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Archives of Clinical Neuropsychology, Vol. 10, No. 6, pp. 489-509, 1995 Copyright 1995 National Academy of Neuropsychology Printed in the USA. All fights reserved 0887-6177/95 $9.50 + .00

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Neurological Soft Signs in Schizophrenia: Are They Related to Negative or Positive Symptoms, Neuropsychological Performance, and Violence?
Claude M. J. Braun and Dominique Lapierre
l aboratoire de Neurosciences Cognitives (UQAM), and D~partement de Psycho/ogle, UniversiM du Quebec ~ Montreal, Montreal, Canada

Sheilagh Hodgins
D~partement de Psychologie, UniversiM de Montreal, Montreal, Canada

Jean Toupin
D~partement de Psycho-Education, Universit6 de 5herbrooke, 5herbrooke, Canada

Suzanne L6veill6 and C61ine Constantineau

Institut Psychiatrique Philippe Pinel, Montreal, Canada

This investigation was carried out on 31 unemployed schizophrenic outpatient men. The general purpose was to explore new aspects of neurological soft signs in schizophrenia. A 108-item version of the Nathan Kline Institute scale of soft signs, the Schedule for Affective Disorders and Schizophrenia psychiatric interview, the negative and positive symptom scale (PANSS), a comprehensive scale of life-time history of violence, and a large set of neuropsychological tests were administered, it was found that "motor" soft signs were significantly more prevalent than "sensory-perceptual'" signs, but that each body side manifested equal numbers of neurological

Address correspondence to: Dr. Claude M.J. Braun, PhD, Psychologie UQAM, C.P. 8888, Succ "A," Montr6al, P.Q., Canada, H3C 3P8.
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signs. Before and after statistical correction for age, education, alcoholism, drug abase disorder, and daily and cumulative neuroleptic dosage, orbitofrontal-type neuropsychological tasks measuring "impulsivity" related very robustly to the soft signs. Furthermore, before and after the same statistical corrections, right body-side signs correlated significantly with the same neuropsychological tests, whereas left bodyside signs did not. The PANSS scores and levels of lifetime violence generally did not correlate significantly with neurological soft signs. The latter negative findings, we think relate to the fact that these were relatively high-functioning (i.e., outpatient) schizophrenics. Overall, the results support notions of frontal lobe and left hemisphere involvement in schizophrenia, these two dysfunctional systems being apparently linked at the level of the orbitofrontal area of the brairL

The incidence of one or more neurological soft signs has been reported to be in the 45-88% range in schizophrenics in several dozen studies. Incidence in normals has been found to be around 5%. This difference between schizophrenics and normals has been found to be statistically significant (Cox & Ludwig, 1979; Rochford, Detre, Tucker, & Harrow, 1970). RELATIONS OF SOFT SIGNS IN SCHIZOPHRENICS WITH OTHER MEASURES Presence of soft signs in schizophrenia has frequently, though not always, been found to relate statistically significantly to negative more than positive symptoms (Buchanan, Kirkpatrick, Heinrichs, & Carpenter, 1990; Liddle, 1987; Merriam, Kay, Opler, Kushner, & Van Praag, 1990; but see Bartko, Zador, Horvath, & Herczeg, 1989, for a nonsignificant finding). Soft signs have also frequently been found to significantly correlate with some, but not all, nonlocalizing cognitive and neuropsychological tests (Kolakowska, Williams, Jambor, & Ardern, 1985; Krakowski, Convit, Jaeger, & Volavka, 1989; Liddle, 1987; but see Bartko et al., 1988, and Merriam et al., 1990 for generally nonsignificant results). Violence on or off psychiatric wards has been found to correlate with prevalence of soft signs (Adams, Meloy, & Moritz, 1990; Krakowski et al., 1989; Lewis, Shanok, Pinkus, & Glaser, 1979; but see Rochford et al., 1970). It has been proposed that frontal dysfunction could help explain neurological soft signs, as well as a negative symptom type, neuropsychological deficits, and even the predisposition to violence which is known to characterize schizophrenics even though most schizophrenics are not violent (Cox & Ludwig, 1979; Heinrichs, 1989; Liddle, 1987; Merriam et al., 1990; Trimble, 1987; Volkow, Wolf, & Van Gelder, 1987). On the other hand, authors focusing on neuropsychological tests have increasingly tended to emphasize findings of left hemisphere dysfunction on cognitive measures (see Bertrand, 1989, for a review). Metabolic and magnetic resonance brain imaging studies of schizophrenics have also supported the left-hemisphere dysfunction hypothesis (Rossi et al., 1990b; Simpson, Slater,

