09209964-S0920996410X00056-S0920996409006148-main.pdf

8/14/2019 09209964-S0920996410X00056-S0920996409006148-main.pdf

1/8

DSM-IV catatonia signs and criteria in rst-episode, drug-naive, psychoticpatients: Psychometric validity and response to antipsychotic medication

Victor Peralta, Maria S. Campos, Elena Garcia de Jalon, Manuel J. Cuesta

Psychiatric Unit, Virgen del Camino Hospital, Irunlarrea 4, 31008 Pamplona, Spain

a r t i c l e i n f o a b s t r a c t

Article histo ry:

Received 29 September 2009

Received in revised form 1 December 2009

Accepted 19 December 2009

Available online 13 January 2010

Objective: To examine the prevalence, psychometric validity and response to antipsychotic

drugs of DSM-IV catatonia signs and criteria in patients with a rst-episode psychotic disorder.

Methods: Two-hundred antipsychotic-naive patients with a DSM-IV nonaffective psychosis

were assessed for catatonia signs and criteria using the Modied Rogers Scale, and the

psychometric validity of the 12 DSM-IV catatonia signs and diagnostic criteria was examined.

Treatment response of catatonia was assessed in 173 patients who completed one-month trial

with haloperidol (n =23), risperidone (n = 93) or olanzapine (n =57).

Results: Sixty-two patients (31%)endorsed at least onecatatonia sign and24 (12%) metDSM-IV

criteria for catatonia. DSM-IV catatonia signs showed an excellent convergent validity ( rN0.8)

with other rating scales, and DSM-IV criteria showed moderate to fair concordance with other

criteria ( from 0.57 to 0.77). The total number of signs reected catatonia severity and

demonstrated excellent diagnostic performance against alternative diagnostic criteria. The

presence of at least any three signs accurately identied patients with catatonia. Three

catatonia domains were identi

ed (hyperkinesia, volitional and hypokinesia), which showed adifferent association pattern with external variables. Overall, catatonia ratings were

particularly related to both dyskinesia and disorganization symptoms and lacked diagnostic

specicity for schizophrenia. Patients with catatonia responded well to antipsychotic

medication irrespective of the type of antipsychotic drug used, although treatment response

was dependent upon the remission of psychotic symptoms.

Conclusions:These results may inform the DSM-V development on diagnosis and classication

of catatonia, and indicate that catatonia signs and syndromes are highly responsive to

antipsychotic drugs.

2009 Elsevier B.V. All rights reserved.

Keywords:

Catatonia

First-episode psychosis

Drug-naive

Diagnosis

Treatment

1. Introduction

Catatonia is an intriguing neuropsychiatric disorder withmany clinical and research challenges. Universally accepted

denitions of the core catatonia signs anddiagnostic criteria are

lacking. The boundaries of the syndrome remain so ill-dened

that different rating scales measuring catatonia include from

10to morethan 40signs(Taylor and Fink, 2003) and a number

of alterative and overlapping denitions have been proposed.

In fact, although the practicing psychiatrists should be familiar

with catatonia, there is general agreement among researchers

that the syndrome is poorly recognized. Many reasons have

been advocatedfor explaining this state of the art, includingthe

way in which catatonia is dened in current diagnostic systemssuch as DSM-IV (APA, 1994) and ICD-10 (WHO, 1993) where

catatonia is mainly recognized as a subtype of schizophrenia.

Despite that the DSM criteria are the primary tool for

diagnosing catatonia, there is little information about the

psychometric characteristics of DSM-IV signs and criteria.

A potential difculty in further understanding catatonia in

psychotic disorders is the fact that catatonia may be

inuenced by antipsychotic medication in two different

ways. On the one hand, antipsychotic drugs may produce

catatonia (Gelenberg and Mandel, 1977; Caroff et al., 2002) or

worsen it to the point of producing malignant catatonia

Schizophrenia Research 118 (2010) 168175

Corresponding author. Tel.: +34 848 422 488; fax: +34 848 429 924.

E-mail address:[email protected](V. Peralta).

0920-9964/$ see front matter 2009 Elsevier B.V. All rights reserved.doi:10.1016/j.schres.2009.12.023

Contents lists available at ScienceDirect

Schizophrenia Research

j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / s c h r e s
mailto:[email protected]://dx.doi.org/10.1016/j.schres.2009.12.023http://www.sciencedirect.com/science/journal/09209964http://www.sciencedirect.com/science/journal/09209964http://dx.doi.org/10.1016/j.schres.2009.12.023mailto:[email protected]

8/14/2019 09209964-S0920996410X00056-S0920996409006148-main.pdf

2/8

(White and Robins, 1991; Taylor and Fink, 2003). On the

other hand, a number of case reports (Van Den Eede et al.,

2005) and a few observational studies (Peralta and Cuesta,

1999; Martnyi et al., 2001) suggest that antipsychotic drugs

may ameliorate catatonic signs. In fact, it has been pointed

out that the introduction of antipsychotic drugs is in part

responsible for catatonia to have both decreased in rate and

become more subtle (Morrison, 1974; Blumer, 1997).

