Schizophrenia Bulletin vol. 43 no. 5 pp.

956–971, 2017
doi:10.1093/schbul/sbx089
Advance Access publication July 22, 2017

LEAD ARTICLE

Motor Abnormalities: From Neurodevelopmental to Neurodegenerative Through

“Functional” (Neuro)Psychiatric Disorders

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Victor Peralta*,1,2 and Manuel J. Cuesta2,3
Mental Health Department, Servicio Navarro de Salud, Pamplona, Spain; 2Instituto de Investigación Sanitaria de Navarra (IdiSNA),
1

Pamplona, Spain; 3Psychiatry Service, Complejo Hospitalario de Navarra, Pamplona, Spain

*To whom correspondence should be addressed; Mental Health Department, Servicio Navarro de Salud, Plaza de la Paz s/n, 31002
Pamplona, Spain; tel: +848422488, fax: +848422488, e-mail: [email protected]

Background: Motor abnormalities (MAs) of severe Introduction

mental disorders have been traditionally neglected both
Motor abnormalities (MAs) of psychiatric disorders have
in clinical practice and research, although they are an
been traditionally a neglected topic in both clinical prac-
increasing focus of attention because of their clinical and
tice and research, and modern taxonomies of psychopa-
neurobiological relevance. For historical reasons, most of
thology continue to ignore them.1–3 MAs are included
the literature on MAs has been focused to a great extent
among diagnostic criteria of many psychiatric disorders4
on schizophrenia, and as a consequence their prevalence
and are present as cardinal or associated features in
and featural properties in other psychiatric or neuropsy-
many others (supplementary table 1); and they also have
chiatric disorders are poorly known. In this article, we
important implications for the etiology,5–7 nosology,5,8,9
evaluated the extent to which catatonic, extrapyramidal
pathophysiology,10–12 and management13–15 of psychiatric
and neurological soft signs, and their associated clinical
disorders. Furthermore, MAs cut-across many psychi-
features, are present transdiagnostically. Methods: We
atric, neuropsychiatric and neurological disorders16 and
examined motor-related features in neurodevelopmental
they have been proposed as a core phenotype dimen-
(schizophrenia, obsessive compulsive disorder, autism
sion of major psychiatric disorders17,18 and as a putative
spectrum disorders), “functional” (nonschizophrenic
domain within the NIMH Research Domain Criteria
nonaffective psychoses, mood disorders) and neurode-
framework (RoDC).19
generative (Alzheimer’s disease) disorders. Examination
Despite the fact that MAs are a ubiquitous condition
of the literature revealed that there have been very few
of many psychiatric disorders, for historical reasons,
comparisons of motor-related features across diagnoses
most studies on the topic have been mainly focused on
and we had to rely mainly in disorder-specific studies to
psychotic disorders and more specifically on schizo-
compare it transdiagnostically. Results: One or more
phrenia, and only a minority of studies have compared
motor domains had a substantial prevalence in all the
MAs across diagnoses. Thus, the extent to which MAs
diagnoses examined. In “functional” disorders, MAs, and
and their associated clinical features are either disorder-
particularly catatonic signs, appear to be markers of epi-
specific or have a transdiagnostic character remains an
sode severity; in chronic disorders, although with different
open question. The present article attempts to meet this
degree of strength or evidence, all motor domains are indi-
challenge through a systematic review of empirical stud-
cators of both disorder severity and poor outcome; lastly,
ies examining MAs in several diagnoses. In this article, we
in Alzheimer’s disease they are also indicators of disor-
consider 3 domains of MAs: catatonic signs, extrapyra-
der progression. Conclusions: MAs appear to represent a
midal symptoms (EPS) and neurological soft signs (NSS).
true transdiagnostic domain putatively sharing neurobio-
Catatonia is a neuropsychiatric psychomotor syndrome
logical mechanisms of neurodevelopmental, functional or
characterized not only by a broad range of MAs, but also
neurodegenerative origin.
by affectivity disturbance and complex behaviors includ-
ing disturbance of will.15,20,21 Insofar as catatonia does not
Key words: schizophrenia/psychosis/mood exclusively affect motility, it can be distinguished from
disorders/obsessive-compulsive disorder/autism pure MAs such as EPS. EPS may present as either abnor-
spectrum disorders/Alzheimer’s disease mal excess or paucity of movements, and commonly used

© The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.
All rights reserved. For permissions, please email: [email protected]

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 Motor Abnormalities in Psychiatric Disorders

terms for the former are dyskinesia, hyperkinesias, and backgrounds.27 For example, we lack universally accepted
abnormal involuntary movements and for the latter hypo- concepts and assessment tools for catatonia4,15,16,28–35 and
kinesia, bradykinesia, and parkinsonism.22,23 Hereinafter, NSS24,36–40 (supplementary tables 2 and 3), and research is
we use mainly the terms dyskinesia and parkinsonism. fragmented according to the predefined motor domains,
The NSS comprise a wide range of subtle abnormalities although a comprehensive instrument for rating the 3
that are usually grouped into sensory integration, motor motor domains is available.36

