,I. psychiat. Res., Vol. 25, NO. 3, pp. 131-140, 1991.
0022-3956/91 $3.00 + .00 © 1991 PergamonPress plc
Printed in Great Britain.
NEGATIVE
SYMPTOMS AND REACTION
T I M E IN
SCHIZOPHRENIA F R E D S C H W A R T Z , R I C H A R D L . M U N I C H , A R T H U R C A R R , ELIZABETH B A R T U C H , BARBARA LESSER, DEBORAH RESCIGNO a n d
BARBARA VIEGENER
Department of Psychiatry, Cornell University Medical College, Westchester Division, The New York Hospital, New York, NY, U.S.A. ( R e c e i v e d 23 A u g u s t 1990; revised 26 N o v e m b e r 1990)
S u m m a r y - - T h i s study explored the association of negative symptoms and reaction time. Negative symptoms were specifically associated with reaction time slowing and variability in schizophrenics, but not in affective disorders. The finding of specificity did not extend to other measures of the deficit syndrome nor to motor performance. An abbreviated version of the negative symptom scale was especially effective in separating groups.
Introduction STUDIES relating laboratory measures and clinical symptoms provide a non-invasive method of identifying basic defects that may underly a patient's clinical presentation. The present study is in this tradition and relates reaction time (RT) variables to negative and positive symptoms. RT latency appears to be mostly independent of acute psychotic symptoms (Zahn & Carpenter, 1978). Two early studies reported modest but significant correlations between RT latency and symptoms of "withdrawal" (Kopfstein & Neale, 1972; Goldberg, Schooler, & Mattsson, 1968). Current interest in this topic was stimulated by a conceptual reorganization of the symptoms of schizophrenia by Strauss, Carpenter, & Bartko (1974). Subsequent empirical work by Crow (1980) and Andreasen and Olsen (1982) resulted in a considerable body of data linking negative symptoms to biological variables, cognitive deficits, and laboratory measures in schizophrenia. At the same time, it became apparent that negative symptoms were not specific to schizophrenia, occurring also in affective illness, and that ratings of negative symptoms may be confounded by clinical depression, psychotic withdrawal, and extrapyramidal side-effects (e.g., Andreasen, 1987; Carpenter, Heinrichs, & Wagman, 1988; Crow, 1985; Mayer, Alpert, Stastiny, Perlick, & Empfield, 1985; Sommers, 1985). This lack of specificity has led to a distinction between negative symptoms and a schizophrenic deficit state, the latter being due presumably to a deteriorating process that is neurosphysiological in aetiology. The deficit state has been defined in two ways; by the persistence of negative symptoms over time (Buchanan, Kirkpatrick, Heinrichs, & Carpenter, 1990); and by the co-occurrence of negative symptoms with cognitive impairment, soft neurological signs, and behavioral disorganization (Owens & Johnstone, Reprint requests to Dr. Fred Schwartz, 21 Bloomingdale Road, White Plains, New York 10605, U.S.A. 131
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1980). The longitudinal approach is consistent with the finding that negative symptoms mostly disappear over time in depressive disorders (Pogue-Geile & Harrow, 1984). Neither approach, however, controls for clinical depression, psychotic withdrawal, or neuroleptics. This study is cross-sectional in design and explores the association of RT and clinical symptoms in schizophrenics and affective disorders. Traditionally, RT slowing in schizophrenia has been interpreted as evidence of an attentional dysfunction (Nuechterlein, 1977). The RT response, however, is correlated with performance on m o t o r tests (Rosofsky, Levin, & Holzman, 1982; Walker & Green, 1982). It has since been shown that schizophrenics are slower than normal controls on the premotor and m o t o r components of the RT response (Vrtunski, Simpson, Weiss, & Davis, 1986). The proposed association between RT and negative symptoms may thus be due to attentional or motoric processes. To clarify this point, we include a measure of motor performance (finger tapping) to control for motor speed. We also include an experimental variation of the RT paradigm to increase the attentional demands of the task. We hypothesize that the association of negative symptoms and RT is specific to schizophrenia, and that such specificity is not found with positive symptoms. The relationship of the deficit syndrome to RT performance is partially evaluated by including a measure of intelligence for cognitive impairment and a measure of neuropsychological performance. We also evaluate the attentional hypothesis and the possible confounding effects of depression and neuroleptics. Method
Subjects Forty-eight schizophrenic inpatients and 80 major affective inpatients were drawn from an ongoing study of attentional and motor performance at this center. The patients were consecutive admissions, excluding those with a clinical diagnosis of organic brain syndrome; of those approached, 95°7o agreed to participate and gave informed consent before beginning the study. Diagnosis was based on a semi-structured interview and research diagnostic criteria (Spitzer & Endicott, 1979; Spitzer, Endicott, & Robins, 1981).
Procedures Negative symptoms were rated with Andreasen's scale (1982), using the sum of the global ratings from five subscales. The sum of the alogia and fiat affect scales was also abstracted, based on Crow's (1985) contention that the full scale is likely to be confounded by depression and psychoticism. The Brief Psychiatric Rating Scale (Overall & G o r h a m , 1962) was used to rate current clinical depression and psychoticism (the latter being the sum of the thought disturbance and paranoid factors, as defined by Guy, 1976). Two other features of the deficit syndome were evaluated--i.e., intelligence and neuropsychological deficits--to form a contrast with negative symptoms. Intelligence was tested using the Full Range Picture Vocabulary Test (Ammons & A m m o n s , 1948). Neuropsychological performance was measured on a 19-item battery (Luria, 1966), and included tests of motor, somatosensory, language, visual-spatial, and m e m o r y functions. Each subtest was rated on a four point scale.
