Peter Falkai, Oliver Gruber and Andrea Schmitt

in The Clinical Neurobiology of the Hippocampus

Published in print July 2012 | ISBN: 9780199592388
Published online September 2012 | e-ISBN: 9780199949922 | DOI:

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Schizophrenia is a chronic neurocognitive brain disorder with unknown pathophysiology. There is evidence for an interaction between risk genes and environmental factors playing a role during early as well as late neurodevelopment leading to symptoms in early adulthood. Deficits in hippocampus-related declarative memory and decreased hippocampal volumes at the stage of first episode and during the course of the disease are key findings. Stereological postmortem studies of the hippocampus in schizophrenia revealed no alterations of neuronal cell numbers but decreased numbers of oligodendrocytes in the posterior part and a lack of astrogliosis, suggesting that schizophrenia is not a classical neurodegenerative disorder. Decreased myelination and synaptic genes support the hypothesis of impaired connectivity of the hippocampus. Dysconnectivity of the hippocampus in schizophrenia may also be related to disturbances in neurogenesis, since a reduced number of proliferating stem cells has been detected in the dentate gyrus of schizophrenia patients. Effects of several risk genes of schizophrenia like D-amino acid oxidase, neuregulin-1, dysbindin, and disrupted-in schizophrenia-1 have been demonstrated in hippocampal tissue or magnetic resonance imaging (MRI) studies. In addition, genome-wide association studies revealed new genes with widely unknown function like ZNF804 or the transcription factor TCF4. Postmortem and animal studies may elucidate the link between these risk factors and behavioural consequences such as deficits of cognition and sensorimotor gating, which are related to hippocampal function. It has, however, to be kept in mind that chronic antipsychotic treatment may have influenced results from postmortem and MRI studies.

Keywords: schizophrenia; hippocampus; cognition; neurobiology; MRI; gene expression; antipsychotics

Chapter.  10702 words.  Illustrated.

Subjects: Neuroscience

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