Limbic-Cortical Neuronal Damage and the Pathophysiology of Schizophrenia

• Published in: Schizophrenia bulletin 1998-01, Vol.24 (2), p.231-248
• Main Authors: Csernansky, John G, Bardgett, Mark E
• Format: Article
• Language: English
• Subjects: 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; Human; Humans; Limbic System; Limbic System - injuries; Limbic System - pathology; Limbic System - physiopathology; Models, Neurological; Neural Pathways - drug effects; Neural Pathways - pathology; Neural Pathways - physiopathology; Schizophrenia; Schizophrenia - drug therapy; Schizophrenia - etiology; Schizophrenia - pathology; Schizophrenia - physiopathology; Severity of Illness Index
• ISSN: 0586-7614; 1745-1701
• DOI: 10.1093/oxfordjournals.schbul.a033323

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.