The Neurologic
Examination in Adult
Of the proliferating approaches to neuropsychiat-
ric assessment, a relatively neglected technique is
the venerable, accessible, noninvasive, and inex-
pensive neurologic examination. This article or-
ganizes and synthesizes the literature on neuro-
logical findings in adult psychiatric patients.
Problems in conducting and interpreting research
in this area are examined, clinically pertinent em-
pirical findings are surveyed, and directions for
future investigation are outlined. Most of the
“soft signs” can be reliably evaluated, and many
have been validated against other techniques. Sev-
eral psychiatric diagnoses are associated with im-
paired neurologic performance. Prognosis and
treatment selection may also be informed by neu-
rologic findings. The neurologic exam should be
regarded as a collection of neurobiologic probes
rather than as a single irreducible variable. Future
work must better establish interrater and test-
retest reliability of individual elements of the neu-
rologic exam in psychiatric populations and focus
on developing the clinical utility of individual and
combined elements of the neurologic exam.
(The Journal of Neuropsychiatry and Clinical
Neurosciences 1998; 10:395–404)
JOURNAL OF NEUROPSYCHIATRY
Psychiatry: From Soft
Signs to Hard Science
Richard D. Sanders, M.D.
Matcheri S. Keshavan, M.D.
T he neurologic examination has two general func-
tions in psychiatry. The first, screening for major
neurological disease, is accomplished with an exami-
nation emphasizing such “hard” or “major” signs as re-
flex and motor asymmetry and the Babinski reflex. The
results of each component of the screening examination
can be described dichotomously as normal or abnormal.
These results reflect the presence or absence of neuro-
pathology, particularly that which is focal and acquired
later in development. This article deals with the second
objective of the psychiatric neurologic exam: evaluating
performance decrements in psychiatric patients without
identifiable neurologic disorders. This evaluation may
be accomplished with an extended exam, which in-
cludes assessment for “soft” signs such as inaccurate
motor sequencing and bilateral dysgraphesthesia. Such
assessments may be described in terms of degree of per-
formance decrement, rather than by the presence or ab-
sence of abnormality. These evaluations are often per-
formed by physicians but are also represented in some
neuropsychological batteries. Although these two func-
tions—screening and evaluation—are conceptually dis-
tinguishable, the examinations serving these ends over-
lap substantially, and findings with significance in either
context are hereafter referred to inclusively as neurologic
exam abnormalities (NEA).
Classic descriptions of the psychiatric disorders often
Received October 7, 1997; revised February 3, 1998; accepted March
20, 1998. From the Veterans Affairs Medical Center and Western Psy-
chiatric Institute and Clinic, Pittsburgh, Pennsylvania. Address cor-
respondence to Dr. Keshavan, Western Psychiatric Institute and Clinic,
3811 O’Hara Street, Pittsburgh, PA 15213; e-mail: keshavan`@pitt.edu
Copyright q 1998 American Psychiatric Press, Inc.
395
NEUROLOGIC EXAMINATION IN PSYCHIATRY
included neurological exam findings. Thus, “insane
temperament,”1 “hysteria,”2 schizophrenia,3,4 mood dis-
orders,5,6 and obsessive-compulsive disorder7 were each
thought to have characteristic NEA. By mid-century the
American psychiatric literature rarely mentioned neu-
rologic findings. NEA research in child psychiatry then
expanded as the concepts of “soft neurological signs”8
and “minimal brain dysfunction”9 became popular in
the 1960s. This trend led to large pediatric studies10,11
and to much conceptual and methodologic clarifica-
tion.12–15 Studies of NEA in adolescent16,17 and then
adult18,19 psychiatric patients followed. Studies of NEA
in adult psychiatric patients have increased in quantity
and quality in recent years; recent texts again include
NEA in descriptions of psychopathology.20,21
Since its use by Bender in 1947 to describe findings
suggesting possible neurologic disease, the term soft
signs has had other connotations, including a lack of di-
agnostic or anatomic specificity, a lack of reliability, and
evanescence. Also “soft” are the boundaries of the cate-
gory, considered by some to include such varied features
as sinistrality, electroencephalographic dysrhythmias,
and learning disabilities, as well as the more widely in-
cluded NEA.22 Not surprisingly, some view the topic
with derision: “The use of the terms ‘soft signs’ and
‘minimal brain damage’ is diagnostic of soft thinking.”23
However, summarily dismissing a heterogeneous col-
lection of simple, noninvasive, and inexpensive assess-
ment tools on the above bases could also be regarded as
“diagnostic of soft thinking.” First, although anatomic
specificity is uniquely valued in neurology, it may not
be as important in psychiatry, in which localization is
less central to diagnosis. Second, although the terms
hard and soft imply that the former are reproducible and
the latter not, the data suggest otherwise. Third, al-
though some of the “soft” NEA may be evanescent, the
extent of this has not been determined in adult psychi-
atric patients. Because state variation is common in psy-
chiatric syndromes, temporal variability in neurological
measures may offer some advantages; variability in per-
formance may itself be an important parameter in psy-
chiatry.24
The term neurological soft signs thus has multiple mis-
leading meanings. Although it may be useful to char-
acterize a set of data as “hard” or “soft” evidence of
major neurologic disease, we suggest that the term not
be used to describe individual signs.
The potential for the neurologic examination to add
to diagnosis, prognosis, and treatment selection in an
era of increasing fiscal limitations warrants an exami-
nation of the significance of NEA in adult psychiatry.
This article, written primarily for researchers, summa-
rizes the current knowledge base on the bedside neu-
396
rologic examination in adult psychiatry, focusing on
methodological issues and on enhancing the clinical
relevance of work in this field. Although the boundaries
blur between this and such related areas as neurophys-
iology and neuropsychology, we address techniques
that can be readily applied in clinical settings and that
would not be considered part of the routine mental
status exam.
RELIABILITY AND VALIDITY
Components of the Examination
Psychiatric research on NEA has employed collections
of neurologic examination items culled from clinical tra-
dition or previous research (Table 1). Some batteries are
partly or entirely drawn from general neurology
texts,25–27 and some are selected from familiar neuropsy-
chological batteries.28,29 Several scales were developed
for use with children in the heyday of research into neu-
rological aspects of pediatric psychiatry10–12,30,31 and
have found application in adult populations.
