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International Studies in Phenomenology and Philosophy

Book | Chapter

181944

"two hit" neurodevelopmental mechanisms in schizophrenia

focus on animal models and the role of bdnf

Maren Klug Rachel Hill

pp. 335-351

Abstract

Schizophrenia is a serious mental illness which is characterized by a range of symptoms, including hallucinations and delusions, social withdrawal, and cognitive deficits. Brain neurotransmitter systems implicated in schizophrenia include subcortical and cortical dopaminergic and glutamatergic projections, with additional involvement of serotonin and cholinergic systems. Currently used antipsychotic drugs only provide relief in some symptomatic domains of schizophrenia and only in a proportion of patients. Therefore, there is an urgent need to better understand the mechanisms involved in the development of this illness.Schizophrenia is most likely caused by a combination of genetic and environmental factors interacting in a "two hit' longitudinal trajectory. This means that early factors, such as certain genetic polymorphisms, can cause increased vulnerability of the brain to environmental factors in late adolescence/young adulthood (e.g., stress or drugs of abuse). This combination might synergize to cause onset of the illness, whereas either of these "hits' by themselves do not have this effect.Brain-derived neurotrophic factor (BDNF) is involved in brain development and neural plasticity. In post-mortem studies, BDNF levels were found to be decreased in several parts of the brains of patients with schizophrenia and animal models of BDNF deficiency show behavioral changes with relevance to schizophrenia. In this chapter we will review evidence that altered BDNF levels could play a role in the "two hit' interaction of early and late developmental factors in schizophrenia. These results could be important for the design of preventative or early intervention treatments in vulnerable individuals targeted at BDNF levels in the brain.

Publication details

Published in:

(2015) Psychiatry and neuroscience update: bridging the divide. Dordrecht, Springer.

Pages: 335-351

DOI: 10.1007/978-3-319-17103-6_24

Full citation:

Klug Maren, Hill Rachel (2015) „"two hit" neurodevelopmental mechanisms in schizophrenia: focus on animal models and the role of bdnf“, In: , Psychiatry and neuroscience update, Dordrecht, Springer, 335–351.