Schizophrenia Research 118 (2010) 168175

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Schizophrenia Research
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / s c h r e s

DSM-IV catatonia signs and criteria in rst-episode, drug-naive, psychotic patients: 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
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 one catatonia sign and 24 (12%) met DSM-IV criteria for catatonia. DSM-IV catatonia signs showed an excellent convergent validity (r N 0.8) 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 identied (hyperkinesia, volitional and hypokinesia), which showed a different 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.

Article history: Received 29 September 2009 Received in revised form 1 December 2009 Accepted 19 December 2009 Available online 13 January 2010 Keywords: Catatonia First-episode psychosis Drug-naive Diagnosis Treatment

1. Introduction Catatonia is an intriguing neuropsychiatric disorder with many clinical and research challenges. Universally accepted denitions of the core catatonia signs and diagnostic criteria are lacking. The boundaries of the syndrome remain so ill-dened that different rating scales measuring catatonia include from 10 to more than 40 signs (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
Corresponding author. Tel.: + 34 848 422 488; fax: +34 848 429 924. E-mail address: victor.peralta.martin@cfnavarra.es (V. Peralta). 0920-9964/$ see front matter 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2009.12.023

that the syndrome is poorly recognized. Many reasons have been advocated for explaining this state of the art, including the way in which catatonia is dened in current diagnostic systems such 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

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(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 conducted 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 in rst-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.

2.2. Assessments 2.2.1. Demographic and clinical variables Demographics, clinical features, psychopathology and diagnosis 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 FamilyHistory 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 describes a broad range of motor behaviors by comprising 33 specic items plus 4 items for other motor abnormalities describing 8 additional motor signs, altogether resulting in the assessment of 41 specic motor features. Each item is rated on a scale of 02 (0= absent, 1 = clearly present, 2 = marked or pervasive) 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 psychiatric 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

2. Methods 2.1. Subjects The study population comprised 200 subjects who were antipsychotic-naive and met DSM-IV criteria for a nonaffective 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 abnormalities 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) had a randomized design and was aimed at examining the effect of risperidone or olanzapine on neurocognition (Cuesta et al., 2009). The two samples did not differ in demographic or clinical background variables. The criteria for inclusion were: (a) patients experiencing 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 retardation, epilepsy, brain injury and neurodegenerative disorders, 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 clinical characteristics of the whole study sample are presented in Table 1.

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)

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(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 catatonic 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 catatonia 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). Treatment groups did not meaningfully differ in background variables nor in their mean daily dose of Chlorpromazine equivalents. Patients initially received a low dose of antipsychotic 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 in Peralta 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 performance 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 by means of principal component analysis. Factors with eigenvalue N 1 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 effect was 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, p b 0.001). 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 (p b 0.001). 3.3. Individual signs and severity of catatonia Individual catatonia signs were strongly and consistently correlated (p b 0.001) 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 hyperactivity 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 correlated with both the DSM-IV (r = 0.79, p b 0.001) and the CASH (r = 0.89, p b 0.001) catatonia severity scores. There was also a strong association between the total number of signs and the MRS total score (r = 0.91, p b 0.001). While this is obvious, since DSM-IV catatonia signs are embedded in the MRS, it indicates that they represent a good index of the rather more global motor disturbance addressed by the MRS.

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

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
Table 2 Pearson's product-moment correlations between individual DSM-IV catatonia signs and alternative denitions of catatonia severity. Total number DSM-IV global CASH global MRS total of DSM-IV severity rating severity rating score signs Catalepsy Waxy exibility Stupor Agitation Mutism Negativism Posturing Mannerisms Stereotypies Grimacing Echolalia Echopraxia 0.67 0.60 0.49 0.30 0.53 0.51 0.68 0.60 0.58 0.47 0.59 0.54 0.60 0.47 0.56 0.39 0.58 0.53 0.60 0.48 0.40 0.34 0.55 0.53 0.59 0.54 0.47 0.33 0.50 0.40 0.63 0.60 0.51 0.33 0.47 0.52 0.63 0.55 0.49 0.28 0.49 0.44 0.67 0.53 0.52 0.41 0.54 0.44

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 classication 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 of agitation, posturing, mannerisms, stereotypies and grimacing. The second 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 factorderived 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 association pattern with external variables (Table 5). The only association

DSM-IV = Diagnostic and Statistical Manual, fourth ed., CASH = Comprehensive Assessment of Symptoms and History, MRS = Modied Rogers Scale.