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coordination and sequencing of complex motor tasks.24 Daniel Rogers41 advanced the idea of a “conflict of
The rationale for selecting these motor domains was that paradigms” to refer to the psychiatric vs neurologic view
catatonic and extrapyramidal signs represent well-known of MAs; nonetheless, there are several other conflict-
phenotypic manifestations of many psychiatric disorders ing views involving broad vs restrictive definitions, cat-
with important clinical and treatment implications. On egorical vs dimensional approaches, cross-sectional vs
the contrary, NSS are subclinical features that are not longitudinal views and primary vs drug-induced MAs,
usually assessed in clinical practice, as they need to be issues to which we’ll refer briefly. Historically, catatonia
elicited by neurological examination; however, they are of was broadly defined as a psychomotor syndrome char-
research relevance because of their value as endopheno- acterized by the most remarkable signs such as stupor,
type candidates for many psychiatric disorders.25 excitation, negativism, mutism, paratonia and waxy flex-
The goal of this study was 2-fold. We first examined the ibility, but also by less dramatic manifestations includ-
phenomenology and factor structure of MAs, in order to ing tic- and dyskinesia-like movements, choreo-athetoid
describe their core clinical phenotype. We next examined movements, rigidity, bradykinesia, release signs and dif-
the main featured characteristics of MAs across disor- ficulties in motor coordination and balance.5,42–44 These
ders of neurodevelopmental, “functional” or neurode- less dramatic signs are now recognized as EPS or NSS
generative origin. Among neurodevelopmental disorders and in general are not included within the catatonia syn-
we specifically examined the diagnoses of schizophrenia, drome, which has led to a more restrictive view of the
obsessive-compulsive disorder (OCD) and autism spec- syndrome.41
trum disorders (ASD); functional disorders included The complexity of the catatonia concept is further
nonschizophrenic nonaffective psychoses (NSNAP) highlighted by uncertainty as to whether it is a discrete
and major mood disorders; lastly, as a neurodegenera- pathology or a dimensional cluster of symptoms, a ques-
tive disorder we examined Alzheimer’s disease (AD). tion that needs to be framed within the broader context
Neurodevelopmental disorders are a group of conditions of categorical vs dimensional representations of psycho-
with onset, or early manifestations, in the developmental pathology. Dimensions cut-across diagnostic categories,
period as a result of early brain dysfunction, which usu- tend to exhibit more predictive value than categories
ally follow a chronic course. Neurodegenerative disorders and are an essential component of the RdoC matrix.
are characterized by late-onset neurodegenerative pro- Catatonia is usually defined as a discrete category and
cesses in the brain in which the clinical course is progres- identified with the most striking manifestations; how-
sive rather than chronic. In opposition to these groups ever, catatonia ratings, particularly when scales with
of disorders, “functional” disorders are mainly character- broad item coverage are used, tend to follow a continu-
ized by onset in early or middle adulthood and by an epi- ous distribution in severe mental disorders18,45–47; thus,
sodic/remitting course that is putatively tied to a mostly choosing a determined cut-off point to make a diagnosis
reversible brain dysfunction. The rationale for selecting is a relatively arbitrary question that may reflect underly-
these diagnoses of varying origin was that they represent ing severity rather than true categorical distinctions. An
major and prevalent psychiatric or neuropsychiatric dis- additional problem is that current catatonia rating scales
orders, in which MAs have been often described. Such and diagnostic criteria essentially define a cross-sectional
an approach may inform on points of commonality and disorder. Catatonia may vary over time according to spe-
divergence of MAs across diagnostic classes and mecha- cific patterns of symptoms and illness-related factors, by
nisms. Before examining these questions, and to illustrate which a longitudinal perspective has been emphasized by
the complexity of motor dysfunction influencing clinical all classical5,42–44 and some modern authors.48,49 Unlike
practice and research, it is necessary to address some rel- catatonia, EPS and NSS lacked of nosological formula-
evant conceptual and methodological issues. tions, and they are usually rated dimensionally and even-
tually categorized according to specific cut-off points or
criteria. A specific problem of NSS is that they lack a val-
Conceptual and Methodological Issues
idate criterion to define abnormality, which favors great
We lack of a unifying theory about normal and abnormal discrepancy between studies in prevalence rates in healthy
motility and there is no guiding principle of what makes a controls and those with psychiatric disorders.24
motor sign or behavior.26 As a consequence, both the defi- Regarding the motor effects of antipsychotic medica-
nition and boundaries of abnormal motility have become tion, it is worth noting that Steck, who was one of the
unclear and changing according to different theoretical first in reporting these effects50 and had been involved
957
V. Peralta & M. J. Cuesta

in studying MAs of severe mental disorders in the pre- 22 exclusively addressed the prevalence of catatonia in
neuroleptic era,10 suggested that antipsychotic drugs may hospital samples and 24 examined some featural prop-
be acting by modifying the expression of disease-based erties of MAs, which should be the main focus of this
motor disorder.50 This view was ignored by contemporary review55,62–85 (supplementary table 4). Most of these
and subsequent authors and the contribution of drugs articles, however, mainly examined the distribution of
to motor disorders was seen as paramount importance. motor features and were of such variable methodology

