Ps~chiutry Research, 18, 16 I - I77

Elsevier 161

Event-Related Potentials in Children at Risk for Schizophrenia During Two Versions of the Continuous Performance Test

David Friedman, Barbara Cornblatt, Herbert Vaughan, Jr., and L. Erlenmeyer-Kimling

Received July 17. 1985; revised version received November 12, 1985; accepted December 3, 1985.

Abstract. Event-related potentials (ERPs) were recorded from children of schizophrenic parents, children of parents with affective disorders, and children of parents without a history of psychiatric illness. ERPs were elicited during two versions of the continuous performance test (CPT), which differed in their level of processing complexity. The data were recorded from electrodes located at midline frontal, central, parietal, and occipital scalp sites. Diagnostic assessments of the parents were performed using the Schedule for Affective Disorders and Schizo- phrenia-Lifetime Version and Research Diagnostic Criteria. Clinical assessments of the children were made with a modified version of the Global Assessment Scale. ERP amplitudes for six electrophysiological events were compared among groups for target and nontarget stimuli using analyses of variance of both factor score and baseline to peak measures. There was one isolated between-group finding: frontal negative slow wave recorded at Fz was of greater magnitude in the high risk (HR) than in either the psychiatric (PC) or normal control (NC) groups. Since only a small percentage of children at risk will eventually develop schizophrenia, ERP amplitude deviance and frequency distribution analyses were also performed and compared among groups. ERP component amplitudes did not distinguish the groups when each component was considered separately. Deviance analyses, using a combination of the amplitudes of the six ERP components, also did not provide evidence of a deviant subgroup within any ofthe three groups. There appeared to be no relationship between ERP component amplitudes and behavioral adjustment in adolescence. Some evidence of a relationship between deviant attentional functioning and ERP component amplitude was found, but the pattern of findings within the attentionally deviant HR subgroup was opposite to that found for the HR group as a whole and more consistent with the pattern found for the NC group.

Key Words. Children at risk for schizophrenia, cognitive event-related brain potentials.

David Friedman, Ph.D., is Associate Research Scientist, Division of Developmental and Behavioral Studies, Department of Medical Genetics, New York State Psychiatric Institute, and Associate Professor, Department of Psychiatry, Columbia University Medical School, New York, NY. Barbara Cornblatt, Ph.D., is Senior Research Scientist, Division of Developmental and Behavioral Studies, Department of Medical Genetics, New York State Psychiatric Institute, and Research Associate, Department of Psychiatry. Columbia University Medical School, New York, NY. Herbert Vaughan, Jr., M.D., is Professor of Neurosciences, Albert Einstein College of Medicine, Bronx, NY, and Director of the Rose F. Kennedy Center for Research in Mental Retardation, Bronx, NY. L. Erlenmeyer-Kimling, Ph.D.. is Director of the Division of Developmental and Behavioral Studies. Department of Medical Genetics, New York State Psychiatric Institute, and Professor, Departments of Psychiatry and Human Genetics, Columbia University Medical School, New York, NY. (Reprint requests to Dr. D. Friedman, N.Y.S. Psychiatric Institute, A308, 722 W. I68 St.. New York, NY 10032. USA.)

01651781,‘86~$03.50 @ 1986 Elsevier Science Publishers B.V.

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In previous publications (Friedman et al., 1979a, 19796, 1982, 1983) we described preliminary analyses of event-related potentials (ERPs) recorded from children at risk for schizophrenia and children of parents without a history of psychiatric disturbance. These data were obtained in a prospective, longitudinal study of children at risk for schizophrenia (see Erlenmeyer-Kimling et al., 1982, 1984 for an overview of the New York High-Risk Project), in which attentional, clinical, and biological indices had been obtained in order to chart those variables that best predicted the development of schizophrenia.

Preliminary data were reported for a subsample of our first sample (Sample A) who were seen in our laboratory for their third round of testing (Sample A3), at which time ERPs were added to the test battery. At the time these preliminary data were analyzed, the majority of the Sample A children had not received the ERP test battery and, of those for whom ERP data were available, there were too few from our psychiatric control group (i.e., children of affectively disordered parents) to permit entering their data into the analyses. In addition, the parents of these children had initially been diagnosed using DSM-II criteria (American Psychiatric Association, 1968). In the current report, the complete Sample A data are described from all three of our subject groups (normal control-NC; psychiatric control-PC; high risk-HR), with risk status defined on the basis of the parents’ diagnoses according to the Research Diagnostic Criteria (Spitzer et al., 1975).