The Neurological Evaluation Scale (NES),32 based on
a review of NEA in schizophrenia,33 is the most fully
described and widely employed instrument in adult
psychiatry.32,34–39 Convit et al.40 also developed a com-
posite examination, the Quantified Neurological Scale,
which has been used mostly within that group. Chen et
al.41 recently published, for use in adult psychiatry, a
heterogeneous inventory of NEA and behavioral obser-
vations, with administration guidelines and reliability
data for some of the inventory. Some scales31,40,41 addi-
tionally include items usually used to screen for frank
neurologic disease but not frequently seen in psychiatric
patients. The primitive (release, frontal release) reflexes
are often dealt with separately.42 Rudimentary sensory
function, extrapyramidal motor function, spontaneous
abnormal movements, and blink rate are not generally
included in these neurologic examination schedules.
Thus, the available scales tap into somewhat different
yet overlapping aspects of neurologic performance. It is
important to note this when comparing studies of NEA,
particularly when only summary scores are presented.
Each of the instruments referenced in Table 1 provides
directions for administration, as well as some reliability
and validity data. These instruments are best viewed as
collections of individual examinations that need not be
adopted in toto. It may often be more suitable to con-
sider the items individually for inclusion in a clinical or
research examination.
Reliability
Numerous threats to the reliability of NEA are worth
considering. Many examination items, such as motor
VOLUME 10 • NUMBER 4 • FALL 1998
 SANDERS AND KESHAVAN

overflow, require subjectivity in rating, defying quanti- or dichotomous formats for uniformity. This practice
fication unless special instruments are employed. Inter- complicates the statistical approach to reliability assess-
rater agreement is more difficult to achieve when the ment of individual exam items, reducing power and
abnormal response is merely an exaggeration of a nor- producing data that fall in the gray zone between what
mal phenomenon (e.g., tremor and postural sway). Sub- is suitable for intraclass correlation and what is suitable
jectivity can also falsely elevate local agreement (attrib- for the kappa statistic.43
utable to the shared experience of examiners, as Empirical data nevertheless suggest that interrater re-
opposed to communicable standards13) and predispose liability is generally quite acceptable.13 It is compro-
to drift (weakening of interrater reliability over time15). mised primarily in the more subjectively assessed
Because of the difficulty of directly quantifying some NEA10,36,44–46 and in those requiring discriminations be-
NEA, these studies tend to collapse all data into ordinal tween normal and slightly abnormal.10,47 Establishing
reliability with some of the “hard” NEA, most strikingly
muscle stretch reflexes, may be at least as problematic
TABLE 1. Elements of the neurological examination pertinent to as it is with psychiatrically significant NEA.10,44,46,48–50
adult psychiatry For example, reliability estimates in the Isle of Wight
Element NES PANESS QNS CNI study10 were higher for measures of coordination and
Motor (station and gait) “developmental abnormalities” than for muscle stretch
Casual gait X X reflexes. In studies of neurology inpatients, 25%50 and
Stressed gaits X
Tandem gait X X X X
43%49 of routinely assessed NEA fell below the common
Hopping X X reliability threshold of kappa40.4; in two populations
Romberg X X X of psychiatric patients, the corresponding percentages
Complex movements were 22% and 11%.36 A clearer understanding of how
Fist-ring X X
Fist-edge-palm X X X to conduct the examination improves reliability.42,44,48
Alternating fist-palm X X X Clinicians might require additional training to assess
Diadochokinesis X X some of these signs as reliably as in research settings.
Finger-thumb opposition X X X
Rhythm tapping X X X Such training could be facilitated by video technology.
Synchronous tapping X Less attention has been paid to test-retest reliability.
Tap production X Prospective studies of patients, involving repeated ex-
Extraocular movements aminations,28,29,51–53 are required to clarify the state or
Visual tracking X X
Convergence X trait aspects of NEA in psychiatric patients. Interpreting
Gaze persistence X X changes in performance over repeated neurologic exams
Other motor in patients as a function of state change, though, will
Drift X
Motor persistence X X
require data on the stability of NEA in the absence of
Finger-nose X X X potentially relevant state changes. Summary indices of
Heel-shin X NEA are stable in chronic schizophrenia.32 However, the
Muscle tone X
Mirror movement X X X
test-retest reliability of individual NEA has rarely been
Synkinesis of head X X examined in adult psychiatric populations. Using kappa
Tremor X X greater than 0.4 as a threshold, and restricting analysis
Choreoathetotic movements X X
to items with adequate interrater reliability, two small
Sensory
Audiovisual integration X studies have found that 33%36 and 44%54 of NEA could
Stereognosis X X X X be consistently reproduced. Thus, temporal stability of
Graphesthesia X X X X NEA in adult psychiatric patients remains uncertain.
Face-hand/extinction X X X X
Face-noise test X Determining which of the NEA are replicable over time
Two-point discrimination X in stable patients is critical for interpreting longitudinal
Right-left orientation X X X studies of state-related influences on neurologic func-
Primitive reflexes tioning in psychiatry.
Glabellar X X
Snout X X
Palmomental X Groupings of Neurologic Exam Elements
Grasp X X Some studies ignore the heterogeneity of NEA, deriving
Suck X
a summary score to represent the overall severity of neu-
Note: NES4Neurological Evaluation Scale;32 PANESS4Physical rologic dysfunction or the total number of abnormal
and Neurological Examination for Soft Signs;30 QNS4Quantified signs.26 At the opposite extreme, analyzing NEA indi-
Neurological Scale;41 CNI4Cambridge Neurological Inventory.42
vidually has limitations due to limited statistical power

JOURNAL OF NEUROPSYCHIATRY 397

NEUROLOGIC EXAMINATION IN PSYCHIATRY
with ordinal and categorical data, variable reliability
among individual items, and problems attendant on
multiple tests of significance. Assigning NEA to sub-
scales might allow one to exploit the heterogeneity of
NEA while avoiding the limitations of item-by-item
analysis.
Some studies have grouped items on the basis of their
presumed neuroanatomic substrates.25,41,55,56 This
grouping is debatable in psychiatric patients without fo-
cal lesions: NEA do not necessarily have localizing sig-
nificance in these populations. Rather than anatomical
regions, NEA batteries could be indexed in terms of dis-
tributed neuroanatomical or neurochemical systems.
Others15,22 categorize individual NEA as signs repre-
senting developmental delay, signs consistent with ac-
quired focal brain injury, and subtle variants of focal
signs. Many other variables might dictate the associa-
tion of individual exam items, including their depen-
dence on general intelligence, sustained attention, or
motivation.
Five adult psychiatric studies, all involving schizo-
phrenic patients, have used factor analytic techniques to
derive item clusters for the neurologic exam,34,37,51,57,58
with inconsistent results. Further study of the natural
organization of NEA in adult psychiatric patients, with
adequate numbers of subjects, using appropriate statis-
tics and limiting entered data to reliably assessed NEA,
should help to establish defensible subscales.
