title: Influence of maternal thyroid hormones during gestation on fetal brain development.
abstract: Thyroid hormones (THs) play an obligatory role in many fundamental processes underlying brain development and maturation. The developing embryo/fetus is dependent on maternal supply of TH. The fetal thyroid gland does not commence TH synthesis until mid gestation, and the adverse consequences of severe maternal TH deficiency on offspring neurodevelopment are well established. Recent evidence suggests that even more moderate forms of maternal thyroid dysfunction, particularly during early gestation, may have a long-lasting influence on child cognitive development and risk of neurodevelopmental disorders. Moreover, these observed alterations appear to be largely irreversible after birth. It is, therefore, important to gain a better understanding of the role of maternal thyroid dysfunction on offspring neurodevelopment in terms of the nature, magnitude, time-specificity, and context-specificity of its effects. With respect to the issue of context specificity, it is possible that maternal stress and stress-related biological processes during pregnancy may modulate maternal thyroid function. The possibility of an interaction between the thyroid and stress systems in the context of fetal brain development has, however, not been addressed to date. We begin this review with a brief overview of TH biology during pregnancy and a summary of the literature on its effect on the developing brain. Next, we consider and discuss whether and how processes related to maternal stress and stress biology may interact with and modify the effects of maternal thyroid function on offspring brain development. We synthesize several research areas and identify important knowledge gaps that may warrant further study. The scientific and public health relevance of this review relates to achieving a better understanding of the timing, mechanisms and contexts of thyroid programing of brain development, with implications for early identification of risk, primary prevention and intervention.
authors.affiliation: Department of Medical Psychology, Charité University Medicine Berlin, Luisenstrasse 57, 10117 Berlin, Germany.
authors.forename: N K
authors.initials: NK
authors.lastname: Moog
authors.affiliation: Department of Medical Psychology, Charité University Medicine Berlin, Luisenstrasse 57, 10117 Berlin, Germany; University of California, Irvine, Development, Health, and Disease Research Program, 333 The City Drive West, Suite 1200, Orange, CA 92868, USA; Department of Pediatrics, University of California, Irvine, School of Medicine, 505 South Main Street, Suite 525, Orange, CA 92868, USA.
authors.forename: S
authors.initials: S
authors.lastname: Entringer
authors.affiliation: Department of Medical Psychology, Charité University Medicine Berlin, Luisenstrasse 57, 10117 Berlin, Germany; Department of Biobehavioral Health, Pennsylvania State University, College of Health and Human Development, 219 Biobehavioral Health Building, University Park, PA 16802, USA.
authors.forename: C
authors.initials: C
authors.lastname: Heim
authors.affiliation: University of California, Irvine, Development, Health, and Disease Research Program, 333 The City Drive West, Suite 1200, Orange, CA 92868, USA; Department of Pediatrics, University of California, Irvine, School of Medicine, 505 South Main Street, Suite 525, Orange, CA 92868, USA; Department of Psychiatry and Human Behavior, University of California, Irvine, School of Medicine, 3117 Gillespie Neuroscience Research Facility, 837 Health Sciences Drive, Irvine, CA 92697, USA; Department of Obstetrics and Gynecology, University of California, Irvine, School of Medicine, 3117 Gillespie Neuroscience Research Facility, 837 Health Sciences Drive, Irvine, CA 92697, USA; Department of Epidemiology, University of California, Irvine, School of Medicine, 3117 Gillespie Neuroscience Research Facility, 837 Health Sciences Drive, Irvine, CA 92697, USA.
authors.forename: P D
authors.initials: PD
authors.lastname: Wadhwa
authors.affiliation: Department of Clinical Psychology, Humboldt-Universität zu Berlin, Rudower Chaussee 18, 12489 Berlin, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Kathmann
authors.affiliation: Department of Medical Psychology, Charité University Medicine Berlin, Luisenstrasse 57, 10117 Berlin, Germany; University of California, Irvine, Development, Health, and Disease Research Program, 333 The City Drive West, Suite 1200, Orange, CA 92868, USA; Department of Pediatrics, University of California, Irvine, School of Medicine, 505 South Main Street, Suite 525, Orange, CA 92868, USA. Electronic address: claudia.buss@charite.de.
authors.forename: C
authors.initials: C
authors.lastname: Buss
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology* / Q000378:metabolism*; D003071:Cognition / Q000502:physiology; D005260:Female; D006801:Humans; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism; D013963:Thyroid Hormones / Q000172:deficiency / Q000378:metabolism*
chemical_list: D013963:Thyroid Hormones
keywords: HPT axis; brain development; fetal programing; pregnancy; stress; thyroid hormones