1. ¹Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
2. ²Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA
3. ³Haskins Laboratories, New Haven, CT, USA
4. ⁴Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA
5. ⁵Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA
6. ⁶Department of Child Study, Yale University School of Medicine, New Haven, CT, USA

Correspondence: Dr LK Jacobsen, Psychiatry and Pediatrics, Yale University School of Medicine, 2 Church Street South, Suite 207, New Haven, CT 06519, USA. Tel: +1 203 764 8480; Fax: +1 203 764 8484; E-mail: leslie.jacobsen@yale.edu

Received 16 May 2005; Revised 13 September 2005; Accepted 13 October 2005; Published online 7 December 2005.

Abstract

Active maternal smoking during pregnancy elevates the risk of cognitive deficits and tobacco smoking among offspring. Preclinical work has shown that combined prenatal and adolescent exposure to nicotine produces more pronounced hippocampal changes and greater deficits in cholinergic activity upon nicotine withdrawal than does prenatal or adolescent exposure to nicotine alone. Few prior studies have examined the potential modifying effects of gestational exposure to active maternal smoking on cognitive or brain functional response to tobacco smoking or nicotine withdrawal in adolescents. We examined visuospatial and verbal memory in 35 adolescent tobacco smokers with prenatal exposure to active maternal smoking and 26 adolescent tobacco smokers with no prenatal exposure to maternal smoking who were similar in age, educational attainment, general intelligence, and baseline plasma cotinine. Subjects were studied during ad libitum smoking and after 24 h of abstinence from smoking. A subset of subjects from each group also underwent functional magnetic resonance imaging while performing a visuospatial encoding and recognition task. Adolescent tobacco smokers with prenatal exposure experienced greater nicotine withdrawal-related deficits in immediate and delayed visuospatial memory relative to adolescent smokers with no prenatal exposure. Among adolescent smokers with prenatal exposure, nicotine withdrawal was associated with increased activation of left parahippocampal gyrus during early recognition testing of visuospatial stimuli and increased activation of bilateral hippocampus during delayed recognition testing of visuospatial stimuli. These findings extend prior preclinical work and suggest that, in human adolescent tobacco smokers, prenatal exposure to active maternal smoking is associated with alterations in medial temporal lobe function and concomitant deficits in visuospatial memory.