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

• Published in: Hormones (Athens, Greece) Vol. 17; no. 1; pp. 25 - 32
• Main Authors: Giannopoulou, Ioanna, Pagida, Marianna A., Briana, Despina D., Panayotacopoulou, Maria T.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.03.2018
• Subjects: Animals; Brain - metabolism; Cognition - physiology; Dopamine - metabolism; Endocrinology; Female; Humans; Hypoxia - complications; Hypoxia - metabolism; Hypoxia - psychology; Infant, Newborn; Male; Medicine; Medicine & Public Health; Mental Disorders - etiology; Mental Disorders - metabolism; Mental Disorders - psychology; Metabolic Diseases; Nerve Growth Factors - metabolism; Review Article; Risk Factors; Signal Transduction - physiology; Dopamine; Neonate; BDNF; Perinatal hypoxia; Attention deficit hyperactivity disorder; Schizophrenia; Tyrosine hydroxylase; Neurotrophins
• ISSN: 1109-3099; 2520-8721
• DOI: 10.1007/s42000-018-0007-7

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.