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Visual RT was measured in milliseconds with fully automated equipment, using a Lafayette Instruments tone and light, programmable timer, digital clock, and printer. Subjects depressed a telegraph key to the tone with their forefinger and responded to the light by lifting their forefinger. The intertrial interval was 3s and the interstimulus interval (tone to light) was 2.5, 3.0, or 3.5s in a random order. Two conditions were employed: simple RT (hereafter designated RT1), and RT while subjects counted out loud by twos (hereafter designated RT2). The second condition tests divided attention and is more demanding (see Schwartz et al., 1989, for further details of the RT procedure). Two motor tests--finger tapping and the Purdue pegboard--were included to form a constrast with the RT conditions. Tapping speed was measured electronically using a handheld debouncer switch. Taps were obtained in five second bursts, five trials per hand, the score being the average for the two hands. Finger dexterity was measured with the Purdue pegboard assembly test, which requires sequential placement of a pin, washer, collar, and washer, alternating hands. Subjects completed eight assemblies twice. The score was the average time for both trials, recorded with a digital stopwatch (see Schwartz et al., 1990, for further details). Finger tapping was also included as a covariate in evaluating the relationship between RT and negative symptoms. Results Demographic and clinical characteristics of the sample are listed in Table 1. The two diagnostic groups differ on sex distribution, verbal intelligence, positive symptoms and the percentage of patients on neuroleptics (p < .05). No other group differences are significant. Table 1
Clinical and Demographic Characteristics of Sample Variable Sample size Mean age (SD) Sex Male Female Duration of illness (SD) Prior hospitalizations (SD) Verbal intelligence in percentiles (SD) Neuropsychological deficits (SD) Depression (SD) Negative symptoms Full Scale (SD) Partial Scale (SD) Psychoticism (SD) Neuroleptics
Schizophrenics
Affective controls
48 26.2 (6.0)
80 25.1 (5.3)
30 18 5.1 3.5 59.9 3.9 11.3
22 58 3.5 3.3 70.3 3.3 11.7
(5.4) (3.2) (24.5) (3.8) (4.1)
7.8 (4.5) 3.0 (2.3) 23.4 (8.2) 37
(4.1) (2.8) (22.7) (3.1) (3.7)
8.1 (5.6) 3.0 (3.0) 19.7 (7.6) 36
Diagnostic groups differed significantly on sex distribution, verbal intelligence, psychoticism, and use of neuroleptics.
Clinical Variables Table 2 lists the zero order correlations among the clinical variables for each diagnostic group. Two patterns emerge: (1) The deficit triad of negative symptoms, intelligence, and
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neuropsychological deficits is significantly interrelated in the schizophrenic group but not in the affective group; (2) The absolute size of the correlations between negative symptoms and depression, positive symptoms, and neuroleptics are all reduced in the schizophrenic sample when the abbreviated version of Andreasen's scale is used. These results support the presence of a deficit syndrome in schizophrenia and suggest that the abbreviated scale is less confounded by depression, neuroleptics, or psychoticism. The correlation of negative symptoms and neuroleptics requires some explanation. We compared patients on and off neuroleptics rather than using dose, as the relationship of blood levels to dose is not linear (Rockland, 1986). In correlating a dichotomy with a continuous variable, the statistic (a point biserial r) is at a maximum when the two groups are of equal size. This is approximately true for the affective group (45% on neuroleptics), but not for the schizophrenic group (77% on neuroleptics). The correlations reported in Table 2 do not support an association of negative symptoms and the use of neuroleptic medication in this sample, the findings being most compelling for the affective group. Table 2
Intercorrelations among Negative Symptoms, Depression, Verbal Intelligence, Neuropsychological Deficits, Positive Symptoms, and Neuroleptics in Schizophrenics and Affective Disorders Variable 1. 2. 3. 4. 5. 6. 7.
Neg. full Neg. partial Depression Intelligence Neuro Positive Neuroleptics
1
2 0.83*
0.85* 0.20 0.11 0.09 0.17 0.10
0.21 0.20 0.10 0.06 -0.10
3 0.40* 0.25 0.05 0.05 0.23* 0.11
4 -0.34* -0.28* 0.04 0.38* -0.06 0.00
5 0.37* 0.30* 0.40* 0.47* 0.14 0.16
6 0.26 0.08 0.50* -0.18 0.38*
7 0.22 0.10 0.43* 0.17 0.24 0.29*
0.23*
Upper right: schizophrenics ( N = 48). Lower left: affective disorders ( N = 80). *p < .05.
Table 3 lists the zero order correlations among the symptom variables and the laboratory measures for each group. The RT measures were first transformed into logarithms so as to minimize the effect of extremely large values on the distributions. Both measures of negative symptoms are associated with the RT variables and finger tapping in the schizophrenics; these correlations are mostly nonsignificant in the affective group. The pattern of results is that schizophrenics with high levels of negative symptoms are more likely to have slower RT's, be more variable, and tap at a slower rate. Positive symptoms in the schizophrenics have an adverse effect on the RT2 condition (latency and variability). An inspection of Table 3 also indicates that the association of negative symptoms and RT is not increased in the divided attention condition (RT2). Point biserial zero order correlations between neuroleptics (on versus off medication) and the RT variables were also computed for each group separately and account for .00 to .08% of the variance in any comparison. This effect is considered to be meaningless, in view of no clear evidence of a relationship between neuroleptics and negative symptoms in this study.
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Table 3
Intercorrelations among Symptoms and Laboratory Measures in Schizophrenics and Affective Disorders Variable
RT 1
RT2
Var I
Var2
Tap
Purdue
-0.29* -0.28** -0.21
0.26** 0.18 -0.18
- 0.14 - 0.22 - 0.05
- 0.08 - 0.02 - 0.05
Schizophrenics ( N = 48) N e g a t i v e (full scale) N e g a t i v e (partial) Positive
0.42* 0.47* 0.14
0.45* 0.44* 0.28**
0.24 0.37* 0.00
0.45* 0.45* 0.29*
A f f e c t i v e disorders ( N = 80) N e g a t i v e (full scale) N e g a t i v e (partial) Positive
0.20 0.26* 0.19"*
0.07 0.02 0.11
0.00 - 0.01 0.08
- 0.10 - 0.11 0.09
RT1 = s i m p l e RT; RT2 = R T d u r i n g divided a t t e n t i o n ; V a r l = RT1 w i t h i n - s u b j e c t variability; Vat2 = RT2 withinsubject variability; T a p = finger t a p p i n g ; P u r d u e = p e r f o r m a n c e o n the P u r d u e p e g b o a r d . *p < .05; **p > .05 < .10.
Negative Symptoms and R T: The Question of Specificity The critical question is whether the association of negative symptoms and the laboratory measures is significantly greater in the schizophrenic group than in the affective group. To test this, the correlation of negative symptoms with the Groups X RT interaction was separately computed for each pair of variables in hierarchial multiple regression analyses (Cohen & Cohen, 1983). A significant interaction signifies that the regression lines relating negative symptoms and RT are not parallel (and hence diverge) for the schizophrenic and affective groups. In these analyses, the variance due to the interaction term was pooled over men and women so as to control for sex differences in the two diagnostic groups. Using the full Andreasen scale, two of four interactions are significant (see Table 4), the variables being RT2 latency and variability. For the abbreviated Andreasen scale, all four RT variables are significant. These results demonstrate that the association of negative symptoms and RT is specific to the schizophrenic group. The results remain unchanged when clinical depression, as measured by the Brief Psychiatric Rating Scale, is included as a covariate. This is as expected, in view of the weak zero order correlations between negative symptoms and clinical depression (see Table 2). Table 4
Tests o f the Specificity o f the Association o f Negative Symptoms and R T Variables; Groups × R T Interaction f o r Full Scale o f Negative Symptoms and Partial Scale o f Negative Symptoms Full scale Variable RT1 RT2 RT1 RT2
mean mean variability variability
*p .05); (3) psychoticism is substituted for negative symptoms (p > .05); and (4) negative symptoms are the dependent variable and tapping speed and pegboard performance are alternately substituted for the RT variables (p > .05). Within the constraints of this study, these results demonstrate that the specific association of negative symptoms and RT in schizophrenia does not extend to other measures of the deficit syndrome, nor to postive symptoms, nor to m o t o r performance.
