Fine motor performance before and after treatment in schizophrenic and schizoaffective patients

Psychiatr_v Research,

ElsevieriNorth-Holland

5, 247-255 (1981)

247

Biomedical Press

Fine Motor Performance Before and After Treatment Schizophrenic and Schizoaffective Patients David J. Goode, Alexander and Barry Williams Received

A. Manning,

in

John F. Middleton,

April 21, 1981: revised version received July 26. 1981; accepted August

3, 1981.

Abstract. Twenty-three hospitalized patients with schizophrenia or schizoaffective disorder were tested for fine motor performance by the Crawford Small Parts Dexterity Test (CSP) and a measure of finger tapping (FT) after a l-week medication-free period. In an attempt to evaluate potential impairment of fine motor performance, these patients were retested after 1 month’s treatment with antipsychotic medication. Thirty-eight control subjects were tested and retested after 1 month by the same procedures. On medication, patients showed no decrement of performance on either test. A small practice effect was observed in both patients and control subjects between initial and second testing. Unmedicated patients had significantly lower CSP and FT scores than control subjects. On repeated testing, medicated patients also had significantly lower scores than control subjects. In the patient group, CSP and FT scores during medication were not related to dosage of medication, use of antiparkinsonian agents, or ratings of motor side effects. CSP and FT scores were significantly and inversely correlated with Brief Psychiatric Rating Scale (BPRS) subscale ratings of withdrawalretardation (R-subscale). FT performance was positively correlated with the schizophrenia (S-subscale) of the BPRS. Global improvement, as measured by change in BPRS total score, was significantly related to improvement in CSP scores, Impairment in fine motor performance after 1 month’s treatment with antipsychotic agents could not be documented. The impairment in fine motor performance in drug-free patients may be in part related to deficits of attention and cooperation. However, other deficits in motor performance have been reported in schizophrenic patients. Failure to identify fine motor impairment produced by psychotropic drugs may be related to competing effects of improved attention and motor impairment of extrapyramidal effects. Key Words. Fine motor performance, schizophrenia, extrapyramidal side effects, antipsychotic drugs. Fine motor performance is impaired by extrapyramidal treatment (Haase, 1961; Simpson et al., 1972; Sovnerand

schizoaffective

effects

disorder,

of antipsychotic

drug

DiMascio, 1978). However, a number of studies have documented the occurrence of motor abnormalities in unmedicated schizophrenic patients. Abnormalities of smooth pursuit eye tracking are present in both schizophrenic patients and their first-degree relatives (Holzman et al., 1973, 1974, 1976; Cegalis and Sweeney, 1979; Holzmanet al., 1980). Abnormalities of the Hoffmann reflex recovery curve have been reported in schizophrenic patients

David H. Goode. M.D.. and Barr) Williams are at Department 01 Psychiatr). Bowman Gray School of Medicine, Winston-Salem, NC 27103, U.S.A. Dr. Goode is also at Broughton State Hospital, Morganton, NC, U.S.A., as are Alexander A. Manning, Ph.D., and John F. Middleton, M.A. (Reprint requests to Dr. D.J. Goode at Bowman Gray School of Medicine.) 0165-1781/81/0000-0000/$02.75

@Elsevier/North-Holland

Biomedical

Press

248

(Crayton et al., 1975; Goode et al., 1977, 1979a, 1979b), as well as changes in the recovery curve produced by antipsychotic medication (Monaco and Eliseo, 1964; Crayton et al., 1975; Goode et al., 1977, 1979b). Neurological abnormalities (Torrey, 1980) and deficits on neuropsychological testing (Rochford et al., 1970) have been reported on evaluation of schizophrenic patients. Abnormalities of perceptual motor development have been observed in children of schizophrenic mothers (Fish et al., 1965; Fish and Hagin, 1973). Objective evaluation of fine motor performance is further complicated by the deficits of attention and lack of cooperation in schizophrenic patients (Nuechterlein, 1977; Wohlberg and Kornetsky, 1973). We have measured fine motor performance before and after treatment with antipsychotic medication in patients with schizophrenia and schizoaffective disorder. We wished to document impairment of fine motor performance produced by antipsychotic medication in this group of patients. However, significant deficits in fine motor performance were found to be present in untreated patients compared to controls, and a slight improvement in performance occurred after medication.

