Alterations in postnatal neurogenesis and dopamine dysregulation in schizophrenia: a hypothesis

Schizophr Bull. 2011 Jul;37(4):674-80. doi: 10.1093/schbul/sbq134. Epub 2010 Nov 19.


An increasing number of studies demonstrate the important role of several susceptibility genes for schizophrenia, such as neuregulin-1 and DISC1, in early postnatal and adult neurogenesis. Its significance for the pathophysiology of the disease, including its relation to neurotransmitter systems implicated in schizophrenia (like the dopamine system), remains, however, unknown. Here, we review molecular and cellular components of the dopamine system associated with postnatal neurogenesis and plasticity, both in rodents and in primates, and discuss their possible implication in schizophrenia. We focus mainly on the islands of Calleja, complex aggregations of granule cells in the ventral striatum, generated early postnatally in the subventricular zone. In contrast to the involution of the primate olfactory bulb, the islands of Calleja attain their maximal development in humans, an evolution paralleled by a larger ventral subventricular zone and more connections with other structures, including temporal cortical areas. The islands of Calleja express high levels of neuronal nitric oxide (NO) synthase and D3 dopamine receptors and are densely interconnected by dopaminergic projections with the ventral tegmental area. D3 receptors modulate subventricular zone neurogenesis and dopamine release. Their genetic deletion induces striatal hyperdopaminergia. We review data indicating a high plasticity of postnatal islands of Calleja, potentially facilitating susceptibility to schizophrenia-related risk factors. In this context, we propose a new pathophysiological model, where altered neurogenesis of the islands of Calleja may contribute to dysfunction of the dopamine and NO systems and psychosis through convergence of genetic and environmental disease-associated factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Animals
  • Brain / physiopathology*
  • Cell Movement / genetics
  • Cell Movement / physiology
  • Dopamine / metabolism*
  • Dopamine Plasma Membrane Transport Proteins / genetics
  • Female
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Infant, Newborn
  • Islands of Calleja / physiopathology*
  • Mice
  • Mice, Knockout
  • Models, Genetic
  • Nerve Tissue Proteins / genetics
  • Neuregulin-1 / genetics
  • Neurogenesis / genetics*
  • Neurogenesis / physiology
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase / metabolism
  • Pregnancy
  • Prenatal Exposure Delayed Effects / genetics
  • Prenatal Exposure Delayed Effects / physiopathology
  • Receptors, Dopamine D3 / physiology
  • Risk Factors
  • Rodentia
  • Schizophrenia / genetics*
  • Schizophrenia / physiopathology*
  • Social Environment


  • DISC1 protein, human
  • Dopamine Plasma Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Neuregulin-1
  • Receptors, Dopamine D3
  • Nitric Oxide Synthase
  • Dopamine