Subgroup Differences The possible role of depression on the association of negative symptoms and laboratory performance was further evaluated by exploring subgroup differences for the schizophrenic
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and affective patients separately. The schizophrenics were subdivided into a schizo-affective schizophrenic group and a purified schizophrenic group, using research diagnostic criteria. With the Andreasen scale as the dependent variable, the Groups × Measure interaction term is significant for RT1 latency, tapping speed, and the Purdue pegboard (i.e., 3 of 6 analyses). In each case, the slope of the regression line is significantly greater (p < .05) for schizophrenics with a major affective component to their illness. No significant interactions are obtained when the abbreviated version of the scale is substituted for the full Andreasen scale (p > .05). The affective disorders were subdivided into a bipolar group and a unipolar depressive group, using research diagnostic criteria. With the Andreasen scale as the dependent variable, the interaction term is significant for RT2 latency, RTI variability, RT2 variability, and the Purdue pegboard (i.e., 4 of 6 analyses). In each case, the slope of the regression line is significantly greater (p < .05) for the bipolars. No significant interactions are obtained when the abbreviated version of the Andreasen scale is used. These results suggest that: (1) The Andreasen scale is confounded by trait measures of affective disturbance, as subgroups defined in terms of affective symptoms have different patterns of association between negative symptoms and laboratory performance; and (2) Use of the abbreviated scale for negative symptoms eliminates subgroub differences and thus yields more homogeneous data.
Negative Symptoms and RT." Controlling for Motor Speed Finally, the hierarchical regression analyses of negative symptoms and the RT variables were repeated, partialling (controlling for) tapping speed. This was done to test whether motor speed accounts for the association of negative symptoms and RT. The interaction terms remain unchanged with tapping speed as a covariate. Specifically, two of four interactions remain significant when the Andreasen scale is the dependent variable (p < .05), and all four interactions (RT1 and RT2 latency and variability) remain significant, using the abbreviated version of the Andreasen scale (19 < .05). The actual correlation of tapping speed and RT latency, however, is approximately .40 across conditions and across groups; while statistically significant, this degree of association accounts for only 16% of the variance. Similar findings have been reported by King (1954). Discussion Slowing and increased within-subject variability characterize the RT performance of schizophrenic patients (Schwartz et al., 1989). This study identifies negative symptoms as a clinical correlate of slowing and variability that is specific to schizophrenic patients. Interpretation of this finding follows two different lines of thought. Negative symptoms are one component of the deficit syndrome, which includes cognitive impairment and neuropsychological dysfunction (Owens & Johnstone, 1980; Silverstein & Artz, 1985). Neither intelligence nor neuropsychological performance, however, was specifically associated with the RT variables in the schizophrenic group. Nor did we find that the ratings of negative symptoms were confounded by clinical depression or neuroleptics (see, also Kay, Fiszbein, & Opler, 1987). Negative symptoms also have an adaptive function, in that withdrawal from environmental influence is one way of reducing arousal due to
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disruptive affects (Carpenter, et al., 1988). The present study does not bear directly on the withdrawal hypothesis; however, the results appear to be inconsistent with a deficit interpretation of the association of negative symptoms and RT. This conclusion may not apply to other samples. The patients studied in this setting were chronically ill but young and cognitively intact, in that no patient had an IQ less than 80 nor clinical or laboratory evidence of cerebral dysfunction. The other main issue is the role of attentional and m o t o r processes in the association of RT and negative symptoms in schizophrenia. Clinical ratings of attention impairment have been reported to be highly correlated with RT slowing (Green & Walker, 1984). In addition, the attention subscale of the Andreasen scale had the highest loading on a negative symptom factor in a large-scale investigation by Andreasen and Grove (1986). Nevertheless, three recent studies found no association between negative symptoms and laboratory measures o f attention (Harvey, 1987; Kay, et al., 1987; Walker, 1987), leading Kay, et al., (1987) to conclude that attention dysfunction is not a negative symptom. Against this backdrop, we found that controlling for m o t o r speed did not influence the specific association of RT and negative symptoms in the schizophrenic group. This would seem to leave us with the attentional hypothesis, as RT is a simple sensori-motor task without a significant cognitive or perceptual component. Nevertheless, the association of RT and negative symptoms in the schizophrenics was of the same magnitude in the simple RT condition (RT1) and the divided attention condition (RT2). The divided attention task, however, was associated with psychoticism, this is consistent with the finding that psychoticism is associated with Digit Span performance during distraction (Harvey, 1987; Walker, 1987). These different findings leave unclear the role of attention in our data. In retrospect, the use of finger tapping to control for m o t o r speed needs to be questioned. This control was included because of the reports by Rosofsky, et al., (1982) and Walker & Green (1982). It seems unlikely, however, that the m o t o r functions involved in finger tapping and RT are identical. Finger tapping is a ballistic response that requires alternating movements and continuous effort. The RT response requires acceleration of force in one direction and is discontinuous. A direct evaluation of the attentional hypothesis is currently underway and tests the association of negative and positive symptoms to the premotor and m o t o r components of the RT response, using a methodology developed by Vrtunksi and Mack (1982). The present study has 2 important methodological implications. First, the attenuated version of the Andreasen scale was less influenced by clinical depression, psychoticism, or the use of neuroleptics, yielded comparable correlations to the full scale with the RT variables, and was more effective in separating the schizophrenic and affective groups. The full Andreasen scale was also sensitive to subgroup differences, whereas the abbreviated version was not, yielding more homogeneous data within the schizophrenic and affective groups. Crow (1985) has suggested that the full Andreasen scale is likely to be confounded by depression and psychoticism, but also that flat affect and paucity of speech are the key symptoms of the negative state. Our findings support this view and simplify the rating of negative symptoms, as ratings of flat affect and paucity of speech are obtained through direct observation and are not dependent upon the patient's self-report. Second, the results suggest that negative symptoms refer to different processes across diagnostic groups. This
