Investigating the Neurodevelopmental Hypothesis of Schizophrenia

Abstract

SUMMARY1. An optimal intra-uterine environment is critical for normal development of the brain. It is now thought that abnormal development in a compromised prenatal and/or early postnatal environment may be a risk factor for several neurological disorders that manifest postnatally, such as cerebral palsy, schizophrenia and epilepsy.2. The present review examines some of the effects of abnormal prenatal brain development and focuses on one disorder that has been hypothesized to have, at least in part, an early neurodevelopmental aetiology: schizophrenia.3. The key neuropathological alterations and changes in some of the neurotransmitter systems observed in patients with schizophrenia are reviewed. Evidence in support of a neurodevelopmental hypothesis for schizophrenia is examined. 4. A summary of the animal models that have been used by researchers in an attempt to elucidate the origins of this disorder is presented. Although no animal model of a complex human disorder is ever likely to emulate deficits in all aspects of structure and function observed in patients with a neuropsychiatric illness, our findings and those of others give support to the early neurodevelopmental hypothesis.5. Thus, it is possible that an adverse event in utero disrupts normal brain development and creates a vulnerability of the brain that predisposes an already at-risk individual (e.g. genetic inheritance) to develop the disorder later in life.

Peripubertal exposure to environmental enrichment prevents schizophrenia-like behaviors in the SHR strain animal model

“…It is considered a neurodevelopmental disorder, where environmental factors, associated with genetic susceptibility, alter the brain maturation, triggering subtle specific neural circuit changes for years, which culminate in the manifestation of the disorder in adolescence or early adulthood (Fatemi and Folsom, 2009;Guo et al, 2010;Jaaro-Peled et al, 2009;Lieberman et al, 2001;Rehn and Rees, 2005;Thaker and Carpenter, 2001).…”

Review: Role of developmental inflammation and blood–brain barrier dysfunction in neurodevelopmental and neurodegenerative diseases

“…Disorders with a well-established developmental aetiology include cerebral palsy and autism [1,2], but even schizophrenia, despite onset primarily in adolescence and early adulthood, may have developmental origins [3]. Other neurological disorders, such as Alzheimer's disease and Parkinson's disease, are considered to be due to degenerative changes in a previously functioning nervous system.…”

Lipid metabolism and the risk factors of cardiovascular disease: implication of dietary omega-3 polyunsaturated fatty acids

“…Abnormalities in the synthesis and release of BDNF are potential culprits for development of neurological disorders (Rehn and Rees, 2005). Interestingly, the cortical mRNA expression of BDNF was higher in the high n-3 PUFA group compared to the low n-3 PUFA; however, age had no effect on the mRNA expression of BDNF.…”