Schizophrenia Elsevier
SCHIZO
Research,
5 (1991) 1355144
135
00178
Specificity of smooth pursuit eye movement and visual fixation abnormalities in schizophrenia Comparison Xavier
to mania and normal
controls*
F. Amador1,2,3v4, Harold A. Sackeim2*3*4, Sukdeb Mukherjee2q4, Ronnie Priscilla Neeley4, Edward Maclin2 and David Schnur2q4
Halperin5,
1Depurtment ofClinical Psychobiology, New York State Psychiatric Institute. ‘Department qf Psychiatry, College q/Physicians and Surgeons. Columbia University, jDepartment of Psychology, New York University, 4Special Treatments Unit, Creedmoor Psychiatric Center, and ‘Department of Psvchology. State University of New York at Purchase, New York, U.S.A. (Received
29 June 1990, accepted
22 January
1991)
Smooth pursuit eye movements (SPEM) were assessed in 30 schizophrenic patients, patients, and 20 normal controls. Compared to schizophrenic patients, manic patients impairment in an attention enhancing, sinusoidal target motion condition and had during a visual fixation condition. SPEM and visual fixation dysfunctions may schizophrenic than in acutely manic patients, even when the latter are characterized dysfunction, poor interepisode psychosocial functioning, and psychosis. Key words: Smooth
pursuit
eye movement;
Mania;
(Schizophrenia)
INTRODUCTION
Since abnormalities in smooth pursuit eye movements (SPEM) in schizophrenic patients were rediscovered by Holzman and associates (l973), numerous independent investigations have replicated the principle findings. The majority of schizophrenic patients exhibit SPEM dysfunction, with a prevalence rate of approximately 50-86%, in contrast to a base rate in the normal population
Correspondence to: X.F. Amador, Department of Clinical Psychobiology, Schizophrenia Research Unit, Box 2, New York State Psychiatric Institute, 722 West 168th Street, New York, NY 10032, U.S.A. (Tel.: 212-960-2352). *Supported in part by grants from the Mental Illness Foundation, the Van Ameringen Foundation, a Basic Research Support Grant, NIH Grant RR05650, and a NARSAD Young Investigator Award. This paper was presented in part at the Annual Meeting of the American Psychopathological Association, March, 1990, New York City.
0920-9964/91/$03.50
12 lithium-free manic evidenced less SPEM superior performance be more common in by marked attentional
f-3 1991 Elsevier Science Publishers
B.V
of about 6-8% (Shagass et al., 1974; Klein et al., 1976; Brezinova and Kendall, 1977; Kuechenmeister et al., 1977; Pass et al., 1978; Iacono et al., 1981a,b; Mialet and Pichot, 1981; Tomer et al., 1981). Approximately 45% of the first degree relatives of schizophrenics exhibit SPEM abnormality (Holzman et al., 1974, 1977, 1980, 1988; Kuechenmeister et al., 1977; Holzman, 1985). In light of these findings, it has been suggested that SPEM dysfunction may be a phenotypic expression of factors associated with the genetic vulnerability to schizophrenia (Matthysse and Holzman, 1986; Holzman et al., 1988). The specificity of the impairment to schizophrenia relative to other functional psychoses is not established. There are some suggestions that the impairment is associated with functional psychosis, but not specifically with schizophrenia (e.g., Shagass et al., 1974; Lipton et al., 1980). Of the nonschizophrenic psychiatric samples studied to date, the overwhelming majority comprised mood disorder patients. Comparative studies of patients
136
with unipolar depressive disorder have generally found higher rates of SPEM disruption in schizophrenic patients (e.g., Couch and Fox, 1934; Shagass et al., 1974; Iacono et al., 1982). However, most of these studies did not distinguish between psychotic versus nonpsychotic patients and psychosis is relatively infrequent among unipolar depressives (Leckman et al., 1984). Of the studies contrasting SPEM in schizophrenic and bipolar (manic or depressed) samples, a number of investigations failed to find differences in rate of SPEM abnormalities (e.g., Shagass et al., 1974; Lipton et al., 1980; Iacono et al., 1982). Complicating comparisons with bipolar disorder is the finding that acute administration of lithium carbonate appears to disrupt SPEM (Levy et al., 1985). In addition, small sample sizes and other possible medication effects (e.g., sodium amytal) make these data difficult to interpret. The one study that examined bipolar patients in an acute psychotic