Developmental Neuroendocrine Effects of PCBs and PBDEs: Parallels with ADHD

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Genetic and endocrine factors are implicated in the etiology of attention deficit disorder with hyperactivity (ADHD). Polychlorinated biphenyls (PCBs) and, we suggest, polybrominated diphenyl ethers (PBDEs) induce similar deficits in attention and impulse control in developmentally exposed children, as well as reducing central catecholamine and thyroid hormone levels in experimental animals?physiological changes also seen in ADHD. We hypothesize that developmental exposure to PCBs and PBDEs, due to their ability to alter central catecholamines and/or thyroid hormones during critical periods of development, are etiologic factors responsible for the contaminant induced behavioral changes that are reminiscent of those seen in ADHD. To better understand the physiological bases for these behavioral alterations and to gain insights to the etiology of ADHD we will determine: (i) the effects of these contaminants, alone and in combination, on central catecholamines and maternal and offspring circulating thyroid hormone levels; (ii) whether experimental reductions in maternal and fetal circulating thyroid hormones (induced with methimazole) mimic the changes seen in central catecholamines with PCBs and/or PBDEs; (iii) whether contaminant-induced reductions in central catecholamines can be ameliorated following either maternal T4 supplementation or adult methylphenidate exposure and (iv) the effects of these manipulations on mRNA expression and proteins that regulate catecholamine function in prefrontal cortex, striatum and hippocampus. These studies, when combined with behavioral data from similarly exposed animals, will begin to determine the mechanisms by which these contaminants alter behaviors reminiscent of ADHD in developmentally exposed children, including the relative contributions that contaminant induced reductions in central catecholamines and thyroid hormone levels play in altering nervous system development and ultimately behavior.