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Antipsychotics may cause a broad range of acute and and quality that we’ll refer to some of them in the fol-
chronic MAs,51 although it appears that illness-related lowing narrative review. Thus, we had to rely on findings
factors,52,53 and particularly preexisting MAs53,54 play also mainly coming from disorder-specific studies. To main-
a role. Studies of drug-naïve subjects showed that spon- tain a balance between findings in schizophrenia and in
taneous MAs may be an indigenous feature of severe other diagnoses, those of schizophrenia were kept at a
mental disorders tied to the underlying pathophysiol- minimum according to their relevance. Lastly, because
ogy,53,55–57 and that antipsychotics, in addition to produce of motor dysfunction is a key component of abnormal
drug-emergent MAs in some subjects, they may improve, neurodevelopment and at-risk states, this issue was also
worsen or left unchanged preexisting catatonic,58 extra- briefly addressed.
pyramidal58 and neurological signs.59 Thus, in subjects
on antipsychotics, MAs and particularly NSS and EPS, Phenomenology and Syndromic Structure of MAs
likely represent a mixture of primary and drug-induced
motor features, and currently, a balanced view of MAs The phenomenology of MAs has been mainly addressed
in treated subjects is one of antipsychotic medication in classical text books5,42–44 and articles11,86–91 not included
interacting with or modifying the disease-based motor in PubMed. This literature was largely based on close
disorder.13,57–61 clinical scrutiny of patients followed-up over years and
laid the foundation of current descriptions. However,
classical and current approaches highly differ in that the
Systematic Review
former is clinically-based and longitudinally-oriented,
We first identified relevant historical literature on MAs and the latter, clinometrically-based and cross-section-
in psychiatric and neuropsychiatric disorders. Then ally-oriented. The classical approach is best represented
we completed an initial search of MeSH terms for by the Wernicke-Kleist-Leonhard school of psychiatry,92
“Catatonia” OR “Abnormal involuntary movements” which set the MAs at the forefront of psychotic disorders
or “Parkinsonism” OR “Extrapyramidal symptoms” because of their clinical, nosological and neurobiological
OR “Neurological soft signs” AND “Mental disorder” relevance. Kleist11 was the first in elaborating a systematic
OR “Medical disease” OR “Factor Analysis”. Search account of catatonic phenomena and in relating them to
dates were not constrained, and pertinent cohort stud- specific brain circuitry dysfunctions. Leonhard, catego-
ies and review articles were identified. Using this initial rized human motility into spontaneous, expressive, reflex,
information, numerous subsequent searches of specific and reactive movements,93,94 and articulated the most
terms were made in order to examine MAs in the dis- clinically detailed description and classification of motor
orders of interest. MeSH terms for specific diagnoses phenomena ever produced (supplementary table 5).5
included “Schizophrenia” OR “Psychotic disorder” OR According to Leonhard, MAs need to be considered in
“Mood disorder” OR “Obsessive-compulsive disorder” relation to the entire illness course, and distinguished
OR “Autism Spectrum Disorder” OR “Alzheimer’s dis- between quantitative increase or decrease of motor
ease”. Many variations on each search for the individual activity and qualitatively distinct motor disturbances.
diagnoses were also conducted. Exclusion criteria were as Indeed, Leonhard’s scheme allows ordering the varied
follows: studies determining MAs exclusively by instru- MAs along a continuum of axial characteristics such as
mental measures, studies of drug-induced motor dis- bipolarity, bizarreness and complexity of motor behav-
orders, and case reports. Studies in English, German, iors. Leonhard’s nosology has been validated to some
French, Italian or Spanish were included. Because of this extent by other authors,95–101 but it had little international
study was mainly concerned with primary MA, we tried impact mainly due to its complexity. Some attempts have
to prioritize studies including subjects who were drug- been made to render this classification more simple and
naïve, minimally treated, drug-free, or treated subjects in operational,102–104 but with limited success in terms of fur-
which the antipsychotic medication was controlled for. ther use. Notwithstanding this, Leonhard’s classification
The great majority of studies had a focus on schizo- remains of high heuristic value and of potential research
phrenia spectrum disorders, which can be explained by interest to address heterogeneity of MAs in psychiatric
historical trends. Most of the remaining studies exam- disorders.92,101
ined MA within specific diagnoses and a total of 46 stud- When catatonia ratings are examined in the context
ies examined MAs in 2 or more diagnoses, one of them of other psychopathological symptoms, a catatonia
usually involving schizophrenia. Of these 46 studies, dimension consistently emerges as a highly differentiated