Our addition of ERPs to the test battery was motivated by the findings that brain potential components thought to reflect both attentional (e.g., Lifshitz et al., 1979; Baribeau-Braun et al., 1983) and cognitive (e.g., Timsit-Berthier and Gerono, 1979; Roth et al., 1980) processes were abnormal in adult schizophrenics. Findings in the behavioral domain had also pointed to attentional (e.g., Rutschmann et al., 1977; MacCrimmon et al., 1980; Cornblatt and Erlenmeyer-Kimling, 1984) and cognitive (e.g., Nuechterlein, 1983) disturbances in children at risk for schizophrenia. Thus, the ERP could provide a more direct measure of brain function in these samples of low- and high-risk children.

Although autonomic functioning has been studied in high-risk samples (e.g., Mednick and Schulsinger, 1968; Fein et al., 1975; Janes and Stern, 1976; Erlenmeyer- Kimling et al., 1985), very little attention has been paid to ERP indices. Those studies that do exist suffer from methodological flaws including small numbers of subjects (only six subjects per group in Herman et al., 1977), the use of a large number of between-group t tests with no control for the number of tests performed (Saletu et al., 1975), and the absence of cognitive and attentional manipulations that would enable between-group differences (if found) to be anchored in behavior.

We report here the ERP data from HR, PC, and NC groups recorded while these subjects performed in two versions of the continuous performance test (CPT), which differed in their processing requirements. The construction of the tasks ensured that we would record ERP components reflecting both attentional and cognitive information processing.

Methods

Subject Selection and Parental Diagnoses. The children of mentally ill parents were ascertained through the admission of the parent to one of several state psychiatric facilities

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in the New York Metropolitan area. Mentally retarded children and children with known psychiatric problems were excluded. All subjects were white and English-speaking. As an initial diagnostic evaluation, records of these patients were reviewed blindly and independently by two psychiatrists. Each of the reviewers assigned a diagnosis based on the record materials using DSM-IZcriteria, completed a symptom checklist, and scored the lOO-point Global Assessment Scale (Endicott et al., 1976) assessing the severity of impairment. Only those subjects for whom there was full diagnostic agreement were retained for study. The parents of these children were recently rediagnosed using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L) (Spitzer and Endicott, 1977) in conjunction with the Research Diagnostic Criteria (RDC) (Spitzer et al., 1975). In the data to be reported here, the children are grouped according to their parents’ RDC diagnoses.

The NC group was obtained with the cooperation of two large school systems within the New York Metropolitan area. Families were excluded from the NC group if either parent was found to have had psychiatric treatment.

For purposes of data analysis, the children of the rediagnosed patient parents were grouped into a “high-risk” group (one or both parents receiving a diagnosis of “pure” schizophrenia or schizoaffective psychosis, mainly schizophrenic), and a psychiatric control group (one or both parents receiving a diagnosis of “pure” affective disorder or schizoaffective psychosis, mainly affective). Table 1 presents the demographic characteristics of the subjects for whom ERP data were available in the third round of testing, including parental diagnoses, Behavioral Global Adjustment Scale scores, and IQ. Between group analyses of variance (ANOVAs) showed that for both socioeconomic status (SES) and IQ, the NC group was significantly higher than either the PC or HR groups, which did not differ from one another. However, subsequent correlational analyses of SES and IQ with the six full-epoch and two short-epoch component scores (see Results section below) produced a few extremely small-magnitude correlations, which were no longer significant when corrected for chance levels. Thus, it is unlikely that either of these variables influenced the ERP results reported below.

Assessment of Adjustment in Adolescence. Behavioral assessments were made on the basis of information obtained from the parents of participating children during routine followup telephone calls (see Cornblatt and Erlenmeyer-Kimling, 1985, for a complete description). Three major areas of functioning were assessed: (1) the child’s overall relationship with family members; (2) peer interactions; and (3) school functioning. Ratings are scored on a five-point scale (the higher the score, the healthier the behavior) and range from gross behavioral disturbance requiring hospitalization (a rating of 1) to above average functioning (a rating of 5). This scale is a modification of the Global Assessment Scale (Endicott et al., 1976) and is called the Behavioral Global Adjustment Scale (BGAS).

Continuous Performance Tests (CPTs). These tasks have been described in detail in Friedman et al. (1981) and only a brief description will be given here. This is the computerized version of the CPT which was introduced into the test battery at Round 3 of laboratory testing. Previous publications by our group (e.g., Cornblatt and Erlenmeyer-Kimling, 1984, 1985) have described a CPT which was administered during Round 1 oftesting. This was the “playingcard” CPT and differs in several respects (including timing) from the CPTs described in the current report.

