title: Cognitive dysfunction in schizophrenia: unifying basic research and clinical aspects.
abstract: Seeking to unite psychological and biological approaches, this paper links cognitive and cellular hypotheses and data about thought and language abnormalities in schizophrenia. The common thread, it is proposed, is a dysregulated suppression of associations (at the behavioral and functional neural systems level), paralleled by abnormalities of inhibition at the cellular and molecular level, and by an abnormal anatomical substrate (reduced MRI gray matter volume) in areas subserving language. At the level of behavioral experiments and connectionist modeling, data suggest an abnormal semantic network connectivity (strength of associations) in schizophrenia, but not an abnormality of network size (number of associates). This connectivity abnormality is likely to be a preferential processing of the dominant (strongest) association, with the neglect of preceding contextual information. At the level of functional neural systems, the N400 event-related potential amplitude is used to index the extent of "search" for a semantic match to a word. In a short stimulus-onset-asynchrony condition, both schizophrenic and schizotypal personality disorder subjects showed, compared with controls, a reduced N400 amplitude to the target words that were related to cues, e.g. cat-dog, a result compatible with behavioral data. Other N400 data strongly and directly suggest that schizophrenics do not efficiently utilize context.
authors.affiliation: Harvard Medical School, Department of Psychiatry, Brockton, MA 02401, USA.
authors.forename: R W
authors.initials: RW
authors.lastname: McCarley
authors.forename: M A
authors.initials: MA
authors.lastname: Niznikiewicz
authors.forename: D F
authors.initials: DF
authors.lastname: Salisbury
authors.forename: P G
authors.initials: PG
authors.lastname: Nestor
authors.forename: B F
authors.initials: BF
authors.lastname: O'Donnell
authors.forename: Y
authors.initials: Y
authors.lastname: Hirayasu
authors.forename: H
authors.initials: H
authors.lastname: Grunze
authors.forename: R W
authors.initials: RW
authors.lastname: Greene
authors.forename: M E
authors.initials: ME
authors.lastname: Shenton
mesh_terms: D001921:Brain / Q000002:abnormalities / Q000378:metabolism / Q000503:physiopathology; D003072:Cognition Disorders / Q000175:diagnosis*; D004298:Dopamine / Q000378:metabolism; D004569:Electroencephalography; D005071:Evoked Potentials / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D009415:Nerve Net / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012559:Schizophrenia / Q000378:metabolism / Q000503:physiopathology
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D004298:Dopamine