Previous studies on catatonia have been typically con-

ducted in patients with different degrees of chronicity and

exposure to antipsychotic medication, which might affect the

prevalence and correlates of catatonia. The characterization of

motor disorders inrst-episode psychotic disorders has been

a neglected area of research, this despite catatonic features

represent a core dimension of the psychotic illness (Peralta

and Cuesta, 2001a). Studying patients early in the course

of illness before antipsychotic exposure and the effect of

chronicity is a strategy that lends itself to addressing basic

questions about catatonia such as its prevalence, correlates

and effect of antipsychotic drugs.

In this study, we aimed at examining the prevalence and

correlates of DSM-IV catatonia signs and criteria in a sample

of neuroleptic-naive psychotic patients. Specic aims were to

examine (a) the prevalence of DSM-IV catatonia signs and

criteria, (b) their psychometric validity including convergent

validity, concordance, diagnostic performance, factor structure,

internal reliability and external validity, and (c) to examine the

treatment response of catatonia after a one-month trial with

antipsychotic medication.

2. Methods

2.1. Subjects

The study population comprised 200 subjects who were

antipsychotic-naive and met DSM-IV criteria for a nonaffec-

tive psychotic disorder. The population sample for this study

was derived from two independent samples sharing identical

ascertainment procedure and assessment instruments for rating

illness-related variables, psychopathology and neuromotor ab-

normalities but differing in their aims. Study A (n=100) had a

naturalistic design and was aimed at examining the one-month

effect of haloperidol, risperidone or olanzapine on primary

neuromotor abnormalities (Peralta et al., in press). Study B

(n= 100) hada randomized designand was aimed at examining

the effect of risperidone or olanzapine on neurocognition (Cuestaet al., 2009). The two samples did not differ in demographic or

clinical background variables.

Thecriteriafor inclusion were: (a)patientsexperiencing their

rst episode of a nonaffective psychotic disorder, (b) no previous

exposure to antipsychotic drugs, and (c) age 1565 years.

Exclusion criteria were: (a) a history of drug dependence,

(b) evidence of organic brain disorder including mental re-

tardation, epilepsy, brain injury and neurodegenerative dis-

orders, and (c) meaningful somatic disease. The study was

approved by the local ethical committee and all the patients

or their legal representatives gave written informed consent

to participate in the study. The main demographic and clin-

ical characteristics of the whole study sample are presentedinTable 1.

2.2. Assessments

2.2.1. Demographic and clinical variables

Demographics, clinical features, psychopathology and di-

agnosis were all rated using the Comprehensive Assessment

of Symptoms and History (CASH; Andreasen et al., 1992).

Premorbid social adjustment was rated according to the

Phillips scale (Harris, 1975). A positive family history of a

nonaffective psychosis was rated by means of the Family-

History Research Diagnostic Criteria (Andreasen et al., 1977)

and scored as 0 (absent), 1 (at least one second-degree relative

affected) and 2 (at least one rst-degree relative affected). Age

at onset and duration of untreated psychosis were assessed by

means of the Symptom Onset in Schizophrenia (SOS) scale

(Perkins et al., 2000).

2.2.2. Catatonia signs and criteria

Motor disorders were evaluated by VP or MJC, and MSC

and EGJ assessed the other aspects of the disease. The

assessment of motor disorders was done using a structured

procedure for all the motor rating scales used in this study.Evaluations were conducted at two time points, before the

beginning of antipsychotic treatment and one month after.

The main outcome measure for catatonia was the Modied

Rogers Scale (MRS,Lund et al, 1991), which has shown robust

psychometric properties across studies (Lund et al, 1991;

McKenna et al., 1991; Starkstein et al. 1996; Peralta and Cuesta

2001b) including an excellent convergent validity with other

catatonia rating scales (Northoff et al., 1999). The MRS de-

scribes a broad range of motor behaviors by comprising

33 specic items plus 4 items for othermotor abnormalities

describing 8 additional motor signs, altogether resulting in the

assessment of 41 specic motor features. Each item is rated on a

scale of 0

2 (0=absent, 1=clearly present, 2=marked orpervasive) following a standardized procedure. To the best of

our knowledge the MRS represents the most comprehensive

rating scale for the assessment of motor features of psy-

chiatric disorders and allows to rate specic catatonia items

according to most diagnostic criteria, including those used in

this study for examining convergent validity: the DSM-IV

Table 1

Demographic and clinical characteristics of the sample ( n =200).