Relationships With Other Neurologic Tests
A variety of neurophysiologic techniques have been
used to characterize phenomena seen in the clinical neu-
rologic exam. Smooth pursuit eye movements (SPEM),59
visual fixation,60 and extrapyramidal motor dysfunc-
tion61 have been studied instrumentally, and the pal-
momental reflex has been quantified following electrical
elicitation.62 These relatively noninvasive and inexpen-
sive methods can obviously help validate the bedside
exam, but they have yet to be applied to most NEA.
Neurophysiologic methods may also be used to explore
biological correlates of NEA; two studies63,64 found re-
lationships between EEG dysrhythmias and NEA, but
others16,19,65 have not. SPEM dysfunction has been re-
lated to NEA among psychotic patients39,66 and nonpa-
tients.67 Startle habituation has been related to global
neurologic performance.34
Functional neuroimaging parameters seem to be un-
related to NEA in resting patients.56,68 However, less ac-
tivation of the appropriate cortical regions is seen dur-
ing motor tasks in schizophrenia and dementia patients
than in comparison subjects.69–71 Further application of
functional imaging and other neurophysiologic meth-
398
ods will be needed to clarify the mechanisms of NEA in
patients without acquired focal lesions.
CLINICAL UTILITY
Differential Diagnosis
Diagnostic comparisons of NEA have mostly focused on
dementia and the psychotic disorders. The neurologic
exam could significantly clarify psychiatric differential
diagnosis, particularly when the available history is lim-
ited. We survey findings to date in dementia and in psy-
chotic, mood, and anxiety disorders (Table 2, first col-
umn).
Dementia has been studied with respect to differential
diagnosis and severity. In contrast with normal control
subjects, Alzheimer’s disease patients have excesses of
astereognosis, agraphesthesia, cerebellar findings, olfac-
tory deficits, primitive reflexes, hyperreflexia, abnormal
plantar responses, and extrapyramidal findings.72,73 Fo-
cal NEA, gait abnormalities, and dysarthria are associ-
ated with multi-infarct dementia, as opposed to other
dementias.74,75 Early extrapyramidal findings may sug-
gest dementia of the Lewy body type.76 Dementia sec-
ondary to alcoholism was strongly associated with
ataxia and polyneuropathy in one study.77 Several other
forms of dementia may be related to specific NEA.78
Primitive reflexes,72,79 olfactory deficits,80 and pyrami-
dal,72 extrapyramidal,81,82 and other motor abnormali-
ties79,81 are associated with the cross-sectional severity
of dementia; this factor thus needs to be controlled for
when comparing NEA across dementias. Potentially, in
addition to helping to identify focal and multifocal le-
sions in patients with dementia, NEA might be found
to distinguish between different types of primary de-
generative dementia and between dementia and de-
pressive pseudodementia.
The primary psychoses, particularly schizophrenia,
are much investigated with respect to NEA (see re-
views33,82). Many NEA, notably abnormalities of motor
sequencing, coordination, and higher order sensory
function,33 are more common in schizophrenic than in
healthy subjects even when only neuroleptic-naive pa-
tients are included.27,35,56 Parkinsonian findings have
also been described in neuroleptic-naive patients.60,83
Most data suggest that schizophrenic patients have
more neurologic dysfunction than nonpsychotic pa-
tients, but the evidence is more mixed when comparing
psychotic patients with different diagnoses.33,84–87 Some
longitudinal data suggest an improvement in neurolog-
ical performance with improvement in clinical state
and/or treatment with antipsychotic medication.51,53
Variation in NEA due to clinical state or medications
VOLUME 10 • NUMBER 4 • FALL 1998

may thus obscure comparisons of diagnostic groups.
Significant clinical benefits might be realized if NEA
could distinguish between psychotic disorders, but fur-
ther studies comparing diagnoses while controlling for
treatment and clinical status will first be necessary.
Mood disorders have been neglected in NEA research.
Abnormalities exceeding those of normal comparison
subjects have been found in manic88 and mixed manic
and depressed patients.89 Differences were found in mo-
tor control and sequencing, stereognosis, and graphes-
thesia. In studies comparing mood-disordered with
schizophrenic patients, global NEA were fewer and/or
milder in mood disorders,18,90–92 although two stud-
ies88,93 found few differences. Consistent with early de-
scriptions of melancholia suggesting extrapyramidal
dysfunction,5,6 depression and extrapyramidal dysfunc-
tion are related in Alzheimer’s disease.81,94 There are few
differences in NEA between unipolar and bipolar pa-
tients.25,29,89,92 The prevalence and diagnostic specificity
of NEA in mood disorders remain unclear. The strong
effects of psychiatric state on general functioning in the
mood disorders, along with the mood-related variability
of neurologic functioning evidenced in psychiatric pa-
tients,29,52 suggest that phase of illness will need to be
considered. Diurnal variation may also have a signifi-
cant impact on neurologic function in the mood disor-
ders.95
Anxiety disorders have scarcely been investigated,
with the exception of obsessive-compulsive disorder
(OCD). NEA are more frequent in OCD patients than in
normal comparison subjects,96–99 although this finding
TABLE 2. Clinical utility of the neurologic examination in psychiatry: current status
Areas of Clinical Utility
Disorder Differential Diagnosis
72,73
Dementia Alzheimer’s vs. normal (S)
Ischemic vs. other (S)74,75
Lewy body variant (W)76
Alcohol-induced (W)77
Psychotic Psychotic vs. normal (S)27,35,56
disorders Psychotic vs. nonpsychotic but psychiatrically ill
(W)88,90–93
Primary psychotic disorder vs. psychiatric disorder
complicated by psychosis (W)85–87,90,92
Mood Mood disorders vs. normal (W)88,89
disorders Psychotic mood disorder vs. primary psychosis
(W)85–87
Anxiety OCD vs. normal (S)96–100
disorders PTSD vs. normal (W)102
SP vs. normal (W)103
OCD, PTSD, SP vs. other psychiatric groups (W)97
Note: S4strong evidence (replicated at least once, minimal conflicting data); W4weak evidence (no replications, or significant conflicting
evidence); N4no evidence to date; EPSE4extrapyramidal side effects; TD4tardive dyskinesia; OCD4obsessive-compulsive disorder;
PTSD4posttraumatic stress disorder; SP4social phobia.
JOURNAL OF NEUROPSYCHIATRY
SANDERS AND KESHAVAN
was not replicated in female OCD patients.100 Specific
findings include poor motor coordination,97,98 disinhi-
bited motor activity,96,98,99 impaired balance,97 an excess
of left-sided dysfunction,96,98,99 and extrapyramidal mo-
tor findings.7,101 Difficulties with motor control and with
presumably right-hemisphere tasks are fairly consistent
findings in this body of work. The diagnostic specificity
of these findings to OCD remains unclear.97 More NEA
are seen in posttraumatic stress disorder patients102 than
in control subjects, with significantly greater abnormal-
ity in motor sequencing and the palmomental reflex. So-
cial phobia patients had marginally more NEA than nor-
mal control subjects in a small study.103 Further work is
needed to address the specificity of these findings to
anxiety disorders generally and to specific anxiety dis-
orders, while considering the possible effects of state
anxiety and medication.