958
 Motor Abnormalities in Psychiatric Disorders

domain.105 The 15 existing factor analytical studies with schizotypy or at-risk individuals. Furthermore,
of catatonia greatly vary about the number of factors meta-analytic evidence indicates that EPS152–154 and NSS155
obtained (from 2 to 7) and their item composition (sup- capture a moderate proportion of psychosis proneness,
plementary table 6).18,30,33,63,72,106–115 The mean number of which supports the endophenotype hypothesis of motor
reported factors was 4.1 and the most replicated ones dysfunction by associating it with neurodevelopmental
were motor excitement and motor retardation (13 and deviance. However, some caution is warranted since at-

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11 studies, respectively), followed to a great distance by risk individuals are not just for schizophrenia but, more
an involuntary movements factor (5 studies). Variability broadly, for other disorders with poor developmental
in the factor structure may be explained by item compo- outcomes.131
sition of the rating scales, method for determining the The catatonic subtype of schizophrenia was dropped
factor solution and sample issues; in fact, a somewhat from DSM-5 due to low diagnostic stability and valid-
different factor structure can be obtained by using differ- ity.156 However; no less important is the poor validity
ent rating scales in the same sample18,113 and by using the of the DSM schizophrenia concept itself in resolving
same rating scale in different samples.18,110 clinical and etiological heterogeneity,101 and that motor
Studies addressing the factor structure of EPS are lack- signs have been de-emphasized in current diagnostic
ing, but when EPS ratings are analyzed together with rat- criteria compared with earlier definitions.157,158 Indeed,
ings of catatonia, they usually form part of overarching Leonhard’s and Bleuler’s classifications diagnose as much
hyperkinetic and hypokinetic dimensions.18 A consistent as 2.5 times more catatonias than current consensus diag-
multidimensionality of NSS has been observed (from 3 noses.157 Catatonic signs are by no means confined to the
to 5 factors) in both exploratory39,79,116 and confirmatory catatonic subform of the disorder, and they appear to
factor analysis117 and most studies provided face validity cut-across schizophrenia subtypes. The Iowa-500 study
for the 3 predefined NSS domains.24,118–121 The only study showed that 32% of people with schizophrenia had cata-
examining conjointly the factor structure of all 3 motor tonia signs and only 6.5% met criteria for the catatonic
domains resulted in 5 dimensions: motor coordination, subtype.159 From a lifetime perspective, the prevalence of
movement abnormalities, increased reflexes, dyskinesias, a catatonia syndrome in schizophrenia raises up to 41%
and catatonia.69 (figure 1), and Manschreck73 noted that most subjects
Strong associations between catatonia and EPS rat- with chronic schizophrenia exhibit mild catatonia-like
ings have been reported,106,122 and to a less degree between movements that do not qualify for a catatonia diagnosis.
these and NSS.123,124 Most importantly, these associations Converging evidence indicates that catatonia signs are
have also been observed in drug-naïve subjects,30,53,116 this linked to severity of schizophrenia. Most,160–163 but not
indicating that associations are genuine and not due to all164 modern outcome studies of schizophrenia exam-
chronicity or drug effects. ining baseline catatonic signs showed that they were
related to a poor outcome, and most subjects with severe
impairment present with catatonic symptoms.41,43,44,165,166
Schizophrenia
Likewise, motor domains have been consistently linked
NSS and dyskinesias, but not catatonic signs, may appear to negative or deficit schizophrenia,167 even in drug-naïve
long before the beginning of the first-episode of psycho- subjects,168 and to poor cognition.166,169 There is a lack of
sis125–128; hence, these MAs may be better understood in prospective studies examining catatonia sings across ill-
the context of neurodevelopment deviations, as results ness stages, but studies using the same rating instrument
of brain insults or dysfunctions during pregnancy and in samples with differing illness stages, provide indirect
perinatal periods129 and genetic or epigenetic factors.130,131 evidence for an overall increase of catatonia signs with ill-
Normal neurodevelopment evolves through a chronolog- ness chronicity and severity (supplementary table 7).18,41,110
ical schedule that is closely entwined with the age-asso- Several systematic reviews have reported prevalence
ciated stage and intrinsically linked to the development rates for spontaneous dyskinesia between 9%56 and 13%56
of motility, cognitive functions and social behavior.132–137 and for spontaneous parkinsonism between 17%56 and
Early motor dysfunctions may be a risky step for the 25%,12 although rates up to 30% have been reported using
development of schizophrenia138–140 and might predict broader definitions of EPS.18 Both dyskinesias and par-
subsequent negative symptoms141 and cognitive perfor- kinsonism have been described in about two-thirds of
mance.142–144 In addition, spontaneous dyskinesias may subjects with chronic schizophrenia,169–171 and although
predict transition to psychosis in at-risk individuals,145,146 they likely represent a mixture of primary and drug-
neuromotor dysfunction in children and adolescents may induced phenomena, the contribution of antipsychotic
precede the prodrome and onset of schizophrenia,147 and drugs appears to be of minor relevance, particularly for
deviant achievement of motor milestones may serve to dyskinesias.170 An outstanding longitudinal study com-
recognize individuals at risk of psychosis.148 paring schizophrenia subjects, who were mostly drug-
Compared to healthy controls, both dyskinesias131,149 naïve, with and without spontaneous dyskinesias showed
and NSS150,151 are significantly more prevalent in subjects that the group with dyskinesias had poorer premorbid
959
V. Peralta & M. J. Cuesta

