Adolescent initiation of tobacco use remains a major public health problem. With nearly 35 percent of high school students currently using tobacco, it is estimated that 5 million children living today will die prematurely as adults due to initiation of tobacco use during adolescence. The high rates of initiation of tobacco use among teenagers is likely multifactorial. However, given the heightened educational demands encountered during adolescence, enhancement of brain function with tobacco use may pose a particularly compelling inducement to transition from infrequent to regular tobacco use. Nicotine has been shown to enhance performance on tests of attention and, in some cases, on tests of memory in nondeprived smokers and in nonsmokers. Enhancement of memory by nicotine may be restricted to infrequent tobacco users. In this proposal the relationship between the effect of recent tobacco use and of nicotine withdrawal on activation of neural circuits that mediate performance of tasks involving working memory and selective attention will be examined in adolescent tobacco users. The relationship between brain response to recent tobacco use and tobacco use outcome at one-year follow-up will then be assessed. Preliminary data from a functional magnetic resonance imaging (fMRI) study of adolescent tobacco users suggests that, relative to nicotine withdrawal, recent tobacco use is associated with greater activation of left prefrontal cortex during high verbal working memory load conditions and greater activation of right dorsolateral prefrontal cortex during high attention load conditions. We will test the hypothesis that greater change in brain activation in response to recent smoking relative to nicotine withdrawal is associated with progression of tobacco use (heavier use, greater degree of nicotine dependence, failure to achieve abstinence) at one year follow-up and that this relationship will be observed chiefly in subjects who used tobacco infrequently at study entry. The relationship between the degree of change cognitive performance (assessed prior to and during scanning) in response to recent tobacco use and tobacco use at one-year follow-up will also be examined.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA014655-04
Application #
6801570
Study Section
Special Emphasis Panel (ZDA1-MXG-S (28))
Program Officer
Stanford, Laurence
Project Start
2001-09-30
Project End
2006-08-31
Budget Start
2004-09-01
Budget End
2006-08-31
Support Year
4
Fiscal Year
2004
Total Cost
$251,310
Indirect Cost
Name
Yale University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Jacobsen, Leslie K; Slotkin, Theodore A; Mencl, W Einar et al. (2007) Gender-specific effects of prenatal and adolescent exposure to tobacco smoke on auditory and visual attention. Neuropsychopharmacology 32:2453-64
Jacobsen, Leslie K; Picciotto, Marina R; Heath, Christopher J et al. (2007) Prenatal and adolescent exposure to tobacco smoke modulates the development of white matter microstructure. J Neurosci 27:13491-8
Jacobsen, Leslie K; Mencl, W Einar; Constable, R Todd et al. (2007) Impact of smoking abstinence on working memory neurocircuitry in adolescent daily tobacco smokers. Psychopharmacology (Berl) 193:557-66
Jacobsen, Leslie K; Pugh, Kenneth R; Constable, Robert T et al. (2007) Functional correlates of verbal memory deficits emerging during nicotine withdrawal in abstinent adolescent cannabis users. Biol Psychiatry 61:31-40
Jacobsen, Leslie K; Pugh, Kenneth R; Mencl, W Einar et al. (2006) C957T polymorphism of the dopamine D2 receptor gene modulates the effect of nicotine on working memory performance and cortical processing efficiency. Psychopharmacology (Berl) 188:530-40
Jacobsen, Leslie K; Krystal, John H; Mencl, W Einar et al. (2005) Effects of smoking and smoking abstinence on cognition in adolescent tobacco smokers. Biol Psychiatry 57:56-66
Jacobsen, Leslie K; D'Souza, D Cyril; Mencl, W Einar et al. (2004) Nicotine effects on brain function and functional connectivity in schizophrenia. Biol Psychiatry 55:850-8
Jacobsen, Leslie K; Mencl, W Einar; Pugh, Kenneth R et al. (2004) Preliminary evidence of hippocampal dysfunction in adolescent MDMA (""ecstasy"") users: possible relationship to neurotoxic effects. Psychopharmacology (Berl) 173:383-90
Jacobsen, Leslie K; Mencl, W Einar; Westerveld, Michael et al. (2004) Impact of cannabis use on brain function in adolescents. Ann N Y Acad Sci 1021:384-90
Jacobsen, Leslie K; Gore, John C; Skudlarski, Pawel et al. (2002) Impact of intravenous nicotine on BOLD signal response to photic stimulation. Magn Reson Imaging 20:141-5