manic episode while free of lithium or central nervous system depressants found that eight out of nine unmedicated subjects performed normally on a tracking task (Levy et al., 1985). When these same subjects were treated with lithium, seven out of eight became abnormal on at least one occasion during serial SPEM testing. Albeit in a small sample, the Levy et al. (1985) findings suggested that SPEM dysfunction may be uncharacteristic of lithiumwithdrawn manic patients. In this study, SPEM was assessed in schizophrenics, manics, and normal controls free of medications known to affect SPEM. The patient sample was recruited from a tertiary-care state hospital. The manic group was unusual in that it contained patients with significant inter-episode psychosocial impairment and psychosis during the index affective episode, making comparison with a schizophrenic sample particularly appropriate. The first aim of this study was to determine whether rate of SPEM dysfunction during an attention enhancing monitoring task differed between schizophrenic and lithium-free manic patients. This task was expected to produce optimal tracking performance in each of the groups. The second aim was to compare performance while following sinusoidal and constant velocity targets in order to evaluate the possible differential effects of these tracking conditions. The third aim was to compare the groups in their capacity to maintain
fixation on a stationary object. Visual fixation was assessed in order to obtain a separate measure of the ability to suppress saccades and maintain voluntary attention.
METHODS Subjects Patients with chronic schizophrenia (n = 30) and acute manic episode, bipolar disorder (n = 12) were recruited from the New York State Psychiatric Institute Division at Creedmoor Psychiatric Center. Diagnosis (DSM-III) was based on independent evaluations by two research psychiatrists using the Schedule for Affective Disorders and Schizophrenia (SADS) (Endicott and Spitzer, 1978). There were no cases of diagnostic disagreement in this sample. Normal controls (n= 20) were recruited from Creedmoor staff and the surrounding community. This group was restricted to individuals with negative personal and family histories of schizophrenia, other functional psychoses and major affective disorder, and who did not meet Research Diagnostic Criteria (RDC) (Spitzer et al., 1978) for any disorder within the past 5 years. Normal controls were excluded if taking prescribed medication. Other exclusion criteria for all subjects were a history of organic brain syndrome, substance abuse, oculomotor or vestibular disease, or deficient corrected visual acuity. Table 1 presents descriptive characteristics of the sample. Manic patients were significantly older than schizophrenic patients both at the time of testing and at the onset of illness (both ps = 0.002), but did not differ in duration of illness. Rating scales (4-point) were developed to assess the level of inter-episode psychosocial functioning in four areas: employment status, independent living and self-care, quality of social interactions, and quality of relations with significant others. The year prior to the index hospitalization was evaluated. Total scores ranged from 4 to 16, with lower scores reflecting greater impairment. Examining the total scores, all schizophrenic patients received ratings of 8 or less, indicating marked psychosocial deficit. Of the 12 manic patients, 8 (67%) scored in this range, indicating that the bulk of this group had marked psychosocial deficits comparable to what was observed in the schizophrenic group. However,
137 TABLE
1
Descripiive
churacterktics
All values mean*SD;
of
the .sample
*psychosocial
functioning
was rated on four, 4-point
Variable
Schi:ophrenic
Manic
Age, years”,” Sex. no. M/F Education, year@’ Age at onset Duration ill. Psychosocial functioning*”
33.53k6.65
40.83i
19’11 11.61 +2.03 19.52c5.88 12.55k6.93
5;1 14.2Ok2.70 27.27i8.68 14.82 f 9.40
5.41*
9.42k4.03
1.59
Normal 13.76
“Schizophrenics differed significantly from manics (p< 0.05). ‘Normal controls differed significantly from both patient groups
relative to the manic group as a whole, the schizophrenic group had greater impairment in total psychosocial scores and on each psychosocial item (all ps < 0.01). The control sample was significantly younger and had more years of education than either patient group (all ps