Mean (s.d.) n (%)

Age, years 29.8 (10.2)

Years of education 11.9 (4.1)Premorbid social adjustment 2.1 (1.5)

Age of illness onset (rst psychotic symptom) 27.4 (9.6)

Duration of untreated psychosis (years) 2.3 (4.2)

Gender (male) 133 (66.5)

Civil status (single) 163 (81.5)

Family history of a nonaffective psychotic disorder

Absent 136 (68.0)

At least one second-degree relative affected 31 (15.5)

At least one rst-degree relative affected 33 (16.5)

DSM-IV diagnosis

Schizophrenia 94 (47.0)

Schizophreniform disorder 36 (18.0)

Schizoaffective disorder 13 (6.5)

Brief psychotic disorder 38 (19.0)

Delusional disorder 15 (7.5)

Psychosis NOS 4 (2.0)

169V. Peralta et al. / Schizophrenia Research 118 (2010) 168175
http://dx.doi.org/10.4088/PPC.09m00799gryhttp://dx.doi.org/10.4088/PPC.09m00799gry

8/14/2019 09209964-S0920996410X00056-S0920996409006148-main.pdf

3/8

(APA, 1994), ICD-10 (WHO, 1993) and Taylor and Fink

(2003)criteria.

The 12 DSM-IV catatonia signs were rated as present or

absent according to the severity level indicated by the

DSM-IV. In addition, a DSM-IV catatonia global severity score

was constructed: 0 (no catatonic signs present), 1 (presence

of catatonic signs not meeting diagnostic criteria), 2 (mild

catatonia), 3 (moderate catatonia), and 4 (severe catatonia).

Catatonia was also rated by means of the catatonic motor

behavior module from the CASH, which includes ve cata-

tonic signs (stupor, rigidity, waxy exibility, excitement

and posturing/mannerisms) each scored on a 02 scale, and

a 6-point scale for rating catatonia severity. Presence of cat-

atonia according to the CASH was dened as a score of two

or more on the global severity rating.

2.2.3. Extrapyramidal symptoms

All the patients were rated for parkinsonism, dyskinesia

and akathisia before starting antipsychotic treatment, which

were respectively assessed by means of the Abnormal

Involuntary Movement Scale (Guy, 1976), the Simpson

Angus Rating Scale (Simpson and Angus, 1970) and the

Barnes Akathisia Rating Scale (Barnes, 1989).

2.2.4. Response to antipsychotic treatment

Of the 200 patients who were assessed at admission for

catatonia, 173 completed one-month trial with haloperidol

(n=23), risperidone (n=93) or olanzapine (n =57). Treat-

ment groups did not meaningfully differ in background

variables nor in their mean daily dose of Chlorpromazine

equivalents. Patients initially received a low dose of antipsy-

chotic drug that was gradually titrated up over the course of

the episode, and other psychotropic medications were

allowed if necessary. A more detailed description of the

treatment procedure can be found inPeralta et al. (in press)

and Cuesta et al. (2009).

2.3. Statistics

Convergent validity for continuous measures of DSM-IV

catatonia was examined by means of Pearson's correlation

coefcients, and concordance among diagnostic criteria by

means of coefcients. A Receiver Operator Characteristic

(ROC) analysis was used to examine the diagnostic perfor-

mance of the total number of catatonia signs and to determine

the optimal number of signs for diagnosing catatonia.

The factor structure of catatonia signs was examined bymeans of principal component analysis. Factors with eigen-

value N1 were extracted and rotated using the varimax

procedure. Factor scores were obtained and subscale scores

were constructed on the basis of those items most loading on a

given factor. Subscale scores were used for subsequent analysis

as they can be easily reproduced by other authors allowing for

a more direct comparison among studies. Internal consistency

of the factor-derived subscales was assessed by means of the

SpearmanBrown formula to adjust for number of items.

The association of catatonia domains and criteria with

demographics, premorbid variables, psychopathology and

extrapyramidal symptoms was examined by means of linear

or logistic regression analysis as appropriate. Treatment effectwas examined by means of repeated-measures analyses of

variance with baseline and 4-week scores as dependent

variables, time as a within-subject repeated measure (overall

treatment effect), and treatment group as a between-subjects

xed factor (specic treatment effect). All tests of hypotheses

were done at a 2-sided 5% level of signicance. The Statistical

Package for the Social Sciences, version 14.0, was used to

perform all analyses.

3. Results

3.1. Inter-rater reliability

Inter-rater reliability was adequate for individual DSM-IV

catatonia signs ( between 0.73 and 0.95) and diagnostic

criteria (=0.86), and excellent for the DSM-IV catatonia

severity score (ICC=0.92), the MRS total score (ICC=0.94)

and the CASH global severity score (ICC=0.90).

3.2. Prevalence of DSM-IV catatonia signs and criteria

Fig. 1 displays a path diagram showing the prevalence rate

of the individual 12 DSM-IV catatonia signs, the 5 specic

criteria and the catatonia syndrome. The most frequent sign

was posturing (n =24, 12%) and the less frequent was waxy

exibility (n= 5, 2.5%). The most frequent criterion was

peculiarities of voluntary movement (n =42, 21%) and the

less frequent was agitation (n= 10, 5%). Twenty-four patients

(12%) met DSM-IV criteria for catatonia, thus is, they had at

least two of the ve criteria. The overall prevalence rate of

catatonia signs was relatively high since 62 patients (31%)

had one or more signs, 33 patients (16.5%) had two or more

signs and 19 patients (9.5%) had three or more signs.

