There is evidence that smoking is becoming concentrated in populations who
because of various risk factors, are more likely to initiate smoking or
have greater difficulty quitting. One of the best documented of these
cofactors is depression. Numerous observers have noted clear
manifestations of depression and dysphoria in women with a history of
Major Depressive Disorder (Hx+ MDD) when they attempt to quit smoking.
The long-term objective is to characterize and possibly modify response
patterns that constitute a diathesis for smoking. Based on the literature
and our own pilot data, we postulate that the reinforcing value of
nicotine self-administration is enhanced in Hx+ MDD by the drug's affect-
normalizing properties and its ability to protect against the
hypothalamic-pituitary-adrenal (HPA) axis dysregulation that often
characterizes episodes of depression, as indicated by elevated cortisol
and ACTH levels following dexamethasone administration, an effect that is
most pronounced in postmenopausal women.
The specific aims are to 1) trace the time course and severity of
depressive symptomatology in Hx+ MDD and Hx- MDD women smokers across
different age categories when they abstain from smoking; 2) determine
susceptibility to induction of depressed mood in Hx+ MDD and Hx- MDD women
smokers; 3) elucidate key biobehavioral mechanisms underlying the
relationship between dysphoria and use of nicotine; and 4) determine the
extent to which pharmacological manipulations can relieve abstinence-
induced depression/dysphoria and concomitant HPA axis dysregulation. The
research design employs both within-subject and between-group comparisons
in two interlocking studies, involving within-subject and between-group
comparisons of women smokers and carefully assessing both psychological
distress and neuroendocrinological dysfunction. STUDY I will assess the
effects of nicotine vs. placebo patch during a week of smoking abstinence
on cognitive and neuroendocrinological variables. STUDY II will
investigate the ability of the antidepressant fluoxetine vs. placebo to
ameliorate depression/dysphoria and restore HPA-axis function during
HEALTH IMPLICATIONS: Depression is a major women's public health problem
in its own right, taking an enormous toll in terms of lost productivity
and diminished quality of life. To the extent that it increases the
likelihood of initiation and maintenance smoking, the health consequences
are magnified---as underscored by the fact that lung cancer has now
surpassed breast cancer as the leading cause of cancer death in women. A
better understanding of the reinforcing effects of smoking, and the
mechanisms underlying these effects in depression-prone smokers, may lead
to the development of rational prevention and cessation strategies
tailored to the special needs of this large at-risk population.
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