Abstract
The hippocampal formation is essential for normal memory function and is implicated in many neurodevelopmental, neurodegenerative and neuropsychiatric disorders. In particular, abnormalities in hippocampal structure and function have been identified in schizophrenic subjects. Schizophrenia has a strong polygenic component, but the role of numerous susceptibility genes in normal brain development and function has yet to be investigated. Here we described the expression of schizophrenia susceptibility genes in distinct regions of the monkey hippocampal formation during early postnatal development. We found that, as compared with other genes, schizophrenia susceptibility genes exhibit a differential regulation of expression in the dentate gyrus, CA3 and CA1, over the course of postnatal development. A number of these genes involved in synaptic transmission and dendritic morphology exhibit a developmental decrease of expression in CA3. Abnormal CA3 synaptic organization observed in schizophrenics might be related to some specific symptoms, such as loosening of association. Interestingly, changes in gene expression in CA3 might occur at a time possibly corresponding to the late appearance of the first clinical symptoms. We also found earlier changes in expression of schizophrenia susceptibility genes in CA1, which might be linked to prodromal psychotic symptoms. A number of schizophrenia susceptibility genes including APOE, BDNF, MTHFR and SLC6A4 are involved in other disorders, and thus likely contribute to nonspecific changes in hippocampal structure and function that must be combined with the dysregulation of other genes in order to lead to schizophrenia pathogenesis.
Highlights
IntroductionThe hippocampal formation is implicated in a number of neurodevelopmental, neuropsychiatric and neurodegenerative disorders including schizophrenia,[1] autism spectrum disorders,[2] temporal lobe epilepsy,[3] Down syndrome,[4] Williams syndrome,[5] antisocial personality disorder and psychopathy,[6] bipolar disorders,[7] major depressive disorder[8] and Alzheimer’s disease.[9]
A number of schizophrenia susceptibility genes including APOE, BDNF, MTHFR and SLC6A4 are involved in other disorders, and likely contribute to nonspecific changes in hippocampal structure and function that must be combined with the dysregulation of other genes in order to lead to schizophrenia pathogenesis
The hippocampal formation is implicated in a number of neurodevelopmental, neuropsychiatric and neurodegenerative disorders including schizophrenia,[1] autism spectrum disorders,[2] temporal lobe epilepsy,[3] Down syndrome,[4] Williams syndrome,[5] antisocial personality disorder and psychopathy,[6] bipolar disorders,[7] major depressive disorder[8] and Alzheimer’s disease.[9]
Summary
The hippocampal formation is implicated in a number of neurodevelopmental, neuropsychiatric and neurodegenerative disorders including schizophrenia,[1] autism spectrum disorders,[2] temporal lobe epilepsy,[3] Down syndrome,[4] Williams syndrome,[5] antisocial personality disorder and psychopathy,[6] bipolar disorders,[7] major depressive disorder[8] and Alzheimer’s disease.[9]. The risk of suffering from schizophrenia in the general population is about 1%; people who have a third-degree relative (great grandparent, first cousin) with schizophrenia are twice as likely to develop schizophrenia (2%); those with a second-degree relative (grandparent, uncle, aunt) have an incidence varying from 2 to 6%; first-degree relatives (parent, sibling) have an incidence of schizophrenia 410 times higher than the general population (13% for children, 17% for twins and 48% for identical twins).[13]
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