Visually-guided saccadic eye movements in adolescents at genetic risk for schizophrenia.

Visually-guided saccades of 21 offspring of schizophrenic parents and 21 individually matched controls were compared with regard to the frequency of occurrence of saccadic hypometria and hypermetria, non-fixations, and omissions of target jumps. Target steps ranged from 10 to 60 degrees, and interstimulus intervals averaged 2.5 s; subjects were promised financial reward depending on performance. Recordings were carried out at the subjects' homes. To screen for cognitive abilities and psychopathological behavior, subjects were tested by means of an intelligence scale and a behavioral checklist. With large target steps (40-60 degrees), the high-risk group made significantly more grossly hypometric saccades (gain < or = 0.8) than the control group; responses to small target steps (10-30 degrees) exhibited a similar, albeit statistically not significant, trend. There were no significant differences with regard to the occurrence of hypermetria. Non-fixations scored marginally higher in the high-risks as compared to controls, but this was again not a significant difference. The incidence of omissions of saccades was very low in both groups. The results of the study suggest that subjects at genetic risk for schizophrenia may differ from controls by an increased incidence of conspicuously hypometric saccades. Clearly, this difference is not caused by a deficit of the saccadic motor circuitry proper; comparison to control data obtained with a similar experimental protocol suggests that it probably reflects an impaired internal control of saccades in the presence of distraction and stress. The relevance of saccades as indicators of a possible schizophrenic vulnerability is discussed.

[Electrophysiologic correlates of selective attention in children and adolescents at increased risk of schizophrenia]. / Elektrophysiologische Korrelate selektiver Aufmerksamkeit bei Kindern und Jugendlichen mit erhöhtem Schizophrenie-Risiko.

Electrophysiological correlates of selective attention in children and adolescents at high risk for schizophrenia. As part of a research project on electrophysiological correlates of attention in young subjects at high genetic risk for schizophrenia, auditory event-related potentials (ERPs) associated with selective attention and automatic information processing were recorded in 21 adolescent (offspring of at least one parent with schizophrenia) and 21 control subjects matched for age, sex and socioeconomic status. The experimental task was a dichotic listening task, and accuracy of counting target pips served as a psychometric control variable. The results showed group-related differences in the ERPs, with a significant reduction being present in the high-risk group concerning the amplitude of the fronto-precentrally located negative difference (Nd) wave and the F3 component elicited by selectively attended stimuli. Comparison of individual matched pairs showed that reduced Nds, characterized 14/21 high-risk individuals and reduced P3s 16/21. Moreover, there were significant correlations between ERP reductions and psychometric deficit (counting accuracy). Finally, 13 latencies tended to be prolonged in the high-risk group. Mismatch negativity (MMN), an ERP correlate of automatic information processing, did not differ significantly in the two groups, although there was a marked reduction in amplitude in the high-risk group. The ERP alterations point to impaired selective attention in a considerable proportion of subjects at high genetic risk for schizophrenia.

Vascular effects of oxytocin on human middle cerebral artery determined by transcranial Doppler sonography.

Neurohypophysial hormones may exert regulatory influences on cerebral blood flow. This double-blind cross-over study in healthy humans (n = 6) examined effects of oxytocin (OX) on blood flow in the middle cerebral artery (MCA) by transcranial Doppler sonography. Compared to placebo, intravenous infusion of OX (0.5 IU, within 2.5 min via a forearm catheter) reduced blood flow velocity (V) within 10 min after the start of the infusion (P < 0.05). The pulsatility index (PI) was at the same time increased following OX (P < 0.05). The effects of OX were not accompanied by changes in expiratory endtidal pCO2 or blood pressure. But, heart rate was slightly enhanced immediately after infusion of OX (P < 0.05). The changes in MCA blood flow velocity following OX could reflect a vasoconstrictory effect on small cerebral resistance vessels or a vasodilating effect on the large cerebral arteries.

Improved event-related potential signs of selective attention after the administration of the cholecystokinin analog ceruletide in healthy persons.

Cholecystokinin (CCK) is co-localized with dopamine (DA) in neurons of the mesolimbic-frontocortical dopamine (DA) system, considered essential for the pathology of psychotic behavior and associated attention deficits. The present experiments in 13 healthy men aimed at examining the effects of the CCK analog ceruletide on attention as reflected by event-related brain potentials (ERPs). Subjects were tested according to a double-blind cross-over design on three occasions, following intravenous infusion of placebo, 0.5 microgram ceruletide, and 2.5 micrograms ceruletide. ERPs were recorded during the subject's performance on an auditory selective attention task including the concurrent presentation of frequent standard tones and infrequent deviant tones which the subject had to listen to, or to ignore. The processing negativity (PN) over frontocentral cortical areas, reflecting selective attention, was higher after ceruletide than placebo, this increase being most pronounced after the 2.5 micrograms dose (placebo -1.29 +/- 0.38 microV versus ceruletide -3.02 +/- 0.65 microV, p < .05). ERP signs of a general increase in cortical arousal after ceruletide did not reach significance. Likewise, mismatch negativity, an indicator of preattentive processing of stimulus deviance, was not significantly affected by the peptide. The results indicate that ceruletide affects human brain function primarily by improving selective attention.

