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Neurodevelopmental and environmental hypotheses of negative symptoms of schizophrenia

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Abstract
The negative symptoms of schizophrenia, avolition, alogia, apathy and impaired or
nonexistent social functioning, are strongly correlated with the progressive course and longterm
prognosis of the disease, undermining the patient’s ability to integrate socially,
interpersonal skills and quality of life. At a time when new drug strategies are being
developed, a better understanding of the etiology and pathogenesis underpinning the
occurrence of negative symptoms constitutes an essential prerequisite for real therapeutic
advances. Approaching this vulnerability from the neurodevelopmental perspective is
especially pertinent with regard to the experimental studies conducted in animals. Several
models have been put forward, involving a variety of topics such as the deleterious impact of
a prenatal infection or of early maternal deprivation on brain development, or else the
consequences of trauma and abuse suffered during childhood. These various models are
based on biological abnormalities that could guide the identification of new therapeutic
targets. They notably include the hyperreactivity of the hypothalamic-pituitary-adrenal axis
and dysfunction of corticostriatal glutamatergic transmission. As such, in the traumagenic
model, which associates neurodevelopmental and neurodegenerative processes, the
dysfunction of corticostriatal glutamatergic transmission, by reducing the tonic dopamine
release, could be the cause of an increase in the phasic dopamine release linked to stress. This
excessive phasic response to stress may induce cerebral damage by increasing excitotoxicity
and oxidative stress.

http://www.biomedcentral.com/content/pdf/1471-244X-14-88.pdf

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