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c o n c l u s i o n is b a s e d o n t h e f i n d i n g t h a t n e g a t i v e s y m p t o m s w e r e c o r r e l a t e d w i t h R T performance only in the schizophrenic sample. Chaturvedi and Sarmukaddam (1986), however, reported that negative symptoms predict outcome in endogenous major depression. Additional empirical work seems warranted to clarify the clinical and laboratory correlates of negative symptoms in schizophrenia and affective disorders. Acknowledgement--This research was supported by the Westchester Division Research Fund. References Ammons, R. B., & Ammons, H. S. (1948). Full-Range Picture Vocabulary Test. Missoula, Montana: Psychological Test Specialists. Andreasen, N. C. (1982). Negative symptoms in schizophrenia: definition and reliability. Archives o f General Psychiatry 39, 784-788. Andreasen, N. C. (1987). The concept of negative symptoms: definition, specificity, and significance. Psychiatric and Psychobiologic 2, 240-249. Andreasen, N. C., & Grove, W. M. (1986). Evaluation of positive and negative symptoms in schizophrenia. Psychiatric and Psychobiologic 1, 108-121. Andreasen, N. C., & Olsen, S. (1982). Negative versus positive schizophrenia: Definition and validation. Archives o f General Psychiatry 39, 789-794. Buchanan, R. W., Kirkpatrick, B., Heinrichs, D. W., & Carpenter, W. T. (1990). Clinical correlates of the deficit syndrome of schizophrenia. American Journal o f Psychiatry 147, 290-294. Carpenter, W. T., Heinrichs, D. W., & Wagman, A. M. I. (1988). Deficit and nondeficit forms of schizophrenia: the concept. American Journal o f Psychiatry 145, 578-583. Chaturvedi, S. K., & Sarmukaddam, S. B. (1986). Prediction of outcome in depression by negative symptoms. A cta Psychiatrica Scandinavica 74, 183-186. Cohen, J., & Cohen, P. (1983). Applied multiple regression~correlation analysis f o r the behavior sciences, (2rid ed.). Hillsdale, New Jersey: Erlbaum. Crow, T. J. (1980). Molecular pathology of schizophrenia: more than one disease process? British Medical Journal 280, 66-68. Crow, T. J. (1985). The two-syndrome concept: origins and current status. Schizophrenia Bulletin 11,471-485. Goldberg, S. C., Schooler, N. R., & Mattsson, N. (1968). Paranoid and withdrawal symptoms in schizophrenia: relationship to reaction time. British Journal o f Psychiatry 114, 1161-1165. Green, M., & Walker, E. (1984). Susceptibility to backward masking in schizophrenic patients with positive or negative symptoms. American Journal o f Psychiatry 141, 1273-1275. Guy, W. (1976). ECDEU Assessment Manual f o r Psychopharmacology. Rockville, Maryland: National Institute of Mental Health. (Department of Health, Education, and Welfare Publ. No. [ADM] 76-338). Harvey, P. D. (1987). Laboratory research: its relevance to positive and negative symptoms. In P. D. Harvey & E. E. Walker (Eds.), Positive and negative symptoms in psychosis: description, research, and future directions (pp. 68-93). Hillsdale, New Jersey: Lawrence Erlbaum Associates. Kay, S. R., Fiszbein, A., & Opler, L. A. (1987). The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13 (2), 261-277. King, H. E. (1954). Psychomotor aspects o f mental disease: An experimental study. Cambridge, Mass.: Harvard University Press. Kopfstein, J. M., & Neale, J. M. (1972). A multivariation study of attention dysfunction in schizophrenia. Journal o f Abnormal Psychology 20, 294-298. Luria, A. R. (1966). Higher Cortical Functions in Man. New York: Basic Books. Mayer, M., Alpert, M., Stastny, P., Perlick, D., & Empfield, M. (1985). Multiple contributions to clinical presentation of flat affect in schizophrenia. Schizophrenia Bulletin 11, 420-426. Nuechterlein, K. H. (1977). Reaction time and attention in schizophrenia: A critical evaluation of the data and theories. Schizophrenia Bulletin 3, 373-428. Overall, J. E., & GoTham, D. R. (1962). The brief psychiatric rating scale. Psychological Reports 10, 799-812. Owens, D. G. C., & Johnstone, E. C. (1980). The disabilities of chronic schizophrenia--their nature and the factors contributing to their development. British Journal o f Psychiatry 136, 384-395. Pogue-Geile, M. F., & Harrow, M. (1984). Negative and positive symptoms in schizophrenia and depression: a follow-up. Schizophrenia Bulletin 10, 371-387.
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Rockland, L. H. (1986). Neuroleptic blood levels and clinical response. Canadian Journal o f Psychiatry 31,299-303. Rosofsky, 1., Levin, S., & Holzman, P. S. (1982). Psychomotility in the functional psychoses. Journal o f Abnormal Psychology 91, 71-74. Schwartz, F., Cart, A., Munich, R., Bartuch, E., Lesser, B., Rescigno, D., & Viegener, B. (1990). Voluntary motor performance in psychotic disorders: a replication study. Psychological Reports 66, 1223-1234. Schwartz, F., Carr, A. C., Munich, R. L., Glauber, S., Lesser, B., & Murray, J. (1989). Reaction time impairment in schizophrenia and affective illness: the role of attention. Biological Psychiatry 25, 540-548. Silverstein, M. L., & Artz, A. T. (1985). Neuropsychological dysfunction in schizophrenia: relation to associative thought disorder. The Journal o f Nervous and Mental Disease 173, 341-346. Sommers, A. A. (1985). Negative symptoms: Conceptual and methodological problems. Schizophrenia Bulletin 11, 364-379. Spitzer, R. L., & Endicott, J. (1979). Schedule f o r affective disorders (SADS). New York: New York State Psychiatric Institute. Spitzer, R. L., Endicott, J., & Robins, E. (1981). Research Diagnostic Criteria (RDC)for a selected group o f functional disorders. New York: New York State Psychiatric Institute. Strauss, J. S., Carpenter, W. T., & Bartko, J. J. (1974). The diagnosis and understanding of schizophrenia, Part II1: Speculations on the processes that underlie schizophrenic symptoms and signs. Schizophrenia Bulletin 11, 61-75. Vrtunski, P. B., & Mack, J. L. (1982). Microbehavioral properties of the choice reaction time response in young and old. Behavior analysis Letters 2, 161-170. Vrtunski, P. B., Simpson, D. M., Weiss, K. M., & Davis, G. C. (1986). Abnormalities of fine motor control in schizophrenia. Psychiatry Research 18, 275-284. Walker, E. (1987). Validating and conceptualizing positive and negative symptoms. In P. D. Harvey & E. E. Walker (Eds.), Positive and negative symptoms in psychosis: Description, research, and future directions (pp. 30-49). Hillsdale, New Jersey: Lawrence Erlbaum Associates. Walker, E., & Green, M. (1982). Motor proficiency and attentional-task performance by psychotic patients. Journal o f Abnormal Psychology 91, 261-268. Zahn, T. P., & Carpenter, W. T. (1978). Effects of short-term outcome and clinical improvement on reaction time in acute schizophrenia. Journal o f Psychiatric Research 14, 59-68.
