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A prospective high-risk study of the association among maternal negativity, apparent frontal lobe dysfunction, and the development of bipolar disorder


In a previous paper, the authors found that impairment on the Wisconsin Card Sorting Test (WCST) in adolescence was predictive of bipolar disorder in young adulthood among offspring of mothers with bipolar illness. In the present study, the authors explore the contribution of maternal characteristics, beyond maternal mood disorder, to the prediction of offspring dysfunction on the WCST. Results showed that maternal bipolar disorder and maternal negativity were both predictive of impaired performance on the WCST during adolescence. The contribution of maternal negativity to offspring WCST impairment was not better explained by maternal personality disorder, mother's functional impairment, family loading for bipolar disorder, or offspring disruptive behavioral disturbance. Findings did not support a moderator model. However, support was found for a mediation model in which maternal negativity contributed to risk for offspring bipolar disorder through its negative association with apparent frontal lobe functioning, as measured by the WCST. Findings are discussed from the perspective of a vulnerability–stress model. In addition, the authors consider the possibility that maternal negativity and offspring impairment on the WCST may be reflective of a common heritable trait.The findings presented in this paper come from the doctoral dissertation of the first author, which was funded by an NIMH Intramural Research Training Award. The authors are enormously grateful to Anne Mayfield, without whom this project would not have been possible. We are deeply indebted to Ann S. Masten, W. Andrew Collins, L. Alan Sroufe, Monica Luciana, and Carrie Borchardt, who provided support and guidance throughout all stages of this project. We are also thankful to Robert Asarnow for his advice and encouragement, and to Roger E. Meyer and Daniel N. Klein for their comments on earlier drafts of this paper. In addition, we acknowledge the contributions of Gail Inoff-Germain, who administered diagnostic interviews and neuropsychological measures at adolescent follow-up; Rula B. Garside, who undertook the painstaking job of establishing interrater reliability; Erika Sundstrom, who devoted many hours to data organization and quality assurance; and Sara Avery Torvik and Patricia Kasdan, whose combined gifts of organization and warmth created a comfortable atmosphere for study participants. Finally, we thank the extraordinary research participants of the NIMH Childrearing Study, who have shown enormous bravery and dedication by sharing with us 23 years of their lives.

Corresponding author
Address correspondence and reprint requests to: Stephanie E. Meyer, Division of Child and Adolescent Psychiatry, Cedars Sinai Medical Center, 8730 Alden Drive, Suite W110, Los Angeles, CA 90048; E-mail:
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