In the computerized version, subjects were instructed to respond to targets as quickly as possible with a finger lift. Speed of responding was stressed. The stimuli for both tasks were the numbers 02 to 19, but the target stimulus differed between tasks. In Task A, the signal (SIG) was the number 08 (15 times per block) and the nonsignals (NSIG) were any other numbers (45 times per block), while in Task B, SIG was the repetition of any immediately preceding numeral (16 times per block), and NSIG were the nonrepeating numerals (48 times per block). The 50-ms duration stimuli were displayed on a DEC VR-14 computer oscilloscope and transmitted to a Sanyo video monitor in the subject’s chamber. The stimuli were presented at

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1 /second and subtended a visual angle of 2 degrees, 20 minutes. Eight blocks of trials were presented for each task but, due to equipment malfunction or time constraints, eight subjects received fewer than eight blocks of Task A (range = 4 to 7) and eight subjects received fewer than eight blocks of Task B (range q 5 to 7) for the NC subjects; for the HR subjects, six children received fewer than eight blocks of Task A (range = 3 to 7) and Task B (range = 3 to 7); for the PC group, three subjects received fewer than eight blocks of Task A (range = 5 to 7) and Task B (range q 5 to 7). The tasks were alternated two blocks at a time, with Task A beginning the recording session.

Table 1. DemoaraDhic characteristics of the samde

Ase

Groups 11 12 13 14 15 16 17 18 19 Totals Mean SD

Normal control 1 7 19 13 8 14 9 3 0 74 14.5 1.7

High risk 0 3 5 6 6 5 4 4 1 34 15.1 1.9

Psychiatric

control 0 3 3 1 6 4 6 1 2 26 15.3 2.1

Totals 1 13 27 20 20 23 19 8 3 134

Parental diagnosis

High risk Psychiatric control

Schizophrenia/ Schizoaffectivel Pure schizonhrenia schizoaffective Pure affective affective

n 21 13 20 6

GrouDs Males

Sex

Females

Normal control 43 31

High risk 20 14

Psychiatric control 10 16

Totals 73 61

SEW IQ BGAS’J

Groups Mean SD Mean SD Mean SD

Normal control 59.0 28 113.3 9.6 3.9 0.9

High risk 84.1 28 103.8 11.3 3.2 0.8

Psychiatric control 84.3 19 107.6 8.1 3.8 1.8

1. Socioeconomic status (higher score indicates lower SES). 2. Behavioral Global Adjustment Scale ihigher rating indicates better adjustment)

Data Acquisition and Recording Procedures. Electroencephalographic (EEG) activity was recorded from electrodes located at midline frontal (Fz), central (CZ), parietal (Pz), and occipital (0~) scalp sites. Vertical electrooculographic (EOG) activity was recorded from an electrode located at the supraorbital ridge of the right eye and, in some instances, from an additional electrode located below the right eye. All leads were referred to an electrode located on the right earlobe (A*). Electrode impedances were never above 5 kR and in most cases were considerably below that value. The physiological signals were amplified on an eight-channel Beckman (Type RM) Dynograph recorder with l-second time constant and 30 Hz high- frequency cutoff.

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Averaged ERPs were computed on line in approximately two-thirds of the subjects with a program that rejected epochs containing eye movement artifacts. In the remaining subjects the averages were computed off-line, with artifactual epochs determined by visual inspection and manually rejected. The two techniques for artifact rejection were compared in several subjects and found to give essentially the same results. The number of sweeps per average varied from 19 to 121 for Task A SIG (mean = 92.9, SD q 23); from 93 to 356 for Task A NSIG (mean q 289, SD q 57);from26to 126forTask B SIG(mean= 100, SD=24); andfrom89to374forTaskBNSIG (mean q 307, SD q 63). There were no differences by ANOVA among the groups in the numbers of sweeps included in the averaged ERPs.

Data Analyses

Baseline to Peak Measures. All peak measures were computed as averaged voltages with respect to the IOO-ms prestimulus epoch. These were based upon the peak of the basis wave (see PCA section below) obtained from principal components analysis (PCA), of the averaged waveforms. These measurements consisted of> 100 ms (depending upon the latency window of the PCA basis wave) of ERP activity, and were obtained by computer program. These windows were (m ms poststimulus): N,,o, O-200; P,,,,, 200-300; P,,,, 300-400; P450, 375-525; slow wave, 700-800. Latency to peak measurements were based on these criteria. However, there were no significant latency differences among the groups for any of the ERP components measured, and these will not be discussed further. The two short-epoch components, “early onset negativity” and peak N,,, (see below), were measured using PCA only.

Principal Components Analyses (PCA). Our rationale for the use of PCA of the averaged waveforms is explained in detail in Friedman et al. (1981). Since the CPTs produce waveforms of complex morphology with multiple, overlapping components (cf. Friedman et al., 1981; Stamm et al., 1983), PCA was used in an attempt to obtain measures of ERP activity in which that overlap had been reduced (see Glaser and Ruchkin, 1976; Donchin and Heffley, 1978). An additional reason for the use of PCA was to obtain objective confirmation, via the basis waves, of components we had visually identified in the individual and grand mean data.