0022-3956/91 $3.00 + .00 © 1991 PergamonPress plc
Printed in Great Britain.
NEGATIVE
SYMPTOMS AND REACTION
T I M E IN
SCHIZOPHRENIA F R E D S C H W A R T Z , R I C H A R D L . M U N I C H , A R T H U R C A R R , ELIZABETH B A R T U C H , BARBARA LESSER, DEBORAH RESCIGNO a n d
BARBARA VIEGENER
Department of Psychiatry, Cornell University Medical College, Westchester Division, The New York Hospital, New York, NY, U.S.A. ( R e c e i v e d 23 A u g u s t 1990; revised 26 N o v e m b e r 1990)
S u m m a r y - - T h i s study explored the association of negative symptoms and reaction time. Negative symptoms were specifically associated with reaction time slowing and variability in schizophrenics, but not in affective disorders. The finding of specificity did not extend to other measures of the deficit syndrome nor to motor performance. An abbreviated version of the negative symptom scale was especially effective in separating groups.
Introduction STUDIES relating laboratory measures and clinical symptoms provide a non-invasive method of identifying basic defects that may underly a patient's clinical presentation. The present study is in this tradition and relates reaction time (RT) variables to negative and positive symptoms. RT latency appears to be mostly independent of acute psychotic symptoms (Zahn & Carpenter, 1978). Two early studies reported modest but significant correlations between RT latency and symptoms of "withdrawal" (Kopfstein & Neale, 1972; Goldberg, Schooler, & Mattsson, 1968). Current interest in this topic was stimulated by a conceptual reorganization of the symptoms of schizophrenia by Strauss, Carpenter, & Bartko (1974). Subsequent empirical work by Crow (1980) and Andreasen and Olsen (1982) resulted in a considerable body of data linking negative symptoms to biological variables, cognitive deficits, and laboratory measures in schizophrenia. At the same time, it became apparent that negative symptoms were not specific to schizophrenia, occurring also in affective illness, and that ratings of negative symptoms may be confounded by clinical depression, psychotic withdrawal, and extrapyramidal side-effects (e.g., Andreasen, 1987; Carpenter, Heinrichs, & Wagman, 1988; Crow, 1985; Mayer, Alpert, Stastiny, Perlick, & Empfield, 1985; Sommers, 1985). This lack of specificity has led to a distinction between negative symptoms and a schizophrenic deficit state, the latter being due presumably to a deteriorating process that is neurosphysiological in aetiology. The deficit state has been defined in two ways; by the persistence of negative symptoms over time (Buchanan, Kirkpatrick, Heinrichs, & Carpenter, 1990); and by the co-occurrence of negative symptoms with cognitive impairment, soft neurological signs, and behavioral disorganization (Owens & Johnstone, Reprint requests to Dr. Fred Schwartz, 21 Bloomingdale Road, White Plains, New York 10605, U.S.A. 131
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1980). The longitudinal approach is consistent with the finding that negative symptoms mostly disappear over time in depressive disorders (Pogue-Geile & Harrow, 1984). Neither approach, however, controls for clinical depression, psychotic withdrawal, or neuroleptics. This study is cross-sectional in design and explores the association of RT and clinical symptoms in schizophrenics and affective disorders. Traditionally, RT slowing in schizophrenia has been interpreted as evidence of an attentional dysfunction (Nuechterlein, 1977). The RT response, however, is correlated with performance on m o t o r tests (Rosofsky, Levin, & Holzman, 1982; Walker & Green, 1982). It has since been shown that schizophrenics are slower than normal controls on the premotor and m o t o r components of the RT response (Vrtunski, Simpson, Weiss, & Davis, 1986). The proposed association between RT and negative symptoms may thus be due to attentional or motoric processes. To clarify this point, we include a measure of motor performance (finger tapping) to control for motor speed. We also include an experimental variation of the RT paradigm to increase the attentional demands of the task. We hypothesize that the association of negative symptoms and RT is specific to schizophrenia, and that such specificity is not found with positive symptoms. The relationship of the deficit syndrome to RT performance is partially evaluated by including a measure of intelligence for cognitive impairment and a measure of neuropsychological performance. We also evaluate the attentional hypothesis and the possible confounding effects of depression and neuroleptics. Method
Subjects Forty-eight schizophrenic inpatients and 80 major affective inpatients were drawn from an ongoing study of attentional and motor performance at this center. The patients were consecutive admissions, excluding those with a clinical diagnosis of organic brain syndrome; of those approached, 95°7o agreed to participate and gave informed consent before beginning the study. Diagnosis was based on a semi-structured interview and research diagnostic criteria (Spitzer & Endicott, 1979; Spitzer, Endicott, & Robins, 1981).
Procedures Negative symptoms were rated with Andreasen's scale (1982), using the sum of the global ratings from five subscales. The sum of the alogia and fiat affect scales was also abstracted, based on Crow's (1985) contention that the full scale is likely to be confounded by depression and psychoticism. The Brief Psychiatric Rating Scale (Overall & G o r h a m , 1962) was used to rate current clinical depression and psychoticism (the latter being the sum of the thought disturbance and paranoid factors, as defined by Guy, 1976). Two other features of the deficit syndome were evaluated--i.e., intelligence and neuropsychological deficits--to form a contrast with negative symptoms. Intelligence was tested using the Full Range Picture Vocabulary Test (Ammons & A m m o n s , 1948). Neuropsychological performance was measured on a 19-item battery (Luria, 1966), and included tests of motor, somatosensory, language, visual-spatial, and m e m o r y functions. Each subtest was rated on a four point scale.
