Neurogenesis and schizophrenia: dividing neurons in a divided mind?


Forty years after the initial discovery of neurogenesis in the postnatal brain of the rat, convincing evidence has been accrued that functional neurons are generated throughout the entire lifespan, particularly in the dentate gyrus (DG) and the subventricular zone (SVZ). This phenomenon has been termed adult neurogenesis (AN) and while it was detected in all examined mammalian species including humans, the physiological role of this process remains unknown. Although a plethora of animal studies indicate an involvement of AN in the pathophysiology of depression, this view has recently kindled considerable controversy. Pertinent studies in humans failed to confirm a role of reduced hippocampal neural stem cell proliferation (NSP) in depression but suggest a contribution to the pathophysiology of schizophrenia. The functional relevance of disturbed AN may encompass erroneous temporal encoding of new memory traces, thereby contributing to cognitive deficits observed in schizophrenia. This AN-hypothesis of schizophrenia is supported by neuroimaging, as well as by several genetically modified rodent models, e.g. reelin and NPAS3 knockout mice. Furthermore, several genes impacting on AN, including NPAS3, were also found to be associated with schizophrenia by case-control studies. In conclusion, several lines of evidence suggest that reduced AN may contribute to the etiopathogenesis of schizophrenic disorders, whereas it does not seem to be a critical risk factor for affective disorders.

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Fig. 1



Adult neurogenesis


Brain derived neurotrophic factor




Dentate gyrus


Disrupted in schizophrenia 1


Electroconvulsive treatment


Fibroblast growth factor 2


Granule cell layer




Nitric oxide


Nitric oxide synthase type I (neuronal)


Nitric oxide synthase type III (endothelial)


Neuronal PAS domain protein 3


Neural stem cell proliferation


Olfactory bulb




Pre-pulse startle inhibition


Subgranular zone


Subventricular zone


Temporal lobe epilepsy


Vascular endothelial growth factor


Wingless-type MMTV integration site family

Wnt 3:

Wnt member 3


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Correspondence to Andreas Reif.

Additional information

The work of the authors is supported by the Deutsche Forschungsgemeinschaft (Grant RE1632/1–1 and 1–3 to A.R., KFO 125/1–1 D to A.R. and K.P.L., and SFB 581 to K.P.L.), BMBF (IZKF 01 KS 9603) and the European Commission (NEWMOOD LSHM-CT-2003-503474).

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Reif, A., Schmitt, A., Fritzen, S. et al. Neurogenesis and schizophrenia: dividing neurons in a divided mind?. Eur Arch Psychiatry Clin Neurosc 257, 290–299 (2007).

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  • adult neurogenesis
  • schizophrenia
  • candidate genes
  • neuronal stem cell
  • psychiatric disorder
  • postmorten study
  • NPAS3