PCA has been shown to be capable of misallocating variance (Wood and McCarthy, 1984). so that caution must be exercised when interpreting results based solely on PCA. Thus, we used both baseline to peak and PCA-derived indices in describing the results of group effects present in these data.

The cross-products matrix was factored since, when using this matrix, no transformations are performed on the data. The BMDP statistical package was used (BMDP4M; Dixon, 1979). The original waveforms were reduced from 250 to 83 points by averaging every three adjacent time points and dropping the last point, so that each “new” voltage represented 12 ms of EEG activity.

Our strategy was first to perform the PCA on each group’s averaged ERP waveforms. If the resultant factor structures were identical, then the PCA was performed across groups, subjects, stimuli, tasks, and electrodes. For the single-group PCAs, there were two stimuli (SIG/ NSIG) by two tasks (A/B) by four electrodes (Fz, CZ, Pa, OZ), and 74 NC subjects (1,184 waveforms), 36 HR subjects (576 waveforms), and 24 PC subjects (384 waveforms). For the PCA performed across groups, there were 2,144 waveforms (134 subjects by 2 stimuli by 2 tasks by 4 electrodes). The PCAs were performed on the full ERP recording epoch (1,000 ms with 100 ms prestimulus baseline and 83 time points at 12 ms per point).

In a previous report (Friedman et al., 1985~) based only on the NC group, PCA of the early portion of the ERP epoch (408 ms, with 100 ms prestimulus baseline; 34 time points at 12 ms per point) uncovered an early onset, endogenous negativity, which we hypothesized might be in the family of attention-sensitive components described by Naatanen and Michie (1979) and Hillyard and Kutas (1983). Since HR subjects have been shown to have attentional deficits (cf. Rutschmann et al., 1977; MacCrimmon et al., 1980; Erlenmeyer-Kimling et al., 1982) we also performed the same analyses across risk groups (separate PCAs of the first 408 ms of each risk

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group’s averaged ERPs produced this early onset negative component). The data base for this analysis consisted of 34 time points at 12 ms per point (408 ms) with 2,144 waveforms (134 subjects by 2 stimuli by 2 tasks by 4 electrodes). In the full-epoch PCAs (based on 1,000 ms of ERP activity), six factors were varimax rotated, and in the short-epoch PCAs (based on the first 408 ms of ERP activity), four factors were varimax rotated.

Analyses of Variance. ANOVAs of baseline to peak, factor score, and behavioral measures were performed using the BMDPZV program. Because of possible nonhomogeneity of variance-covariance measures associated with repeated measures, the degrees of freedom were adjusted using E, according to the method outlined by Jennings and Wood (1976). Since risk group, age, and sex were not repeated measures, no adjustment of the numerator degrees of freedom associated with F tests of these variables was made.

There were no Group by Age or Group by Sex effects for the amplitude of any component and, therefore, these will not be discussed further.

Results

ERP Waveforms. Fig. 1 depicts the grand mean waveforms for the two stimuli, tasks,

and four electrode sites averaged across all subjects (n = 134). This figure demonstrates the effects of stimuli and tasks on the ERP components recorded during these CPTs. The main effects shown in this figure have been detailed previously (cf. Friedman et al., 1981, 1985b). Since these data with the addition of more subjects show the same ERP-stimulus-task relationships as in our previously published findings for the NC sample, only a brief description of nongroup effects will be presented here. In addition, since there were no Group by Age or Group by Sex effects, the reader is referred to Friedman et al. (1985~) for a description of age and sex findings based upon the NC sample.

Fig. 1. Grand mean event-related potential waveforms averaged across all subjects (n = 134) for each task, stimulus, and electrode site

Fz

=*

Pz

%

signal non-signal + I_ 1ouv

__TASK A

__.TASK B

Time lines every 100 ms. Arrows mark stimulus onset

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As can be seen in Fig. 1, the waveforms are composed of multiple positivities (cf. Friedman et al., 1981). In order of increasing latency, they are: PldO, with fronto- central topography; P,,, with a parietal maximum; PdSO, with a parietally focused distribution; and P550r with a parietal maximum. Slow wave activity is negative or near zero at FZ and positive at Pz. A slow negativity, which begins before the stimulus, culminates with central maximum and peak negativity at 150 ms poststimulus.

Fig. 2 presents the grand mean waveforms, averaged across subjects within each group, which show few areas of difference among the three groups. Baseline to peak findings were identical to the PCA findings. Thus, only the PCA results will be discussed in detail.

Fig. 2. Grand mean event-related potential waveforms sorted according to risk group, depicted for each stimulus, task, and electrode site

TASK A TASK B

Signal Cz

Pz

Oz

l

I. lOW

non-signal

-NC -HR . . . . . . . pc

Vertical bars mark mean reaction time, with plus and minus the mean within-subject standard deviation of . reaction time indicated by horizontal bars. Time markers are the same as for Fig. 1.