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Visual RT was measured in milliseconds with fully automated equipment, using a Lafayette Instruments tone and light, programmable timer, digital clock, and printer. Subjects depressed a telegraph key to the tone with their forefinger and responded to the light by lifting their forefinger. The intertrial interval was 3s and the interstimulus interval (tone to light) was 2.5, 3.0, or 3.5s in a random order. Two conditions were employed: simple RT (hereafter designated RT1), and RT while subjects counted out loud by twos (hereafter designated RT2). The second condition tests divided attention and is more demanding (see Schwartz et al., 1989, for further details of the RT procedure). Two motor tests--finger tapping and the Purdue pegboard--were included to form a constrast with the RT conditions. Tapping speed was measured electronically using a handheld debouncer switch. Taps were obtained in five second bursts, five trials per hand, the score being the average for the two hands. Finger dexterity was measured with the Purdue pegboard assembly test, which requires sequential placement of a pin, washer, collar, and washer, alternating hands. Subjects completed eight assemblies twice. The score was the average time for both trials, recorded with a digital stopwatch (see Schwartz et al., 1990, for further details). Finger tapping was also included as a covariate in evaluating the relationship between RT and negative symptoms. Results Demographic and clinical characteristics of the sample are listed in Table 1. The two diagnostic groups differ on sex distribution, verbal intelligence, positive symptoms and the percentage of patients on neuroleptics (p < .05). No other group differences are significant. Table 1
Clinical and Demographic Characteristics of Sample Variable Sample size Mean age (SD) Sex Male Female Duration of illness (SD) Prior hospitalizations (SD) Verbal intelligence in percentiles (SD) Neuropsychological deficits (SD) Depression (SD) Negative symptoms Full Scale (SD) Partial Scale (SD) Psychoticism (SD) Neuroleptics
Schizophrenics
Affective controls
48 26.2 (6.0)
80 25.1 (5.3)
30 18 5.1 3.5 59.9 3.9 11.3
22 58 3.5 3.3 70.3 3.3 11.7
(5.4) (3.2) (24.5) (3.8) (4.1)
7.8 (4.5) 3.0 (2.3) 23.4 (8.2) 37
(4.1) (2.8) (22.7) (3.1) (3.7)
8.1 (5.6) 3.0 (3.0) 19.7 (7.6) 36
Diagnostic groups differed significantly on sex distribution, verbal intelligence, psychoticism, and use of neuroleptics.
Clinical Variables Table 2 lists the zero order correlations among the clinical variables for each diagnostic group. Two patterns emerge: (1) The deficit triad of negative symptoms, intelligence, and
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neuropsychological deficits is significantly interrelated in the schizophrenic group but not in the affective group; (2) The absolute size of the correlations between negative symptoms and depression, positive symptoms, and neuroleptics are all reduced in the schizophrenic sample when the abbreviated version of Andreasen's scale is used. These results support the presence of a deficit syndrome in schizophrenia and suggest that the abbreviated scale is less confounded by depression, neuroleptics, or psychoticism. The correlation of negative symptoms and neuroleptics requires some explanation. We compared patients on and off neuroleptics rather than using dose, as the relationship of blood levels to dose is not linear (Rockland, 1986). In correlating a dichotomy with a continuous variable, the statistic (a point biserial r) is at a maximum when the two groups are of equal size. This is approximately true for the affective group (45% on neuroleptics), but not for the schizophrenic group (77% on neuroleptics). The correlations reported in Table 2 do not support an association of negative symptoms and the use of neuroleptic medication in this sample, the findings being most compelling for the affective group. Table 2
Intercorrelations among Negative Symptoms, Depression, Verbal Intelligence, Neuropsychological Deficits, Positive Symptoms, and Neuroleptics in Schizophrenics and Affective Disorders Variable 1. 2. 3. 4. 5. 6. 7.
Neg. full Neg. partial Depression Intelligence Neuro Positive Neuroleptics
1
2 0.83*
0.85* 0.20 0.11 0.09 0.17 0.10
0.21 0.20 0.10 0.06 -0.10
3 0.40* 0.25 0.05 0.05 0.23* 0.11
4 -0.34* -0.28* 0.04 0.38* -0.06 0.00
5 0.37* 0.30* 0.40* 0.47* 0.14 0.16
6 0.26 0.08 0.50* -0.18 0.38*
7 0.22 0.10 0.43* 0.17 0.24 0.29*
0.23*
Upper right: schizophrenics ( N = 48). Lower left: affective disorders ( N = 80). *p < .05.
Table 3 lists the zero order correlations among the symptom variables and the laboratory measures for each group. The RT measures were first transformed into logarithms so as to minimize the effect of extremely large values on the distributions. Both measures of negative symptoms are associated with the RT variables and finger tapping in the schizophrenics; these correlations are mostly nonsignificant in the affective group. The pattern of results is that schizophrenics with high levels of negative symptoms are more likely to have slower RT's, be more variable, and tap at a slower rate. Positive symptoms in the schizophrenics have an adverse effect on the RT2 condition (latency and variability). An inspection of Table 3 also indicates that the association of negative symptoms and RT is not increased in the divided attention condition (RT2). Point biserial zero order correlations between neuroleptics (on versus off medication) and the RT variables were also computed for each group separately and account for .00 to .08% of the variance in any comparison. This effect is considered to be meaningless, in view of no clear evidence of a relationship between neuroleptics and negative symptoms in this study.
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Table 3
Intercorrelations among Symptoms and Laboratory Measures in Schizophrenics and Affective Disorders Variable
RT 1
RT2
Var I
Var2
Tap
Purdue
-0.29* -0.28** -0.21
0.26** 0.18 -0.18
- 0.14 - 0.22 - 0.05
- 0.08 - 0.02 - 0.05
Schizophrenics ( N = 48) N e g a t i v e (full scale) N e g a t i v e (partial) Positive
0.42* 0.47* 0.14
0.45* 0.44* 0.28**
0.24 0.37* 0.00
0.45* 0.45* 0.29*
A f f e c t i v e disorders ( N = 80) N e g a t i v e (full scale) N e g a t i v e (partial) Positive
0.20 0.26* 0.19"*
0.07 0.02 0.11
0.00 - 0.01 0.08
- 0.10 - 0.11 0.09
RT1 = s i m p l e RT; RT2 = R T d u r i n g divided a t t e n t i o n ; V a r l = RT1 w i t h i n - s u b j e c t variability; Vat2 = RT2 withinsubject variability; T a p = finger t a p p i n g ; P u r d u e = p e r f o r m a n c e o n the P u r d u e p e g b o a r d . *p < .05; **p > .05 < .10.
Negative Symptoms and R T: The Question of Specificity The critical question is whether the association of negative symptoms and the laboratory measures is significantly greater in the schizophrenic group than in the affective group. To test this, the correlation of negative symptoms with the Groups X RT interaction was separately computed for each pair of variables in hierarchial multiple regression analyses (Cohen & Cohen, 1983). A significant interaction signifies that the regression lines relating negative symptoms and RT are not parallel (and hence diverge) for the schizophrenic and affective groups. In these analyses, the variance due to the interaction term was pooled over men and women so as to control for sex differences in the two diagnostic groups. Using the full Andreasen scale, two of four interactions are significant (see Table 4), the variables being RT2 latency and variability. For the abbreviated Andreasen scale, all four RT variables are significant. These results demonstrate that the association of negative symptoms and RT is specific to the schizophrenic group. The results remain unchanged when clinical depression, as measured by the Brief Psychiatric Rating Scale, is included as a covariate. This is as expected, in view of the weak zero order correlations between negative symptoms and clinical depression (see Table 2). Table 4
Tests o f the Specificity o f the Association o f Negative Symptoms and R T Variables; Groups × R T Interaction f o r Full Scale o f Negative Symptoms and Partial Scale o f Negative Symptoms Full scale Variable RT1 RT2 RT1 RT2
mean mean variability variability
*p .05); (3) psychoticism is substituted for negative symptoms (p > .05); and (4) negative symptoms are the dependent variable and tapping speed and pegboard performance are alternately substituted for the RT variables (p > .05). Within the constraints of this study, these results demonstrate that the specific association of negative symptoms and RT in schizophrenia does not extend to other measures of the deficit syndrome, nor to postive symptoms, nor to m o t o r performance.
