Contribution of hypothalamic-pituitary-adrenal activity and environmental stress to vulnerability for smoking in adolescents.

Although tobacco smoking, which has been linked to depression, is a major public health problem, little is known about the neurobiological factors that confer vulnerability to smoking in youngsters and the effects of adolescent smoking on the course of depression. This study examined whether hypothalamic-pituitary-adrenal (HPA) activity and stressful life experiences are related to smoking behavior in depressed and non-depressed adolescents, and whether smoking predicts a worsening course of depression. Smoking history and stressful experiences were assessed in 151 adolescents (48 with no personal or family history of psychiatric disorder, 48 with no psychiatric history, but at high risk for depression by virtue of parental depression, and 55 with current major depressive disorder). Evening salivary cortisol and nocturnal urinary-free cortisol were measured for three consecutive evenings. The participants were then followed at regular intervals for up to 5 years to assess smoking history, clinical course of depression and stressful experiences during the follow-up period. Increased evening/night-time cortisol levels were associated with both initiation and persistence of smoking during follow-up. Stressful life experiences further increased the risk for smoking in depressed as well as non-depressed youth. Smoking was also associated with a higher frequency of depressive episodes during follow-up. A model that included stressful experiences and cortisol levels reduced the contribution of smoking per se to depression. High evening/night-time cortisol level appears to be a vulnerability marker for smoking in adolescents, with stressful experiences further increasing the risk for smoking in vulnerable youth. High evening/night-time cortisol levels and stressful experiences accounted, at least partially, for the association between depressive illness and smoking behavior.