Elucidating Early Mechanisms of Developmental Psychopathology: The Case of Prenatal Smoking and Disruptive Behavior Lauren S. Wakschlag and Bennett L. Leventhal Institute for Juvenile Research, University of Illinois at Chicago Daniel S. Pine National Institute of Mental Health Kate E. Pickett University of York Alice S. Carter University of Massachusetts-Boston There is a robust association between prenatal smoking and disruptive behavior disorders, but little is known about the emergence of such behaviors in early development. The association of prenatal smoking and hy- pothesized behavioral precursors to disruptive behavior in toddlers (N 5 93) was tested. Exposed toddlers demonstrated atypical behavioral patterns, including (1) escalating externalizing problems from 18 to 24 months and (2) observed difficulty modulating behavior in response to social cues. Specification of exposure-related behaviors is a first step toward generating testable hypotheses about putative mechanisms of effect. While it remains unclear whether prenatal exposure plays an etiologic role in the emergence of disruptive behavior, atypical exposure-related behavioral patterns are evident in the first years of life and demonstrate develop- mental coherence. Increasingly there is evidence that prenatal events contribute to the development of psychopathology (Cicchetti & Cannon, 1999; Huizink, Mulder, & Bui- telaar, 2004; Machon, Mednick, & Huttunen, 1997; Nelson et al., 2002; Neugebauer, Hoek, & Susser, 1999; Van den Bergh & Marcoen, 2004; Watson, Mednick, Huttunen, & Wang, 1999). In particular, there is growing evidence that maternal smoking during pregnancy is robustly associated with in- creased risk of serious and persistent disruptive behavior (for reviews, see Ernst, Moolchan, & Rob- inson, 2001; Wakschlag, Pickett, Cook, Benowitz, & Leventhal, 2002). However, as the majority of studies have focused on older youth, little is known about the developmental pathways from exposure to the development of disruptive behavior over time. ‘‘Unpacking’’ this association by establishing how atypical behavior patterns in exposed offspring un- fold from early in development is a critical step to- ward identifying potential mechanisms of effect. This requires specification of the particular dimen- sions and patterns of behavior associated with ex- posure from early in life. This is the focus of the present paper. Recent findings from teratologic and develop- mental research provide a strong foundation for this line of investigation. In particular, (1) there is evidence from animal studies that nicotine is a neurobehavioral teratogen (Benowitz, 1998); (2) a clear and consistent association between exposure to nicotine and dis- ruptive behavior has been established (Wakschlag et al., 2002); and (3) there is robust evidence that disruptive behavior patterns often emerge very early in development (Shaw, Bell, & Gilliom, 2000). On the basis of the foregoing, we hypothesize that exposure will be associated with an atypical pattern of behavior r 2006 by the Society for Research in Child Development, Inc. All rights reserved. 0009-3920/2006/7704-0006 The Family Health and Development Project was supported by grant K08 DA00330 from the National Institute of Drug Abuse to Dr Wakschlag. Support for Drs Wakschlag, Leventhal, and Pickett was also provided by National Institute of Drug Abuse grant R01 DA15223 during the writing of this paper. In addition, Drs Le- venthal and Wakschlag received support from The Walden and Jean Young Shaw Foundation, the Irving B. Harris Center for Developmental Studies and the Children’s Brain Research Foun- dation. We are indebted to Sydney Hans, PhD, Richard Campbell, PhD, Vince Smeriglio, PhD, and Neal Benowitz, MD, for generous mentorship and wise counsel on study design and methodology. Penny Tenzer, MD, importantly facilitated the conduct of the study. We are very appreciative of our research team and the clinic physicians and staff whose assistance in study recruitment was invaluable. In particular, we acknowledge the outstanding efforts of Laura Walton, RN, MEd, and Radiah Smith-Donald. Portions of this paper were presented at the Meetings of the American Psy- chiatric Association, New York, NY, May 2004. Correspondence concerning this article should be addressed to Lauren S. Wakschlag, Institute for Juvenile Research, Department of Psychiatry, University of Illinois at Chicago, 1747 W. Roosevelt Rd, MC 747, Room 155, Chicago, IL 60608. Electronic mail may be sent to lwakschlag@psych.uic.edu. Child Development, July/August 2006, Volume 77, Number 4, Pages 893 – 906