Treatment Selection and Prognosis
To the extent that they are static or trait-like, NEA might
be expected to predict such aspects of psychopathology
as illness onset, outcome, and complications of treat-
ment. These are areas in which the neurologic exam has
clear potential for complementing clinical assessment of
psychiatric patients. These areas of clinical utility are
represented in the last two columns of Table 2.
Onset Prediction: Follow-up of subsamples from the
National Collaborative Perinatal Project found that NEA
at age seven, particularly motor abnormalities, predict
depression,14,104 anxiety,14,104 and delinquency105 in ad-
Treatment Selection Prognosis
Treatment of cardiovascular risk Predict onset (W)113
factors (S)74,75 Rapid decline (S)114–116,118,119
Select cases for more aggressive
treatment (N)
Choice of antipsychotic agent (N) Long-term poor prognosis
EPSE prophylaxis (N) (W)83,121,122
Persisting negative symptoms
(W)40
EPSE (W)83,129
TD (N)
Choice of medication (N) Predict relapse in bipolar (W)123
Choice of psychotherapy (N)
Choice of medication (N)
Choice of psychotherapy N)
Short-term poor prognosis (W)124,125
399
NEUROLOGIC EXAMINATION IN PSYCHIATRY
olescence and also predict criminality105 and perhaps
anxiety106 in adulthood. Motor dysfunction and general
neurological impairment in preadolescence predicted
psychiatric morbidity in the New York schizophrenia
high-risk project.107 Children with motor impairments
are more likely to develop schizophrenia by adult-
hood,108–110 and sensory deficits may also enhance vul-
nerability to psychosis in youth111 as well as in old
age.112 In elderly persons, extrapyramidal findings may
predict the onset of dementia.113
Outcome Prediction: Neurologic findings with possible
prognostic value in Alzheimer’s disease include extra-
pyramidal signs,114–116 myoclonus,114,117 parietal
signs,114,117–119 and primitive reflexes.115 In schizophre-
nia and mood disorders, NEA at baseline may not pre-
dict short-term amelioration of psychiatric symp-
toms.33,53,89,120 However, negative symptoms persisting
after treatment with conventional antipsychotic medi-
cation were predicted by baseline NEA.40 Long-term
global outcome in schizophrenia was also anticipated by
NEA, including motor sequencing and extrapyramidal
dysfunction.83,121,122 Stable, medicated bipolar patients
with neurologic findings were more likely to relapse
during follow-up.123 NEA predicted a poor response to
medication in one of two studies of obsessive-
compulsive disorder.124,125 Thus, neurologic signs may
have prognostic importance in a variety of psychiatric
contexts, with implications for treatment selection.
Predictions of Treatment Complications: Although NEA
might predict neurologic side effects from a variety of
psychiatric medications, the only data known to us per-
tain to typical antipsychotic agents. Tardive dyskinesia,
noted to coincide with motor and sensory findings and
primitive reflexes,126–128 may also be predicted by such
findings: withdrawal-emergent dyskinesia was pre-
dicted by the number of NEA in one study.26 Low blink
rate129 and other parkinsonian signs83 predict parkin-
sonism after treatment with conventional antipsychotic
drugs. Baseline neurological data may help to inform
choices regarding antipsychotics and prophylactic anti-
parkinsonian agents.
CONCLUSIONS
Psychiatry is progressively informed by the brain sci-
ences, but it is constrained in applying this knowledge
to the clinical assessment of the individual patient by
the high cost of the technologies applied in neuropsy-
chiatric research. The neurologic examination is inex-
pensive and available to all physicians, and thus it has
400
the potential to bridge the gulf between neurobiologic
research and clinical practice. It has shown promise as
an aid in differential diagnosis, prognosis, and treat-
ment selection in a variety of psychiatric conditions.
The neurologic examination also has important limi-
tations. It offers only indirect reflections of the salient
properties of the brain, and it is presumably inferior to
such approaches as functional imaging and histopa-
thology in characterizing specific neural systems or in
elucidating the neurobiologic bases of psychiatric dis-
orders. Some may thus find it less intellectually exciting
than many other techniques, and its utility may lie in
more immediately clinical questions. A second limita-
tion is that an extended neurologic exam requires time
to complete. Clinicians tend to avoid devoting time to
evaluative activities that shed only ambiguous light on
the case at hand and thus may be reluctant to perform
entire exam schedules routinely. Any extension beyond
the traditional cursory “rule out” examination will be
adopted only to the extent that it has clear implications
for patient care. The limitations on reliability, although
neither trivial nor entirely determined (especially in the
case of test-retest reliability), appear to be comparable
to those of the conventional neurologic exam.
Establishing efficient applications of the neurologic
exam for specific clinical questions will require consid-
erable refinement of the knowledge base. As Table 2 il-
lustrates, many potential clinical applications have been
investigated insufficiently, if at all.
First, it must be clearly established, for a given clinical
population, which examination items are frequently
enough abnormal to be of interest and can be readily
assessed with adequate interrater reliability. Batteries
must be developed that are limited to such items.
The reliability and validity of individual and aggre-
gate neurologic tests should be assessed as methodically
as are neuropsychological tests. These tests will require
further validation against other measures, particularly
those measuring regional brain function, so that we may
better understand the nature of the abnormalities and
explore the possibility that these tests offer more effi-
cient alternative routes to similar information yielded by
these less accessible methods.
We need comprehensive developmental and norma-
tive assessments of such examinations, especially before
they are otherwise used in studies involving elderly sub-
jects. The exams should be applied to large samples of
diagnostically heterogeneous patients to clarify their
value in differential diagnosis; to longitudinal studies to
clarify their value in prognosis; and to therapeutic trials
to clarify their value in treatment selection. The current
tendency toward descriptive studies will have to give
way to the testing of more specific hypotheses.
VOLUME 10 • NUMBER 4 • FALL 1998

Much of the promise of the extended neurological ex-
amination lies in its heterogeneity. Its numerous ele-
ments individually have potential utility that may well
be lost when they are combined into summary indices
of “soft signs” or “neuromotor dysfunction.” Their po-
tential may be realized only through item-by-item anal-
yses. This approach is more feasible if these measures
are continuous, rather than categorical or ordinal. Com-
binations of items should be empirically rather than in-
tuitively determined; this might be done through a
quantitative distillation such as factor analysis.
