Demographic, Clinical and Biological Parameters at Baseline
Demographic, clinical and biological features of the three groups of adolescents are outlined in . The groups did not differ significantly with respect to age, gender or ethnicity. High-risk and depressed groups had significantly lower socioeconomic score than normal controls. Depressed adolescents scored significantly higher on the BDI, HDRS and stressful experiences, but lower on CGAS, than both comparison groups. The groups did not differ significantly with respect to smoking status or salivary cortisol, but depressed youth had higher nocturnal urinary-free cortisol than normal controls, whereas the high-risk subjects had intermediate levels.
Baseline demographic, clinical and biological parameters by diagnosis
Three initially normal controls, four high-risk subjects and four depressed adolescents only were assessed at intake and did not complete any follow-up evaluations. Subjects that did not participate in follow-up assessments did not differ significantly from those with follow-up information on any demographic or clinical characteristics. Recruitment did not occur simultaneously and, therefore, not all subjects were studied longitudinally for the same period of time. Of the 140 adolescents that had follow-up information, 9.3% were followed for 2 years, 19.3% for 3 years, 31.4% for 4 years and 40.0% for 5 years. The three groups were comparable on the mean follow-up interval (mean follow-up interval = 3.6 years, SD = 1.0).
Initiation of Smoking
Of a total of 140 adolescents who had follow-up information, 109 (77.9%) had no prior smoking history at intake. Of these 109 participants, 21 (19.3%) initiated smoking during the study. The mean FTQ score in the smokers was 3.7 (SD = 1.3; range 2.0-6.5). Based on the FTQ score, four (19.0%) showed no evidence of nicotine dependence, 15 (71.4%) had moderate level of dependence and two (9.5%) manifested high level of dependence. Severity of nicotine dependence was comparable among the three diagnostic groups. Demographic and clinical characteristics of subjects who initiated smoking and those who never smoked are provided in . The groups did not differ significantly on any demographic or clinical variables but there was a trend for adolescents who initiated smoking to have a longer follow-up period compared with non-smokers.
Demographic and clinical parameters in adolescents who reported no prior smoking history at intake, stratified on smoking initiation during follow-up
Of a total of 37 depressed youth with no prior smoking history at intake, 6/13 (46.2%) participants with comorbid anxiety disorder initiated smoking compared to 3/24 (12.5%) subjects without anxiety disorder (FET, p = .04). Of 5 youth with comorbid disruptive disorder, one (20%) initiated smoking compared to 8/32 (25.0%) without disruptive disorder (FET, NS).
Effects of HPA Activity and Stress on Smoking Initiation
There was a high correlation among the three cortisol measures (r = .66 between salivary cortisol and urinary free cortisol concentration; r = .62 between salivary cortisol and total urinary cortisol; and r = .94 between the two urinary cortisol measures). Hence, a composite measure of HPA activity was derived by taking a mean of the three measures.
Among adolescents who had no prior smoking history at intake, after accounting for differential follow-up period, higher evening/night-time cortisol levels predicted initiation of smoking (see ). Stressful experiences also made an independent contribution to the initiation of smoking. The analyses were run separately in depressed adolescents and control subjects (combining normal and high-risk groups), and the same pattern emerged even after controlling for comorbid disorders in the depressed cohort.
Cox regression model predicting initiation of smoking in adolescents who had no prior smoking history at intake
For the purpose of graphical representation, the sample was stratified into four groups based on a median split of HPA activity (evening/night-time cortisol levels) and stress at follow-up: low HPA activity-low stress (n = 39); low HPA activity-high stress (n = 22); high HPA activity-low stress (n = 22); and high HPA activity-high stress (n = 26). These groups then were compared on the probability of smoking initiation (see ). Among adolescents who experienced high stress levels in combination with elevated HPA activity, 53.3% were likely to initiate smoking in comparison with 3.0% of youngsters in the low HPA activity-low stress category (Mantle-Cox χ2 = 20.35, df = 3, p = .0001). Among youth in the low HPA activity-high stress group, 35.0% were likely to smoke during the follow-up period compared to 24.1% in the high HPA activity-low stress group.
