title: Neurodevelopmental and environmental hypotheses of negative symptoms of schizophrenia.
abstract: The negative symptoms of schizophrenia, avolition, alogia, apathy and impaired or nonexistent social functioning, are strongly correlated with the progressive course and long-term 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.
authors.affiliation: Department of Adult and Geriatric Psychiatry, Hôpitaux Universitaires Paris Ouest (AP-HP), Hôpital Corentin-Celton, 4, parvis Corentin-Celton, 92133 Issy-les-Moulineaux, France. frederic.limosin@ccl.aphp.fr.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Limosin
mesh_terms: D000328:Adult; D001921:Brain / Q000378:metabolism; D002648:Child; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology*; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000503:physiopathology*; D012559:Schizophrenia / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D004298:Dopamine