SCHIZO
Research,
5 (1991) 1355144
135
00178
Specificity of smooth pursuit eye movement and visual fixation abnormalities in schizophrenia Comparison Xavier
to mania and normal
controls*
F. Amador1,2,3v4, Harold A. Sackeim2*3*4, Sukdeb Mukherjee2q4, Ronnie Priscilla Neeley4, Edward Maclin2 and David Schnur2q4
Halperin5,
1Depurtment ofClinical Psychobiology, New York State Psychiatric Institute. ‘Department qf Psychiatry, College q/Physicians and Surgeons. Columbia University, jDepartment of Psychology, New York University, 4Special Treatments Unit, Creedmoor Psychiatric Center, and ‘Department of Psvchology. State University of New York at Purchase, New York, U.S.A. (Received
29 June 1990, accepted
22 January
1991)
Smooth pursuit eye movements (SPEM) were assessed in 30 schizophrenic patients, patients, and 20 normal controls. Compared to schizophrenic patients, manic patients impairment in an attention enhancing, sinusoidal target motion condition and had during a visual fixation condition. SPEM and visual fixation dysfunctions may schizophrenic than in acutely manic patients, even when the latter are characterized dysfunction, poor interepisode psychosocial functioning, and psychosis. Key words: Smooth
pursuit
eye movement;
Mania;
(Schizophrenia)
INTRODUCTION
Since abnormalities in smooth pursuit eye movements (SPEM) in schizophrenic patients were rediscovered by Holzman and associates (l973), numerous independent investigations have replicated the principle findings. The majority of schizophrenic patients exhibit SPEM dysfunction, with a prevalence rate of approximately 50-86%, in contrast to a base rate in the normal population
Correspondence to: X.F. Amador, Department of Clinical Psychobiology, Schizophrenia Research Unit, Box 2, New York State Psychiatric Institute, 722 West 168th Street, New York, NY 10032, U.S.A. (Tel.: 212-960-2352). *Supported in part by grants from the Mental Illness Foundation, the Van Ameringen Foundation, a Basic Research Support Grant, NIH Grant RR05650, and a NARSAD Young Investigator Award. This paper was presented in part at the Annual Meeting of the American Psychopathological Association, March, 1990, New York City.
0920-9964/91/$03.50
12 lithium-free manic evidenced less SPEM superior performance be more common in by marked attentional
f-3 1991 Elsevier Science Publishers
B.V
of about 6-8% (Shagass et al., 1974; Klein et al., 1976; Brezinova and Kendall, 1977; Kuechenmeister et al., 1977; Pass et al., 1978; Iacono et al., 1981a,b; Mialet and Pichot, 1981; Tomer et al., 1981). Approximately 45% of the first degree relatives of schizophrenics exhibit SPEM abnormality (Holzman et al., 1974, 1977, 1980, 1988; Kuechenmeister et al., 1977; Holzman, 1985). In light of these findings, it has been suggested that SPEM dysfunction may be a phenotypic expression of factors associated with the genetic vulnerability to schizophrenia (Matthysse and Holzman, 1986; Holzman et al., 1988). The specificity of the impairment to schizophrenia relative to other functional psychoses is not established. There are some suggestions that the impairment is associated with functional psychosis, but not specifically with schizophrenia (e.g., Shagass et al., 1974; Lipton et al., 1980). Of the nonschizophrenic psychiatric samples studied to date, the overwhelming majority comprised mood disorder patients. Comparative studies of patients
136
with unipolar depressive disorder have generally found higher rates of SPEM disruption in schizophrenic patients (e.g., Couch and Fox, 1934; Shagass et al., 1974; Iacono et al., 1982). However, most of these studies did not distinguish between psychotic versus nonpsychotic patients and psychosis is relatively infrequent among unipolar depressives (Leckman et al., 1984). Of the studies contrasting SPEM in schizophrenic and bipolar (manic or depressed) samples, a number of investigations failed to find differences in rate of SPEM abnormalities (e.g., Shagass et al., 1974; Lipton et al., 1980; Iacono et al., 1982). Complicating comparisons with bipolar disorder is the finding that acute administration of lithium carbonate appears to disrupt SPEM (Levy et al., 1985). In addition, small sample sizes and other possible medication effects (e.g., sodium amytal) make these data difficult to interpret. The one study that examined bipolar patients in an acute psychotic manic episode