Bringing neurobiological knowledge to bear on clini-
cal psychiatry is a task that can differ conceptually and
methodologically from the more vigorously pursued
References
1. Maudsley H: Body and Mind: An Inquiry Into Their Connec-
tion and Mutual Influence, Especially in Reference to Mental
Disorders. New York, Appleton, 1874
2. Charcot JM: Clinical Lectures on Certain Diseases of the Ner-
vous System. Detroit, MI, GS Davis, 1888
3. Kraepelin E: Dementia Praecox and Paraphrenia. Huntington,
NY, Krieger, 1919
4. Bleuler E: Dementia Praecox or the Group of Schizophrenias.
New York, International Universities Press, 1911
5. Kraepelin E: Manic-Depressive Insanity and Paranoia. New
York, Arno, 1921
6. Stoddart WHB: Mind and Its Disorders: A Textbook for Stu-
dents and Practitioners of Medicine, 5th edition. London, Lewis
and Co, 1926
7. Schilder P: The organic background of obsessions and com-
pulsions. Am J Psychiatry 1938; 94:1397–1416
8. Bender L, Fink N, Green M: Childhood schizophrenia: clinical
study of 100 schizophrenic children. Am J Orthopsychiatry
1947; 17:40–56
9. Clements SD, Peters J: Minimal brain dysfunction in the school-
age child. Arch Gen Psychiatry 1962; 6:185–197
10. Rutter M, Graham P, Yule W: A neuropsychiatric study in child-
hood (monograph). Clin Dev Med 1970; 35–36:1–272
11. Nichols PL, Chen TC: Minimal Brain Dysfunction: A Prospec-
tive Study. Hillsdale, NJ, Erlbaum, 1981
12. Tupper DE: Soft Neurological Signs. New York, Grune and
Stratton, 1987
13. Shafer SQ, Shaffer D, O’Connor PA, et al: Hard thoughts on
neurological “soft signs,” in Developmental Neuropsychiatry,
edited by Rutter M. New York, Guilford, 1983, pp 133–143
14. Shaffer D, O’Connor PA, Shafer S, et al: Neurological “soft
signs”: their origins and significance for behavior, in Develop-
mental Neuropsychiatry, edited by Rutter M. New York, Guil-
ford, 1983, pp 144–163
15. Neeper R, Greenwood RS: On the psychiatric importance of
neurological soft signs, in Advances in Clinical Child Psychol-
ogy, vol 10, edited by Lahey BB, Kazdin AE. New York, Plenum,
1987, pp 217–258
16. Kennard M: The value of equivocal signs in neurological di-
agnosis. Neurology 1960; 10:753–764
17. Hertzig ME, Birch HG: Neurologic organization in psychiatri-
cally disturbed adolescent girls. Arch Gen Psychiatry 1966;
15:590–598
JOURNAL OF NEUROPSYCHIATRY
SANDERS AND KESHAVAN
task of uncovering the neurobiological bases of psychi-
atric disorders.130 If pursued with comparable fervor to
that aroused by the more fundamental questions, such
work could have a substantial impact on the practice of
clinical psychiatry. The neurological examination offers
promising avenues for the reintegration of neurobiology
into psychiatric assessment.
The authors thank Joseph Pierri, M.D., for his comments on
this manuscript, Melissa Knox for library assistance, and
Tamera McLaughlin for secretarial support. This work was
supported in part by National Institute of Mental Health
Grants MH45203, MH01180, and MH45156 (M.S.K.) and
was previously presented at the Society of Biological Psychi-
atry annual meeting, San Diego, CA, May 15–18, 1997.
18. Rochford JM, Detre T, Tucker GJ, et al: Neuropsychological im-
pairments in functional psychiatric diseases. Arch Gen Psychi-
atry 1970; 22:114–119
19. Mosher LR, Pollin W, Stabenau JR: Identical twins discordant
for schizophrenia: neurologic findings. Arch Gen Psychiatry
1971; 24:422–430
20. American Psychiatric Association: Diagnostic and Statistical
Manual of Mental Disorders, 4th edition. Washington, DC,
American Psychiatric Association, 1994
21. Lipton AA, Cancro R: Schizophrenia: clinical features, in Com-
prehensive Textbook of Psychiatry, 6th edition, edited by Kap-
lan HI, Sadock BJ. Baltimore, Williams and Wilkins, 1995,
pp 968–987
22. Taylor HG: The meaning and value of soft signs in the behav-
ioral sciences, in Soft Neurological Signs, edited by Tupper DE.
New York, Grune and Stratton, 1987, pp 297–335
23. Ingram TTS: Soft signs. Dev Med Child Neurol 1973; 15:527–
529
24. King HE: Psychomotor Aspects of Mental Disease. Cambridge,
MA, Harvard University Press, 1954
25. Cox SM, Ludwig AM: Neurological soft signs and psychopa-
thology: incidence in diagnostic groups. Can J Psychiatry 1979;
24:668–673
26. Schultz SK, Miller DD, Arndt S: Withdrawal-emergent dyski-
nesia in patients with schizophrenia during antipsychotic dis-
continuation. Biol Psychiatry 1995; 38:713–719
27. Gupta S, Andreasen NC, Arndt S, et al: Neurological soft signs
in neuroleptic-naive and neuroleptic-treated schizophrenic pa-
tients and in normal comparison subjects. Am J Psychiatry
1995; 152:191–196
28. Guenther W, Guenther R, Eich FX, et al: Psychomotor distur-
bances in psychiatric patients as a possible basis for new at-
tempts at differential diagnosis and therapy, II: cross validation
study on schizophrenic patients: persistence of a “psychotic
motor syndrome” as possible evidence of an independent bio-
logical marker syndrome for schizophrenia. Eur Arch Psychi-
atry Clin Neurosci 1986; 235:301–308
29. Guenther W, Guenther R, Streck P, et al: Psychomotor distur-
bances in psychiatric patients as a possible basis for new at-
tempts at differential diagnosis and therapy, III: cross valida-
tion study on depressed patients: the psychotic motor
syndrome as a possible state marker for endogenous depres-
sion. Eur Arch Psychiatry Clin Neurosci 1988; 224:65–73
401
NEUROLOGIC EXAMINATION IN PSYCHIATRY
30. Denckla MB: Revised PANESS. Psychopharmacol Bull 1985;
21:773–800
31. Hertzig ME: Neurologic Evaluation Schedule, in Soft Neuro-
logical Signs, edited by Tupper DE. New York, Grune and Strat-
ton, 1987, pp 355–368
32. Buchanan RW, Heinrichs DW: The Neurological Evaluation
Scale (NES): a structured instrument for the assessment of neu-
rological signs in schizophrenia. Psychiatry Res 1989; 27:335–
350
33. Heinrichs DW, Buchanan RW: Significance and meaning of
neurological signs in schizophrenia. Am J Psychiatry 1988;
145:11–18
34. Karper L, Grillon C, Lysaker P, et al: Soft signs, attention, and
startle in schizophrenia (abstract), in New Research Abstracts.