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Deakin, Rayston, & Skan, 1989; Suddarth, Casanova, Goldberg, & Daniel, 1989). Both the neuropsychological and brain metabolic data suggest a temporal lobe focus for the left hemisphere dysfunction effect. However, no study has yet adequately tested the hypothesis of a predominance of right body-side (left hemisphere) neurological soft signs in schizophrenics. Though the laterality of soft signs was not statistically tested by Nasrallah, Tippin, and McCaUey-Whitters (1983), these authors reported that there were, in fact, very slightly more than 11 lateralized signs on the left body side (47%) than right (45%) in their sample of schizophrenics; a difference which when tested with the Chi-Square (Goodness of Fit) test, is far from significant. Similarly, Buchanan and Heinrichs (1989) found that 14 lateralized signs were equally frequent at each body side (26% right, 28% left). In their samples of mixed and asocial schizophrenics, Quitkin, Rifkin, and Klein (1976) found 34 right-sided occurences and 31 left-sided occurences of six lateralized soft signs, a difference which was nonsignificant when tested by us with the Chi-Square Goodness of Fit test. Though several authors have compiled motor and sensory soft signs separately, none have ever tested a hypothesis of greater prevalence of one over the other in schizophrenia. The scale used by Quitkin et al. (1976) comprised 20 motor signs and 5 sensory signs. Their mixed and asocial schizophrenics, presented 99 of the former and 46 of the latter. We conducted a Chi-Square Goodness of Fit test on those data and found that the sensory signs were significantly (proportionally) more prevalent than the motor (p < .000). The scale used by Rochford et al. (1970) comprised six motor and four sensory signs. Incidence of each type of sign in their schizophrenic group was 17 and 14, respectively. The difference between these proportions did not reach significance when we tested them with the Chi-Square Goodness of Fit test. The scale used by Krakowski et al. (1989) comprised six motor and four sensory signs. There were 67 and 47 signs of each type in their schizophrenic sample, and we found that these observed frequencies were virtually identical to the theoretical (proportionally adjusted) frequencies in the Chi-Square Goodness of fit test (p = ns). Buchanan et al. (1989) used a scale with seven sensory and seven motor items. Their schizophrenics manifested more sensory (N = 39) than motor (N = 22) signs. When tested by us, this difference reached statistical significance (p < .05). Nasrallah et al. (1983) found proportionally more sensory than motor signs in their schizophrenic group. Their data were not presented in a manner allowing a statistical test of this difference. SHORTCOMINGS OF PREVIOUS STUDIES AND OBJECTIVES OF THE PRESENT INVESTIGATION Most, though not all, previous studies have comprised rather rudimentary scales of soft signs with 20 items or less. Negative and positive symptoms have often been measured with nonstandardized scales. Neuropsychological tests have usually consisted of standardized but nonlocalizing measures.

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Finally, violence has never been assessed by extensive interview (with crossverification) of life-long aggression. Rather, schizophrenic violence in neurologically and/or neuropsychologically oriented research reports has usually been operationalized either in terms of tallies of nonsystematic charted observations, or of systematic observation of violent behavior on the ward. No study has measured all of these dimensions in a schizophrenic sample. The present study was designed to overcome these shortcomings by using an extensive and standardized scale of neurological soft signs, including large numbers of motor and sensory-perceptual items forming potentially reliable subscales, and large numbers of right and left body-side items also forming potentially reliable subscales, a standardized scale of negative and positive symptoms, neuropsychological tests with at least some localizing validity (especially within the frontal lobes), and a complex and extensive assessment procedure of the subject's history of aggressive behaviors. The research hypothesis was that motor soft signs, right body-side soft signs, frontal lobe test measures, negative symptoms, and violent behavior would all be significantly intercorrelated in a schizophrenic sample.
METHOD
Subjects

A sample of 31 male outpatient schizophrenics was obtained from three psychiatric hospitals in Montreal. Ten received a primary diagnostic subcharacterization of paranoid schizophrenia, eight of undifferentiated schizophrenia, six of residual schizophrenia, and seven of schizo-affective schizophrenic psychosis, based on the Schedule for Affective Disorders and Schizophrenia (SADS) or Research Diagnostic Criteria (Endicott & Spitzer, 1978; Spitzer, Endicott, & Robins, 1978). Ten cases received a secondary diagnosis of alcohol abuse and/or dependence at least once in the past and 16 received a secondary diagnosis of drug abuse and/or dependence at least once in the past. Of the ten cases with an alcohol problem, seven also had a drug abuse problem. Inter-rater reliability for the diagnosis of schizophrenia was adequate (kappa coefficient of .92). Diagnosis of drug abuse and/or dependence or alcohol abuse and/or dependence yielded an interrater reliability kappa coefficient of .79. All were receiving several psychiatric medications at the time of testing, including neuroleptics in all cases. Mean chlorpromazine-equivalent daily dose was 808 mg (SD = 553, range = 67-2400 mg). These were patients very much stabilized in terms of medication regimen; the average duration of neuroleptic medication was 13 years (SD = 5.4). Excusion criteria consisted exclusively of the following: female sex (because schizophrenic violence floors in women), inpatient status (we were interested in patients with a stabilized disease process and neuroleptic maintenance doses), unwillingness to sustain several days of interviewing and testing, unavailability

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because of current employment, having a primary diagnosis other than schizophrenia or a secondary diagnosis of another psychosis (ex: manic-depressive), or of an organic disorder (i.e., dementing process), or of a systemic disease. A sample of 30 normal male subjects was obtained from advertisements in coin-wash parlors in Montreal. They were carefully screened for drug abuse, alcoholism, neurological or psychiatric background, and systemic disease. The normal group was matched for age and education with the group of schizophrenics (see Table 1).

Procedure
All subjects signed a consent form. Each of the schizophrenics was tested on several occasions while the normal subjects were tested in a single session.

Neurological Soft Signs

A 108-item version of the Nathan Kline Institute (NKI) neurological scale of soft signs was administered by two psychologists to the schizophrenic subjects only. These two clinicians were trained by a psychologist trained directly by the author of the NKI (Convit). Reliability and other clinical and psychometric properties of early versions of the scale have been reported by Brizer, Convit, and Krakowski (1987), Convit, Jaeger, and Lin (1988), and Krakowski et al.

