title: Early iron deficiency has brain and behavior effects consistent with dopaminergic dysfunction.
abstract: To honor the late John Beard's many contributions regarding iron and dopamine biology, this review focuses on recent human studies that test specific hypotheses about effects of early iron deficiency on dopamine system functioning. Short- and long-term alterations associated with iron deficiency in infancy can be related to major dopamine pathways (mesocortical, mesolimbic, nigrostriatal, tuberohypophyseal). Children and young adults who had iron deficiency anemia in infancy show poorer inhibitory control and executive functioning as assessed by neurocognitive tasks where pharmacologic and neuroimaging studies implicate frontal-striatal circuits and the mesocortical dopamine pathway. Alterations in the mesolimbic pathway, where dopamine plays a major role in behavioral activation and inhibition, positive affect, and inherent reward, may help explain altered social-emotional behavior in iron-deficient infants, specifically wariness and hesitance, lack of positive affect, diminished social engagement, etc. Poorer motor sequencing and bimanual coordination and lower spontaneous eye blink rate in iron-deficient anemic infants are consistent with impaired function in the nigrostriatal pathway. Short- and long-term changes in serum prolactin point to dopamine dysfunction in the tuberohypophyseal pathway. These hypothesis-driven findings support the adverse effects of early iron deficiency on dopamine biology. Iron deficiency also has other effects, specifically on other neurotransmitters, myelination, dendritogenesis, neurometabolism in hippocampus and striatum, gene and protein profiles, and associated behaviors. The persistence of poorer cognitive, motor, affective, and sensory system functioning highlights the need to prevent iron deficiency in infancy and to find interventions that lessen the long-term effects of this widespread nutrient disorder.
authors.affiliation: Center for Human Growth and Development and Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI 48109, USA. blozoff@umich.edu
authors.forename: Betsy
authors.initials: B
authors.lastname: Lozoff
mesh_terms: D001519:Behavior; D001921:Brain / Q000502:physiology*; D003071:Cognition; D003342:Corpus Striatum / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D006801:Humans; D000090463:Iron Deficiencies; D008032:Limbic System / Q000502:physiology; D011388:Prolactin / Q000097:blood; D013378:Substantia Nigra / Q000502:physiology
chemical_list: D011388:Prolactin; D004298:Dopamine