Washington, DC, American Psychiatric Association, 1994, p 358
35. Sanders RD, Keshavan MS, Schooler NR: Neurologic exam ab-
normalities in first-break, neuroleptic-naive schizophrenia: pre-
liminary results. Am J Psychiatry 1994; 151:1231–1233
36. Sanders RD, Forman SD, Pierri JN, et al: Interrater reliability of
the Neurological Examination in Schizophrenia. Schizophr Res
1998; 29:287–292
37. Sanders RD, Forman SD, Gupta B, et al: Factor structure of the
Neurological Evaluation Scale (abstract). Biol Psychiatry 1995;
37:680
38. Sanders RD, Forman SD, Keshavan MS, et al: Test-retest stabil-
ity of the neurologic examination in schizophrenia (abstract).
Biol Psychiatry 1996; 39:548
39. Schlenker R, Cohen R, Berg P, et al: Smooth-pursuit eye move-
ment dysfunction in schizophrenia: the role of attention and
general psychomotor dysfunction. Eur Arch Psychiatry Clin
Neurosci 1994; 244:153–160
40. Convit A, Volavka J, Czobor P, et al: Effect of subtle neurolog-
ical dysfunction on response to haloperidol treatment in schizo-
phrenia. Am J Psychiatry 1994; 151:49–56
41. Chen EYH, Shapleske J, Luque R, et al: The Cambridge Neu-
rological Inventory: a clinical instrument for assessment of soft
neurological signs in psychiatric patients. Psychiatry Res 1995;
56:183–204
42. Vreeling FW, Jolles S, Verhey FRJ, et al: Primitive reflexes in
healthy, adult volunteers and neurological patients: methodo-
logical issues. J Neurol 1993; 240:495–504
43. Streiner DL: Learning how to differ: agreement and reliability
statistics in psychiatry. Can J Psychiatry 1995; 40:60–66
44. Kuzma JW, Tourtelotte WW, Remington RD: Quantitative clini-
cal neurological testing, II: some statistical considerations of a
battery of tests. Journal of Chronic Diseases 1965; 18:303–311
45. Stokman C, Shafer SQ, Shaffer D, et al: Assessment of neuro-
logical “soft signs” in adolescents: reliability studies. Dev Med
Child Neurol 1986; 28:428–439
46. Mayo NE, Sullivan SJ, Swaine B: Observer variation in assess-
ing neurophysical signs among patients with head injuries. Am
J Phys Med Rehabil 1991; 3:118–123
47. Richards M, Marder K, Bell K, et al: Interrater reliability of ex-
trapyramidal signs in a group assessed for dementia. Arch
Neurol 1991; 48:1147–1149
48. Sisk C, Ziegler DK, Zileli T: The discrepancies in recorded re-
sults from duplicate neurological history and examination in
patients studied for prognosis in cerebrovascular disease.
Stroke 1970; 1:14–18
49. Shinar D, Gross CR, Mohr JP, et al: Interobserver variability in
the assessment of neurologic history and examination in the
Stroke Data Bank. Arch Neurol 1985; 42:557–565
50. Hansen M, Sindrup SH, Christensen PB, et al: Interobserver
402
variation in the evaluation of neurological signs: observer de-
pendent factors. Acta Neurol Scand 1994; 90:145–149
51. Schroder J, Niethammer R, Geider FJ, et al: Neurological soft
signs in schizophrenia. Schizophr Res 1992; 6:25–30
52. Bulbena A, Berrios GE: Cognitive function in the affective dis-
orders: a prospective study. Psychopathology 1993; 26:6–12
53. Duncan E, Sanfilipo N, Wieland S, et al: Neurological soft signs
in schizophrenia: relationship to thought disorder (abstract).
Biol Psychiatry 1994; 35:715
54. Quitkin F, Rifkin A, Klein DF: Neurologic soft signs in schizo-
phrenia and character disorders. Arch Gen Psychiatry 1976;
33:845–853
55. Buchanan RW, Koeppl P, Breier A: Stability of neurological
signs with clozapine treatment. Biol Psychiatry 1994; 36:198–
200
56. Rubin P, Vorstrup S, Hemmingsen R, et al: Neurological ab-
normalities in patients with schizophrenia or schizophreniform
disorder at first admission to hospital: correlations with com-
puterized tomography and regional cerebral blood flow find-
ings. Acta Psychiatr Scand 1994; 90:385–390
57. Faber A, Costello R, Mitzel H, et al: Dimensionality of a neu-
ropsychiatric soft sign battery (abstract). Schizophr Res 1991;
5:382–383
58. Malla AK, Norman RMG, Aguilar O, et al: Relationship be-
tween neurological “soft signs” and syndromes of schizophre-
nia. Acta Psychiatr Scand 1997; 96:274–280.
59. Levy DL, Holzman PS, Matthysse S, et al: Eye-tracking dys-
function and schizophrenia: a critical perspective. Schizophr
Bull 1993; 19:461–536
60. Amador XF, Malaspina D, Sackeim HA, et al: Visual fixation
and smooth pursuit eye movement abnormalities in patients
with schizophrenia and their relatives. J Neuropsychiatry Clin
Neurosci 1995; 7:197–206
61. Caligiuri MP, Lohr JB, Jeste DV: Parkinsonism in neuroleptic-
naive schizophrenic patients. Am J Psychiatry 1993; 150:1343–
1348
62. Kleu G: The palmomental reflex in psychiatry. Acta Psychiatr
Scand 1971; 47:230–236
63. Davies RK, Neil JF, Himmelhoch JM: Cerebral dysrhythmias in
schizophrenics receiving phenothiazines: clinical correlates.