TABLE 1 T-Test Comparisons of the Schizophrenic Group (N = 31) With the Normal Control Group (N = 30)

Group Matching Variables Variable Age (years) Education (years) Neuropsychological Variables Test Measure Verbal Fluency (correct words) Trail Making Test (Form A; seconds) Trail Making Test (Form B; seconds) WCST (perseverative errors) WCST (categories achieved) WCST (category breaks)

Mean

SD

Schizophrenic Control Schizophrenic Control

36 36 l0 11

6.09 9.67 2.74 2.75

.33 .71

.74 .48

Schizophrenic Control Schizophrenic Control Schizophrenic Control Schizophrenic Control Schizophrenic Control Schizophrenic Control

31.03 38.87 68.69 31.07 156.38 72.62 35.61 14.07 2.33 6.40 1.08 0.93

8.66 7.64 35.89 10.23 85.29 26.44 22.06 11.75 1.83 2.76 1.16 0.91

3.71 5.43 4.80 4.24 6.48 0.52

.000 .000 .000 .000 .000 .604

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(1989). The scale has several advantages over other scales of soft signs: (a) it contains a very large number and diversity of items, perhaps sufficient to overcome problems of ceiling effects in schizophrenics; (b) it contains a large number of items (39) which relate selectively and unequivocally to the left and to the right body side and also unequivocally to integrity of the contralateral brain hemisphere, supporting potentially reliable tests of hypotheses about lateralized brain dysfunction; and (c) it contains a sufficiently large number and diversity of sensory-perceptual signs (43) and motor signs (63) to support derivation of potentially reliable such subscales.
Negative and Positive Symptoms

The Positive and Negative Syndrome Scale (PANSS; Andreason, 1982) was administered by a psychologist to the schizophrenic subjects. This scale yields three scores which we used for subsequent anlayses, the negative symptom score, the positive symptom score, and the global psychopathology score which is the sum of the two previous scores. Inter-rater reliability and other clinical and psychometric properties of the scale have been reported by numerous researchers.
Neuropsychological Tests

A subset of neuropsychological tests was administered to both the normal and schizophrenic groups. The sole purpose of this exercise was to summarily establish the degree of cognitive impairment of the schizophrenic group. The measures derived from these tests included the number of correct words pronounced on the Controlled Oral Word Association Test, number of perseverative errors, category breaks, and categories-achieved on the Wisconsin Card Sorting Test, as well as time to completion on the Trail Making Test, forms A and B. Another subset of neuropsychological tests was administered to the schizophrenic subjects only in view of exploring in greater detail profiles of deficits and more particularly, relationships between these profiles and other dependent measures of this study. The measures derived from these neuropsychological tests included the quantitative performance score and qualitative error score (pencil lifts and wall traversals) on the Porteus Mazes test, the performance level and "inertia" (error) score (McFie & Thompson, 1972) on the Picture Arrangement scale of a French Canadian WAIS analog (Barbeau & Pinard, 1963), and performance on the Rey-Osterrieth Complex Figure Test. Finally, a stimulus-discrimination or go/no-go reaction time task was implemented by us on a microcomputer. The task consisted of a set of 150 trials requiring the subject to respond by pressing the space bar to either a white square or a buzz sound as fast as possible. Visual target location was equiprobable for each screen quadrant, and each type of stimulus (square or buzz) was also equiprobable. Once this simple reaction time condition was completed in view of creating a positive response bias, the subject was required to respond by a space bar press only to

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the squares and to refrain from responding to the buzz during a set of 50 trials structured as previously. Median reaction time of correct responses and number of commission errors on this latter task were retained for further analysis. This selection of neuropsychological tests was made in view of supporting tests of local brain dysfunction within and outside of the frontal lobes. For example, certain measures of impulsivity have been most closely associated with orbitofrontal damage: the qualitative score on the Porteus Mazes has been linked to orbitofrontal dysconnection in leukotomy cases by Crown (1952), Gow and Ward (1982), Tow (1955), Petrie (1952), and Porteus (1942). Commission errors on a go-no-go task have been associated with orbitofrontal and orbitomesiofrontal tumoral lesions by Drewe (1975). Though their intrafrontal localization is less clear, there is evidence that mental sluggishness, as indexed by low verbal fluency and high inertia on the Picture Arrangement test, result as much from mesial frontal (primarily tumoral) damage as from dorsolateral frontal damage (H6caen & Ruel, 1981; McFie & Thompson, 1972). In a classical study, Milner (1964) showed that the perseverative error score on the Wisconsin Card Sorting Test is significantly higher in lobectomy patients with dorsolateral than orbitofrontal resections. Finally, Eslinger and Grattan (1990) have shown that the performance score on the Rey-Osterreith Complex Figure Test (presumably consisting of visuo-spatial integration) depends slightly more heavily on posterorolandic than antero-rolandic cortex.

Assessment of Violent Behavior

Psychiatric files, official criminal records and in-depth interviews of the schizophrenic patients and of staff were used to complete the Aggressivess Protocol (Grille de l'Histoire d'Agression: Tremblay & Hodgins, 1988). This protocol was designed to assess aggressive behavior across the life span. After exploration of numerous violence-related variables drawn from this protocol, it was found that they were all significantly intercorrelated. Consequently, only one of them, namely "number of incidents of aggressive behavior causing injury to another person" was retained for analysis. Inter-rater reliability in the determination of "incidents of aggressive behavior causing injury to another person" was adequate (a kappa of .96). Though the schizophrenic group was more violent (33% had been sentenced) than normal subjects, the former group was not explicitely selected on the basis of violent behavior.

Psychiatric Assessment
The French-language version of the Schedule for Affective Disorders and Schizophrenia (SADS; Endicott & Spitzer, 1978; Spitzer et al., 1978), a standardized interview comprising a large number of questions, was administered in an individual interview by a clinical psychologist previously trained to use this instrument. This protocol was used to determine diagnoses (see Subjects section).

