Current Molecular Medicine

David W. Li  
College of Medicine
University of Nebraska Medical Center
Omaha, NE
USA

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The Role of Genes Involved in Neuroplasticity and Neurogenesis in the Observation of a Gene-Environment Interaction (GxE) in Schizophrenia

Author(s): Yann Le Strat, Nicolas Ramoz and Philip Gorwood

Affiliation: INSERM U675, Centre of Psychiatry and Neuroscience, Sainte-Anne Hospital 100 rue de la Sante, 75014 Paris, France.

Keywords: Genetics, schizophrenia, neuron, plasticity, association, single nucleotide polymorphism

Abstract:

Schizophrenia is a multifactorial disease characterized by a high heritability. Several candidate genes have been suggested, with the strongest evidences for genes encoding dystrobrevin binding protein 1 (DTNBP1), neuregulin 1 (NRG1), neuregulin 1 receptor (ERBB4) and disrupted in schizophrenia 1 (DISC1), as well as several neurotrophic factors. These genes are involved in neuronal plasticity and play also a role in adult neurogenesis. Therefore, the genetic basis of schizophrenia could involve different factors more or less specifically required for neuroplasticity, including the synapse maturation, potentiation and plasticity as well as neurogenesis. Following the model of Knudson in tumors, we propose a two-hit hypothesis of schizophrenia. In this model of gene-environment interaction, a variant in a gene related to neurogenesis is transmitted to the descent (first hit), and, secondarily, an environmental factor occurs during the development of the central nervous system (second hit). Both of these vulnerability and trigger factors are probably necessary to generate a deficit in neurogenesis and therefore to cause schizophrenia. The literature supporting this gene x environment hypothesis is reviewed, with emphasis on some molecular pathways, raising the possibility to propose more specific molecular medicine.

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Article Details

VOLUME: 9
ISSUE: 4
Page: [506 - 518]
Pages: 13
DOI: 10.2174/156652409788167104