Comparative assessment of saccadic eye movements, psychomotor and cognitive performance in schizophrenics, their first-degree relatives and control subjects.

This study is aimed at detecting biological markers for schizophrenia. For this purpose, a total of 70 subjects (21 schizophrenic patients, 27 first-degree relatives and 22 controls) performed a series of tests assessing various attentional, psychomotor and cognitive functions and saccadic eye movements. The schizophrenics performed significantly poorer than both high-risk and control subjects in most of the tests demanding attention, concentration and psychomotor speed (d2 concentration test, reaction times and Stroop test of perceptual interference) as well as cognition (Wechsler intelligence scales). On the other hand, these tests did not differentiate between the high-risk and control subjects. This distinction, however, could be made by two other parameters: hypometria score of saccadic eye movements and ratio of verbal to performance intelligence scores. Both parameters were significantly increased in both the schizophrenic and the high-risk group, distinguishing both from the control group. The relevance of these findings in indicating a schizophrenic disposition is discussed.

Attention, cognition, and motor perseveration in adolescents at genetic risk for schizophrenia and control subjects.

Twenty-three offspring of schizophrenic parents (mean age = 12.1 years, SD = 3.2) and 61 adolescent control subjects (mean age = 12.3 years, SD = 3.3) were compared in their performance of the following psychometric tests: simple reaction times (RTs), warned RTs in a monomodal and cross-modal design, d2 concentration test, a motor perseveration test, and a cognitive performance measure (Wechsler Intelligence Scale). The results were validated in a second analysis in which a subgroup of the control subjects were matched to the high-risk subjects for the following characteristics: age, gender, education, and environmental background. Significant deficits were found in the high-risk group in tests that required sustained attention and information processing under high perceptual load (RT measures and d2 concentration test). Deficits were particularly prominent for the processing of visual stimuli; sensory incongruence might also have been a contributor to this deficit. The attentional dysfunction of high-risk subjects might explain their tendency to show less structured behavior and distractibility as reflected by their higher entropy scores in a motor perseveration test. Cognitive evaluation showed a significant deficit in the high-risk group, primarily as reflected in the verbal IQ score.

Event-related potential correlates of impaired selective attention in children at high risk for schizophrenia.

Auditory event-related potentials (ERPs) associated with selective attention were recorded in 21 children at high-risk for schizophrenia and in 21 matched controls. The subjects performed a selective listening task. For behavioral evaluation, target counts on the selective listening task and on cognitive performance were assessed. Group-specific differences of ERP components could be demonstrated, as reflected by significant amplitude reductions of the frontally located negative difference wave (Nd) and of the P3 component, following selectively attended stimuli, in the high-risk children. P3 latencies tended to be prolonged in the high-risk group. Reduced Nd was found in 14 and reduced P3 in 16 high-risk children among the 21 matched pairs. Significant correlations between the ERP reductions and psychometric deficit (counting accuracy) were observed. Mismatch negativity (MMN), an ERP component associated with automatic processing of physically deviant stimuli, did not differentiate significantly between groups, but was distinctly reduced in the high-risk group. The Nd and P3 reductions suggest deficits of selective attention in a considerable number of the subjects genetically at risk for schizophrenia. The present findings are discussed with respect to their relevance as indicators of a predisposition to schizophrenia.

Endogenous event-related brain potentials and psychometric performance in children at risk for schizophrenia.

Two independent groups of high-risk children for schizophrenia and their matched control children were submitted to the following experiments: an auditory oddball paradigm registrating late event-related potentials (ERPs) and a psychometric test battery including the assessment of Wechsler Intelligence Scales, reaction times (after regular and irregular preparatory intervals), and the d2-attention test. The study was intended to clarify whether long-latency ERPs and the selected psychometric tests would contribute to reliably differentiating between these groups. The results showed significantly prolonged latencies of the P3 component of the ERPs to rare, task-relevant target stimuli in both high-risk groups compared with the controls. Similarly, the N2 latencies were delayed in both groups. By contrast, ERP patterns to frequent, nontask-relevant stimuli were very similar, with no significant differences between high-risks and normals; nor did any ERP amplitudes show significant differences. The data are interpreted as a reflection of a subtle deficit in maintaining attention and a subsequent impairment of stimulus discrimination in high-risk children. This is consistent with the psychometric findings of higher error scores in target counts and d2-test, and significantly prolonged reaction times after regular preparatory intervals (PIs) in the high-risks. The findings may hint at a vulnerability for schizophrenia in high-risk children. Given the high prevalence of the attentional dysfunctions in both high-risk groups, however, it is hypothesized their presence does not necessarily imply an unequivocal manifestation of schizophrenia.