Materials

and Methods

The 23 patients were hospitalized on the Clinical Research Unit of the Broughton State Hospital (see Table I for diagnostic and demographic data). Diagnoses were based on the Research Diagnostic Criteria of Feighner et al. (1972). Patients were referred to the unit because of failure to respond to conventional treatment during current hospitalization or history of several recent hospitalizations. They were withdrawn from all medications and placed on placebo for 1week.

Table 1. Diagnostic Demographic

and demographic

Control subjects

data

24F 38

Sex

Race Age (mean ? SD)

12M 2ow 25.3 + 3.9 18-32

Age range Diagnosis Schizophrenia, chronic Disorganized type Paranoid type Undifferentiated type

Patients 4F 38

14M 33w 32.0 + 9.4 19-40

(n = 9)

Schizoaffective disorder (n = 141 Acute, manic type, mainly schizophrenic Subchronic, depressed type, mainly affective Chronic, depressed type, mainly schizophrenic Chronic, manic type, mainly schizophrenic Chronic, depressed type, mainly affective Chronic, manic type, mainly affective Total

data

1 4 4

1 1 7 1 3 1 23

Initial testing was performed on the last day of the placebo week. Patients were then placed on thiothixene, loxapine, or molindone with order of presentation systematically rotated. Dosage of each agent was systematically increased to a maximum dose over a IO-day period until

249 appearance of a therapeutic response or of significant side effects. Antiparkinsonian medication was used if necessary to control extrapyramidal symptoms (EPS) when troublesome to the patient. Patients were maintained for 28 days on the medication. Clinical evaluation of psychopathology by the Brief Psychiatric Rating Scale (BPRS) (Overall and Gorham, 1962) was performed on the 7th day of the placebo week and on the 28th day of medication. Crawford Small Parts Dexterity (CSP) and finger tapping (FT) testing were performed on the same days. Patients were questioned and observed as to the presence or absence of five types of EPS during each week of medication: muscle spasms, restlessness, stiffness, tremor, and abnormal movements of mouth and tongue. Part 1 of the CSP consists of a task in which subjects are required to use tweezers to place small metal pins in holes and to place a metal collar around each pin. Beginning with the preferred hand, subjects completed one 3-minute trial with each hand. The score for each hand was the total number of items assembled. Mean scores of right and left hand were computed and used for the present study. FT scores were determined using the device employed in the Reitan Finger Oscillation Test. All subjects began with the preferred hand and then alternated hands until four IO-second trials were completed for each hand. A 15-second intertrial interval was employed. Mean tapping speed was computed for each hand, and then the mean value of both hands was computed and used for the present study. Thirty-eight control subjects, generally hospital employees, between the ages of 18 and 40, were solicited as volunteers. All control subjects had no personal or primary family history of mental illness, no history of recent (1 week) psychoactive drug use, and were free of neurological disease. Control subjects were administered the CSP and FT tests on two occasions approximately 1 month (t 1 week) apart.

Results I presents results of CSP testing in control subjects and patients. Initial and second testing sessions in control subjects are compared to placebo and postdrug testing sessions in patients. Second testing of control subjects revealed a small practice effect, with an increment in mean CSP performance from 19.4 to 2 1.6. Similarly, mean values for CSP performance of patients increased from 11.4 during placebo to 12.8 while on medication. Although sex ratios of patients and control subjects were different, there was no significant difference in CSP performance between male and female control subjects (t = 1.54, df = 36, NS). Performance on CSP was significantly poorer among psychiatric patients than controls on both initial (t = -11.46, n =48, p < 0.001) and second (t = -9.40, n = 48, p < 0.001) testing. In fact, there was little overlap in CSP scores between the patient and control groups. Fig. 2 presents results of FT testing in control subjects and patients. Initial and repeated testing sessions in control subjects are compared to placebo and postdrug testing sessions in patients. Second testing of control subjects revealed a practice effect with an increment from 47.1 to 50.0 in mean values. A similar increment in mean performance was observed on repeated testing of patients on medication (placebo mean, 34.9; drug mean, 40.2). On initial FT testing, male control subjects performed significantly better than female subjects (t = 7.45, df = 36, p < 0.01).For this reason, male subjects were compared separately from female subjects. On initial testing, male patients performed significantly more poorly than male control subjects (t = 6.6 1, df = 21, p < 0.01)and female patients performed more poorly than female control subjects (t = 16.82, df = 30, p < 0.01). On second testing, male patients also performed more poorly than male control subjects (t = 4.93, df = 18, p < 0.01) and female patients performed more poorly than female control subjects (t = 7.64, df = 21, p < 0.01). Fig.