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Principal Components Analyses (PCAs)

Full-Epoch Analyses-Basis Waves. Fig. 3 depicts the varimax-rotated basis waves resulting from PCA performed across groups and the midline scalp distribu- tions plotted separately for each group for each of the six extracted components.

Fig. 3. Varimax rotated basis waves (i.e., factor loading functions) obtained from principal components analysis of the cross-products matrlx performed across groups on the full event-related potential recording epoch

-+-L

J-&&zzL 2

1 P3SO P4SO /’

,.- ,.*’ P NOmId

controla -

c2Eikl‘ - + 4 NighRisk .________

tt

Psso SW

hlP _. _- .\

*.. _.-*-

Topographic distributions for each group are depicted below each basis waveform. Arrows mark stimulus onset, with time lines every 100 ms.

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Separate PCAs of each group’s ERPs produced identical factor structures, thus justifying the performance of the PCA across groups. For the PCA waveforms

depicted in Fig. 3, N,,, accounted for 5% of the energy; PZ4,,, 17%; P,,,, 1%; Pd5,,, 59%, and slow wave, 14%.

Inspection of Figs. 2 and 3, and results of the baseline to peak ANOVAs, showed that with the exception of slow wave, the effects of stimulus task, and electrode are the same for each of the three groups. For slow wave, the Stimulus by Electrode by Group interaction (F q 3.00, df reduced to 4, 290; p < 0.05) indicated that HR subjects produced more negative frontal slow wave activity than the NC or PC subjects (which did not differ) for SIG but not for NSIG. This was the only significant group effect

noted.

Full-Epoch Analyses-Factor Scores. Results of Group by Stimulus by Task by Electrode Location ANOVAs showed that, in addition to a Group by Stimulus by Electrode interaction (F= 3.30; dfreduced to 4,291;~ < 0.05) there was also a Group by Electrode location interaction (F = 2.50; df reduced to 4, 291; p < 0.05) for slow wave (not shown by the baseline to peak measures). ANOVAs at each electrode site showed that for slow wave the Group by Stimulus interaction was significant only at Fz (F= 3.27; df= 2, 131;~ < 0.05). Separate ANOVAs showed that the HR subjects had greater frontal negativity than either PC (Fz4.44; df =2, 127;~ <0.05) or NC (F q 6. 16; df = 2, 25 1; p < 0.05) subjects, but only to SIG. There were no significant differences between PC and NC subjects.

Additional analyses using “wide” and “narrow” definitions of schizophrenia were performed. A “wide” HR group was formed by including within the HR group all children from the PC group whose parents received a diagnosis of schizoaffective, mainly affective (n = 40). “Narrow” definition groups consisted of children whose parents received a diagnosis of “pure” schizophrenia (n = 21) or a diagnosis of “pure” affective disorder (n = 20).

For the wide definition and for slow wave, the significant Stimulus by Task by Group (F= 4.8 1; df= 1, 112;~ < 0.05), Electrode Location by Group (Fz4.62; df = 2, 247;~ < 0.05), and Stimulus by Electrode Location by Group (F= 5.70; df=2,262;p < 0.05) interactions indicated a similar pattern of findings as for the regular analyses detailed above: the children of parents diagnosed as schizoaffective and schizophrenic showed more negative frontal slow waves than the NC group but only to SIG.

For the narrow definition analyses, there were significant Task by Group interactions when the “pure” HR subjects were contrasted with the NC group (F = 5.00; df q 1, 93; p < 0.05) and when the “pure” PC subjects were compared with the HR group (F = 6.06, df= 1, 39; p < 0.05). In both analyses, the “pure” HR group showed more negative slow wave activity, but only to Task B stimuli. The “pure” PC group did not differ significantly from the NC group. Unlike the regular analyses or the results of the “wide" definition analyses, there were no interactions with Electrode Location in the “narrow” definition ANOVAs.

Factor Score Analyses-Short Epoch PCAs. Because of the possibility that N,,, might represent the summation of “processing negativity” (Naatanen and Michie, 1979; Hansen and Hillyard, 1980) with the N,,, peak (see Friedman et al., 1981,

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198%~) additional PCAs were performed on the first 408 ms of the ERP recording epoch. Since so much variance is in the P,,, and slow wave portions of the ERP, a finer resolution of these earlier ERP components could be achieved by eliminating the later components from the analysis. In a previous publication (Friedman et al., 1985~) we showed that this “early onset negativity” (EON) could be dissociated from the N,,, peak using PCA. This dissociation occurred because each of these components displayed different midline topographies and different relationships to the stimulus and task variables. This analysis was performed across all subjects and conditions, and the resultant PCA waveforms appear in Fig. 4. These correspond in latency to EON (% energy = 9), and the peak of N,,, (9’ o energy = 9). Two other components (not depicted) were extracted and correspond to the negative-going peak of the visual evoked potential at OZ (10% energy) and PZdO (72% energy). Only the EON and N,,, factors were subjected to Group by Stimulus by Task by Electrode ANOVAs. As can be seen from the topographic plots depicted in Fig. 4, the HR group showed the least negative EON amplitude (mean HR = -0.54; mean PC = -0.63; mean NC = -0.73). However, there were no significant group effects for either EON or N,,,.