while free of lithium or central nervous system depressants found that eight out of nine unmedicated subjects performed normally on a tracking task (Levy et al., 1985). When these same subjects were treated with lithium, seven out of eight became abnormal on at least one occasion during serial SPEM testing. Albeit in a small sample, the Levy et al. (1985) findings suggested that SPEM dysfunction may be uncharacteristic of lithiumwithdrawn manic patients. In this study, SPEM was assessed in schizophrenics, manics, and normal controls free of medications known to affect SPEM. The patient sample was recruited from a tertiary-care state hospital. The manic group was unusual in that it contained patients with significant inter-episode psychosocial impairment and psychosis during the index affective episode, making comparison with a schizophrenic sample particularly appropriate. The first aim of this study was to determine whether rate of SPEM dysfunction during an attention enhancing monitoring task differed between schizophrenic and lithium-free manic patients. This task was expected to produce optimal tracking performance in each of the groups. The second aim was to compare performance while following sinusoidal and constant velocity targets in order to evaluate the possible differential effects of these tracking conditions. The third aim was to compare the groups in their capacity to maintain
fixation on a stationary object. Visual fixation was assessed in order to obtain a separate measure of the ability to suppress saccades and maintain voluntary attention.
METHODS Subjects Patients with chronic schizophrenia (n = 30) and acute manic episode, bipolar disorder (n = 12) were recruited from the New York State Psychiatric Institute Division at Creedmoor Psychiatric Center. Diagnosis (DSM-III) was based on independent evaluations by two research psychiatrists using the Schedule for Affective Disorders and Schizophrenia (SADS) (Endicott and Spitzer, 1978). There were no cases of diagnostic disagreement in this sample. Normal controls (n= 20) were recruited from Creedmoor staff and the surrounding community. This group was restricted to individuals with negative personal and family histories of schizophrenia, other functional psychoses and major affective disorder, and who did not meet Research Diagnostic Criteria (RDC) (Spitzer et al., 1978) for any disorder within the past 5 years. Normal controls were excluded if taking prescribed medication. Other exclusion criteria for all subjects were a history of organic brain syndrome, substance abuse, oculomotor or vestibular disease, or deficient corrected visual acuity. Table 1 presents descriptive characteristics of the sample. Manic patients were significantly older than schizophrenic patients both at the time of testing and at the onset of illness (both ps = 0.002), but did not differ in duration of illness. Rating scales (4-point) were developed to assess the level of inter-episode psychosocial functioning in four areas: employment status, independent living and self-care, quality of social interactions, and quality of relations with significant others. The year prior to the index hospitalization was evaluated. Total scores ranged from 4 to 16, with lower scores reflecting greater impairment. Examining the total scores, all schizophrenic patients received ratings of 8 or less, indicating marked psychosocial deficit. Of the 12 manic patients, 8 (67%) scored in this range, indicating that the bulk of this group had marked psychosocial deficits comparable to what was observed in the schizophrenic group. However,
137 TABLE
1
Descripiive
churacterktics
All values mean*SD;
of
the .sample
*psychosocial
functioning
was rated on four, 4-point
Variable
Schi:ophrenic
Manic
Age, years”,” Sex. no. M/F Education, year@’ Age at onset Duration ill. Psychosocial functioning*”
33.53k6.65
40.83i
19’11 11.61 +2.03 19.52c5.88 12.55k6.93
5;1 14.2Ok2.70 27.27i8.68 14.82 f 9.40
5.41*
9.42k4.03
1.59
Normal 13.76
“Schizophrenics differed significantly from manics (p< 0.05). ‘Normal controls differed significantly from both patient groups
relative to the manic group as a whole, the schizophrenic group had greater impairment in total psychosocial scores and on each psychosocial item (all ps < 0.01). The control sample was significantly younger and had more years of education than either patient group (all ps