250 Fig. 1. Crawford

Small Parts (CSP) scores of control subjects and patients . .

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am O.0

__._

a& A.

--z-.

e r

.

. :

. . .

: 0 ”

” Y ” ______

A__ Am . . . .

”

. ” . .

A A Initial Repeat Testing Control

Subjects

A A Placebo Drug Testing Patient

Subjects

Repeated testing in control subjects was performed 4 weeks after initial testing. Drug testing was performed after 4 weeks of active medication in the patient group.

Table 2 relates occurrence of EPS to CSP and FT performance in medicated patients. Analysis of variance revealed no significant difference in CSP and FT scores in patients with different numbers of EPS observed. CSP and FT performance in medicated patients was not correlated with dose of medication, expressed as percent of maximum dose for each medication (for CSP: r = -0.290, n = 20, NS; for FT: r = -0.136, n = 18, NS). CSP and FT scores were related to ratings of psychopathology on placebo testing of patients. These relationships are presented as correlation coefficients in Table 3. Global psychopathology as measured by total scores of the BPRS was not related to either CSP or FT performance. The withdrawal-retardation(R) subscale of the BPRS was significantly and inversely correlated with both CSP and FT performance, such that higher R scores were associated with lower CSP and FT scores. The schizo-

251 Fig. 2. Finger Tapping

(FT) scores of control subjects and patients a

8

I

A_

.

1 f.

__

_

..

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:

t

88

_ A__ f

__s__

1:

.

:

:

.

0L

*

Initial Testing Control

A Repeat

Sublects

A A Placebo Drug Test1 ng Patient

Subjects

Repeated testing in control subjects was performed 4 weeks after initial testing. after 4 weeks of active medication in the patient group

Drug testing was performed

phrenia (S) subscale of the BPRS was not related to CSP performance significantly and positively correlated with FT scores. The paranoid depression-anxiety (D) subscales were not related to CSP or FT performance. improvement, as measured by change in total BPRS scores from placebo to tion period, was significantly correlated with increases in CSP scores (r=0.574, p < 0.05) but not FT scores (r = 0.155, n = 13, NS).

but was (P) and Clinical medican = 14,

Discussion The present data do not support either an inhibitory or facilitatory effect of the antipsychotic agents studied on fine motor performance after 1 month’s treatment in psychotic patients. A small improvement in both CSP and FT performance was observed after medication, but this was of approximately the same magnitude as the

252 practice effect observed in control subjects on repeated testing after 1 month. CSP and FT scores on second testing were not related to reports of EPS by medicated patients or to dosage of medication. Extrapyramidal effects of the tested antipsychotic agents had no observable deleterious effects on fine motor performance in the patient population studied. It is possible that deleterious effects of antipsychotics are present but are counterbalanced by augmenting effects mediated through an increase in cooperation and attention associated with clinical improvement. This hypothesis is supported by the observation that improvement in FT performance from placebo to medication testing was significantly correlated with global clinical improvement as measured by the total BPRS score. Table 2. Relation of extrapyramidal symptoms and FT oerformance of medicated oatientsl

