[Advances in neurobiological understanding of schizophrenia. Perspectives for new therapeutic concepts]

Nervenarzt. 2006 Nov:77 Suppl 2:S65-74; quiz S75-6. doi: 10.1007/s00115-006-2197-5.
[Article in German]

Abstract

Causal treatment options for schizophrenia are lacking due to our restricted knowledge of its etiology and pathogenesis. However, recently three postulated disposition genes for schizophrenia have been increasingly better confirmed: dysbindin, neuregulin-1, and G(72)/DAOA genes. These genes code proteins involved in processes ranging from brain development to the maintenance of glutamatergic transmission in the mature brain. Current interpretation of neuroanatomical findings points at reminiscences of disturbed brain development and a loss of nonneuronal elements, the so-called neuropil, as a correlate of brain atrophy. This reduction in neuropil is mainly caused by synaptic elements. Biochemical findings supporting this show that besides the dopaminergic and serotonergic system, glutamatergic transmission is also disturbed in schizophrenia. All these findings fit very well with the presumed functions of the disposition genes. Hypothesis-free approaches in structural brain imaging and the combination of functional imaging with relevant gene variants open new avenues for using markers from brain imaging to improve the diagnosis of schizophrenia and judge the response to neuroleptic treatment. Despite the enormous increase in knowledge for example in genetic research, the risk variants known until now provide no contribution to early diagnosis of schizophrenia. Furthermore, pharmacogenetics is currently unable to give a clear answer as to whether a single patient is responding to treatment or not.

Publication types

  • Review

MeSH terms

  • Animals
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Brain / pathology
  • Brain / physiopathology
  • Carrier Proteins / genetics*
  • Diffusion Magnetic Resonance Imaging
  • Disease Models, Animal
  • Dopamine / physiology
  • Dysbindin
  • Dystrophin-Associated Proteins
  • Glutamine / physiology
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Magnetic Resonance Spectroscopy
  • Nerve Tissue Proteins / genetics*
  • Neuregulin-1
  • Neurons / pathology
  • Neuropil / pathology
  • Risk Factors
  • Schizophrenia / genetics*
  • Schizophrenia / pathology
  • Schizophrenia / physiopathology
  • Synaptic Transmission / physiology

Substances

  • Carrier Proteins
  • DAOA protein, human
  • DTNBP1 protein, human
  • Dysbindin
  • Dystrophin-Associated Proteins
  • Intracellular Signaling Peptides and Proteins
  • NRG1 protein, human
  • Nerve Tissue Proteins
  • Neuregulin-1
  • Glutamine
  • Aspartic Acid
  • N-acetylaspartate
  • Dopamine