Cortical brain dysfunction in early schizophrenia: secondary pathogenetic hierarchy of neuroplasticity, psychopathology and social impairment.
Schizophrenia has the quality of a 'top-down' disorder with perturbation of self, and malattuned appraisal of basic experience of the outside world, and of intentionality. There is dissonance between the faculties of consciousness. The neuronal cortical network displays distributed activation of the sensory cortices during perception, and retroactivation during recall. This multimodal organization is sensitive to aberrations of structure and informational content during the metabolically dynamic phases of expansion and pruning in childhood and adolescence. There is substantial evidence of deviant function of the cortical network in schizophrenia. This includes increased neuronal density, reduced prefrontal capacity for activation, impaired fronto-temporal interaction during language production, defect monitoring of inner speech, activation of secondary sensory cortices during hallucinations, reduced cortical and thalamic volume, reduced thalamic activation (filtering) and sensitization of dopaminergic modulation. As a hypothesis the cortical defects lead to secondary causation of abnormalities at the levels of neuroplasticity, symptomatology and social competence. Suggestions for empirical testing are presented for the hypothesis that neocortical defects are primary, thalamic defects secondary and dopaminergic aberrations tertiary in the schizophrenic process. This testing of hypotheses involves prospective studies of patient groups at various ages of onset, as well as comparison of neurobiological measures in remitting vs. treatment-resistant cases.
Hemmingsen
R
R
Department of Psychiatry E, Bispebjerg Hospital, University of Copenhagen, Denmark.
Madsen
A
A
Glenthøj
B
B
Rubin
P
P
D002540:Cerebral Cortex / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology*; D003072:Cognition Disorders / Q000473:pathology / Q000503:physiopathology*; D003243:Consciousness / Q000502:physiology; D018450:Disease Progression; D004198:Disease Susceptibility / Q000503:physiopathology; D004298:Dopamine / Q000502:physiology; D006801:Humans; D008568:Memory / Q000502:physiology; D008959:Models, Neurological; D009415:Nerve Net / Q000254:growth & development / Q000503:physiopathology; D009434:Neural Pathways / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D019954:Neurobehavioral Manifestations / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D012559:Schizophrenia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D012918:Social Alienation; D013788:Thalamus / Q000473:pathology / Q000503:physiopathology
D004298:Dopamine