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Table 3 Diagnostic performance of the total number of DSM-IV catatonia signs against alternative diagnostic criteria for catatonia. ROC curve (95% CI) DSM-IV criteria (n = 24) 1 or more signs 2 or more signs 3 or more signs 4 or more signs ICD-10 criteria (n = 39) 1 or more signs 2 or more signs 3 or more signs 4 or more signs Taylor and Fink criteria (n = 21) 1 or more signs 2 or more signs 3 or more signs 4 or more signs CASH criteria (n = 30) 1 or more signs 2 or more signs 3 or more signs 4 or more signs Either criteria present (n = 52) 1 or more signs 2 or more signs 3 or more signs 4 or more signs All criteria present (n = 15) 1 or more signs 2 or more signs 3 or more signs 4 or more signs 0.98 (0.971.0) 1.0 1.0 0.67 0.50 0.87 (0.790.94) 0.85 0.56 0.44 0.31 0.97 (0.950.99) 1.0 0.90 0.76 0.57 0.93 (0.870.98) 0.93 0.70 0.63 0.43 0.89 (0.820.95) 0.85 0.54 0.36 0.25 0.99 (0.981.0) 1.0 1.0 1.0 0.73 0.75 0.90 0.98 0.99 0.24 0.45 0.79 0.85 1.0 1.0 1.0 0.98 0.76 0.91 0.98 0.97 0.88 0.97 1.0 1.0 0.71 0.85 1.0 1.0 0.94 0.86 0.82 0.79 0.87 0.85 0.83 0.80 0.80 0.93 1.0 1.0 0.45 0.63 1.0 1.0 0.98 0.94 0.94 0.90 0.82 0.89 0.94 0.91 0.77 0.92 0.98 0.99 0.34 0.57 0.84 0.92 1.0 0.99 0.97 0.95 0.79 0.92 0.96 0.95 0.82 0.93 0.99 1.0 0.53 0.67 0.89 0.92 0.95 0.89 0.88 0.85 0.81 0.86 0.88 0.86 0.78 0.95 0.98 0.99 0.39 0.72 0.84 0.92 1.0 1.0 0.95 0.93 0.81 0.95 0.94 0.93 S SP PPV NPV EF

had unique associations with poor premorbid social adjustment, 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 onemonth trial with antipsychotics (Table 6), and no specic treatment 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 p b 0.001). Because the response of catatonia to antipsychotic medication 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 with the 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. Main ndings 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 correlated 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, volitional and hypokinetic factors, which showed adequate internal consistency and a rather different correlational pattern with external variables. Overall, catatonia ratings were particularly 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 positive symptoms.

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).

shared by all catatonia ratings was with disorganization symptoms. All catatonia ratings, excepting the volitional domain, were related to dyskinesia. The hyperkinesia domain
Table 4 Principal component analysis of DSM-IV catatonia signs. Hyperkinesia Catalepsy Waxy exibility Stupor Agitation Mutism Negativism Posturing Mannerisms Stereotypies Grimacing Echolalia Echopraxia Eigenvalue Variance explained Internal Consistency 0.42 0.29 0.07 0.41 0.11 0.04 0.63 0.78 0.65 0.65 0.21 0.19 3.80 31.7 0.67 Volitional 0.23 0.24 0.09 0.31 0.70 0.62 0.12 0.01 0.19 0.03 0.80 0.77 1.70 14.2 0.70 Hypokinesia 0.65 0.71 0.76 0.40 0.40 0.36 0.36 0.13 0.14 0.01 0.05 0.04 1.37 11.4 0.75

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

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Table 5 Regressions a of clinical characteristics relating to demographic and clinical variables, psychopathological syndromes and extrapyramidal signs on DSM-IV catatonia ratings. Hyperkinesia dimension Demographic and clinical Age, yrs Gender Years of education FH of nonaffective psychosis Premorbid social adjustment Age of onset, yrs DUP Diagnosis (schizophrenia) Psychopathology Mania Depression Reality-distortion Disorganization Negative Extrapyramidal symptoms Parkinsonism Dyskinesia Akathisia 0.03 0.01 0.02 0.04 0.11 0.04 0.01 0.29 0.00 0.03 0.03 0.19 0.11 (0.05) (0.13) (0.02) (0.09) (0.05)* (0.05) (0.00) (0.14)* (0.01) (0.05) (0.06) (0.05)*** (0.04)* Volitional dimension 0.03 0.02 0.01 0.09 0.07 0.03 0.00 0.10 0.01 0.06 0.04 0.09 0.04 (0.04) (0.10) (0.01) (0.07) (0.04) (0.04) (0.00) (0.10) (0.05) (0.04) (0.05) (0.04)* (0.03) Hypokinesia dimension 0.01 (0.03) 0.00 (0.07) 0.00 (0.01) 0.01 (0.05) 0.05 (0.03) 0.02 (0.03) 0.00 (0.00) 0.06 (0.08) 0.02 (0.04) 0.02 (0.03) 0.05 (0.03) 0.08 (0.03)** 0.03 (0.02) 0.01 (0.01) 0.07 (0.01)*** 0.11 (0.06) Total number of signs 0.07 0.03 0.01 0.11 0.22 0.09 0.01 0.24 0.03 0.01 0.12 0.36 0.18 (0.08) (0.23) (0.03) (0.15) (0.08)** (0.08) (0.01) (0.24) (0.11) (0.08) (0.10) (0.08)*** (0.08)* Diagnostic criteria 0.08 0.56 0.04 0.03 0.36 0.14 0.01 0.01 0.20 0.01 0.17 0.67 0.11 (0.20) (0.48) (0.06) (0.32) (0.15)* (0.20) (0.02) (0.50) (0.23) (0.19) (0.22) (0.18)*** (0.16)