Figure 1 Probability of smoking during follow-up in adolescents who reported no prior smoking history at intake, stratified on HPA activity (a composite measure of evening/night-time cortisol levels) measured at baseline and stressful experiences at follow-up. (more ...)
When HPA activity and stressful experiences were tested as predictors of nicotine dependence symptoms, only HPA activity was significant (std. β = 0.70, CI = 0.54-1.67, t = 4.11, p = .001; adjusted R2 = 0.43, F2,18 = 8.43, p = .003).
Persistence of Smoking
At intake, 31 adolescents reported prior smoking history. Of these, 19 (61.3%) youth also reported smoking during follow-up (persistent smokers). Adolescents who persisted with smoking during follow-up did not differ significantly from abstainers on any demographic or clinical variables (see ). There was, however, a trend for persistent smokers to experience higher stress at baseline compared with abstainers. The mean FTQ score in the smokers was 4.2 (SD = 1.5; range 1.5-7.0). Based on the FTQ score, one (5.3%) persistent smoker showed no evidence of nicotine dependence, 14 (73.7%) had moderate level of dependence and four (21.1%) manifested high level of dependence.
Demographic and clinical parameters in adolescents who reported prior smoking history at intake, stratified on smoking status during follow-up
Of a total of 14 depressed youth with prior smoking history at intake, 4/5 (80.0%) adolescents with comorbid anxiety disorder persisted with smoking during follow-up in comparison with 5/9 (55.6%) participants without anxiety disorder (FET, NS). Also, 2/2 (100.0%) youth with comorbid disruptive disorder persisted with smoking compared to 7/12 (58.3%) without disruptive disorder (FET, NS).
Effects of HPA Activity and Stress on Persistent Smoking
There was a trend for adolescents who reported smoking at the time of intake (current smokers; n = 15) to have higher HPA activity compared with past smokers (0.8 ± 1.1 vs. 0.2 ± 0.9, t29 = 1.72, p = .10). After controlling for smoking status and magnitude of stress at the time intake, elevated HPA activity (higher evening/night-time cortisol levels) was associated with persistence of smoking during follow-up (see ). Stressful experiences did not significantly influence persistent smoking. After accounting for the effects of smoking status and magnitude of stress at intake, HPA activity (evening/night-time cortisol levels) made a significant contribution to nicotine dependence symptoms in persistent smokers (R2 change = 0.31, F3,15 = 3.84, p = .03). The analyses were run separately in depressed adolescents, and the same pattern emerged even after controlling for comorbid disorders. Among controls, stressful experiences moderated the effect of HPA activity (evening/night-time cortisol levels) on persistent smoking in such a way that the effect of elevated HPA activity (higher evening/night-time cortisol levels) on the likelihood of persistent smoking was reduced under conditions of low stress (βe = 0.19, CI = 0.05-0.71, p = .02).
Cox regression model predicting persistence of smoking during follow-up in adolescents who had prior smoking history at intake
Relationship between Smoking and Depression during Follow-up
Among control subjects, 6/22 (27.3%) smokers developed a major depressive episode during follow-up compared with 8/67 (11.9%) non-smokers (Fisher’s Exact Test, p = .10). Of the six participants with both depression and smoking history, five subjects initiated smoking first and a depressive episode preceded smoking in one participant. Within the depressed group, 12/18 (61.1%) adolescents who reported smoking during follow-up developed a recurrent depressive episode compared to 9/33 (27.3%) youth with no smoking history (χ2 = 5.60, p = .02). Of the 12 youngsters with both depression and smoking history, smoking preceded recurrent depressive episode in seven subjects and smoking initiation followed a recurrent depressive episode in five.
In order to examine whether the relationship between smoking and depression was accounted, in part, by HPA activity (evening/night-time cortisol levels) and stressful experiences, all three diagnostic groups were combined. Smoking during follow-up predicted depressive disorder (βe = 3.61, CI = 1.60-8.16, p = .002; χ2 =9.49, p = .002). When HPA activity (evening/night-time cortisol levels) and stressful experiences were included in the model, the effect of smoking on depression was reduced (βe = 1.28, CI = 0.46-3.56, NS; δχ2 = 14.47, p = .001).