Subgroup Differences The possible role of depression on the association of negative symptoms and laboratory performance was further evaluated by exploring subgroup differences for the schizophrenic
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and affective patients separately. The schizophrenics were subdivided into a schizo-affective schizophrenic group and a purified schizophrenic group, using research diagnostic criteria. With the Andreasen scale as the dependent variable, the Groups × Measure interaction term is significant for RT1 latency, tapping speed, and the Purdue pegboard (i.e., 3 of 6 analyses). In each case, the slope of the regression line is significantly greater (p < .05) for schizophrenics with a major affective component to their illness. No significant interactions are obtained when the abbreviated version of the scale is substituted for the full Andreasen scale (p > .05). The affective disorders were subdivided into a bipolar group and a unipolar depressive group, using research diagnostic criteria. With the Andreasen scale as the dependent variable, the interaction term is significant for RT2 latency, RTI variability, RT2 variability, and the Purdue pegboard (i.e., 4 of 6 analyses). In each case, the slope of the regression line is significantly greater (p < .05) for the bipolars. No significant interactions are obtained when the abbreviated version of the Andreasen scale is used. These results suggest that: (1) The Andreasen scale is confounded by trait measures of affective disturbance, as subgroups defined in terms of affective symptoms have different patterns of association between negative symptoms and laboratory performance; and (2) Use of the abbreviated scale for negative symptoms eliminates subgroub differences and thus yields more homogeneous data.
Negative Symptoms and RT." Controlling for Motor Speed Finally, the hierarchical regression analyses of negative symptoms and the RT variables were repeated, partialling (controlling for) tapping speed. This was done to test whether motor speed accounts for the association of negative symptoms and RT. The interaction terms remain unchanged with tapping speed as a covariate. Specifically, two of four interactions remain significant when the Andreasen scale is the dependent variable (p < .05), and all four interactions (RT1 and RT2 latency and variability) remain significant, using the abbreviated version of the Andreasen scale (19 < .05). The actual correlation of tapping speed and RT latency, however, is approximately .40 across conditions and across groups; while statistically significant, this degree of association accounts for only 16% of the variance. Similar findings have been reported by King (1954). Discussion Slowing and increased within-subject variability characterize the RT performance of schizophrenic patients (Schwartz et al., 1989). This study identifies negative symptoms as a clinical correlate of slowing and variability that is specific to schizophrenic patients. Interpretation of this finding follows two different lines of thought. Negative symptoms are one component of the deficit syndrome, which includes cognitive impairment and neuropsychological dysfunction (Owens & Johnstone, 1980; Silverstein & Artz, 1985). Neither intelligence nor neuropsychological performance, however, was specifically associated with the RT variables in the schizophrenic group. Nor did we find that the ratings of negative symptoms were confounded by clinical depression or neuroleptics (see, also Kay, Fiszbein, & Opler, 1987). Negative symptoms also have an adaptive function, in that withdrawal from environmental influence is one way of reducing arousal due to
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disruptive affects (Carpenter, et al., 1988). The present study does not bear directly on the withdrawal hypothesis; however, the results appear to be inconsistent with a deficit interpretation of the association of negative symptoms and RT. This conclusion may not apply to other samples. The patients studied in this setting were chronically ill but young and cognitively intact, in that no patient had an IQ less than 80 nor clinical or laboratory evidence of cerebral dysfunction. The other main issue is the role of attentional and m o t o r processes in the association of RT and negative symptoms in schizophrenia. Clinical ratings of attention impairment have been reported to be highly correlated with RT slowing (Green & Walker, 1984). In addition, the attention subscale of the Andreasen scale had the highest loading on a negative symptom factor in a large-scale investigation by Andreasen and Grove (1986). Nevertheless, three recent studies found no association between negative symptoms and laboratory measures o f attention (Harvey, 1987; Kay, et al., 1987; Walker, 1987), leading Kay, et al., (1987) to conclude that attention dysfunction is not a negative symptom. Against this backdrop, we found that controlling for m o t o r speed did not influence the specific association of RT and negative symptoms in the schizophrenic group. This would seem to leave us with the attentional hypothesis, as RT is a simple sensori-motor task without a significant cognitive or perceptual component. Nevertheless, the association of RT and negative symptoms in the schizophrenics was of the same magnitude in the simple RT condition (RT1) and the divided attention condition (RT2). The divided attention task, however, was associated with psychoticism, this is consistent with the finding that psychoticism is associated with Digit Span performance during distraction (Harvey, 1987; Walker, 1987). These different findings leave unclear the role of attention in our data. In retrospect, the use of finger tapping to control for m o t o r speed needs to be questioned. This control was included because of the reports by Rosofsky, et al., (1982) and Walker & Green (1982). It seems unlikely, however, that the m o t o r functions involved in finger tapping and RT are identical. Finger tapping is a ballistic response that requires alternating movements and continuous effort. The RT response requires acceleration of force in one direction and is discontinuous. A direct evaluation of the attentional hypothesis is currently underway and tests the association of negative and positive symptoms to the premotor and m o t o r components of the RT response, using a methodology developed by Vrtunksi and Mack (1982). The present study has 2 important methodological implications. First, the attenuated version of the Andreasen scale was less influenced by clinical depression, psychoticism, or the use of neuroleptics, yielded comparable correlations to the full scale with the RT variables, and was more effective in separating the schizophrenic and affective groups. The full Andreasen scale was also sensitive to subgroup differences, whereas the abbreviated version was not, yielding more homogeneous data within the schizophrenic and affective groups. Crow (1985) has suggested that the full Andreasen scale is likely to be confounded by depression and psychoticism, but also that flat affect and paucity of speech are the key symptoms of the negative state. Our findings support this view and simplify the rating of negative symptoms, as ratings of flat affect and paucity of speech are obtained through direct observation and are not dependent upon the patient's self-report. Second, the results suggest that negative symptoms refer to different processes across diagnostic groups. This
