Limbic-cortical neuronal damage and the pathophysiology of schizophrenia.
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.
Csernansky
J G
JG
Washington University School of Medicine, Metropolitan St. Louis Psychiatric Center, MO 63110, USA.
Bardgett
M E
ME
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004298:Dopamine / Q000502:physiology; D015259:Dopamine Agents / Q000494:pharmacology; D004351:Drug Resistance / Q000502:physiology; D005625:Frontal Lobe / Q000503:physiopathology; D018698:Glutamic Acid / Q000502:physiology; D006624:Hippocampus / Q000293:injuries / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008032:Limbic System / Q000293:injuries / Q000473:pathology* / Q000503:physiopathology; D008959:Models, Neurological; D009434:Neural Pathways / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D012559:Schizophrenia / Q000188:drug therapy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D012720:Severity of Illness Index
D014150:Antipsychotic Agents; D015259:Dopamine Agents; D018698:Glutamic Acid; D004298:Dopamine