All the catatonia signs were signicantly more prevalent in

catatonic than in noncatatonic patients (

2 from 23.0 to 68.6,

df= 1,pb0.001). In the total sample, the mean number of signs

was 0.74 (s.d.= 1.56, range= 010), and that in patients with

and without catatonia was 4.04 (s.d.=2.21, range =210)and

0.29 (s.d.= 0.64, range= 04), respectively (pb0.001).

3.3. Individual signs and severity of catatonia

Individual catatonia signs were strongly and consistently

correlated (pb0.001) with alternative ratings of catatonia

severity (Table 2). However, the degree of relatedness varied

across signs, with catalepsy and posturing sowing the highest

correlations (between 0.59 and 0.68), and grimacing and hy-

peractivity showing the lowest ones (between 0.27 and 0.47).

The various signs bore different correlations with their total

number with coefcients ranging from 0.30 (hyperactivity) to

0.68 (posturing).

3.4. Concurrent validity

The total number of DSM-IV catatonia signs strongly cor-

related with both the DSM-IV (r=0.79, pb0.001) and the

CASH (r=0.89, pb0.001) catatonia severity scores. There

was also a strong association between the total number of

signs and the MRS total score (r=0.91, pb0.001). While this

is obvious, since DSM-IV catatonia signs are embedded in the

MRS, it indicates that they represent a good index of therather more global motor disturbance addressed by the MRS.

170 V. Peralta et al. / Schizophrenia Research 118 (2010) 168175
http://dx.doi.org/10.4088/PPC.09m00799gryhttp://dx.doi.org/10.4088/PPC.09m00799gryhttp://dx.doi.org/10.4088/PPC.09m00799gryhttp://dx.doi.org/10.4088/PPC.09m00799gry

8/14/2019 09209964-S0920996410X00056-S0920996409006148-main.pdf

4/8

The number (and percent) of patients meeting catatonia

criteria according to the ICD-10, CASH and Taylor and Fink

were 39 (19.5%), 30 (15%) and 21 (10.5%), respectively; and

their concordance () with the DSM-IV criteria was 0.61, 0.57

and 0.77, respectively.

3.5. Diagnostic performance of the total number of catatonia signs

Table 3 depicts diagnostic performance of the total

number of catatonia signs against alternative diagnostic

criteria. The total number of signs performed well across all

diagnostic systems (area under the ROC curve from 0.87 to

0.99), however, the optimally efcient number of signs

necessary for diagnosis varied across diagnostic systems. For

example, if we consider diagnostic efciency (correct classi-

cation rate) parameter, one or more signs yielded the best

diagnostic efciency for either criteria present (0.87), two or

more signs yielded the best efciency for DSM-IV criteria

(0.95), three or more signs yielded the best efciency for

ICD-10 (0.88), Taylor and Fink (0.96), CASH (0.94) and all

criteria present (0.98). Increasing the cutoff score to 4 or

more signs yielded a decrease of the diagnostic efciency

across diagnostic systems.

3.6. Factorial validity and internal consistency

Principal component analysis of the 12 catatonia signs

resulted in 3 factors that accounted for 57.3% of variance

(Table 4). The

rst factor (hyperkinesia) was made up ofagitation, posturing, mannerisms, stereotypies and grimacing.

Thesecond factor (volitional)was made of negativism, mutism,

echolalia and echopraxia. The third factor was composed of

catalepsy, waxy exibility and stupor. The internal consistency

for the three catatonia domains was adequate and slightly

higher than that for the 12 catatonia signs (0.66). Factor

scores were highly correlated with their corresponding factor-

derived subscales: hyperkinesia (r= 0.96), volitional (r=0.95)

and hypokinesia (r=0.88).

3.7. Association with external variables

Overall, catatonia domains showed a different associationpattern with external variables (Table 5). The only association

Fig. 1.Path diagram showing the prevalence rate of DSM-IV catatonia signs and criteria.

Table 2

Pearson's product-moment correlations between individual DSM-IV catato-

nia signs and alternative denitions of catatonia severity.

Total number

of DSM-IV

signs

DSM-IV global

severity rating

CASH global

severity rating

MRS total

score

Catalepsy 0.67 0.60 0.59 0.63

Waxy

exibility

0.60 0.47 0.54 0.55

Stupor 0.49 0.56 0.47 0.49

Agitation 0.30 0.39 0.33 0.28

Mutism 0.53 0.58 0.50 0.49

Negativism 0.51 0.53 0.40 0.44

Posturing 0.68 0.60 0.63 0.67

Mannerisms 0.60 0.48 0.60 0.53

Stereotypies 0.58 0.40 0.51 0.52

Grimacing 0.47 0.34 0.33 0.41

Echolalia 0.59 0.55 0.47 0.54

Echopraxia 0.54 0.53 0.52 0.44

DSM-IV = Diagnostic and Statistical Manual, fourth ed., CASH =

Comprehensive Assessment of Symptoms and History, MRS = ModiedRogers Scale.