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Methodological Considerations The first objective of this study was to determine, summarily but precisely, the overall level of cognitive impairment of the schizophrenic group. The tests used for this purpose have frequently been used to describe deficits in schizophrenics and serve here only to demonstrate that this sample of patients is a neuropsychologically "typical" group of outpatient schizophrenics. Table 1 presents comparisons of the scores of the normal and schizophrenic subjects on the neuropsychological tests. To clarify the importance of disparate clinical variables in potential modulation of the tests of the hypotheses, univariate correlations were calculated on the schizophrenics only. For example the global score on the NKI scale of soft signs correlated in the following manner with the following variables: age of schizophrenia onset, r = 33; lifelong number of psychiatric hospitalizations, r = -. 12; total duration of such hospitalizations, r = -.08; current age, r = .22; current education, r = -.15; presence or absence of alcoholism, r = .23; presence or absence of drug abuse disorder, r = .37; daily chlorpromazine-equivalent neuroleptic dose, r = .06; duration of neuroleptic medication, r = -.03. None of these coefficients reached statistical significance individually. Neurological Soft Signs A second objective was to determine the incidence of neurological soft signs in the schizophrenic sample using a large number of varied items. Table 2 presents the percentage of schizophrenic subjects found to manifest the mild to severe forms of each soft sign. Our identification of "left" and "right" bodyside items and of "motor" and "sensory-perceptual" items is also presented in Table 2. Table 3 presents the scores of the schizophrenic subjects on subscales of the NKI scale of neurological soft signs. In order to test hypotheses of prevalence of motor over sensory-perceptual signs and of signs on the right over the left body-side, theoretical frequencies adjusted for number of items on each scale were computed, and Chi-Square Goodness of Fit tests calculated. Motor signs (N = 162) were significantly more (proportionally) prevalent than sensory signs (N = 69; chi-square = 12.09, df= 1, p < .000). The prevalence of "right" body-side signs (N = 83) was less than that of "left" body-side signs (N = 90). This difference did not reach statistical significance however (chi-square = 3, df= 1, p = ns). Psychopathology and I/iolence The Wilcoxon signed ranks test revealed no difference in soft signs between the subgroups of schizophrenics by subcharacterization of the primary (SADSC) diagnosis. Table 4 presents the negative/positive symptom scale results, the

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TABLE 2 The NKI Scale of Neurological Soft Signs, Identification of Sensory, Motor, Right and Left Body-Side Signs, and Percentages of the Schizophrenic Group (N = 31) Manifesting Each Sign
Item Description Lateral Dominance Right-Left Orientation (RH) Right-Left Orientation (LH) Right-Left Orientation (RH-RE) Right-Left Orientation (LH-LE) Right-Left Orientation (RH-LE) Right-Left Orientation (LH-RE) Patient-Examinor Right-Left Orientation Pupillary Reaction Nystagmus Eye Pursuit Peripheral Field Vision (Unilateral) Peripheral Field Vision (Bilateral) Facial Asymmetry Rinne Auditory Test (RE Error) Rinne Auditory Test (LE Error) Weber Auditory Test (RE Error) Weber Auditory Test (LE Error) Tongue Asymmetry Romberg Test Right Foot Hopping Left Foot Hopping Standing Balance Gait-Associated Movement Gait Asymmetry Strength Asymmetry Arm Drift RH Finger-Nose (eyes open) LH Finger-Nose (eyes open) RH Finger-Nose (eyes closed) LH Finger-Nose (eyes closed) RH Finger-Thumb LH Finger-Thumb RH Finger-Thumb (overflow) LH Finger-Thumb (overflow) Bilateral Finger-Thumb (RH error) Bilateral Finger-Thumb (LH error) RH Pronation-Supination LH Pronation-Supination Bilateral Pronation-Supination (RH error) Bilateral Pronation-Supination (LH error) Right Foot Taps Left Foot Taps Right Foot Taps (overflow) Left Foot Taps (overflow) Bilateral Foot Taps (R error) Bilateral Foot Taps (L error) Right Heel to Shin Left Heel to Shin Tandem Gait Reflexes (asymmetry) Reflexes (amplitude) Sensory/Motor M S S S S S S S M M M S S M S S S S M M M M M M M M m M M M M M M M M M M M M M M M M M M M M M M M M M Right/Left % 16/1 0 0 0 0 6.5 0 12.9 9.7 3.3 0 0 0 3.2 3.2 0 3.4 17.2 0 0 0 6.5 0 0 0 0 48.4 0 0 22.6 25.8 3.2 3.2 0 0 3.2 0 3.2 0 6.5 6.5 0 0 0 0 6.4 6.4 3.2 6.5 35.5 0 10.7

R L R L

R L

R L R L R L R L R L R L R L R L R L R L R L

(continued on next page)

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TABLE 2 (Continued)

Item Description Leg Clonus Response (R) Leg Clonus Response (L) Babinski Sign (R) Babinski Sign (L) Left Face/Right Hand Extinction (R error) Left Face/Right Hand Extinction (L error) Right Face/Left Hand Extinction (R error) Right Face/Left Hand Extinction (L error) Face-Face Extinction (R error) Face-Face Extinction (L error) Hand-Hand Extinction (R error) Hand-Hand Extinction (L error) Graphesthesia (#1) RH Graphesthesia (# 1) LH Graphesthesia (#3) RH Graphesthesia (#3) LH Graphesthesia (#7) RH Graphesthesia (#7) LH Graphesthesia (#8) RH Graphesthesia (#8) LH Astereognosis (Key) RH Astereognosis (Key) LH Astereognosis (quarter) RH Astereognosis (quarter) LH Astereognosis (comb) RH Astereognosis (comb) LH Aslcereognosis (penny) RH Astereognosis (penny) LH Fist-Ring Alternation (RH) Fist-Ring Alternation (LH) Fist-Edge-Palm (RH) Fist-Edge-Palm (LH) Fist-Edge-Palm (RH overflow) Fist-Edge-Palm (LH overflow) RH-LH Fist-Stretch Alternation (RH error) RH-LH Fist-Stretch Alternation (LH error) RH-LH Fist-Stretch Alternation (RH overflow) RH-LH Fist-Stretch Alternation (LH overflow) Right-Face/Right Hand Left-Face/Left Hand RH Palmomental Test LH Palmomental Test RH Grasp Reflex LH Grasp Reflex Patient-Examinor Orientation (RH-LE) Patient-Examinor Orientation (LH-RE) Patient-Examinor Orientation (RH-LK) Patient-Examinor Orientation (LH-RK) Patient-Examinor Tongue Orientation Complex Sequencing (to auditory cues) Complex Sequencing (to visual cues) Immediate Recall (10 words)

