The dopamine ontogeny hypothesis of schizophrenia integrates two aspects of the development of schizophrenia for which there is substantial evidence, (1) that dopamine signaling is affected and (2) that adverse events occurring during either gestation or at birth can increase disease risk; it postulates that transient dysregulation of the dopaminergic system during fetal brain development increases the likelihood of developing the disorder in adulthood. It has also been suggested that developing dopaminergic neurons and circuitry are particularly vulnerable to an array of adverse environmental factors during fetal and neonatal development.
Work in Drosophila has characterized the impact of perturbations during later brain development, since the fly brain continues to develop past the pupal stage and into the first several days of adulthood. By manipulating the activity of dopaminergic neurons, it was found that a transient increase of dopamine activity during the late pupal stage permanently alters behavior, brain activity, and sleep patterns in adult animals. Transient reduction in the expression of dopamine receptor Dop1R1 or Dop1R2 during the late pupal stage also results in permanent behavioral changes.
[updated Jul. 2018 by FlyBase; FBrf0222196]
See also 'Schizophrenia: Symptoms, causes, and treatments' (http://www.medicalnewstoday.com/articles/36942.php).
Schizophrenia is a psychosis, a disorder of thought and sense of self. Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Schizophrenia often develops in young adults who were previously normal, and is characterized by a constellation of symptoms including hallucinations and delusions (psychotic symptoms) and symptoms such as severely inappropriate emotional responses, disordered thinking and concentration, erratic behavior, as well as social and occupational deterioration (Andreasen, 1995; pubmed:7637483). [from MIM:181500; 2017.04.18]
The dopamine ontogeny hypothesis of schizophrenia proposes that transient dysregulation of the dopaminergic system during brain development increases the likelihood of developing the disorder in adulthood (Kesby et al., 2013 pubmed:23882183; Eyles et al., 2012, pubmed:22832818).
Fetal hypoxia, 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; these events can result in selective long-term disturbances of the dopaminergic systems that persist in adulthood (Giannopoulou et al., 2018; pubmed:29858855).
