry 1997;54 (4) 337- 343
PubMed
Höfler  M Causal inference based on counterfactuals. BMC Med Res Methodol 2005;5- 28[published online September 13, 2005].
PubMeddoi:10.1186/1471-2288-5-28
Kraemer  HCStice  EKazdin  AOfford  DKupfer  D How do risk factors work together? mediators, moderators, and independent, overlapping, and proxy risk factors. Am J Psychiatry 2001;158 (6) 848- 856
PubMed

Figures

Place holder to copy figure label and caption
Figure.

Overall age-dependent cumulative lifetime incidence of social anxiety disorder (SAD) and of depression (major depressive episode or dysthymia) in cases with or without the presence of SAD to age 33 years (based on a total of 3021 subjects [A], including 1533 males [B] and 1488 females [C] in up to 4 waves).

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Risk for Subsequent Depression Among Individuals With or Without SAD by Onset of SAD Before a Specific Age
Table Graphic Jump LocationTable 2. Variables Predicting the Onset of Depression Among Those Who Have Ever Had SAD Before the Respective Age (Cox Regression With Time-Dependent Covariate)

References

Magee  WJEaton  WWWittchen  H-UMcGonagle  KAKessler  RC Agoraphobia, simple phobia, and social phobia in the National Comorbidity Survey. Arch Gen Psychiatry 1996;53 (2) 159- 168
PubMed
Kessler  RCMcGonagle  KAZhao  SNelson  CBHughes  MEshleman  SWittchen  H-UKendler  KS Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: results from the National Comorbidity Survey. Arch Gen Psychiatry 1994;51 (1) 8- 19
PubMed
Kessler  RCStang  PWittchen  H-UStein  MBWalters  EE Lifetime comorbidities between social phobia and mood disorders in the US National Comorbidity Survey. Psychol Med 1999;29 (3) 555- 567
PubMed
Offord  DRBoyle  MHCampbell  DGoering  PLin  EWong  MRacine  YA One-year prevalence of psychiatric disorder in Ontarians 15 to 64 years of age. Can J Psychiatry 1996;41 (9) 559- 563
PubMed
Bijl  RVde Graaf  RRavelli  ASmit  FVollebergh  WAM Gender and age-specific first incidence of DSM-III-R psychiatric disorders in the general population. Soc Psychiatry Psychiatr Epidemiol 2002;37 (8) 372- 379
PubMed
Bijl  RVRavelli  AVan Zessen  G Prevalence of psychiatric disorder in the general population: results of the Netherlands Mental Health Survey and Incidence Study (NEMESIS). Soc Psychiatry Psychiatr Epidemiol 1998;33 (12) 587- 595
PubMed
Wittchen  H-UNelson  CBLachner  G Prevalence of mental disorders and psychosocial impairments in adolescents and young adults. Psychol Med 1998;28 (1) 109- 126
PubMed
Stein  MBFuetsch  MMüller  NHöfler  MLieb  RWittchen  H-U Social anxiety disorder and the risk of depression: a prospective community study of adolescents and young adults. Arch Gen Psychiatry 2001;58 (3) 251- 256
PubMed
Wittchen  H-UStein  MBKessler  RC Social fears and social phobia in a community sample of adolescents and young adults: prevalence, risk factors and comorbidity. Psychol Med 1999;29 (2) 309- 323
PubMed
Jacobi  FWittchen  H-UHölting  CHöfler  MPfister  HMüller  NLieb  R Prevalence, comorbidity and correlates of mental disorders in the general population: results from the German Health Interview and Examination Survey (GHS). Psychol Med 2004;34 (4) 597- 611
PubMed
Wittchen  H-UJacobi  F Size and burden of mental disorders in Europe: a critical review and appraisal of 27 studies. Eur Neuropsychopharmacol 2005;15 (4) 357- 367
PubMed
Andrews  GHenderson  SHall  W Prevalence, comorbidity, disability and service utilisation: overview of the Australian Mental Health Survey. Br J Psychiatry 2001;178145- 153
PubMed