Sensory/Motor M M M M S S S S S S S S S S S S S S S S S S S S S S S S M M M M M M M M M M S S M M M M S S S S S M M

Right/Left

% 0 0 0 5.3 0 0 3.2 0 0 0 0 3.2 6.5 3.2 16.1 25.8 41.9 25.8 25.8 24.1 0 0 0 0 O 0 0 3.2 3.2 9.7 32.3 35.5 45.2 51.7 0 0 0 3.2 0 0 0 0 0 0 12.9 12.9 6.5 6.5 22.6 22.6 6.7 27.5

R L R L R L R L R L R L R L R L R L R L R L R L R L R L R L R L R L R L

R L R L

Note. RH = right hand; LH = left hand; RE = right ear; LE = left ear; RK = right knee; LK = left
knee; S = sensory-perceptual; M = motor; R = right; L = left.

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TABLE 3

499

Means, Standard Deviations, Ranges, and Coefficients of Variation of the Subscales of the NKI

Scale NKI "Motor" Subscale (number of signs) NKI "Sensory" Subscale (number of signs) NKI "Right Body-Side" Subscale (number of signs) NKI "Left Body-Side" Subscale (number of signs)
absence of a sign regardless of whether it is mild or severe.

M
5.23 2.23 2.64 3.00

SD
2.83 1.52 1.85 1.52

Range 0-15 0-6 0-8 0-6

CV 54.28 68.34 70.08 50.91

Note. These scores are not based on the NKI standard scoring system. They reflect presence or

n e u r o p s y c h o l o g i c a l test results, and the l e v e l s o f a g g r e s s i v e b e h a v i o r in the schizophrenic group.

Relations Between Neurological Soft Signs, Neuropsychological Tests, Psychopathology Ratings, and Violence
T h e principal o b j e c t i v e o f this i n v e s t i g a t i o n was to d e s c r i b e relationships b e t w e e n n e u r o l o g i c a l soft signs and other schizophrenic characteristics, neur o p s y c h o l o g i c a l p e r f o r m a n c e s , n e g a t i v e and p o s i t i v e s y m p t o m s , a g g r e s s i v e b e h a v i o r with special reference to distinction b e t w e e n " m o t o r and sensory-perceptual," and " b o d y - s i d e " o f soft signs. To this end, correlational analyses o f the overall score on the N e u r o l o g i c a l Soft Sign Scale (NKI) as well as right and left body-side subscales and sensory-perceptual and m o t o r subscales on the one hand, with the a b o v e - m e n t i o n e d variables on the other hand, were carried out.

TABLE 4 Means, Standard Deviations, and Ranges of Measures Obtained From the Schizophrenic Group (N = 31)

Measure Standardized Score on the NKI (neurological soft signs) Negative Symptom Scale of the PANSS Positive Symptom Scale of the PANSS Score on the Psychopathology Scale of the PANSS Porteus Mazes (qualitative score) Commission Errors on the Go/No-Go Reaction Time Task Inertia Score on the Picture Arrangement Test Porteus Mazes (quantitative score) Quantitative Score on the Rey Complex Figure Picture Arrangement Test (scaled score) Lifetime Number of Assaults on Another Person Lifetime Duration of Hospitalization (days) Average Age at Time of First Hospitalization (years)

M
9.90 14.32 12.54 26.86 40.00 9.80 4.93 121.54 60.87 6.55 7.83 1401.58 23

SD
6.48 5.86 5.26 9.00 24.67 15.03 3.52 28.20 9.72 2.35 5.20 896.70 4.58

Range 2-36 7-26 7-25 16-56 8-89 0-74 0-15 70-170 35-72 4-13 2-27 72-3416 17-32

Note. Typical scores of schizophrenic chronic inpatients on the positive, negativ,e and global
psychopathology subscales of the PANSS are 21.57, 22.90, and 43.56, respectively (Kay, Opler, & Fiszbein, 1987). Typical scores of acute inpatient cases are 18.44, 19.96, and 39-48 (Kay, Opler, & Lindenmayer, 1988).

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Though we demonstrated previously that clinical variables do not significantly relate to soft signs univariately, it remains plausible that multivariate associations do reach significance. For example, simple bivariate correlation analysis does not control for age and education simultaneously, which may significantly affect neuropsychological test performance (Braun & Lalonde, 1990). Partial correlations, in which the effects of age and education variance were statistically removed, were therefore computed (see Table 5). Because severe alcohol and drug abuse can also introduce several complicating sources of variance (subject selection bias, neuropsychological deficits, addict-career violence, etc.; Parsons, Butters, & Nathan, 1987), these latter variables were also both partialed-out using partial correlation analysis (see Table 5). Finally, since neuroleptic medication level has been found by a few authors to correlate with neurological soft signs and cognitive tests (King, Wilson, Cooper, & Waddington, 1991; Merriam et al., 1990), daily chlorpromazine-equivalent neuroleptic intake variance was also partialed out of the correlations simultaneously with duration of the medication (see Table 5). The same analytical structure was used to explore the significance of the four new NKI subscales (motor, sensory, left, and right) in relation to the psychiatric scales, neuropsychological tests, and violence-related variables. These coefficients are presented in Tables 6-9. DISCUSSION Neuropsychological Functional Level of the Schizophrenics This sample of schizophrenics was highly significantly impaired at the general cognitive neuropsychological level (see Goldstein, 1986, for a review and Taylor & Abrams, 1987). Neurological Soft Signs Every schizophrenic of the present study manifested at least two neurological soft signs. This should not however be construed to mean that these patients were more neurologically impaired than those described in other studies. The larger number of items of the NKI scale is probably primarily responsible for this effect. The mean standardized score on the NKI (9.9) is indicative of a "moderate" level of impairment. The finding of a relatively high incidence of soft signs in the schizophrenics in the present study will be useful because it indicates that the NKI Scale can be used in correlational analyses in future studies because it has been shown to have no ceiling effect (patients with no signs). Sensory and Motor Soft Signs Contrary to previous studies, we found that motor signs were much more prevalent, very significantly so, than sensory-perceptual signs. However, this issue will