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c o n c l u s i o n is b a s e d o n t h e f i n d i n g t h a t n e g a t i v e s y m p t o m s w e r e c o r r e l a t e d w i t h R T performance only in the schizophrenic sample. Chaturvedi and Sarmukaddam (1986), however, reported that negative symptoms predict outcome in endogenous major depression. Additional empirical work seems warranted to clarify the clinical and laboratory correlates of negative symptoms in schizophrenia and affective disorders. Acknowledgement--This research was supported by the Westchester Division Research Fund. References Ammons, R. B., & Ammons, H. S. (1948). Full-Range Picture Vocabulary Test. Missoula, Montana: Psychological Test Specialists. Andreasen, N. C. (1982). Negative symptoms in schizophrenia: definition and reliability. Archives o f General Psychiatry 39, 784-788. Andreasen, N. C. (1987). The concept of negative symptoms: definition, specificity, and significance. Psychiatric and Psychobiologic 2, 240-249. Andreasen, N. C., & Grove, W. M. (1986). Evaluation of positive and negative symptoms in schizophrenia. Psychiatric and Psychobiologic 1, 108-121. Andreasen, N. C., & Olsen, S. (1982). Negative versus positive schizophrenia: Definition and validation. Archives o f General Psychiatry 39, 789-794. Buchanan, R. W., Kirkpatrick, B., Heinrichs, D. W., & Carpenter, W. T. (1990). Clinical correlates of the deficit syndrome of schizophrenia. American Journal o f Psychiatry 147, 290-294. Carpenter, W. T., Heinrichs, D. W., & Wagman, A. M. I. (1988). Deficit and nondeficit forms of schizophrenia: the concept. American Journal o f Psychiatry 145, 578-583. Chaturvedi, S. K., & Sarmukaddam, S. B. (1986). Prediction of outcome in depression by negative symptoms. A cta Psychiatrica Scandinavica 74, 183-186. Cohen, J., & Cohen, P. (1983). Applied multiple regression~correlation analysis f o r the behavior sciences, (2rid ed.). Hillsdale, New Jersey: Erlbaum. Crow, T. J. (1980). Molecular pathology of schizophrenia: more than one disease process? British Medical Journal 280, 66-68. Crow, T. J. (1985). The two-syndrome concept: origins and current status. Schizophrenia Bulletin 11,471-485. Goldberg, S. C., Schooler, N. R., & Mattsson, N. (1968). Paranoid and withdrawal symptoms in schizophrenia: relationship to reaction time. British Journal o f Psychiatry 114, 1161-1165. Green, M., & Walker, E. (1984). Susceptibility to backward masking in schizophrenic patients with positive or negative symptoms. American Journal o f Psychiatry 141, 1273-1275. Guy, W. (1976). ECDEU Assessment Manual f o r Psychopharmacology. Rockville, Maryland: National Institute of Mental Health. (Department of Health, Education, and Welfare Publ. No. [ADM] 76-338). Harvey, P. D. (1987). Laboratory research: its relevance to positive and negative symptoms. In P. D. Harvey & E. E. Walker (Eds.), Positive and negative symptoms in psychosis: description, research, and future directions (pp. 68-93). Hillsdale, New Jersey: Lawrence Erlbaum Associates. Kay, S. R., Fiszbein, A., & Opler, L. A. (1987). The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13 (2), 261-277. King, H. E. (1954). Psychomotor aspects o f mental disease: An experimental study. Cambridge, Mass.: Harvard University Press. Kopfstein, J. M., & Neale, J. M. (1972). A multivariation study of attention dysfunction in schizophrenia. Journal o f Abnormal Psychology 20, 294-298. Luria, A. R. (1966). Higher Cortical Functions in Man. New York: Basic Books. Mayer, M., Alpert, M., Stastny, P., Perlick, D., & Empfield, M. (1985). Multiple contributions to clinical presentation of flat affect in schizophrenia. Schizophrenia Bulletin 11, 420-426. Nuechterlein, K. H. (1977). Reaction time and attention in schizophrenia: A critical evaluation of the data and theories. Schizophrenia Bulletin 3, 373-428. Overall, J. E., & GoTham, D. R. (1962). The brief psychiatric rating scale. Psychological Reports 10, 799-812. Owens, D. G. C., & Johnstone, E. C. (1980). The disabilities of chronic schizophrenia--their nature and the factors contributing to their development. British Journal o f Psychiatry 136, 384-395. Pogue-Geile, M. F., & Harrow, M. (1984). Negative and positive symptoms in schizophrenia and depression: a follow-up. Schizophrenia Bulletin 10, 371-387.
140
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Rockland, L. H. (1986). Neuroleptic blood levels and clinical response. Canadian Journal o f Psychiatry 31,299-303. Rosofsky, 1., Levin, S., & Holzman, P. S. (1982). Psychomotility in the functional psychoses. Journal o f Abnormal Psychology 91, 71-74. Schwartz, F., Cart, A., Munich, R., Bartuch, E., Lesser, B., Rescigno, D., & Viegener, B. (1990). Voluntary motor performance in psychotic disorders: a replication study. Psychological Reports 66, 1223-1234. Schwartz, F., Carr, A. C., Munich, R. L., Glauber, S., Lesser, B., & Murray, J. (1989). Reaction time impairment in schizophrenia and affective illness: the role of attention. Biological Psychiatry 25, 540-548. Silverstein, M. L., & Artz, A. T. (1985). Neuropsychological dysfunction in schizophrenia: relation to associative thought disorder. The Journal o f Nervous and Mental Disease 173, 341-346. Sommers, A. A. (1985). Negative symptoms: Conceptual and methodological problems. Schizophrenia Bulletin 11, 364-379. Spitzer, R. L., & Endicott, J. (1979). Schedule f o r affective disorders (SADS). New York: New York State Psychiatric Institute. Spitzer, R. L., Endicott, J., & Robins, E. (1981). Research Diagnostic Criteria (RDC)for a selected group o f functional disorders. New York: New York State Psychiatric Institute. Strauss, J. S., Carpenter, W. T., & Bartko, J. J. (1974). The diagnosis and understanding of schizophrenia, Part II1: Speculations on the processes that underlie schizophrenic symptoms and signs. Schizophrenia Bulletin 11, 61-75. Vrtunski, P. B., & Mack, J. L. (1982). Microbehavioral properties of the choice reaction time response in young and old. Behavior analysis Letters 2, 161-170. Vrtunski, P. B., Simpson, D. M., Weiss, K. M., & Davis, G. C. (1986). Abnormalities of fine motor control in schizophrenia. Psychiatry Research 18, 275-284. Walker, E. (1987). Validating and conceptualizing positive and negative symptoms. In P. D. Harvey & E. E. Walker (Eds.), Positive and negative symptoms in psychosis: Description, research, and future directions (pp. 30-49). Hillsdale, New Jersey: Lawrence Erlbaum Associates. Walker, E., & Green, M. (1982). Motor proficiency and attentional-task performance by psychotic patients. Journal o f Abnormal Psychology 91, 261-268. Zahn, T. P., & Carpenter, W. T. (1978). Effects of short-term outcome and clinical improvement on reaction time in acute schizophrenia. Journal o f Psychiatric Research 14, 59-68.