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Fig. 1. Data were re-analyzed from Peralta et al.101 This sample population was derived from a family study comprising 1094 subjects
affected with psychotic or mood disorders, who were recruited from out and inpatients facilities in Navarra (Spain) between years 1990
and 2014. Subjects were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (4th edition), and catatonia
was assessed by means of the Comprehensive Assessment of Symptoms and History (CASH).

adjustment, earlier illness onset, more severe disorga- series of subjects with catatonia.186 When catatonia is the
nized and catatonic signs, and much more poor function- main manifestation of the psychotic disorder, it is usu-
ing.172 Another study reported that subjects with chronic ally much more severe than catatonia in other psychiatric
schizophrenia and dyskinesias had greater negative and conditions.5,185
disorganization symptoms, more voluntary MAs, lower The relevance of catatonia within NSNAP contrasts
premorbid IQ and higher cognitive impairment.173 with the paucity of studies of catatonia and other motor
NSS are prominent during the acute exacerbations of domains within this diagnostic grouping. Only one study
schizophrenia and to a less extent during the stabiliza- reported prevalence rates of spontaneous dyskinesias in
tion phase174–177; furthermore, their decreasing during the schizoaffective (11.4%) and schizophreniform disorder
episode remission runs parallel to remission of symptom- (0%).55 Consistent evidence indicates that levels of NSS
atology,37 even in drug-naïve samples.176,178 Duration of in NSNAP did not differ from those observed in schizo-
illness is significantly associated with NSS,124 and some phrenia74,80 or psychotic mood disorder.74,81
evidence indicates that NSS are related to both poor cog-
nitive functioning,179,180 although subscale motor scores Mood Disorders
may differ in this regard,74 and poor social functioning.81
The prevalence of catatonia in manic episodes ranges from
17%187 to 31%188 (figure 1), these rates being much higher in
Nonschizophrenic Nonaffective Psychoses
mixed mania: between 28%187 and 61%.189 The major MAs
This diagnostic grouping entails the diagnoses of schizo- in mood disorders are psychomotor agitation and retar-
phreniform disorder, schizoaffective disorder, brief psy- dation, which are closely tied to mood states. Catatonic
chotic disorder and other unspecified psychotic disorder; signs are related to severity of the manic episode188,190;
and Kalbaum’s catatonia original concept mainly cor- and some,68,189 but not all190 studies revealed that catatonic
responds with NSNAP.181 Within NSNAP, catatonia manics displayed higher levels of comorbidity and poorer
may appear either in association with other psychotic global functioning compared with their noncatatonic
syndromes or as the main manifestation of the disor- counterparts; furthermore, the poor prognosis of manic
der. Disorders with episodic-remitting course in which subjects with catatonia appears to be mediated by the
abnormal motility is the predominant manifestation have higher comorbidity associated with the mixed states.191,192
been historically acknowledged as periodic psychoses The only study examining the prevalence of spontane-
with disturbed motility43 or motility psychoses,5,182,183 and ous dyskinesias in bipolar disorder (BD) reported a fig-
more recently as idiopathic or recurrent catatonia.184–186 ure of 14.3%.55 Additionally, mood disorders may present
Catatonia cut-across all NSNAP with lifetime prevalence a risk factor for developing tardive dyskinesias (TD),193
rates of 35%–45% (figure 1). Motility psychoses repre- and a relationship appears to exist between affective
sent the 18% of all NSNAP,5 and the idiopathic/recur- states and TD as increased severity of depression often is
rent catatonias have been described in 4%–46% of case coupled with TD worsening and TD often diminish with
960
 Motor Abnormalities in Psychiatric Disorders

mania.194,195 Bipolar subjects show significantly more NSS comorbid tics exhibit earlier age of onset, male prepon-
than healthy controls,196–199 though without clear detach- derance, greater likelihood of family members also having
ment from nonaffective psychoses.24,74,79–81 NSS occur in OCD, chronic course of symptoms and a poorer response
decreasing degree in psychotic mania,77 nonpsychotic to treatment.216 Furthermore, subjects with OCD, and
mania,77 euthymic bipolars,200 unaffected first-degree rela- particularly those with tic disorder, are more likely to
tives,200 and healthy controls.199,200 Thus, NSS appear to have comorbid conditions characterized by abnormal