Alonso  JAngermeyer  MCBernert  SBruffaerts  RBrugha  TSBryson  Hde Girolamo  Gde Graaf  RDemyttenaere  KGasquet  IHaro  JMKatz  SJKessler  RCKovess  VLepine  JPOrmel  JPolidori  GRusso  LJVilagut  GAlmansa  JArbabzadeh-Bouchez  SAutonell  JBernal  MBuist-Bouwman  MACodony  MDomingo-Salvani  AFerrer  MJoo  SSMartinez-Alonso  MMatschinger  HMazzi  FMorgan  ZMorosini  PPalacin  CRomera  BTaub  NVollebergh  WAMESEMeD/MHEDEA 2000 Investigators, European Study of the Epidemiology of Mental Disorders, (ESEMeD) Project. Prevalence of mental disorders in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project. Acta Psychiatr Scand Suppl 2004; (420) 21- 27
PubMed
Alonso  JAngermeyer  MCBernert  SBruffaerts  RBrugha  TSBryson  Hde Girolamo  Gde Graaf  RDemyttenaere  KGasquet  IHaro  JMKatz  SJKessler  RCKovess  VLepine  JPOrmel  JPolidori  GRusso  LJVilagut  GAlmansa  JArbabzadeh-Bouchez  SAutonell  JBernal  MBuist-Bouwman  MACodony  MDomingo-Salvani  AFerrer  MJoo  SSMartinez-Alonso  MMatschinger  HMazzi  FMorgan  ZMorosini  PPalacin  CRomera  BTaub  NVollebergh  WAMESEMeD/MHEDEA 2000 Investigators, European Study of the Epidemiology of Mental Disorders, (ESEMeD) Project. 12-Month comorbidity patterns and associated factors in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project. Acta Psychiatr Scand Suppl 2004; (420) 28- 37
PubMed
Grant  BFStinson  FSDawson  DAChou  SPDufour  MCCompton  WPickering  RPKaplan  K Prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry 2004;61 (8) 807- 816
PubMed
Kessler  RCChiu  WTDemler  OWalters  EE Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication [published correction appears in Arch Gen Psychiatry. 2005;62(7):709]. Arch Gen Psychiatry 2005;62 (6) 617- 627
PubMed
Kessler  RCBerglund  PDemler  OJin  RMerikangas  KRWalters  EE Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication [published correction appears in Arch Gen Psychiatry. 2005;62(7):768]. Arch Gen Psychiatry 2005;62 (6) 593- 602
PubMed
Wittchen  HUFehm  L Epidemiology and natural course of social fears and social phobia. Acta Psychiatr Scand Suppl 2003; (417) 4- 18
PubMed
Heimberg  RGStein  MBHiripi  EKessler  RC Trends in the prevalence of social phobia in the United States: a synthetic cohort analysis of changes over four decades. Eur Psychiatry 2000;15 (1) 29- 37
PubMed
Van Ameringen  MMancini  CStyan  GDonison  D Relationship of social phobia with other psychiatric illness. J Affect Disord 1991;21 (2) 93- 99
PubMed
Lépine  J-PWittchen  HUEssau  CA Lifetime and current comorbidity of anxiety and affective disorders: results from the International WHO/ADAMHA CIDI field trials. Int J Methods Psychiatr Res 1993;3 (2) 67- 77
Bittner  AGoodwin  RDWittchen  H-UBeesdo  KHöfler  MLieb  R What characteristics of primary anxiety disorders predict subsequent major depressive disorder? J Clin Psychiatry 2004;65 (5) 618- 626
PubMed
Essau  CAConradt  JPetermann  F Frequency and comorbidity of social phobia and social fears in adolescents. Behav Res Ther 1999;37 (9) 831- 843
PubMed
de Graaf  RBijl  RSpijker  JBeekman  ATFVollebergh  WAM Temporal sequencing of lifetime mood disorders in relation to comorbid anxiety and substance use disorders. Soc Psychiatry Psychiatr Epidemiol 2003;38 (1) 1- 11
PubMed
Schneier  FRJohnson  JHornig  CDLiebowitz  MRWeissman  MM Social phobia: comorbidity and morbidity in an epidemiologic sample. Arch Gen Psychiatry 1992;49 (4) 282- 288
PubMed
Pine  DSCohen  PGurley  DBrook  JMa  Y The risk for early-adulthood anxiety and depressive disorders in adolescents with anxiety and depressive disorders. Arch Gen Psychiatry 1998;55 (1) 56- 64
PubMed