8/14/2019 09209964-S0920996410X00056-S0920996409006148-main.pdf

5/8

shared by all catatonia ratings was with disorganization

symptoms. All catatonia ratings, excepting the volitional

domain, were related to dyskinesia. The hyperkinesia domain

had unique associations with poor premorbid social adjust-

ment, negative symptoms and a diagnosis of schizophrenia,

and the volitional domain had unique correlates with

parkinsonism. Overall, DSM-IV criteria, and particularly the

number of catatonia signs, captured well the associations of

the specic domains.

3.8. Response to antipsychotic treatment

All the catatonia ratings improved signicantly after one-

month trial with antipsychotics (Table 6), and no specic treat-

ment effect was observed. These results remained unmodied

after controlling for concomitant medication and antipsychotic

dose. The difference in the proportion of patients with DSM-IV

catatonia at admission (n=24, 12%) and one month after

treatment (n=4, 2.1%) was highly signicant (McNemar test

pb0.001).

Because the response of catatonia to antipsychotic medi-

cation may be due to the effect on positive symptoms rather

than an effect on catatonia itself, we tested this hypothesis by

introducing change of psychotic symptoms as assessed withthe Scale for the Assessment of Positive Symptoms as a

covariable in the repeated design model. After adjusting for

change in positive symptoms, the time effect for each catatonia

rating was no longer signicant: hyperkinesia dimension (F=

0.07, df=1, p=0.786), volitional dimension (F=2.93, df=1,

p=0.089), hypokinesia dimension (F=1.73,df=1,p =0.190),

total number of signs (F=1.84,df=1,p =0.176) and catatonia

severity (F=1.70, df=1,p=0.193).

4. Discussion

4.1. Mainndings

Catatonia signs, as described in DSM-IV, were relatively

prevalent in this sample of rst-episode never-treated

psychotic patients, as 62 patients (31%) endorsed at least

one sign and 24 patients (12%) met diagnostic criteria for

catatonia. All single signs considered were strongly correlated

with their total number, which in turn was strongly cor-

related with severity of catatonia, giving strength to the

syndromic conception of catatonia. The DSM-IV criteria were

most similar to the Taylor and Fink than to any other criteria,

which seems to be due to the similar number and type of

signs included along with the fact that the two systems

require signs from two domains for diagnosing the disorder.The total number of DSM-IV catatonia signs demonstrated

excellent diagnostic performance, and the presence of at least

three signs best discriminated between patients with and

without catatonia across most denitions. The 12 DSM-IV

catatonic signs clustered together into hyperkinetic, voli-

tional and hypokinetic factors, which showed adequate in-

ternal consistency and a rather different correlational pattern

with external variables. Overall, catatonia ratings were par-

ticularly associated with disorganization symptoms and

dyskinesia, and diagnostically unspecic. Catatonia ratings

responded well to a one-month trial with typical and atypical

antipsychotic drugs, but this effect was not specic as it was

entirely dependent on the effect of medication on positivesymptoms.

Table 4

Principal component analysis of DSM-IV catatonia signs.

Hyperkinesia Volitional HypokinesiaCatalepsy 0.42 0.23 0.65

Waxy exibility 0.29 0.24 0.71

Stupor 0.07 0.09 0.76

Agitation 0.41 0.31 0.40

Mutism 0.11 0.70 0.40

Negativism 0.04 0.62 0.36

Posturing 0.63 0.12 0.36

Mannerisms 0.78 0.01 0.13

Stereotypies 0.65 0.19 0.14

Grimacing 0.65 0.03 0.01

Echolalia 0.21 0.80 0.05

Echopraxia 0.19 0.77 0.04

Eigenvalue 3.80 1.70 1.37

Variance explained 31.7 14.2 11.4

Internal Consistency 0.67 0.70 0.75

DSM-IV = Diagnostic and Statistical Manual, fourth ed.

Table 3

Diagnostic performance of the total number of DSM-IV catatonia signs

against alternative diagnostic criteria for catatonia.