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represent both severity and trait deficits in BD. motility such as attention deficit hyperactivity disorder
As many as 20% of depressed subjects may present with (ADHD),217 ASD,218 and basal ganglia disorders.219,220
a catatonia syndrome,201 and compared with noncatatonic Subjects with OCD and parkinsonism differ from those
depressed they were older, more cognitively impaired without parkinsonism in having more severe compulsions,
and presented more severe depression.201 Psychomotor lower IQ scores and poorer cognitive performance.214
retardation indicates episode severity202 and is central A subgroup of severely impaired OCD subjects present
to the melancholic subtype of depression203; although it obsessional slowness,221,222 a concept highly overlapping
may also appear in mixed states as inhibited mania.204 with parkinsonism.223,224 The majority of subjects with
Psychomotor agitation in major depression has been obsessional slowness (76%) also present with a broad range
reported to be a strong predictor of mood switching.205 of mild catatonia-like signs, EPS and NSS.222 Subjects
The prevalence of spontaneous dyskinesias in major with OCD consistently exhibit lower NSS ratings than
depression appears to be as low as 6.3%.55 The only those with schizophrenia,66,76,84 but higher ratings than
study specifically addressing parkinsonism in depression their first-degree relatives225 and healthy controls.66,224,226
reported a 20% prevalence rate, and it was related to older
age, severity of depression and cognitive impairment.206 Autism Spectrum Disorders
Levels of NSS in major depression are significantly lower
As a typical neurodevelopmental disorder, the majority of
than in psychotic disorders and BD and do not mean-
children with ASD exhibit varying degrees of MAs. The
ingfully differ from those observed in healthy controls207;
association of ASD with psychosis and catatonia has long
however, psychotic depression exhibit NSS levels compa-
been recognized,227,228 since they share many abnormal
rable to other psychotic disorders.77
patterns of movement. In their study of 117 cases of cata-
tonic schizophrenia in children, Leonhard held that they
Obsessive-Compulsive Disorder “correspond to many of the autistic children studied by
Kanner”.229 Based on this overlap, some modern authors
Despite poor and nonfunctional motor behavior has
conceptualize catatonia in ASDs as a deterioration of
been acknowledged in most subjects with OCD,208,209
the previous level of motor behavior or the emergence of
only one study has examined catatonia ratings in subjects
“new” motor signs.45,230,231 Although up to 20% of subjects
with this diagnosis66; and it reported that OCD subjects
with ASD develop a catatonia syndrome,231 this syndrome
had significantly lower catatonia ratings than those with
is poorly recognized in the clinical practice as there is a
schizophrenia but higher ratings than healthy controls.
general bias to diagnose catatonia in its severe form.231
A phenomenological overlap exists between catatonia
For example, Wing and Shah45 examined 28 catatonia-like
and OCD regarding complex repetitive compulsions and
behaviors and reported that the lifetime prevalence of at
catatonic mannerisms and repetitive/perseverative behav-
least 1 motor sign in subjects with ASDs, learning dis-
iors210; and evidence for a relationship between OCD and
abilities and typically developing children was 100%, 93%,
catatonia comes from the study of the so-called schizo-
and 33%, respectively. The finding of catatonia signs in
obsessive disorder.211 Compared with their schizophrenia
typically developing children is of interest and may reflect
counteparts, the majority of schizo-obsessive subjects
age-dependent reversible developmental traits. Levels of
exhibit both catatonia (83%) and EPS (58%),210 a clinical
catatonia in ASD are inversely related to IQ,45,230–232 a
picture highly resembling Leonhard’s manneristic catato-
finding in line with the frequently reported association
nia.5 The only study systematically examining catatonia
between catatonia and intellectual disability.233–236
in Tourette’s syndrome, a disorder highly comorbid with
The only studies examining EPS in autism reported
OCD, found that it was present in 87% of the subjects.212
prevalence rates of 25% for parkinsonism237 and 18% for
About one-third of subjects with OCD exhibit both
dyskinesias.238 Levels of NSS in ASD are similar to those
dyskinesias other than tics213 and parkinsonism,214
reported in early-onset schizophrenia,82,83 and are related
although studies differ in their comparative levels in rela-
to low IQ or cognitive impairment.239–241
tion to schizophrenia.66,76 The most common movement
disorders comorbid with OCD are tics, now recognized
Alzheimer’s Disease
as a diagnostic specifier in DSM5. On a lifetime basis,
tics have been reported to co-occur in 22%–44% of sub- A broad range of catatonia-like signs, which are gener-
jects with OCD, and inversely, the 20%–40% of subjects ally described as neurological or EPS, have been exten-
with tic disorders have OCD.215 Subjects with OCD and sively documented in AD.242,243 However, these MAs have
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V. Peralta & M. J. Cuesta

been often poorly described,244 and no single study has multidimensional structure of this motor domain. Given
addressed the prevalence of catatonia in AD. Nevertheless, that highly differentiated symptoms tend to display a
factor-analytical studies of the neuropsychiatric inven- hierarchical arrangement,259,260 likely the catatonia syn-
tory, which comprises some catatonia-like signs within drome may be viewed as a higher-order dimension with 2
the “aberrant behavior” item, have consistently identified middle-order dimensions and various lower-order dimen-
a psychomotor factor, which has been reported to be as sions that are close to the item level. This view appears to

