Early developmental disturbances of cortical inhibitory neurons: contribution to cognitive deficits in schizophrenia.
Cognitive dysfunction is a disabling and core feature of schizophrenia. Cognitive impairments have been linked to disturbances in inhibitory (gamma-aminobutyric acid [GABA]) neurons in the prefrontal cortex. Cognitive deficits are present well before the onset of psychotic symptoms and have been detected in early childhood with developmental delays reported during the first year of life. These data suggest that the pathogenetic process that produces dysfunction of prefrontal GABA neurons in schizophrenia may be related to altered prenatal development. Interestingly, adult postmortem schizophrenia brain tissue studies have provided evidence consistent with a disease process that affects different stages of prenatal development of specific subpopulations of prefrontal GABA neurons. Prenatal ontogeny (ie, birth, proliferation, migration, and phenotypic specification) of distinct subpopulations of cortical GABA neurons is differentially regulated by a host of transcription factors, chemokine receptors, and other molecular markers. In this review article, we propose a strategy to investigate how alterations in the expression of these developmental regulators of subpopulations of cortical GABA neurons may contribute to the pathogenesis of cortical GABA neuron dysfunction and consequently cognitive impairments in schizophrenia.
['Volk|David W|DW|', 'Lewis|David A|DA|']
D000818:Animals D003072:Cognition Disorders D047109:Fetal Development D059330:GABAergic Neurons D006801:Humans D017397:Prefrontal Cortex D012559:Schizophrenia
prefrontal cortex GABA neuron development postmortem prenatal ontogeny interneuron parvalbumin somatostatin