ROC curve

(95% CI)

S SP PPV NPV EF

DSM-IV criteria

(n =24)

0.98 (0.971.0)

1 or more signs 1.0 0.78 0.39 1.0 0.81

2 or more signs 1.0 0.95 0.72 1.0 0.95

3 or more signs 0.67 0.98 0.84 0.95 0.94

4 or more signs 0.50 0.99 0.92 0.93 0.93

ICD-10 criteria

(n =39)

0.87 (0.790.94)

1 or more signs 0.85 0.82 0.53 0.95 0.81

2 or more signs 0.56 0.93 0.67 0.89 0.86

3 or more signs 0.44 0.99 0.89 0.88 0.88

4 or more signs 0.31 1.0 0.92 0.85 0.86

Taylor and Fink

criteria (n =21)

0.97 (0.950.99)

1 or more signs 1.0 0.77 0.34 1.0 0.79

2 or more signs 0.90 0.92 0.57 0.99 0.92

3 or more signs 0.76 0.98 0.84 0.97 0.96

4 or more signs 0.57 0.99 0.92 0.95 0.95

CASH criteria

(n =30)

0.93 (0.870.98)

1 or more signs 0.93 0.80 0.45 0.98 0.82

2 or more signs 0.70 0.93 0.63 0.94 0.89

3 or more signs 0.63 1.0 1.0 0.94 0.94

4 or more signs 0.43 1.0 1.0 0.90 0.91

Either criteria

present (n =52)

0.89 (0.820.95)

1 or more signs 0.85 0.88 0.71 0.94 0.87

2 or more signs 0.54 0.97 0.85 0.86 0.85

3 or more signs 0.36 1.0 1.0 0.82 0.83

4 or more signs 0.25 1.0 1.0 0.79 0.80

All criteria present

(n =15)

0.99 (0.981.0)

1 or more signs 1.0 0.75 0.24 1.0 0.76

2 or more signs 1.0 0.90 0.45 1.0 0.91

3 or more signs 1.0 0.98 0.79 1.0 0.984 or more signs 0.73 0.99 0.85 0.98 0.97

DSM-IV = Diagnostic and Statistical Manual, fourth ed., ROC = Receiver

Operating Characteristic, S = Sensitivity, SP = Specicity, PPV = Positive

Predictive Value, NPV = Negative Predictive Value, EF = Efciency (correct

classication rate).


8/14/2019 09209964-S0920996410X00056-S0920996409006148-main.pdf

6/8

4.2. Comparison with previous studies

A direct comparison of our ndings with those of previous

literature is difcult given the unique characteristics of our

sample. Notwithstanding, comparison with other studies may

shed some light on the stability ofndings across samplesand

stages of the psychotic illness. The prevalence of catatonia in

this rst-episode population was in the range reported in

patients hospitalized with acute psychotic episodes (Caroff etal., 2004), and the 2-fold prevalence variability of catatonia

across diagnostic systems was in line with that reported

previously by our group in chronic schizophrenia (Peralta and

Cuesta, 2001c). Accordingly, prevalence of catatonia seems to

be rather stable across episodes of the psychotic illness.

Previous factor-analytic studies of catatonia signs have

shown great variability in the number of factors reported,

ranging from 1 (Oulis et al., 1997) to 6(Peralta and Cuesta,

2001b). While thismay be in part attributedto differing samples

and statistical procedures, the most likely source of variability is

the rating scale used to assess catatonia, as scales vary highly in

terms of the number and type of signs included. Most previous

studies, however, converge to indicate the existence of at least

two factors, hyperkinetic and hypokinetic (Abrams et al., 1979;

McKenna et al., 1991; Northoff et al., 1999;Ungvari et al., 2007),

which have a similar symptom composition to that observed in

our study. Our volitional factor has not been described

previously. It includes seemingly contradictory signs such asechophenomena and mutism/negativism that may be concep-

tualized as disorders of the behavioral interaction between the

patientand others. Bleuler (1911) already noted the association

between these two kinds of phenomena that ts well to

Kraepelin's concept ofparabulia(Kraepelin, 1913).

There is no general agreement about the number of signs

both necessary and sufcient to diagnose catatonia and from

one (ICD-10) to four or more signs (Rosebush et al., 1990,

Bruning et al., 2000) have been proposed, mainly on the

Table 5

Regressionsa of clinical characteristics relating to demographic and clinical variables, psychopathological syndromes and extrapyramidal signs on DSM-IV

catatonia ratings.

Hyperkinesia dimension Volitional dimension Hypokinesia dimension Total number of signs Diagnostic criteria

Demographic and clinical

Age, yrs 0.03 (0.05) 0.03 (0.04) 0.01 (0.03) 0.07 (0.08) 0.08 (0.20)

Gender 0.01 (0.13) 0.02 (0.10) 0.00 (0.07) 0.03 (0.23) 0.56 (0.48)

Years of education 0.02 (0.02) 0.01 (0.01) 0.00 (0.01) 0.01 (0.03) 0.04 (0.06)

FH of nonaffective psychosis 0.04 (0.09) 0.09 (0.07) 0.01 (0.05) 0.11 (0.15) 0.03 (0.32)

Premorbid social adjustment 0.11 (0.05)* 0.07 (0.04) 0.05 (0.03) 0.22 (0.08)** 0.36 (0.15)*