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clinically significant in 11% of newly diagnosed subjects fit well how catatonia is currently approached, since on
with AD245 and in 32% of subjects with varying sever- the one side, it is considered as an unspecific syndrome
ity of the disorder246; furthermore, this factor has been with similar phenomenological presentation in psychi-
related to poor functional outcome, rapidity of evolution atric, medical and neurological conditions15,261–263; and
and severity of AD.245 On the other hand, in the neuro- on the other side, clinical lore and distribution of signs
logical literature, the single most recognized catatonic across diagnoses indicates that lower-order dimensions
feature in AD is paratonia (gegenhalten), which was first are to some extent disorder-specific.
described by Dupré247 in subjects with intellectual dis- Second, one or more motor domains had a sub-
ability and afterwards by Kleist in dementia.89 Paratonia stantial prevalence across all the examined diagnoses.
usually occurs with other catatonia signs such as auto- Notwithstanding this, prevalence rates are highly con-
matic obedience, motor perseveration, echopraxia and tingent on the methodological issues described above.
frontal release signs.248 Paratonia has been found in 10% Catatonic signs had a substantial prevalence in all diag-
of early stages and in 90% of late stages of AD,249 and it noses excepting OCD, a diagnosis in which they have
is a robust independent indicator of severity and progres- been poorly examined. Particularly high rates of cata-
sion of the illness.250 Thus, if we consider aberrant motor tonic signs were observed across all classes of psychotic
behavior and paratonia as proxy indicators of catatonia, disorders, although enduring signs were mainly confined
the prevalence of a catatonia syndrome in AD appears to to schizophrenia; this suggesting that non-enduring cata-
be substantial and of most clinical relevance. tonia signs are a hallmark transdiagnostic feature of psy-
Although cognitive impairment is the signature feature chotic illness, while enduring catatonic signs are specific
of AD, EPS are extremely common with a prevalence rate to schizophrenia. EPS had a substantial prevalence in
ranging from 12% in mild stages251 up to 92% in severe disorders of neurodevelopmental or neurodegenerative
stages,252 with parkinsonism being much more prevalent origin; and NSS showed similar high levels across diag-
than dyskinesias.253 Furthermore, mild parkinsonism in noses excepting OCD and depression. The transdiagnos-
the elderly has been reported as a risk factor for devel- tic prevalence of MAs is in a small part definitional since
oping dementia.254 Based on the presence or absence of only catatonic signs are included in the diagnostic criteria
EPS 2 AD subphenotypes can be recognized: “cognitive/ of psychotic and ASD.
pure” and “cognitive/motor,” mirroring the classification Third, MAs were a severity marker of either the illness
of Parkinson disease (PD) into “motor” and “motor/cog- episode or the disorder. In “functional” disorders, MAs,
nitive” forms. Such distinction is extremely important, as and particularly catatonia, appear to be markers of epi-
individuals with AD and EPS show a faster course of the sode severity. In neurodevelopmental and neurodegen-
disorder.253,255 Furthermore, EPS share a pattern of pre- erative (ie, chronic) disorders, but with different degree of
sentation similar to that seen in PD, suggesting common strength or evidence, all motor domains were indicators
pathogenic mechanisms across the 2 neurodegenerative of both illness severity and poor outcome. Dementia is
disorders.256 an interesting case in relation to transdiagnostic mecha-
There are few studies of NSS in AD, but they con- nisms, since it has an established neuropathology. In AD,
sistently show that AD exhibit higher NSS compared abnormal motility in addition to being a marker of sever-
with mild cognitive impairment257 and healthy old con- ity was also a marker of illness progression.
trols.257,258 Furthermore, NSS appear to increase with pro- A subordinate but interesting finding was that one
gression of AD and cognitive deterioration.258 or more motor domains were consistently related with
poor cognition in neurodevelopmental disorders; fur-
thermore, in schizophrenia both motor and cognitive
Discussion
dysfunctions appear to be stable traits long before illness
This revision raised some relevant findings that could onset. Motor and cognitive dysfunctions are also inex-
eventually inform the transdiagnostic issue of MAs in tricably linked in AD and other widespread neurodegen-
psychiatric disorders. First, MAs represent an overarch- erative disorders such as PD256; thus, it could be argued
ing concept entailing inter-related motor domains, which that the 2 domains are intimately related in both neuro-
in turn can be further differentiated into several subdo- developmental and neurodegenerative disorders, which
mains. Of particular concern was the lack of a consistent further support the transdiagnostic character of MAs.
syndromic structure of catatonia beyond the excite- Interestingly, in schizophrenia, dyskinesias may appear
ment and retarded factors, which poorly account for the long before illness onset as a manifestation of deviant
962
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neurodevelopment125–128 (see Schiffman, this issue), and Limitations

they increase with age,55 particularly after age 65,264 this
Several limitations apply to the present study. First, while
suggesting that for this particular motor domain 2 over-
our study covered the major clinical domains of MAs
lapping and age-dependent neurobiological mechanisms
observed in psychiatric disorders, we excluded studies
are possible.
using instrumental measures274,275 and experimental par-
Although not object of this review, some etiologi-