(EPS) to CSP

Degree of EPS

CSP

FT

None reported Mean SD n

9.75 4.87 6

39.80 ii.98 5

One EPS present Mean SD n

15.20 4.48 5

40.25 7.42 2

Two or ,nore EPS present Mean SD n

13.4 4.23 4

42.58 3.99 6

2.06 2,13 0.17

0.16 2,lO 0.85

ANOVA df iJ

F value

1. Five EPS were rated clinically

CSP and FT performance during placebo and after medication in patients was significantly poorer than that in control subjects on initial and repeated testing, respectively. The discrepancy of performance between patients and control subjects on the CSP was large. On placebo testing, only 4 of 22 patients (18%) had CSP scores within the range observed in initial testing of control subjects. The CSP is a more complex test than the FT. The subject must pick up small rods by means of tweezers, insert them in a hole, and then retrieve a collar from another compartment with the tweezers and place it around the rod. Performance is the number of completions over a fixed 3-minute trial period with each hand. FT consists of repetitive depression of a counter in three trials with each hand. Although both tests are subject-paced, CSP requires considerably more attention and coordination than FT. Function on both tests was significantly impaired in the patient group. Attentional factors do not appear to be of primary importance, since differential effects on the two tests would have been observed had this been the case. Thus, our data indicate that fine motor performance is impaired in untreated schizophrenic patients. This is consistent with the findings of a

253 range of motor performance defects in schizophrenia: abnormalities of smooth pursuit eye movements (Holzman et al., 1973, 1974, 1976; Cegalis and Sweeney, 1979), spinal reflex abnormalities (Crayton et al., 1975; Goode et al., 1977, 1979a, 19796) abnormalities of perceptual motor development (Fish et al., 1965; Fish and Hagin, 1973), and neurological abnormalities (Torrey, 1980). Table 3. Relation of psychopathology as measured by BPRS and subscales to CSP and FT performance in patients on placebo BPRS psychopathology rating Total BPRS

score

Correlation coefficients relating BPRS scores to FT CSP 0.062 jn= 19)

0.136 in = 16)

R-subscale

-0.4511 (n = 19)

-0.5952 (n = 16)

S-subscale

0.196 in = 19)

0.5891 (n = 16)

P-subscale

0.061 (n = 19)

0.119 (n = 16)

D-subscale

-0.074 in = 191

0.049 in = 16)

1. p'

0.05.

2. D < 0.01.

CSP and FT performance was related to clinical ratings of psychopathology. The relationship between lower CSP and FT scores and higher ratings on the R-subscale of the BPRS is understandable, since motor retardation is one of three items contributing to the R-subscale. However, the other items of blunted affect and emotional withdrawal are unrelated to observed motor activity. The positive correlation between FT performance and the S-subscale of the BPRS is very interesting. The S-subscale comprises conceptual disorganization, hallucinatory behavior, and unusual thought content. The opposite relation would have been predicted - an association between schizophrenic psychopathology and impaired motor performance. It is possible that the finding is purely a chance observation, but patients with the symptom complex reflected by high scores on the S-subscale may represent a subpopulation of patients with schizophrenia and schizoaffective disorder who have less motor impairment. Patients with predominantly negative symptomatology and lack of such positive symptoms have been identified as pharmacologically distinct (Gerlach and Luhdorf, 1975; Chouinard and Jones, 1980). In summary, motor performance, as measured by CSP and FT, was impaired in hospitalized, psychotic patients. Severity of illness may have been a factor in the observed motor impairment, as all patients were severely ill as judged by failure to respond to treatment before referral to the clinical research unit. Factors of impaired attention and lack of cooperation with testing are at least partially related to the

254

impaired performance. Impaired CSP and FT performance were significantly correlated with lower R-subscale scores on BPRS. However, the positive relation between FT performance and higher scores on S-subscale ratings remains problematic. Antipsychotic drugs had no demonstrable deleterious effects on either CSP or FT performance. In fact, an increase in performance on both tests was observed in patients from placebo to medication testing. This increase was of similar magnitude to the practice effect observed on retesting of control subjects. Ratings of EPS and medication dose were unrelated to either CSP or FT performance under conditions of medication. Acknowledgment. the North Carolina Acknowledgment is Broughton Hospital,

This work was supported in part by the Small Grant Program of Division of Mental Health and Developmental Disabilities. made to the clinical staff of the Clinical Research Unit of the under Miss Maggie Ware and Mrs. Sarah Cash for patient care.

References Cegalis,

J.A.,

Biological

and Sweeney, J.A. Eye movements Psychiatry,

in schizophrenia:

A quantitative

analysis.

14, 13 (1979).

