Abstract The neurodevelopmental hypothesis of schizophrenia provided a valuable framework that allowed a condition that usually presents with frank disorder in adolescence or early adulthood to be understood at least in part as a consequence of events occurring early in development. However, the implications of the neurodevelopmental hypothesis for nosological conceptions of the disorder can only now be fully appreciated. These findings challenge the aetiological basis of current diagnostic categories and, together with evidence for frequent comorbidity, suggest that we should view the functional psychoses as members of a group of related and overlapping syndromes that result in part from a combination of genetic and environmental effects on brain development and that are associated with specific and general impairments of cognitive function. This has important implications for future research and for the configuration of psychiatric services.
Hossein Fatemi Timothy D.
Folsom Find articles by Timothy D. For permissions, please email: This article has been cited by other articles in PMC. Abstract While multiple theories have been put forth regarding the origin of schizophrenia, by far the vast majority of evidence points to the neurodevelopmental model in which developmental insults as early as late first or early second trimester lead to the activation of pathologic neural circuits during adolescence or young adulthood leading to the emergence of positive or negative symptoms.
In this report, we examine the evidence from brain pathology enlargement of the cerebroventricular system, changes in gray and white matters, and abnormal laminar organizationgenetics changes in the normal expression of proteins that are involved in early migration of neurons and glia, cell proliferation, axonal outgrowth, synaptogenesis, and apoptosisenvironmental factors increased frequency of obstetric complications and increased rates of schizophrenic births due to prenatal viral or bacterial infectionsand gene-environmental interactions a disproportionate number of schizophrenia candidate genes are regulated by hypoxia, microdeletions and microduplications, the overrepresentation of pathogen-related genes among schizophrenia candidate genes in support of the neurodevelopmental model.
We relate the neurodevelopmental model to a number of findings about schizophrenia. Finally, we also examine alternate explanations of the origin of schizophrenia including the neurodegenerative model.
According to the neurodevelopmental hypothesis, the etiology of schizophrenia may involve pathologic processes, caused by both genetic and environmental factors, that begin before the brain approaches its adult anatomical state in adolescence.
Slater also referred to maldevelopmental similarities between temporal lobe epilepsy and schizophrenia and stressed their possible neuropathologic basis.
The concept of schizophrenia as a neurodevelopmental disorder is also consistent with other epidemiologic and clinical lines of evidence, discussed in the following sections.
According to this model, early developmental insults may lead to dysfunction of specific neural networks that would account for premorbid signs and symptoms observed in individuals that later develop schizophrenia. Presence of low-set ears, epicanthal eye folds, and wide spaces between the first and second toes are suggestive of first trimester anomalies.
Environmental Factors There is a large body of epidemiologic research showing an increased frequency of obstetric and perinatal complications in schizophrenic patients.
In contrast, such retroviral sequences were not found in any individuals with noninflammatory neurological illnesses or in normal subjects.
An alternate approach would be to vaccinate against influenza thus influencing the course and outcome of schizophrenia in the susceptible individuals.
There are clinical, as well as direct experimental, reports 36 — 39 showing that human influenza A viral infection of a pregnant mother may cause transplacental passage of viral load to the fetus.
Viral RNA and nucleoprotein were detected in fetal brains, and viral RNA persisted in the brains of exposed offspring for at least 90 days of postnatal life thus showing evidence for transplacental passage of influenza virus in mice and the persistence of viral components in the brains of progeny into young adulthood.
The product of NS1 gene is known to play a regulatory role in the host cell metabolisms. Multiple clinical and experimental reports show the ability of human influenza infection to induce production of systemic cytokines by the maternal immune system, the placenta, or even the fetus itself.
C, a synthetic double-stranded RNA that stimulates a cytokine response in mice, can cause abnormalities in prepulse inhibition PPI 60 or, after maternal exposure to E. C also causes disrupted latent inhibition in rat.
Other factors associated with increased schizophrenic births include famine during pregnancy, 6364 Rh factor incompatibility, 65 and autoimmunity due to infectious agents. These studies showed the deleterious effects of influenza on growing brains of exposed offspring.
Pregnant mice were allowed to deliver pups. The day of delivery was considered day 0. C exposure on E9 and E Additionally, prenatal viral infection on E9 resulted in various behavioral abnormalities. The offspring of exposed mice showed significantly less time exploring their environment vs control mice.
Prenatally infected brains from P0 displayed decreases in neocortical and hippocampal thickness.The neurodevelopmental hypothesis of schizophrenia has become a paradigm broadly accepted in today’s research in schizophrenia and its spectrum.
This . Schizophrenia is a neurodevelopmental disorder that affects youth in puberty and is manifested by a disruption in cognition and emotion along with negative (ie, avolition, alogia, apathy, poor or nonexistent social functioning) and positive (presence of hallucinations, delusions) symptoms.
According to the neurodevelopmental . The neurodevelopmental hypothesis of schizophrenia has gained increasing acceptance.
This hypothesis assumes a disruption in the normal development of the brain, secondary to genetic factors, environmental factors, or, most likely, a combination of both.
The Neurodevelopment Hypothesis-Neurodevelopmental hypothesis of schizophrenia posits that schizophrenia is caused in part by various disruptions in the normal maturational process of the brain before or at birth.-Viral infects of or malnutrition during prenatal development and obstetrical complications during the birth process-Research suggests that minor physical anomalies (slight .
Schizophrenia: A neurodevelopmental disorder — Integrative genomic hypothesis and therapeutic implications from a transgenic mouse model. Schizophrenia is a neurodevelopmental disorder featuring complex aberrations in the structure, wiring, and chemistry of multiple neuronal systems.
A neurodevelopmental hypothesis . According to the Neurodevelopmental Hypothesis, changes begin ____ ____, are affected by events that occur around birth, and become fully expressed in .