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adigms276,277 of motor dysfunction. These measures and
cal, therapeutic and neurobiological questions can also
paradigms are increasingly used to disentangle mecha-
illustrate the transdiagnostic issue of MAs. Regarding
nisms underlying abnormal motility and ideally they
familial-genetic factors, catatonic schizophrenia appears
should be used together with clinical ratings of MAs.
to exhibit higher familial loading of psychotic disorders
Second, some disorders defined by abnormal motility
than noncatatonic schizophrenia,265,266 and Leonhard’s
such as ADHD and tic disorders were not included in
periodic catatonia has been consistently considered as
this review; these diagnoses, however, are important tar-
highly familial5,97 with a morbidity risk of 26.9% and
gets for transdiagnostic research that should be exam-
major gene effect and anticipation.267 As showed in
ined in future studies. Third, we largely relied on articles
this review, compared to healthy controls, higher levels
focused on specific disorders, which had a highly variable
of NSS have been found in the first-degree relatives of
methodology; therefore, some subjectivity in selecting
subjects with schizophrenia, BD, and OCD, while in the
the most informative articles cannot be excluded; fur-
other diagnoses there was a lack of studies thereof. Thus,
thermore, the range of MAs-related features reviewed
familiality of catatonia may be disorder-specific, while
here was necessarily limited and highly dependent on
that of NSS cut-across several diagnoses. Regarding
the quality of individual studies. Fourth, in analyzing
treatment, lorazepam and electroconvulsive therapy are
the existing data we mainly focused on general measures
highly effective in treating acute catatonia regardless
of catatonic, extrapyramidal and neurological signs, and
the underlying etiology, with response rates of 70%–
it is possible that focusing on more specific dimensions
90%.268,269 Although these treatments appear to be some-
of MAs might reveal a somewhat different pattern of
what less effective in neurodevelopmental and medical
MAs-related features across disorders. Lastly, the studies
conditions,270 their overall effectiveness for catatonia is
reviewed adopted widely varying measures and designs,
one of the major arguments for considering this syn-
and further progress in transdiagnostic comparison of
drome transdiagnostically.
MAs arguably requires consistency of measures across
Lastly, given the transdiagnostic character of MAs
the groups studied.
in most of the realms addressed in this review, it could
be argued that they share abnormal brain circuitry
Conclusions and Future Directions
functioning involving the motor system, which may be
viewed as common pathway of the various motor loop Despite their clinical and neurobiological relevance, MAs
networks related to different disorders and brain mech- continue to be a neglected area in clinical practice and
anisms. In this regard, some plausible models of brain research. Domains of MAs cut-across neurodevelop-
dysfunction underlying motor domains have been pro- mental, “functional” and neurodegenerative disorders,
posed271–273 (also see Pantelis and Mittal et al, this issue). although with different expressivity or prevalence. They
For example, Northoff,271 attempted to explain catatonic are markers of episode or illness severity across diagno-
and extrapyramidal signs by integrating dysfunction of ses, and in AD are also indicators of illness progression.
brain circuitry and neurotransmission; to explain cata- MAs appear to represent a true transdiagnostic domain
tonia, he suggested a deranged “top-down” modulation putatively sharing neurobiological mechanisms of neu-
of cortical-subcortical connections (as reflected, eg, in rodevelopmental, functional or neurodegenerative ori-
the modulation of basal ganglia by lateral orbito-frontal gin, this being a strong argument for studying MAs on
cortex) related to cortical GABAergic-mediated dys- their own, irrespective of diagnostic categories. MAs are
function; and to explain EPS, he suggested a “bottom- closely tied to neurobiological mechanisms, and thus, they
up” modulation of cortical-subcortical connections are a window to the brain mechanisms of psychiatric and
related to basal ganglia dopamine dysfunction. More neuropsychiatric disorders, but we know virtually noth-
recently, Hiryak272 developed a 3-stage severity model ing about the shared and disorder-specific mechanisms.
of catatonic, extrapyramidal and neurological signs in Thus, unraveling these mechanisms may share light on
schizophrenia on the basis of a graded dysfunction of the nature of both motor dysfunction and the underlying
the cortico-cerebelar-thalamo-cortical loop. The 2 mod- diagnoses.
els appear to work well across the 3 neurobiological Given the complexities surrounding the definition and
mechanisms involved in the diagnoses examined: stable assessment of abnormal motility in psychiatry, we first
dysfunction in neurodevelopmental disorders, reversible need a unified theory and assessment tool for MAs, and
dysfunction in functional disorders, and progressive dys- the 3 motor domains should be examined concurrently
function in AD. along with instrumental measures of motor function. The
963
V. Peralta & M. J. Cuesta

ideal methodological requirements would be the prospec- 11. Kleist K. Die Katatonien. Nervenarzt. 1943;16:1–10.
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1997;38:193–201.
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