Age of onset, yrs 0.04 (0.05) 0.03 (0.04) 0.02 (0.03) 0.09 (0.08) 0.14 (0.20)

DUP 0.01 (0.00) 0.00 (0.00) 0.00 (0.00) 0.01 (0.01) 0.01 (0.02)

Diagnosis (schizophrenia) 0.29 (0.14)* 0.10 (0.10) 0.06 (0.08) 0.24 (0.24) 0.01 (0.50)

Psychopathology

Mania 0.00 (0.01) 0.01 (0.05) 0.02 (0.04) 0.03 (0.11) 0.20 (0.23)

Depression 0.03 (0.05) 0.06 (0.04) 0.02 (0.03) 0.01 (0.08) 0.01 (0.19)

Reality-distortion 0.03 (0.06) 0.04 (0.05) 0.05 (0.03) 0.12 (0.10) 0.17 (0.22)

Disorganization 0.19 (0.05)*** 0.09 (0.04)* 0.08 (0.03)** 0.36 (0.08)*** 0.67 (0.18)***

Negative 0.11 (0.04)* 0.04 (0.03) 0.03 (0.02) 0.18 (0.08)* 0.11 (0.16)

Extrapyramidal symptoms

Parkinsonism 0.00 (0.01) 0.04 (0.01)** 0.01 (0.01) 0.06 (0.03)* 0.18 (0.19)

Dyskinesia 0.20 (0.02)*** 0.01 (0.01) 0.07 (0.01)*** 0.29 (0.03)*** 0.33 (0.10)***

Akathisia 0.05 (0.08) 0.05 (0.08) 0.11 (0.06) 0.12 (0.17) 1.0 (0.97)

DSM-IV = Diagnostic and Statistical Manual, fourth ed., FH = family history, DUP = duration of untreated psychosis.*p0.05, **p0.01, ***p0.001.a Values are regression coefcients (and standard errors).

Table 6

Mean (SD) catatonia ratings at baseline and endpoint in the whole sample and by treatment group.

Whole sample Treatment group

Haloperidol (n =23) Risperidone (n =93) Olanzapine (n = 57) Time effect Treatment

effect

Baseline 4 weeks Baseline 4 weeks Baseline 4 weeks Baseline 4 weeks F(df=1) p F(df=2) p

Hyperkinesia

dimension

0.410.90 0.150.50 0.430.78 0.130.34 0.481.04 0.160.59 0.300.68 0.140.39 15.42 b0.001 0.49 0.608

Volitional

dimension

0.210.67 0.030.19 0.521.16 0.040.20 0.190.64 0.020.14 0.130.42 0.030.25 18.10 b0.001 2.97 0.059

Hypokinesia

dimension

0.130.49 0.010.10 0.040.21 0.000.00 0.170.54 0.020.14 0.110.47 0.000.00 5.28 0.023 0.94 0.393

Total number

of signs

0.751.57 0.190.59 1.001.53 0.170.49 0.831.80 0.200.66 0.531.11 0.170.52 22.32 b0.001 0.81 0.447

Catatonia global

severity rating

0.631.22 0.150.49 0.871.36 0.170.49 0.661.23 0.160.55 0.631.22 0.150.50 26.49 b0.001 0.62 0.535


8/14/2019 09209964-S0920996410X00056-S0920996409006148-main.pdf

7/8

basis of theoretical considerations. The only previous study

empirically addressing this question reported that three or

more signs best discriminated between catatonic and non-

catatonic psychotic patients (Peralta and Cuesta, 2001c), which

is line with ndings of the present study.

Previous studies have generally reported an association of

catatonia with extrapyramidal syndromes such as dyskinesia

or parkinsonism (Bush et al., 1997; Northoff et al., 1999;

Peralta and Cuesta, 1999; Mckenna et al., 1991; Ungvari et al.,

2007) and negative symptoms (Peralta and Cuesta, 1999;

Salokangas et al., 2003; Ungvari et al., 2005). We found a clear

association of catatonia with dyskinesia, and a weak one with

parkinsonism and negative symptoms, which would partly

support the consideration of catatonia as an extrapyramidal

disorder (Rogers, 1985). On the basis of the different asso-

ciation pattern observed between previous studies and the

present one, it could be argued that while the association of

catatonia with dyskinesia may be due to a primary underlying

extrapyramidal dysfunction, that of catatonia with parkin-

sonism and negative symptoms is inuenced by the effect of

antipsychotic medication and/or chronicity. We found a lack

of association of catatonia with akathisia, which suggests that

these types of phenomena are mediated by different path-

ophysiological processes.

The efcacy of antipsychotic drugs for catatonia has been

traditionally put in doubt, and some authors have argued that

antipsychotic exposure usually worsens catatonia (Taylor and

Fink, 2003), however, it has been claimed that the scientic

evidence supporting it is sparse (van den Eede and Sabbe,

2003). In fact,and althoughthistopic has been poorlystudied, a

fewstudiessuggestthatboth typical (Peralta and Cuesta, 1999)

and atypical antipsychotic drugs such as risperidone (Valevski

et al., 2001) and olanzapine (Martnyi et al., 2001) may ame-

liorate catatonic signs. Our study supports these ndings by

showing a marked response of catatonia signs and syndromes

to antipsychotic medication with no efcacy differences be-

tween typical and atypical drugs.