Fig. 4. Varimax-rotated basis waves obtained from principal components analysis performed on the cross-products matrix from the first 408 ms of the event-related potential recording epoch

EARLY ONSET NEGATIVITY

Normal - Controls

Nl50 Psych

- Controls

------- High Risk Depicted below each basis waveform is the topographic distribution for each group. Arrow marks StimUlUS onset with time lines every 100 ms.

The “wide” and “narrow” analyses detailed above for the full-epoch factor scores were also performed for the short-epoch factor scores. For the wide definition analysis, there were no significant group effects. For the narrow definition analyses, the“pure”HR group (F= 3.95; df= 1,93;p<O.O5) and the“pure”PC group(F= 2.91; df= 2,195;~ < 0.053) (in the case of the “pure” PC group versus the NC group, this was manifested as an Electrode by Group interaction) produced less negative EON

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amplitudes than the NC group, but the “pure” PC group did not differ significantly from the “pure” HR group. These results suggest that reduced EON amplitude is not specific to HR subjects.

Stimulus task, and electrode effects were the same as those reported for the NC group (Friedman et al., 1985a), and the reader is referred to that publication for a detailed treatment of those data.

Behavioral Data. Percentages of hits and correct rejections were subjected to Group by Task repeated measures ANOVAs (Table 2). For hits, the effect of Group was marginally significant (F = 3.00; df = 2, I3 1; p < 0.053). Additional analyses showed that the HR group produced a smaller percentage of hits in both tasks than either the NC(F=4.14;df=l, 106;p<0.05)orthePC(F=4.47;df=1,58;p<O.O5)groups, while the PC and NC groups did not differ significantly.

Table 2. Behavioral data summary

Normal control High risk

Measure Mean SD Mean SD

Reaction time

Task A 438 831 457 87

Task B 473 119 477 121

Percentage hits

Task A 96 7 94 9

Task B 94 9 89 13

Percentage errors

Task A 4 6 4 6

Task B 5.5 6 6 8

1. Mean within-subject standard deviation.

Psychiatric control Grand

Mean SD mean SD

447 92 445 86

467 123 473 120

96 7 95

95 5 93

5 6 4

5 7 5.5

For the wide definition analysis, children of parents diagnosed as either schizo- affective or schizophrenic produced a smaller percentage of hits in both tasks than NC subjects (F = 4.63; df= 1, 112; p < 0.05). For the narrow analyses, the findings were similar to those of the regular analyses: “Pure” HR subjects produced a smaller percentage ofhits thaneither the“pure” PC(Fz7.2; df= 1,39;p<O.O5) or theNC(F= 4.5; df = 1, 93; p < 0.05) groups, while the “pure” PC and NC groups did not differ significantly.

Collapsed across groups, the effect of Task was significant (F= 7.07; df = 1, 13 1;p < 0.05), with Task A producing a greater percentage of hits than Task B. For percentage of errors (a response to a NSIG), Task B produced a greater percentage than Task A (F= 8.92; df= 1, 131;~ < 0.05).

For reaction time (RT), Task B produced longer and more variable RTs than Task A (Fs = 37.2 and 134.2, respectively; df = 1, I3 1; ps < 0.05). There were no Group or Group by Task effects on either of these RT measures.

ERP Amplitude Distributional and Deviance Analyses. Since only a small percentage of HR children are expected to develop schizophrenia (Erlenmeyer-

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Kimling, 1968; Zerbin-Rudin, 1968) we wanted to determine visually whether an outlying subgroup was present in the data sets of the HR group. Frequency distributions of ERP amplitudes were computed for each group (NC, PC, and HR) for each component, stimulus, task, and electrode site. These were visually inspected (all three groups for a given condition and electrode on the same axes) and did not provide evidence for an outlying subgroup in any of the three diagnostic groups. The degree of overlap among the three groups for each of the six electrophysiological events was striking. The impressions from this “visual” analysis were statistically supported by computing the measures of skewness and kurtosis for each ERP component separately for each group. The computed value was divided by its standard error in order to obtain an approximate measure of whether either index of normality was significantly different from zero. For the HR group, only the measure of skewness for frontal negative slow wave elicited by SIG of Task B was significantly different from zero (positively skewed), and for the NC group both skewness and kurtosis were significantly different from zero (positively skewed) for P450 amplitude elicited by SIG of Task A. In view of the large number of variables for which these indices were computed, the data do not provide strong evidence for a systematic outlying subgroup within the HR group.