Wittchen  H-UPerkonigg  ALachner  GNelson  CB Early Developmental Stages of Psychopathology Study (EDSP): objectives and design. Eur Addict Res 1998;4 (1-2) 18- 27
PubMed
Lieb  RIsensee  Bvon Sydow  KWittchen  H-U The Early Developmental Stages of Psychopathology Study (EDSP): a methodological update. Eur Addict Res 2000;6 (4) 170- 182
PubMed
Wittchen  H-UPfister  H DIA-X-Interviews: Manual für Screening-Verfahren und Interview; Interviewheft Längsschnittuntersuchung (DIA-X-Lifetime); Ergänzungsheft (DIA-X-Lifetime); Interviewheft Querschnittuntersuchung (DIA-X-12 Monate); Ergänzungsheft (DIA-X-12Monate); PC-Programm zur Durchführung des Interviews (Längs- und Querschnittuntersuchung); Auswertungsprogramm.  Frankfurt, Germany Swets & Zeitlinger1997;
Wittchen  H-ULachner  GWunderlich  UPfister  H Test-retest reliability of the computerized DSM-IV version of the Munich–Composite International Diagnostic Interview (M-CIDI). Soc Psychiatry Psychiatr Epidemiol 1998;33 (11) 568- 578
PubMed
Reed  VGander  FPfister  HSteiger  ASonntag  HTrenkwalder  CSonntag  AHundt  WWittchen  H-U To what degree does the Composite International Diagnostic Interview (CIDI) correctly identify DSM-IV disorders? testing validity issues in a clinical sample. Int J Methods Psychiatr Res 1998;7 (3) 142- 155
Wittchen  H-U Reliability and validity studies of the WHO–Composite International Diagnostic Interview (CIDI): a critical review. J Psychiatr Res 1994;28 (1) 57- 84
PubMed
Wittchen  H-ULieb  RSchuster  POldehinkel  AJ When is onset? investigations into early developmental stages of anxiety and depressive disorders. Rapoport  JLedChildhood Onset of “Adult” Psychopathology: Clinical and Research Advances. Washington, DC American Psychiatric Press1999;259- 302
Reznick  JSHegeman  IMKaufman  ERWoods  SWJacobs  M Retrospective and concurrent self-report of behavioral inhibition and their relation to adult mental health. Dev Psychopathol 1992;4 (2) 301- 321
Liebowitz  MR Social phobia. Mod Probl Pharmacopsychiatry 1987;22141- 173
PubMed
Heimberg  RGHorner  KJJuster  HRSafren  SABrown  EJSchneier  FRLiebowitz  MR Psychometric properties of the Liebowitz Social Anxiety Scale. Psychol Med 1999;29 (1) 199- 212
PubMed
Franke  G Die Symptom-Checkliste von Derogatis: SCL-90-R: Deutsche Version.  Göttingen, Germany Beltz1995;
Lieb  RIsensee  BHöfler  MPfister  HWittchen  H-U Parental major depression and the risk of depressive and other mental disorders in offspring: a prospective-longitudinal community study. Arch Gen Psychiatry 2002;59 (4) 365- 374
PubMed
Andreasen  NCEndicott  JSpitzer  RLWinokur  G The family history method using diagnostic criteria: reliability and validity. Arch Gen Psychiatry 1977;34 (10) 1229- 1235
PubMed
StataCorp, Stata Statistical Software: Release 9.0.  College Station, TX StataCorp2006;
Royall  RM Model robust confidence intervals using maximum likelihood estimators. Int Stat Rev 1986;54 (2) 221- 226
Wacholder  S Binomial regression in GLIM: estimating risk ratios and risk differences. Am J Epidemiol 1986;123 (1) 174- 184
PubMed
Joffe  MMGreenland  S Standardized estimates from categorical regression models. Stat Med 1995;14 (19) 2131- 2141
PubMed
Greenland  S Basic problems in interaction assessment. Environ Health Perspect 1993;Dec;101 (Suppl 4) 59- 66
PubMed
Therneau  TMGrambsch  PM Modeling Survival Data: Extending the Cox Model.  New York, NY Springer-Verlag NY Inc2000;
Rothman  KJGreenland  S Modern Epidemiology.  Philadelphia, PA Lippincott & Lippincott1998;
Weissman  MMBland  RCCanino  GJFaravelli  CGreenwald  SHwu  H-GJoyce  PRKaram  EGLee  C-KLellouch  JLépine  J-PNewman  SCRubio-Stipec  MWells  JEWickramaratne  PJWittchen  H-UYeh  E-K Cross-national epidemiology of major depression and bipolar disorder. JAMA 1996;276 (4) 293- 299
