Limbic-cortical neuronal damage and the pathophysiology of schizophrenia

Schizophr Bull. 1998;24(2):231-48. doi: 10.1093/oxfordjournals.schbul.a033323.

Abstract

Neurobiological studies of patients with schizophrenia suggest that abnormalities of both anatomy and function occur in limbic-cortical structures. An anatomical circuit links the functioning of the ventral striatum (i.e., nucleus accumbens) with the hippocampus and other limbic-cortical structures where neurobiological abnormalities have been found. In animals, lesions of limbic-cortical neurons cause decreases in glutamatergic input to the nucleus accumbens and are also associated with decreases in presynaptic dopamine release, increases in the density of D2-like dopamine receptors, and insensitivity to the actions of dopamine antagonists such as haloperidol. These experiments suggest a plausible pathophysiology of schizophrenia, in that schizophrenic symptoms may be caused by an abnormal dopaminergic state brought about by a primary limbic-cortical lesion and deficits in glutamatergic inputs to the ventral striatum.

Publication types

  • Review

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology
  • Brain / drug effects
  • Brain / pathology
  • Brain / physiopathology
  • Disease Models, Animal
  • Disease Progression
  • Dopamine / physiology
  • Dopamine Agents / pharmacology
  • Drug Resistance / physiology
  • Frontal Lobe / physiopathology
  • Glutamic Acid / physiology
  • Hippocampus / injuries
  • Hippocampus / pathology
  • Hippocampus / physiopathology
  • Humans
  • Limbic System / injuries
  • Limbic System / pathology*
  • Limbic System / physiopathology
  • Models, Neurological*
  • Neural Pathways / drug effects
  • Neural Pathways / pathology
  • Neural Pathways / physiopathology
  • Schizophrenia / drug therapy
  • Schizophrenia / etiology
  • Schizophrenia / pathology
  • Schizophrenia / physiopathology*
  • Severity of Illness Index

Substances

  • Antipsychotic Agents
  • Dopamine Agents
  • Glutamic Acid
  • Dopamine