Chouinard, G., and Jones, B.D. Neuroleptic-induced supersensitivity psychosis: Clinical and pharmacologic characteristics. American Journal of Psychiatry, 137, 16 (1980). Crayton, J.W., Meltzer, H.Y., and Goode, D.J. Motor neuron instability in psychotic patients, Presented at Annual Meeting of the Society for Biological Psychiatry, New York (1975). Feighner, J.P., Robins, E., Guze, S.B., Woodruff, R.A., Winokur, G., and Munoz. R. Diagnostic criteria for use in psychiatric research. Archives of General Psl*chiatr>,, 26, 57 (1972).

Fish, B., and Hagin, R. Visual-motor General

Psychiatry,

disorders

in infants at risk for schizophrenia.

ilrchi\aes qf

28, 900 (1973).

Fish, B., Shapiro, T., Halpern, F., and Wile, R. The prediction ofschizophrenia in infancy: 111. A ten-year follow-up report of neurological and psychological development, American Journal

of Psychiatry.

121, 768 (1965).

Gerlach, J., and Luhdorf, K. The effect of L-dopa on young patients with simple schizophrenia, treated with neuroleptic drugs. Psychopharmacologia, 44, 105 (1975). Goode, D.J., Manning, A.A., and Middleton, J.F. Cortical laterality and asymmetry of the Hoffmann reflex in psychiatric patients. Presented at the Annual Meeting of the Society for Biological Psychiatry, Chicago, IL (1979a). Goode, D.J., Meltzer, H.Y., Crayton, J.W., and Mazura, T.A. Physiologic abnormalities of the neuromuscular system in schizophrenia. Schizophrenia Bulletin, 3, 121 (1977). Goode, D.J., Meltzer, H.Y., and Mazura, T.A. Hoffmann reflex abnormalities in psychotic patients. Biological Psychiatry, 14, 95 (1979b). Haase, H.J. Extrapyramidal modification of fine movement-A “conditio sine qua non” of the fundamental therapeutic action of neuroleptic drugs. Revue Canadienne de Biologic, 20,425 (1961). Holzman, P.S., Kringlen, E., Levy, D.L., and Haberman, S.J. Deviant eye tracking in twins discordant for psychosis. Archives of General Psychiatry. 37, 627 (1980). Holzman, P.S., Levy, D.L., and Proctor, L.R. Smooth pursuit eye movements, attention, and schizophrenia. Archives of General Psychiatry, 33, 1415 (1976). Holzman, P.S., Proctor, L.R., and Hughes, D.W. Eye-tracking patterns in schizophrenia. Science, 181, 179 (1973). Holzman, P.S., Proctor, L.R., Levy, D.L., Yasillo, N.J., Meltzer, H.Y., and Hurt, S.W. Eye-tracking dysfunctions in schizophrenic patients and their relatives. ArchiLses qfGenera1 Psvchiatry, 31, 143 (1974). Monaco, P., and Eliseo, M. Neurophysiological analysis of spinal excitability in psychiatric patients. Revista di Parologia Nervosa e Mentale, 85, 69 (1964).

255

Nuechterlein, K.H. Reaction time and attention in schizophrenia: A critical evaluation of the data and theories. Schizophrenia Bulletin, 3, 373 (1977). Overall, J.E., and Gorham, D.R. The Brief Psychiatric Rating Scale. Ps_whological Repurts, 10, 799 (1962). Rochford, J.M., Detre, T., Tucker, G.J., and Harrow, M. Neuropsychological impairments in functional psychiatric diseases. Archives of General Psychiatry, 22, 114 (1970). Simpson, G.M., Beckles, D., Isalski, Z., and Lee, J.H. Some methodological considerations in the evaluation of drug-induced extrapyramidal disorders: A study of EXIO-029. a new morphantridine derivative. Journal of Clinical Pharmacology, 12, 142 (1972). Sovner, R., and DiMascio, A. Extrapyramidal syndromes and other neurological side effects of psychotropic drugs. In: Lipton, M.A., DiMascio, A., and Killam, K.F.. eds. Psj,chopharmacology: A Generation of Progress. Raven Press, New York, p. 1021 (1978). Torrey, E.F. Neurological abnormalities in schizophrenic patients. Biological PsJ,chiatr.\,. 15. 381 (1980). Wohlberg, G.W., and Kornetsky, C. Sustained attention in remitted schizophrenics. Archir,es of General

Psychiatry,

28, 533 (1973).