PubMed
Andrade  LCaraveo-Anduaga  JJBerglund  PBijl  Rde Graaf  RVollebergh  WAMDragomirecká  EKohn  RKeller  MBKessler  RCKawakami  NKilic  COfford  DÜstün  TBWittchen  H-U The epidemiology of major depressive episodes: results from the International Consortium of Psychiatric Epidemiology (ICPE) Surveys. Int J Methods Psychiatr Res 2003;12 (1) 3- 21
PubMed
Gaynes  BNMagruder  KMBurns  BJWagner  HRYarnall  KSHBroadhead  WE Does a coexisting anxiety disorder predict persistence of depressive illness in primary care patients with major depression? Gen Hosp Psychiatry 1999;21 (3) 158- 167
PubMed
Lecrubier  YWittchen  H-UFaravelli  CBobes  JPatel  AKnapp  M A European perspective on social anxiety disorder. Eur Psychiatry 2000;15 (1) 5- 16
PubMed
Kagan  J Temperamental contributions to social behavior. Am Psychol 1989;44 (4) 668- 674
Schwartz  CESnidman  NKagan  J Adolescent social anxiety as an outcome of inhibited temperament in childhood. J Am Acad Child Adolesc Psychiatry 1999;38 (8) 1008- 1015
PubMed
Rosenbaum  JFBiederman  JHirshfeld  DRBolduc  EAChaloff  J Behavioral inhibition in children: a possible precursor to panic disorder or social phobia. J Clin Psychiatry 1991;52 ((suppl)) 5- 9
PubMed
Biederman  JHirshfeld-Becker  DRRosenbaum  JFHérot  CFriedman  DSnidman  NKagan  JFaraone  SV Further evidence of association between behavioral inhibition and social anxiety in children. Am J Psychiatry 2001;158 (10) 1673- 1679
PubMed
Caspi  AMoffitt  TENewman  DLSilva  PA Behavioral observations at age 3 years predict adult psychiatric disorders. Arch Gen Psychiatry 1996;53 (11) 1033- 1039
PubMed
Goodwin  RDLieb  RHöfler  MPfister  HBittner  ABeesdo  KWittchen  H-U Panic attack as a risk factor for severe psychopathology. Am J Psychiatry 2004;161 (12) 2207- 2214
PubMed
Jack  MSHeimberg  RGMennin  DS Situational panic attacks: impact on distress and impairment among patients with social phobia. Depress Anxiety 1999;10 (3) 112- 118
PubMed
Shear  MKBjelland  IBeesdo  KGloster  ATWittchen  H-U Supplementary dimensional assessment in anxiety disorders. Int J Methods Psychiatr Res 2007;16 ((suppl 1)) S52- S64
Goodwin  ROlfson  M Treatment of panic attack and risk of major depressive disorder in the community. Am J Psychiatry 2001;158 (7) 1146- 1148
PubMed
Pini  SCassano  GBSimonini  ESavino  MRusso  AMontgomery  SA Prevalence of anxiety disorders comorbidity in bipolar depression, unipolar depression and dysthymia. J Affect Disord 1997;42 (2-3) 145- 153
PubMed
Rush  AJZimmerman  MWisniewski  SRFava  MHollon  SDWarden  DBiggs  MMShores-Wilson  KShelton  RCLuther  JF Comorbid psychiatric disorders in depressed outpatients: demographic and clinical features. J Affect Disord 2005;87 (1) 43- 55
PubMed
Kraemer  HCKazdin  AEOfford  DRKessler  RCJensen  PSKupfer  DJ Coming to terms with the terms of risk. Arch Gen Psychiatry 1997;54 (4) 337- 343
PubMed
Höfler  M Causal inference based on counterfactuals. BMC Med Res Methodol 2005;5- 28[published online September 13, 2005].
PubMeddoi:10.1186/1471-2288-5-28
Kraemer  HCStice  EKazdin  AOfford  DKupfer  D How do risk factors work together? mediators, moderators, and independent, overlapping, and proxy risk factors. Am J Psychiatry 2001;158 (6) 848- 856
PubMed

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Topics
PubMed Articles
JAMAevidence.com

The Rational Clinical Examination
Make the Diagnosis: Depression

The Rational Clinical Examination
Original Article: Is This Patient Clinically Depressed?