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TABLE 5 Significant Correlations and/or Partial Correlations Between Standard Global Scores on the NKI Scale of Neurlogical Soft Signs and Other Measures

R Neuropsychological Test Measures Qualitive Errors (Porteus Mazes) Commission Errors (go/no-go procedure) Perseveration Errors (WCST) Quantitative Performance (Porteus Mazes) Picture Arrangement Performance (WAIS) Time-to-Completion TMT (form A) Inertia Score (Picture Arrangement-WAIS) Categories Achieved (WCST) Clinical Scales Aggressiveness Protocol .43* .80*** .50** -.40* .40* .51 * .20 -.38 -.37*

Rp 1 .40 .80*** .47 .34 -.37 .47 .12 -.34 -.37*

Rp2 .47 .46 .26 -.28 -.44 .50* .65** -.41 -.24

Rp3 .49 .48 .29 -.30 -.47 .49 .66** -.66** -.42

Notes. All other measures presented in the procedure section correlated nonsignificantly with
the NKI global score. R = Pearson correlation; Rpl = partial correlation with age and education variance removed; Rp2 = partial correlation with alcoholism and drug abuse disorder variance removed; Rp3 = partial correlation with chlorpromazine-equivalent neuroleptic daily dose and cumulative dose variance removed. Alpha levels are corrected for number of variables for each partial correlation only. *p <.05; ** = p <.01; *** =p <.001.

n o t b e r e s o l v e d u n t i l t h e f o l l o w i n g s t u d y is c a r r i e d out. A l a r g e s a m p l e o f schizophrenics and o f n o r m a l controls will h a v e to be assessed with a n extensive scale o f neurological soft signs. Prevalence o f soft signs will h a v e to b e d e t e r m i n e d b y statistical c o m p a r i s o n o f schizophrenics with normals, thereby ruling o u t sources o f bias (such as easier or harder items in o n e or the other category o f soft signs). M o s t p r o t a g o n i s t s o f a " f r o n t a l l o b e " deficit in s c h i z o p h r e n i a p r o p o s e prefrontal (dorsolateral and/or orbitomedial) involvement rather than frontal

TABLE 6 Significant Correlations and/or Partial Correlations Between Motor Signs of the NKI Scale of Neurological Soft Signs and Other Measures

Neuropsychological Test Measure Qualitative Errors (Porteus Mazes) Commission Errors (go/no-go procedure) Categories Achieved (WCST) Picture Arrangement Performance (WAIS) Time-to-Completion (TMT Form A) Inertia Score (Picture Arrangement-WAIS)

R .53** .75** -.49* -.37* .47** .34

Rp 1 .48 .72*** -.42 -.33 .40 .26

Rp2 .52* .65** -.41 -.43 .03 .38

Rp3 .62** .57* -.54* -.39 .28 .52*

Notes. All other measures presented in the procedure section correlated nonsignificantly with
the NKI global score. R = Pearson correlation; Rpl = partial correlation with age and education variance removed; Rp2 = partial correlation with alcoholism and drug abuse disorder variance removed; Rp3 = partial correlation with chlorpromazine-equivalent neuroleptic daily dose and cumulative dose variance removed. Alpha levels are corrected for number of variables for each partial correlation only. *p < .05; ** = p <.01; *** = p <.001.

502

C. M. J. Braun et al. TABLE 7 Significant Correlations and/or Partial Correlations Between Sensory Signs of the NKI Scale of Neurological Soft Signs and Other Measures

NeuropsychologicalTest Measure Qualitative Errors (Porteus Mazes) Time-to-Completion(TMT Form A) Categories Achieved (WCST) Commission Errors (go/no-go procedure)

R .35 .28 -. 18 .37

Rpl .41 .37 -.27 .38

Rp2 .45 .55* -.51 * .55*

Rp3 .59* .25 -.52* .57*

Notes. All other measures presented in the procedure section correlated nonsignificantly

with the NKI global score. R = Pearson correlation; Rpl = partial correlation with age and education variance removed; Rp2 = partial correlation with alcoholism and drug abuse disorder variance removed; Rp3 = partial correlation with chlorpromazine-equivalent neuroleptic daily dose and cumulative dose variance removed. Alpha levels are corrected for number of variables for each partial correlation only. *p < .05.

motor or premotor involvement (see introduction). Levin (1984) has proposed that the now well known eye movement impairment in schizophrenia can best be interpreted as a premotor dysfunction and that this impairment is characteristic o f the negative subtype. However, Levin was careful not to suggest that this particular specific functional-anatomic system is capable o f explaining the overall neurological or neuropsychological profile o f schizophrenics. There are very few, if any, "neurological signs" o f prefrontal damage. Indeed, prefrontal lesions are typically neurologically "silent." Their functional identification requires complex higher order tests. This is why the inclusion o f prefrontal tests in studies of soft signs in schizophrenia might be important and revealing. Our finding of highly significant impairment of the schizophrenics on the Wisconsin Card Sorting Test, and the finding of significant predominance of "motor" signs over "sensory" signs suggests frontal involvement. However, after correction for neuroleptic dose, the motor and sensory subscales both cor-

