Modulation of language processing in schizophrenia: effects of context and haloperidol on the event-related potential.

BACKGROUND: Disturbances in language associations were among the first clinical symptoms reported for individuals described as schizophrenic (Bleuler 1911/1950). Currently, associative language disturbance is a diagnostic feature of schizophrenia (American Psychiatric Association 1994); however, the mechanisms that produce this symptom remain unknown. In the present study, two candidate psychological functions were examined: sensitivity to semantic context and expectancy (attention). METHODS: Visual event-related potentials were recorded during a lexical decision task in which semantic relationship and expectancy (relatedness proportions) were varied. Semantic priming processes were compared between 34 male normal control subjects tested once and 37 male schizophrenic inpatients evaluated during their participation in a double-blind haloperidol maintenance therapy and placebo replacement protocol. RESULTS: Schizophrenic patients failed to discriminate between associated and unassociated words, as measured by the amplitude of the N400 component (i.e., absence of the N400 priming effect); however, the overall mean amplitude of N400 did not differ between patients and control subjects. In addition, patients and control subjects did not differ significantly in the amplitude of N400 elicited to associated words or to unassociated words. Finally, the effect of expectancy-based processing on the magnitude of the N400 priming effect did not differ between patients and control subjects. CONCLUSIONS: On the basis of these findings, a tentative hypothesis is suggested that schizophrenic patients are characterized by a pattern of indiscriminate or random spread of activation in their semantic network during the processing of single-word semantic contexts.

Genetic association between reduced P300 amplitude and the DRD2 dopamine receptor A1 allele in children at high risk for alcoholism.

BACKGROUND: There is evidence that both reduction in P300 amplitude and the presence of the A1 allele are risk markers for alcoholism. We hypothesized that demonstration of a relationship between the marker and the trait in young children who had not begun to drink regularly would provide evidence for dopaminergic mediation of the reduction in P300 often seen among high-risk children. A previous association between the A1 and the P300 amplitude in screened controls supports the hypothesis that this association occurs in the general population. METHODS: Children were assessed using both visual and auditory paradigms to elicit event-related potentials (ERPs). The P300 component of the ERP was investigated with respect to the genetic variation of the Taq1A D2 receptor in these children. RESULTS: Genetic association between a marker locus (Taq1 A RFLP near the D2 receptor locus) and the amplitude of P300 was found to be present in 58 high-risk children and their relatives (a total of 100 high-risk individuals). CONCLUSIONS: A higher proportion of children from alcoholic families may exhibit lower P300 because more of these children carry the A1 allele than is seen in the normal population.

Event-related potentials in women at risk for alcoholism.

Event-related potentials (ERPs) elicited during information processing tasks are useful for assessing brain function. Abstinent male alcoholics exhibit deficits in ERPs. The present study found that female alcoholics with early onset alcoholism (18.3 +/- 1.3 years) showed significant deficits in P300 amplitude relative to both high-risk and low-risk controls. Two interpretations of these findings are possible. P300 amplitude reduction among the alcoholic women might be a neuropathological consequence of excessive drinking. Alternatively, lower amplitude of the P300 wave may be a marker for alcoholism risk segregating within high-risk families and associated with development of alcoholism. The later interpretation is favored based on the unlikely possibility that the nonalcoholic high-risk women would later convert to alcoholic status due to their age (mean age of 35.6 +/- 1.6 years).

Beat-by-beat cardiac responses in normals and schizophrenics to events varying in conditional probability.

Anticipatory cardiac deceleration and poststimulus acceleration were studied in schizophrenic inpatients and controls during performance of a counting task. Reduced cardiac responding has been reported for schizophrenic patients for paradigms using relatively long intertrial intervals. During a relatively fast rate of stimulus presentation (3-s interstimulus interval), changes in cardiac interbeat interval were measured in 20 inpatient male chronic schizophrenics and 18 control volunteers. Subjects counted an infrequent tone which was always followed by at least one frequent tone. Control subjects showed significant anticipatory cardiac deceleration preceding the unpredictable tones, whereas patients did not show a differential cardiac deceleration. Control subjects showed poststimulus acceleration that was inversely proportional to the conditional probability of events, whereas patients exhibited greatly reduced poststimulus acceleration; patterns for both groups resembled findings previously observed for event-related potential and pupillary dilation data. Analysis of cardiac cycle time indicated significant variation in primary bradycardia associated with the delay between stimuli and immediately preceding R-waves in controls (replicating Lacey & Lacey, 1980), with only an immediate bradycardia at stimulus reception for patients regardless of cardiac cycle time. The data reinforce the notion that the manner in which information is used by schizophrenics, as reflected by cardiac responsivity, differs both quantitatively and qualitatively from that of controls.