An additional analysis of ERP amplitude deviance was performed. The NC distribution was used to obtain a cutoff amplitude (one > 90% of the NC subjects’ amplitudes) at the electrode where the component in question produced its maximum amplitude. On the basis of the strategy used by Cornblatt and Erlenmeyer-Kimling (1985), any subject who exceeded this score (in the theoretically appropriate directions-for N,,,, P 240, P,,@ P,SOJ P5,,, and slow wave at Pz, we used a lower cutoff; for slow wave at Fz, we used an upper cutoff) received a “1” and those who did not received a “0.” The number of “1”s was summed for each individual and that sum became the subject’s deviance score. Before this analysis was carried out, the amplitudes were averaged across tasks, so that each subject had a SIG and NSIG score for each component. The results did not confirm a deviant subgroup in any of the diagnostic samples. The percentages of deviant subjects on one to two indices for SIG were: NC-46%, HR-50%, and PC-73%; for NSIG: NC43% HR-70%, PC- 50%. The figures for deviant amplitudes on three to five components for SIG were: NC-3%, HR-9%, and PC-O%; for NSIG: NC--I%, HR-3%, and PC-4%.

Behavioral Adjustment in Adolescence. In order to determine whether clinical status was related to ERP component amplitude, subjects within each of the three risk groups were categorized on the basis of their ratings on the BGAS. Subjects were divided into three groupings: scores of 1-2 (severely impaired functioning); 3 (moderately impaired), and 4-5 (average and above average functioning). ANOVAs were performed on the short- and full-epoch factor scores using these groupings. There were no significant differences as a function of BGAS rating for any of the six full- and two short-epoch components.

Attentional Deviance. When these children were seen for the first time in the laboratory (Sample Al), they were given a battery of tests that tapped attentional processing (cf. Erlenmeyer-Kimling et al., 1982; Cornblatt and Erlenmeyer-Kimling,

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1985). These subjects were later characterized as being deviant or nondeviant on the various measures that comprised the test battery (Cornblatt and Erlenmeyer-Kimling, 1984, 1985). For each response variable, a cutoff score was selected that identified the most poorly performing 5% of the normal control group. Subjects in each group (NC, HR, and PC) who performed below this score were considered deviant on that particular variable. Each of the 15 attentional indices was dichoto- mized, with subjects defined as deviant receiving a score of “1”and all others receiving a score of “0.” The 15 dichotomized variables were then combined into a single composite attentional deviance index by tallying the number of “1”s each subject received.

We wanted to determine whether these attentionally deviant subjects had different patterns of ERP component amplitudes compared to those subjects characterized as being nondeviant on the attentional index. Of the 26 subjects defined as deviant at Round 1 according to the criteria described above, only 11 had Round 3 ERP data available. Seven of the subjects were in the HR group, three were in the NC group, and one was in the PC group. Therefore, only the 32 HR subjects who had both attentional and ERP data were grouped according to whether they were attentionally deviant or not at Round 1. We compared ERP amplitudes between the deviant and nondeviant subjects using Subgroup (Deviant/Nondeviant) by Stimulus by Task by Electrode Location ANOVAs. Due to the small number of subjects falling into these subgroupings, conservative degrees of freedom (1 /N-2) were used to test all main and

interaction effects. For the full-epoch factor scores, the only significant effect was for slow wave, which

showed a Subgroup by Stimulus by Task by Electrode Location interaction (F= 5.49; df = 1,30; p < 0.05). This interaction indicated that the attentionally deviant subjects showed more positive slow wave activity than the nondeviant subjects but only for SIG, at the two anterior electrode sites. These findings for slow wave in the attentionally deviant subgroup are opposite to those found for the HR group as a whole (i.e., more negative slow wave activity than either the NC or PC groups).

For the short-epoch factor scores, EON showed a Subgroup by Stimulus by Task by Electrode Location interaction (F q 4.66; df = 1, 30; p < 0.05). This interaction indicated that the attentionally deviant subgroup produced greater negative EON amplitudes than the nondeviant subgroup to SIG of Task B, but this effect was limited to central and parietal scalp sites. As with the finding for slow wave, this effect is opposite to the trend shown by the HR group as a whole (i.e., less negative EON amplitudes than the NC group).