TABLE 8 Significant Correlations and/or Partial Correlations Between Left Body-Side Signs of the NKI Scale of Neurological Soft Signs and Other Measures

NeuropsychologicalTest Measure Commission Errors (go/no-go procedure) Reaction Time (go trials of go/no-go procedure)

R .48** .44*

Rpl .41 .43

Rp2 .47 .22

Rp3 .41 .45

Notes. All other measures presented in the procedure section correlated nonsignificantly

with the NKI global score. R = Pearson correlation; Rpl = partial correlation with age and education variance removed; Rp2 -- partial correlation with alcoholism and drug abuse disorder variance removed; Rp3 = partial correlation with chlorpromazine-equivalent neuroleptic daily dose and cumulative dose variance removed. Alpha levels are corrected for number of variables for each partial correlation only. *p<.05; ** =p<.01.

Neurological Soft Signs in Schizophrenia

TABLE 9 Significant Correlations and/or Partial Correlations Between Right Body-Side Signs of the NKI Scale of Neurological Soft Signs and Other Measures

503

NeuropsychologicalTest Measure Qualitative Errors (Porteus Mazes) Commission Errors (go/no-goprocedure) Quantitative Performance(Porteus Mazes) Picture ArrangementPerformance (WAIS) Time-to-Completion(TMT Form A) Categories Achieved (WCST)

R .56** .59* -.43* -.37* .50** -.35

Rpl

Rp2

Rp3 .68** .59* -.35 -.22 .25 .55*

.55* .67** .63** .55* -.40 -.25 -.40 -.14 .53* .22 -.35 -.51 *

Notes. All other

measures presented in the procedure section correlated nonsignificantly with the NKI global score. R = Pearson correlation; Rpl = partial correlation with age and education variance removed; Rp2 = partial correlation with alcoholism and drug abuse disorder variance removed; Rp3 = partial correlation with chlorpromazine-equivalent neuroleptic daily dose and cumulative dose variance removed. Alpha levels are corrected for number of variables for each partial correlation only. *p < .05; ** =p < .01.

related with the "orbitofrontal" tests contra-indicating interpreting the deficit patterns as involving only the frontal lobes. Finally, it is worthy of note that only one schizophrenic obtained a clean slate on the motor subscale of the NKI. Likewise, only one case obtained an error-free score on the sensory subscale presented here. This means that there was absolutely no ceiling effect on these measures. Furthermore, as can be gleaned from Table 3, the coefficients of variation of these two subscales is comfortingly low, suggesting that these subscales are probably reasonably reliable, and can certainly be used for clinical classification.

Right and Left Body-Side Soft Signs

The present results confirm those of most previous studies which have not revealed a preponderance of right body-side soft signs. Interestingly, however, right body-side neurological soft signs correlated significantly with the same neuropsychological test measures as the global score on the NKI Scale, whereas left body-side neurological soft signs did not. Does this signify that there is no preponderance of left hemispheric disorder in schizophrenia? Or is the left-hemisphere dysfunction effect rather not fully reflected in neurological soft signs? The left hemisphere dysfunction in schizophrenia, visible in neuropsychological test results and metabolic imaging, might, for example, be largely hereditary, whereas neurological soft signs could well be more a consequence of perinatal complications. Alternatively, left hemisphere dysfunction and neurological soft signs might reflect the incapacitation of different neural systems, probably more cortical in the former (and even temporal-lobe based) and more subcortical (and to a lesser extent sensorimotor cortex-based) in the latter. Interesting tests of these issues would

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include (a) a twin study comprising the appropriate neuropsychological tests and a scale of neurological soft signs, and (b) a metabolic imaging study comprising the appropriate neuropsychologicai tests and a scale of neurological soft signs. Despite what precedes, it appears that right body-side neurological signs are more closely related to cognitive brain-based impairment in schizophrenia than are left body-side neurological signs. This provides some further and new support for a "left hemisphere dysfunction" model of schizophrenia.

Soft Signs and Negative~Positive Symptoms

Scores on scales of negative and of positive symptoms were not significantly related to the sum total of neurological soft signs in the present study. The nonsignificant relationships were, however, consistently in a direction concordant with previous reports: The negative symptom scale was positively related, and the positive symptom scale negatively related to soft signs. Reports of significant relationships between neurological soft signs and symptom types have come from studies of chronic inpatients, rather than outpatients such as those assessed in the present investigation.

Soft Signs and Neuropsychological Tests

Before and after statistical correction for extraneous variance (age and/or education, alcohol and/or drug abuse, neuroleptic daily and/or cumulative dose), all the neuropsychological test measures correlated with neurological soft signs in a direction indicating that impairment on one is related to impairment on the others. The correlational approach used in Tables 5-9, did not entirely control for number of comparisons (i.e., type 1 error). To remedy this, we treated the 12 neuropsychological measures as 12 tosses of a coin. All twelve coefficients gave a valence indicating that soft signs are linked with neuropsychological impairment. In the absence of a meaningful overarching trend to this effect, six exceptions out of twelve would have been expected. The appropriate binomial probability test of 12 consecutive heads (or tails) being tossed, in a row, gives a probability o f p = .001. The pattern of these correlations, some of which were highly significant, suggests frontal lobe involvement in the global score of the NKI scale of neurological soft signs. The primary cognitive deficit related to general presence of soft signs seems to be one of behavioral impulsivity. Cognitive perseveration, of which perseverative errors on the Wisconsin Card Sorting Test are only one of a multitude of types (Daigneault, Braun, & Whitaker, 1992), and cognitive inertia seem to be generally only weakly related to presence of soft signs. These findings suggest that orbitofrontal systems are dysfunctional (go/no-go errors and rulebreaking behavior), and that this dysfunction is a major cortical correlate of soft signs in schizophrenia.

