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Perinatal hypoxia as a risk factor for psychopathology later in life: the role of dopamine and neurotrophins

  • Ioanna Giannopoulou
  • Marianna A. Pagida
  • Despina D. Briana
  • Maria T. Panayotacopoulou
Review Article


Brain development is influenced by various prenatal, intrapartum, and postnatal events which may interact with genotype to affect the neural and psychophysiological systems related to emotions, specific cognitive functions (e.g., attention, memory), and language abilities and thereby heighten the risk for psychopathology later in life. Fetal hypoxia (intrapartum oxygen deprivation), hypoxia-related obstetric complications, and hypoxia during the early neonatal period are major environmental risk factors shown to be associated with an increased risk for later psychopathology. Experimental models of perinatal hypoxia/ischemia (PHI) showed that fetal hypoxia—a consequence common to many birth complications in humans—results in selective long-term disturbances of the dopaminergic systems that persist in adulthood. On the other hand, neurotrophic signaling is critical for pre- and postnatal brain development due to its impact on the process of neuronal development and its reaction to perinatal stress. The aim of this review is (a) to summarize epidemiological data confirming an association of PHI with an increased risk of a range of psychiatric disorders from childhood through adolescence to adulthood, (b) to present immunohistochemical findings on human autopsy material indicating vulnerability of the dopaminergic neurons of the human neonate to PHI that could predispose infant survivors of PHI to dopamine-related neurological and/or cognitive deficits in adulthood, and (c) to present and discuss older and recent findings on the differential expression of neurotrophins (BDNF, NGF, NT-3, and NT-4) in neonates following hypoxic/ischemic insults and its significance for the development of the human brain and the induction of psychopathology later in life.


Attention deficit hyperactivity disorder BDNF Dopamine Neonate Neurotrophins Perinatal hypoxia Schizophrenia Tyrosine hydroxylase 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Hellenic Endocrine Society 2018

Authors and Affiliations

  • Ioanna Giannopoulou
    • 1
  • Marianna A. Pagida
    • 2
    • 3
  • Despina D. Briana
    • 4
  • Maria T. Panayotacopoulou
    • 2
    • 3
  1. 1.2nd Department of PsychiatryNational and Kapodistrian University of AthensAthensGreece
  2. 2.1st Department of PsychiatryNational and Kapodistrian University of AthensAthensGreece
  3. 3.Laboratory of Neurobiology and HistochemistryUniversity Mental Health Research InstitutePapagouGreece
  4. 4.Neonatal Unit, 1st Department of PediatricsNational and Kapodistrian University of AthensAthensGreece

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