Discussion

The ERPs recorded from all three groups (NC, HR, and PC) displayed highly similar

morphologies (see Fig. 2), so that visual inspection and quantitative analyses yielded few areas of difference among the groups along the ERP waveform. Topographic distributions for all six electrophysiological events recorded during these CPTs were also highly similar for the three groups. Only one modest, but significant interaction (Electrode by Group) occurred, and this was for slow wave. This interaction indicated greater frontal negativity for the HR subjects than for PC or NC groups, which did not

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differ from each other. However, in view of the fact that this was only one of several Group effects that were tested (for each ANOVA there were 48 Ftests involving Group as a variable) and found to be significant, it is difficult to interpret this finding. In addition, when the groups were made more homogeneous by excluding schizo- affective diagnoses in either the HR or PC groups, the interaction with Electrode Location was no longer present. Only in the “wide” definition analysis was the interaction with Electrode Location still significant. Further, neither the ERP amplitude nor the attentional deviance analyses yielded evidence of a subgroup within the HR sample in which increased frontal negativity was a common characteristic. In fact, the attentionally deviant subgroup showed less negative slow wave activity at the two anterior electrode locations, a finding more consistent with the pattern shown by the NC group.

The ERP amplitude distributional and deviance analyses suggest that the visual ERP parameters obtained from these data cannot, by themselves, differentiate subjects at risk from children of parents without psychiatric disturbance or from children of parents with affective disorders. Whether taken component by component (frequency distribution analyses) or as a composite (deviance analyses), the data failed to yield evidence of an outlying subgroup which could be considered to comprise the most vulnerable subjects within the high-risk sample.

Age and sex trends for each of the two experimental groups (HR and PC) were similar to those found for the NC group. This suggests that hypotheses of maturational lag (cf. Herman et al., 1977) as explanatory of the deficits seen in HR subjects are not tenable for this sample of subjects.

In a previous publication, we (Friedman et al., 1982) reported that P,,, amplitude to infrequent auditory targets was reduced in the HR subjects’ waveforms compared to Pr,, recorded from children of parents without a history of psychiatric problems. These data were preliminary and the analyses did not include the ERPs recorded from the psychiatric control group (i.e., children of affectively disordered parents). More recent analyses of those data (Friedman et al., 198%) which include the children of affectively disordered parents, showed no differences in Pj,,, or slow wave amplitudes among the three groups of subjects. Since reduction of PjoO amplitude is one of the most consistently found waveform abnormalities in adult schizophrenics, finding this same deviation in the child at genetic risk could be taken as evidence of the amplitude reduction as a premorbid indicator for the development of schizophrenia. However, in the overall group analyses performed on the current visual ERP data, there was also no evidence of Pro,, (P,,, in these CPT data) reduction, whether assessed by ANOVA, ERP amnlitude freouencv distribution, or deviance analyses.

Although very few studies of ERPs have been performed with HR samples, these subjects have been well studied from a behavioral perspective (see, for example, the volume edited by N. Watt et al., 1984). The most consistent finding that cuts across samples and tasks is for HR subjects to display subtle disturbances in attentional functioning relative to normal and psychiatric controls (Rutschmann et al., 1977; Erlenmeyer-Kimling and Cornblatt, 1978; MacCrimmon et al., 1980; Nuechterlein, 1983; Cornblatt and Erlenmeyer-Kimling, 1985). We sorted our HR subjects for whom we had ERP data collected at Round 3 on the basis of whether they were

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deviant or not on a battery of attentional tests given at Round 1. When subjects were subdivided in this manner, some evidence of a differential pattern of slow wave activity and EON amplitude between the deviant and nondeviant subgroups was found. However, the pattern shown by the attentionally deviant subgroup was opposite to that found for the HR sample as a whole, and more consistent with the pattern found for the NC group: less negative frontal slow wave activity and more negative EON amplitudes at central and parietal scalp locations.

Due to small ns (only IO-15% of children of schizophrenic parents are expected eventually to develop the psychosis, compared to 1% of children of normal and affectively disordered parents) and modest significance levels, caution must be exercised in interpreting the strength and significance of the current findings.

Furthermore, behavioral adjustment ratings (BGAS) were not related to ERP amplitudes in any of the three samples. However, since the current study has only assessed whether ERP parameters can predict the nonspecific behavioral problems measured by the BGAS ratings, it remains to be seen whether these ERP indices are, in fact, predictors of adult schizophrenia. Ultimate validation of this kind must wait for definitive outcome measures, obtained after these subjects have passed through the major risk period for schizophrenia. It is only then that we will be able to determine, with any certainty, whether these cognitive ERP indices are of predictive value.

Acknowledgments. The authors thank Mr. Charles Brown, Jr., for programming and aid with preliminary data reduction and Mr. John Boltri for aid with data reduction. Ms. Susan Ball aided in the construction of figures. Dr. Samuel Sutton read an earlier version of this manuscript and made many useful suggestions. The research reported here was supported in part by grants MH-19560 to Dr. Erlenmeyer-Kimling. HD-14959 to Dr. Friedman, and by the Department of Mental Hygiene of New York State. Dr. Friedman is supported in part by a Research Scientist Development Award (MH-00510) from the National Institute of Mental Health. The Computer Center at New York State Psychiatric Institute is supported in part by a grant (MH-30906) from the National Institute of Mental Health.

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