0.00 (0.01) 0.20 (0.02)*** 0.05 (0.08)

0.04 (0.01)** 0.01 (0.01) 0.05 (0.08)

0.06 (0.03)* 0.29 (0.03)*** 0.12 (0.17)

0.18 (0.19) 0.33 (0.10)*** 1.0 (0.97)

DSM-IV = Diagnostic and Statistical Manual, fourth ed., FH = family history, DUP = duration of untreated psychosis. * p 0.05, ** p 0.01, *** p 0.001. a Values are regression coefcients (and standard errors).

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 of ndings across samples and 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 et al., 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 this may be in part attributed to 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 as echophenomena and mutism/negativism that may be conceptualized as disorders of the behavioral interaction between the patient and others. Bleuler (1911) already noted the association between these two kinds of phenomena that ts well to Kraepelin's concept of parabulia (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 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 F(df = 2) p 0.608 0.059 0.393 0.447 0.535

Baseline Hyperkinesia dimension Volitional dimension Hypokinesia dimension Total number of signs Catatonia global severity rating

4 weeks

Baseline

4 weeks

Baseline

4 weeks

Baseline

4 weeks

F(df = 1) p

0.41 0.90 0.15 0.50 0.43 0.78 0.13 0.34 0.48 1.04 0.16 0.59 0.30 0.68 0.14 0.39 15.42 0.21 0.67 0.03 0.19 0.52 1.16 0.04 0.20 0.19 0.64 0.02 0.14 0.13 0.42 0.03 0.25 18.10 0.13 0.49 0.01 0.10 0.04 0.21 0.00 0.00 0.17 0.54 0.02 0.14 0.11 0.47 0.00 0.00 5.28

b 0.001 0.49 b 0.001 2.97 0.023 0.94 b 0.001 0.81 b 0.001 0.62

0.75 1.57 0.19 0.59 1.00 1.53 0.17 0.49 0.83 1.80 0.20 0.66 0.53 1.11 0.17 0.52 22.32 0.63 1.22 0.15 0.49 0.87 1.36 0.17 0.49 0.66 1.23 0.16 0.55 0.63 1.22 0.15 0.50 26.49

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basis of theoretical considerations. The only previous study empirically addressing this question reported that three or more signs best discriminated between catatonic and noncatatonic 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 association 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 parkinsonism 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 pathophysiological 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 although this topic has been poorly studied, a few studies suggest that both typical (Peralta and Cuesta, 1999) and atypical antipsychotic drugs such as risperidone (Valevski et al., 2001) and olanzapine (Martnyi et al., 2001) may ameliorate catatonic signs. Our study supports these ndings by showing a marked response of catatonia signs and syndromes to antipsychotic medication with no efcacy differences between 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 arbitrary. In this regard, the diagnosis of catatonia on the basis of 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 of Movement Disorders (Taylor and Fink, 2003). Once a diagnosis of catatonia 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

major mood disorder) or to a medical condition. A more unied and separate DSM diagnostic criteria set for catatonia will certainly aid in our understanding of its phenomenology, comorbidities, natural history, neurobiology and treatment. It will also increase psychiatrist's recognition of this common condition, and stimulate further research. Our results clearly show that both typical and atypical antipsychotic drugs produce a dramatic reduction in catatonic signs and syndromes, and thus treatment of catatonia with antipsychotics seems to be clearly justied within the nonaffective psychoses. In our study, the improvement of catatonia signs with antipsychotic drugs ran parallel to that of psychotic symptoms, which suggests the existence of a common mechanism for both symptom domains, presumably a pre-existing hyperdopaminergic state at the nigrostriatal system (Kapur et al., 2005), which appears to be balanced by antipsychotic druginduced 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 possibility that antipsychotic drugs are also effective for the treatment 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 rstepisode 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 rstepisode sample of psychotic patients never exposed to antipsychotic 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 recently developed 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 dimensional scale to rate catatonia signs might have resulted in different 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 considered. 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

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because of the exploratory nature of the study, accordingly, false positive ndings cannot be excluded, particularly those based on weak associations (p N 0.01). Lastly, catatonic features are also highly prevalent in major mood disorders where they may have specic clinical and treatment correlates (Abrams et al., 1979; Starkstein et al., 1996), thus our results cannot generalize to catatonia in mood disorders.
Role of funding source This study was partly funded by the Department of Health of the Government of Navarra (grants 946/2005 and 55/2007). Contributors Victor Peralta and Manuel J. Cuesta designed the study and wrote the manuscript. Each author assessed different aspects of the patients and all the authors approved the nal manuscript. Conict of interest None. Acknowledgement None.

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