Perinatal iron deficiency as an early risk factor for schizophrenia

Andrea M. Maxwell, Raghavendra B. Rao

Research output: Contribution to journalReview articlepeer-review


Growing evidence indicates that a suboptimal intrauterine environment confers risk for schizophrenia. The developmental model of schizophrenia posits that aberrant brain growth during early brain development and adolescence may interact to contribute to this psychiatric disease in adulthood. Although a variety of factors may perturb the environment of the developing fetus and predispose for schizophrenia later, a common mechanism has yet to be elucidated. Micronutrient deficiencies during the perinatal period are known to induce potent effects on brain development by altering neurodevelopmental processes. Iron is an important candidate nutrient to consider because of its role in energy metabolism, monoamine synthesis, synaptogenesis, myelination, and the high prevalence of iron deficiency (ID) in the mother-infant dyad. Understanding the current state of science regarding perinatal ID as an early risk factor for schizophrenia is imperative to inform empirical work investigating the etiology of schizophrenia and develop prevention and intervention programs. In this narrative review, we focus on perinatal ID as a common mechanism underlying the fetal programming of schizophrenia. First, we review the neural aberrations associated with perinatal ID that indicate risk for schizophrenia in adulthood, including disruptions in dopaminergic neurotransmission, hippocampal-dependent learning and memory, and sensorimotor gating. Second, we review the pathophysiology of perinatal ID as a function of maternal ID during pregnancy and use epidemiological and cohort studies to link perinatal ID with risk of schizophrenia. Finally, we review potential confounding phenotypes, including nonanemic causes of perinatal brain ID and future risk of schizophrenia.

Original languageEnglish (US)
Number of pages10
JournalNutritional Neuroscience
Early online dateJun 24 2021
StatePublished - Jun 24 2021

Bibliographical note

Publisher Copyright:
© 2021 Informa UK Limited, trading as Taylor & Francis Group.


  • Brain
  • brain development
  • iron
  • iron deficiency
  • perinatal iron deficiency
  • psychiatric disease
  • schizophrenia
  • two-hit hypothesis

PubMed: MeSH publication types

  • Journal Article


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