Neurological Soft Signs in Schizophrenia Soft Signs and Violence

505

There was a nonsignificant relationship between the frequency of aggressive behavior and neurological soft signs in the present study. This could well be due to sampling. Indeed, in studies where such a relationship was found, subjects were either more violent or more psychotic (chronic, deteriorated, etc.).

Methodological and Clinical Considerations in Schizophrenic Soft Signs

In the present study, neurological soft signs (the global standard NKI score) did not significantly correlate with past alcoholism (r = .23), age of onset of schizophrenia, severity of psychopathology (Psychopathology scale of the PANSS), or neuroleptic daily or cumulative dose. Age and education were also unrelated to neurological soft signs. However, having received a diagnosis of drug abuse and/or dependence came very close to significance (r = .37, p < .051). These variables, including drug abuse, have usually been found to relate nonsignificantly to neurological soft signs in schizophrenia (Bartko et al., 1989; Gureje, 1988; Kennard, 1960; Kolakowska et al., 1985; Liddle, 1987; Merriam et al., 1990; Quitkin etal., 1976; Rochford et al., 1970; Rossi et al., 1990a; Woods, Yurgelun, & Kinney, 1987. Exceptionally, Tucker and Silberfarb (1978) found a significant relationship between a general psychopathology rating and soft signs. Kolakowska et al. (1985) found a significant relationship between duration of illness and soft signs. King etal. (1991) found a very strong correlation between neurological soft signs and tardive dyskinesia, psychopathology, negative symptoms, positive symptoms, and treatment duration in a group of 16 chronic schizophrenic inpatients, suggesting that these "methodological" issues remain controversial and are worthy of further investigation. Tardive dyskinesia was not measured in the present study. It remains possible that neurological soft signs in schizophrenia are an early indicator of tardive dyskinesia, whether neuroleptic-induced or not.

Soft Signs and Neuroleptic Medication

Attempts have often been made in schizophrenia research to convert multiple sets of medication to a common reference (usually chlorpromazine) and to determine the contribution of this "composite" to effects of interest. We found no relationship between soft signs and neuroleptic dally or cumulative dose. Furthermore, the Wilcoxon signed ranks test revealed no difference in number of soft signs between patients receiving antiparkinsonian medication (n = 26) and patients not receiving them (n = 5). The numerous previous analyses of the relationship between neuroleptic drug dosage and overall neurological soft signs have nearly always indicated it to be nonsignificant (see the review by Heinrichs & Buchanan, 1988). Another data base indicating that some determination of neurological soft signs is not medication-related is the now well established set of demonstrations of significant occurence of soft signs in unmedicated

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children of schizophrenics. Likewise, Quitkin and colleagues (1976) found that large numbers of unmedicated schizophrenic adults manifested high levels of neurological soft signs. Buchanan and Heinrichs (1989) also found no difference between medicated and unmedicated schizophrenics. Finally, in a retrospective study, Ricks and Berry (1970) found that schizophrenics were more at risk for having had neurological soft signs as children than normals. However, Merriam et al. (1990) did find a significant relationship between neuroleptic drag dose and neurological soft signs in schizophrenics. King et al., (1991) also reported a significant relation between neuroleptic dose and soft signs. These authors did not control for severity of disease, either by sampling or by statistical correction. Consequently, the likelyhood that this relation of neuroleptics to soft signs was confounded by severity of the disease is very high, leaving open the possibility (and even the plausibility) that neuroleptic drugs, themselves, are an insignificant source of soft signs.
Impulsivity and Soft Signs in Other Neurological and Psychiatric Disorders

It would be misguided to claim that any kind of prefrontal dysfunction, or presence of soft signs, is a specific characteristic of schizophrenia. On the one hand, focal prefrontal lesions in general (Stuss & Benson, 1986), and focal orbitofrontal lesions in particular (Damasio, Tranel, & Damasio, 1990; Malloy, Bihrle, Duffy, & Cimino, 1993), do not typically result in schizophrenic symptoms, Diffuse traumatic injury usually involving orbitofrontal damage (Braun, Daigneanlt, & Champagne, 1989) also does not usually result in schizophrenic symptoms. Furthermore, several other psychiatric disorders characterized by extreme impulsivity as well as "prefrontal" deficits, such as hyperactivity (Mattes, 1980) and psychopathy (Lapierre & Braun, 1993) are not noticeably associated with schizophrenia. Finally, links between orbitofrontal-like impulsivity and soft signs have also been observed in several other psychiatric conditions such as antisocial personality (Quitldn et al., 1976), learning disabilities and hyperactivity (see Shaffer, O'Connor, Sharer, & Prupis, 1983), and mania (Nasrallah et al., 1983). REFERENCES Adams,J. J., Meloy,J. R., & Moritz,M. S. (1990).Neuropsychologicaldeficitsand violentbehavior in incarceratedschizophrenics.Journal of Nervous and Mental Disease, 178(4), 253-256. Andreasson,N. C. (1982). Negativevs. positiveschizophrenia:Definitionand validation.Archives of General Psychiatry, 39, 789-794. Barbeau, G. L., & Pinard,A. (1963).l~preuve individuelle d'inteUigence gdndrale: Manuel abrdgd. Montreal:lnstitutde RecherchesPsychologiques. Bartko, G., Zador, G., Horvath, S., & Herezeg, I. (1989). Neurological soft signs in chronic schizophrenicpatients:Clinicalcorrelates.Biological Psychiatry, 24(4), 458-460. Bertrand,L (i989). Asymttriefonctionnellehtmisphtriqueetrtbraleet entittspsyehopathologiques (Cerebral hemisphericfunctionalasymmetryand psychopathologicalentities). Psychologic Mddicale, 21, 2115-2118.

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