Clin Electroencephalogr 1975; 6:103–115
64. Monroe R, Hulfish B: Neurologic abnormalities in prison sub-
jects, in Brain Dysfunction in Aggressive Criminals, edited by
Monroe RR. Lexington, MA, Lexington Books, 1978, pp 141–
147
65. Woods BT, Short MP: Neurological dimensions of psychiatry.
Biol Psychiatry 1985; 20:192–198
66. Siever LJ, Coursey RD, Alterman IS, et al: Psychological and
physiological correlates of variations in smooth pursuit eye
movements, in Biological Markers in Psychiatry and Neurol-
ogy, edited by Usdin E, Hanin I. New York, Pergamon, 1982,
pp 359–370
67. Siever LJ, Coursey RD, Alterman IS, et al: Clinical, psycho-
physiological, and neurological characteristics of volunteers
with impaired smooth pursuit eye movements. Biol Psychiatry
1989; 26:35–51
68. Baker RW, Schooler NR, Shah AN, et al: Association of clinical
variables with SPECT findings in schizophrenia (abstract). Schi-
zophr Res 1993; 7:192
69. Guenther W, Giunta R, Klages U, et al: Findings of electroen-
cephalographic brain mapping in mild to moderate dementia
of the Alzheimer type during resting, motor, and music-
perception conditions. Psychiatry Res 1993; 50:163–176
VOLUME 10 • NUMBER 4 • FALL 1998

70. Guenther W, Brodie JD, Bartlett EJ, et al: Diminished cerebral
metabolic response to motor stimulation in schizophrenics: a
PET study. Eur Arch Psychiatry Clin Neurosci 1994; 244:115–
125
71. Schroder J, Wenz F, Schad LR, et al: Sensorimotor cortex and
supplementary motor area changes in schizophrenia: a study
with functional magnetic resonance imaging. Br J Psychiatry
1995; 167:197–201
72. Franssen EH, Reisberg B, Kluger A, et al: Cognition-
independent neurologic symptoms in normal aging and prob-
able Alzheimer’s disease. Arch Neurol 1991; 48:148–154
73. Funkenstein HH, Albert MS, Cook NR, et al: Extrapyramidal
signs and other neurologic findings in clinically diagnosed Alz-
heimer’s disease: a community-based study. Arch Neurol 1993;
50:51–56
74. Gilleard CJ, Kellett JM, Coles JA, et al: The St. George’s demen-
tia bed investigation study: cardiovascular, neurological and
neuropsychological correlates. Acta Psychiatr Scand 1993;
87:273–278
75. Roman GC, Tatemichi TK, Erkinjuntti T, et al: Vascular demen-
tia: diagnostic criteria for research studies. Report of the
NINDS-AIREN International Workshop. Neurology 1993;
43:250–260
76. Forstl H, Burns A, Luthert P, et al: The Lewy-body variant of
Alzheimer’s disease: clinical and pathological findings. Br J
Psychiatry 1993; 162:385–392
77. Osuntokun BO, Hendrie HC, Fisher K, et al: The diagnosis of
dementia associated with alcoholism: a preliminary report of
new approach. West Afr J Med 1994; 13:160–163
78. Sanson TA, Price BH: Diagnostic testing and dementia. Neurol
Clin 1996; 14:45–59
79. Benesch CG, McDaniel KD, Cox C, et al: End-stage Alzheimer’s
disease: Glasgow Coma Scale and the neurologic examination.
Arch Neurol 1993; 50:1309–1315
80. Bell IR, Amend D, Kaszniak AW, et al: Memory deficits, sensory
impairment, and depression in the elderly (letter). Lancet 1993;
341:62
81. Bakchine S, Lacomblez L, Palisson E, et al: Relationship be-
tween primitive reflexes, extrapyramidal signs, and reflective
apraxia and severity of cognitive impairment in dementia of
the Alzheimer type. Acta Neurol Scand 1989; 79:38–46
82. Cadet JL, Rickler KC, Weinberger DL: The clinical neurologic
examination in schizophrenia, in The Neurology of Schizo-
phrenia, edited by Nasrallah H, Weinberger D. New York, El-
sevier, 1986, pp 1–47
83. Chatterjee A, Chakos M, Koreen A, et al: Prevalence and clinical
correlates of extrapyramidal signs and spontaneous dyskinesia
in never-medicated schizophrenic patients. Am J Psychiatry
1995; 152:1724–1729
84. Tucker GJ, Silverfarb PM: Neurologic dysfunction in schizo-
phrenia: significance for diagnostic practice, in Psychiatric Di-
agnosis: Exploration of Biological Predictors, edited by Akiskal
HS, Webb WL. New York, Spectrum, 1978, pp 453–462
85. Woods BT, Kinney DIC, Yurgelun-Todd D: Neurologic abnor-
malities in schizophrenic patients and their families, I: com-
parison of schizophrenic, bipolar and substance abuse patients
and normal controls. Arch Gen Psychiatry 1986; 43:657–663
86. Walker E, Shaye J: Familial schizophrenia: a predictor of neu-
romotor and attentional abnormalities in schizophrenia. Arch
Gen Psychiatry 1982; 39:1153–1156
87. Schwartz F, Carr A, Munich R, et al: Voluntary motor perfor-
mance in psychotic disorders: a replication study. Psychol Rep
1990; 66:1223–1234
JOURNAL OF NEUROPSYCHIATRY
SANDERS AND KESHAVAN
88. Nasrallah HA, Tippin J, McCalley-Whitters M: Neurological
soft signs in manic patients: a comparison with schizophrenic
and control groups. J Affect Disord 1983; 5:45–50
89. Cherian A, Kuruvilla K: Prevalance of neurological “soft signs”
in affective disorder and their correlation with response to
treatment. Indian Journal of Psychiatry 1989; 31:224–229
90. Walker E: Attentional and neuromotor functions of schizo-
phrenics, schizoaffectives and patients with other affective dis-
orders. Arch Gen Psychiatry 1981; 38:1355–1358
91. Manschreck TC, Ames D: Neurologic features and psychopa-
thology in schizophrenic disorders. Biol Psychiatry 1984;
19:703–719
92. Kinney DK, Yurgelun-Todd D, Woods BT: Neurological hard
signs in schizophrenia and major mood disorders. J Nerv Ment
Dis 1993; 181:202–203
93. Gureje O: Neurological soft signs in Nigerian schizophrenics: a
controlled study. Acta Psychiatr Scand 1988; 78:505–509
94. Merello M, Sabe L, Teson A, et al: Extrapyramidalism in Alz-
heimer’s disease: prevalence, psychiatric, and neuropsycholog-
ical correlates. J Neurol Neurosurg Psychiatry 1994; 57:1503–
1509
95. Moffoot APR, O’Carroll RE, Bennie J, et al: Diurnal variation
of mood and neuropsychological function in major depression
with melancholia. J Affect Disord 1994; 32:257–269
96. Denckla MB: Neurological examination, in Obsessive Compul-
sive Disorder in Children and Adolescents, edited by Rapoport
JL. Washington, DC, American Psychiatric Press, 1989, pp 107–
115
97. Conde López V, de la Gandara Martı́n JJ, Blanco Lozano ML,
et al: Signos neurológicos menores en los trastornos obsesivo-
compulsivos [Neurologic soft signs in obsessive-compulsive
disorders]. Actas Luso Esp Neurol Psiquiatr Cienc Afines1990;
18:143–164
98. Hollander E, Schiffman E, Cohen B, et al: Signs of central ner-
vous system dysfunction in obsessive-compulsive disorder.