4.3. Implications

Findings of the present study have some diagnostic and

therapeutic implications. Our ndings may inform the DSM-V

development for dening and classifying catatonia. For example,

while the 12 DSM-IV signs appears to have face and convergent

validity, their grouping into 5 criteria sets, any two of them

being necessary for diagnosing the disorder, seems to be ar-

bitrary. In this regard, the diagnosis of catatonia on the basisof the presence of any three signs is simpler and has similar

diagnostic accuracy to the DSM-IV diagnostic criteria. The

lack of diagnostic specicity of catatonia within the psychotic

illness raises doubts about the unbalanced weight given in

DSM-IV to catatonic phenomena across diagnoses. Moreover,

it is becoming increasingly clear that catatonia occurs more

frequently in mood disorders than in schizophrenia (Abrams

and Taylor, 1976; Bruning et al., 1998). Our ndings support

the idea heralded by other authors for considering catatonia as

a distinct diagnosis in DSM-V within a category ofMovement

Disorders (Taylor and Fink, 2003). Once a diagnosis of cata-

tonia is met, catatonia could be further classied as (i) primary

or idiopathic (i.e., periodic catatonia, motility psychosis), or (ii)secondary, either to psychiatric illness (i.e., schizophrenia or

majormood disorder)or to a medical condition.A more unied

and separate DSM diagnostic criteria set for catatonia will cer-

tainly aid in our understanding of its phenomenology, co-

morbidities, naturalhistory, neurobiology andtreatment. It will

also increase psychiatrist's recognition of this common condi-

tion, and stimulate further research.

Our results clearly show that both typical and atypical an-

tipsychotic drugs produce a dramatic reduction in catatonic

signs and syndromes, and thus treatment of catatonia with

antipsychotics seems to be clearly justied within the non-

affective psychoses.

In our study, the improvement of catatonia signs with

antipsychotic drugs ran parallel to that of psychotic symp-

toms, which suggests the existence of a common mechanism

for both symptom domains, presumably a pre-existing hyper-

dopaminergic state at the nigrostriatal system (Kapur et al.,

2005), which appears to be balanced by antipsychotic drug-

induced D2-receptor blockage. Antipsychotic drugs are also

widely used and effective in the treatment of bipolar disorder

and psychotic depression, thus we can speculate on the pos-

sibility that antipsychotic drugs are also effective for the treat-

ment of catatonia in the affective psychoses. However, it has

been claimed that catatonia in the affective psychoses is more

treatment-responsive than catatonia in schizophrenia, which

would suggests different underlying mechanisms for catatonia

across disorders (Ungvari et al., in press). Notwithstanding, the

extent to which both catatonia mechanisms and response to

antipsychotic drugs operate across schizophrenia and affective

psychoses would require careful, controlled studies that do not

exist to date.

4.4. Strengths and limitations

Strengths of the study include the large sample of rst-

episode patients never exposed to antipsychotic medication,

the comprehensive examination of psychometric properties

of DSM-IV catatonia signs and criteria, and the one-month

trial with antipsychotic drugs. To the best of our knowledge

this is the rst study examining these variables in a rst-

episode sample of psychotic patients never exposed to anti-

psychotic medication.

A number of limitations should also be considered when

interpreting the ndings. First, we only examined the 12

catatonia signs included in DSM-IV. While many other signs

have been described, those included in DSM-IV are among the

most consistently described by classical authors (Kahlbaum,

1874; Bleuler, 1911; Kraepelin, 1913) and in the more recentlydeveloped rating scales (Lund et al., 1991; Bush et al., 1996;

Northoff et al, 1999; Bruning et al., 2000). Second, testretest

reliability could not be performed because of the nature of the

study. Third, catatonic signs were rated on the basis of their

absence vs. presence. We acknowledge that using a dimen-

sional scale to rate catatonia signs might have resulted in dif-

ferent ndings; however, it has been shown that using binary

catatonia signs yields better psychometric properties than an

ordinal scoring system (Wong et al., 2007). Fourth, catatonia

signs were rated on the basis of a single examination at each

assessment point, and thus symptom duration was not con-

sidered. Given that catatonia behaviors may wax and wane, a

more longitudinal assessment procedure is clearly desirable.Fifth, we decided not to correct for multiple comparisons

http://dx.doi.org/10-schbul/sbp105http://dx.doi.org/10-schbul/sbp105

8/14/2019 09209964-S0920996410X00056-S0920996409006148-main.pdf

8/8

Documents

09209964-S0920996410X00056-S0920996409006148-main.pdf