Arch Gen Psychiatry 1990; 47:27–32
99. Bihari K, Pato MT, Hill JL, et al: Neurologic soft signs in
obsessive-compulsive disorder (letter). Arch Gen Psychiatry
1991; 48:278–279
100. Stein DJ, Hollander E, Simeon D, et al: Neurological soft signs
in female trichotillomania patients, obsessive-compulsive dis-
order patients, and healthy control subjects. J Neuropsychiatry
Clin Neurosci 1994; 6:184–187
101. Hymas N, Lees A, Bolton D, et al: The neurology of obsessional
slowness. Brain 1991; 114:2203–2233
102. Gurvits TV, Lasko NB, Schachter SC, et al: Neurological status
of Vietnam veterans with chronic posttraumatic stress disorder.
J Neuropsychiatry Clin Neurosci 1993; 5:183–188
103. Hollander E, Weiller F, Cohen L, et al: Neurological soft signs
in social phobia. Neuropsychiatry Neuropsychol Behav Neurol
1996; 9:182–185
104. Pine D, Shaffer D, Schonfeld IS: Persistent emotional disorder
in children with neurological soft signs. J Am Acad Child Ado-
lesc Psychiatry 1993; 32:1229–1236
105. Denno DW: Biology and Violence: From Birth to Adulthood.
New York, Cambridge University Press, 1990
106. Hollander E, DeCaria CM, Aronowitz B, et al: A pilot follow-
up study of childhood soft signs and the development of adult
psychopathology. J Neuropsychiatry Clin Neurosci 1991; 3:186–
189
107. Erlenmeyer-Kimling L, Kestenbaum C, Bird H, et al: Assess-
ment of the New York high-risk project subjects in sample A
who are now clinically deviant, in Children at Risk for Schizo-
403
NEUROLOGIC EXAMINATION IN PSYCHIATRY
phrenia: A Longitudinal Perspective, edited by Watt F, Wynne
LC, Rolf JE. New York, Cambridge University Press, 1984, pp
227–239
108. Fish B, Marcus J, Hans SL, et al: Infants at risk for schizophre-
nia: sequelae of a genetic neurointegrative defect. Arch Gen
Psychiatry 1992; 49:221–235
109. Jones P, Rodgers B, Murray R, et al: Child developmental risk
factors for adult schizophrenia in the British 1946 birth cohort.
Lancet 1994; 344:1398–1402
110. Walker EF, Savoic T, Davis D: Neuromotor precursors of schizo-
phrenia. Schizophr Bull 1994; 20:441–451
111. David AS, Maimberg A, Lewis G, et al: Are there neurological
and sensory risk factors for schizophrenia? Schizophr Res 1995;
14:247–251
112. Kay DWK, Roth M: Environmental and hereditary factors in
the schizophrenias of old age (“late paraphrenia”) and their
bearing on the general problem of causation in schizophrenia.
J Ment Sci 1961; 107:649–686
113. Richards M, Stern Y, Mayeux R: Subtle extrapyramidal signs
can predict the development of dementia in elderly individu-
als. Neurology 1993; 43:2184–2188
114. Mayeux R, Stern Y, Spanton S: Heterogeneity in dementia of
the Alzheimer type: evidence of subgroups. Neurology
1985;35:453–461
115. Burns A, Jacoby R, Levy R: Neurological signs in Alzheimer’s
disease. Age Ageing 1991; 20:45–51
116. Stern Y, Liu X, Albert M, et al: Modeling the influence of extra-
pyramidal signs on the progression of Alzheimer’s disease.
Arch Neurol 1996; 53:1121–1126
117. Chui HC, Teng EL, Henderson VW, et al: Clinical subtypes of
dementia of the Alzheimer type. Neurology 1985; 35:1544–1550
118. Gilleard CJ, Spain E, O’Carroll RE: Senile dementia and parietal
lobe dysfunction. Br J Psychiatry 1987; 150:114–117
119. O’ Carroll RE, Whittick S, Baikie E: Parietal signs and sinister
prognosis in dementia: a four-year follow-up study. Br J Psy-
chiatry 1991; 158:358–361
404
120. Bartko G, Frecska E, Zador G, et al: Neurological features, cog-
nitive impairment and neuroleptic response in schizophrenic
patients. Schizophr Res 1989; 2:311–313
121. Johnstone EC, Macmillan JF, Frith CD, et al: Further investi-
gation of the predictors of outcome following first schizo-
phrenic episodes. Br J Psychiatry 1990; 157:182–189
122. Vaid G, Smith RC, Rosenberger S, et al: Neurological and neu-
ropsychological tests in schizophrenics (abstract). Biol Psychi-
atry 1993; 33:92A
123. Mukherjee S, Shukla S, Rosen A: Neurological abnormalities in
patients with bipolar disorder. Biol Psychiatry 1984; 19:337–345
124. Hollander E, Decaria CM, Sanoud J, et al: Neurologic soft signs
in obsessive-compulsive disorder (reply). Arch Gen Psychiatry
1991; 48:278–279
125. Thienemann N, Koran LM: Do soft signs predict treatment out-
come in obsessive-compulsive disorder? J Neuropsychiatry
Clin Neurosci 1995; 7:218–222
126. Wegner JT, Catalano R, Gibralter S, et al: Schizophrenics with
tardive dyskinesia: neuropsychological deficit and family psy-
chopathology. Arch Gen Psychiatry 1985; 42:860–865
127. Manschreck TC: Motor and cognitive disturbances in schizo-
phrenic disorders, in Schizophrenia: Scientific Progress, edited
by Schulz SC, Tamminga CA. New York, Oxford University
Press, 1989, pp 372–380
128. Waddington JL, Youssef HA, King DJ, et al: Association of cog-
nitive dysfunction, altered brain morphology, and release of
developmental reflexes with tardive dyskinesia in schizophre-
nia and bipolar disorder, in Schizophrenia: Scientific Progress,
edited by Schulz SC, Tamminga CA. New York Oxford Uni-
versity Press, 1989, pp 396–403
129. Keshavan MS, Narasimha RIVL, Narayanan HS: Rate of blink-
ing may predict neuroleptic-induced parkinsonism (letter). Br
J Psychiatry 1983; 142:423
130. Luchins DJ: How about something practical? Biol Psychiatry
1991; 30:1179–1181
VOLUME 10 • NUMBER 4 • FALL 1998