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Kraepelinian subtype and deficit syndrome in chronic schizophrenia
Psychiatry Research 144 (2006) 221 – 225 www.elsevier.com/locate/psychres
Brief report
Kraepelinian subtype and deficit syndrome in chronic schizophrenia Makoto Nakaya *, Kenich Ohmori Department of Psychiatry, Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi 321-0293, Japan Received 19 August 2004; received in revised form 7 March 2005; accepted 28 May 2005
Abstract The present study examined the clinical overlap between the Kraepelinian and deficit subtypes of schizophrenia. A total of 103 patients with schizophrenia were divided into four groups on the basis of the presence or absence of the two classifications, and the demographic and clinical characteristics of the groups were statistically compared. There was a significant overlap of Kraepelinian and deficit status, but nevertheless the retention of both classifications appears to be justified. D 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Positive symptoms; Negative symptoms; Depressive symptoms
1. Introduction In response to the heterogeneity of schizophrenia, numerous attempts have been made to define homogeneous subgroups within the disorder. Keefe et al. (1987) used longitudinal criteria to identify a subgroup of severely deteriorated schizophrenic patients, and postulated a subtype, Kraepelinian schizophrenia. This diagnosis is indicated if any one of the following criteria has been satisfied for the past 5 years: (1) continuous hospitalization or, if living outside the hospital, complete dependence on others for basic needs; (2) no gainful work or employment; or (3) no occurrence of complete remission of symptoms. Recent studies have suggested that the following characteristics distinguish Kraepelinian patients from non-Kraepelinian patients: more leftsided structural brain abnormalities; more severe negative symptoms and formal thought disorders; less severe affective symptoms; poorer premorbid sociosexual func* Corresponding author. Tel.: +81 28286 1111; fax: +81 28286 5187. E-mail address: [email protected] (M. Nakaya).
tioning; relative non-responsiveness to haloperidol treatment (Keefe et al., 1987, 1996); association with summer birth (Bralet et al., 2002); greater impairment of fine motor dexterity and executive functioning (Roy et al., 2003); greater thalamic reduction of ventral–dorsal volumes (Brickman et al., 2004); and reduced gray matter in the posterior cingulate (Mitelman et al., 2005). Additionally, biological relatives exhibit a greater morbid risk for schizophrenia spectrum disorders (Keefe et al., 1987). The concept of a deficit syndrome in schizophrenia has also been introduced to describe a relatively homogeneous subgroup of patients characterized by the presence of the following enduring negative symptoms: restricted affect; diminished emotional range; poverty of speech; curbing of interests; lack of a sense of purpose; and diminished social drive. Deficit syndrome is rated as present if two of these enduring negative symptoms are primary and stable (Carpenter et al., 1988). It is suggested that compared with non-deficit patients, patients with deficit syndrome display poorer premorbid adjustment, carry a greater genetic load for schizophrenia, and more frequently suffer an insidious
0165-1781/$ - see front matter D 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.psychres.2005.05.021
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M. Nakaya, K. Ohmori / Psychiatry Research 144 (2006) 221–225
The subjects were 106 consecutive patients with schizophrenia admitted to a long-stay psychiatric unit associated with Dokkyo University School of Medicine. All patients were formally diagnosed with schizophrenia using DSM-IV criteria (American Psychiatric Association, 1994). The diagnosis of schizophrenia was independently confirmed in a diagnostic interview conducted by the two research psychiatrists. Patients with evidence of organic brain disorders (e.g. brain injury), mental retardation, severe abuse of alcohol or other drugs, illness duration b72 months, or age N 65 years were excluded, as were three patients who declined to participate in the study. Onset of illness was defined as time of the first psychotic episode. Data from 103 patients were available for analysis. All subjects gave written informed consent to their participation in the study. The patient sample included chronic inpatients at various stages after acute flare-up (n = 5) and in the stable stage of illness (n = 98). At the time of the study, all subjects were hospitalized in the unit and were undergoing neuroleptic treatment. Typical neuroleptics commonly used were haloperidol, chlorpromazine, levomepromazine, and perphenazine; other typical neuroleptics were administered to only a very small number of patients. Six patients were treated using only atypical neuroleptics (risperidone: range, 6–12 mg/day).
care, history of gainful work or employment, and remission of symptoms was obtained from interviews with psychiatrists and other mental health professionals who had treated the patients and had been in long-term contact with them. All medical records were reviewed to verify and supplement information gathered in the interviews. The validity of the assessment of Kraepelinian status using this methodology is inferior to that obtained in a prospective study. The subjects were divided into two clinical groups, Kraepelinian; and non-Kraepelinian, on the basis of the criteria prescribed by Keefe et al. (1987). Two independent investigators determined the Kraepelinian status of the 103 subjects on the basis of all the clinical information gathered. Most patients diagnosed as Kraepelinian met the criteria by virtue of having been hospitalized for N 5 years in psychiatric hospitals. Conversely, regardless of recent chronic status, non-Kraepelinian patients had shorter durations of past hospitalization and some periods after onset in which they cared for themselves. Kraepelinian status was determined with a high degree of reliability, and no disagreements between raters occurred. All subjects were also diagnosed as deficit or nondeficit subtype in accordance with the Schedule for the Deficit Syndrome (SDS; Kirkpatrick et al., 1989). The schedule provides for specific categorization of schizophrenia patients into deficit and non-deficit subtypes on the basis of a differentiation between primary and enduring negative symptoms and secondary or transient negative symptoms. Two researchers conducted joint practice interviews before the commencement of the study, and joint ratings (n = 30) were made at intervals during the process of classification to monitor interrater agreement on deficit subtype. Inter-rater reliability for deficit categorization was 0.98 (Cohen’s kappa). Additional information was obtained from clinicians in long-term contact with the patient and from family members, as needed. Schizophrenic symptoms were assessed by one of the researchers using the Positive and Negative Syndrome Scale (PANSS; Kay et al., 1987). In our previous study of another patient population (Nakaya et al., 1997), interrater reliability for PANSS items ranged from 0.65 to 0.95. The Simpson–Angus Extrapyramidal Rating Scale (EPRS; Simpson and Angus, 1970) and the Abnormal Involuntary Movement Scale (AIMS; National Institute of Mental Health, 1974) were also administered.
2.2. Procedures
2.3. Statistical analysis
Information on the subjects regarding the number and duration of hospitalizations, ability to administer self-
The subjects were allocated to one of four groups (Table 1): Kraepelinian schizophrenia with deficit syn-
onset of the illness; they show a similar severity of productive symptoms and a lower severity of dysphoria, more frequently are resistant to antipsychotic treatment, and have a worse long-term outcome (Carpenter et al., 1988; Kirkpatrick et al., 1994; Tek et al., 2001); and there is a significant correlation with summer birth (Kirkpatrick et al., 2000). It can be seen that there is a partial overlap in the definitions of these two schizophrenia subtypes. However, the extent of the overlap remains unclear. If they fully overlap, the postulated Kraepelinian subtype is inferior in practical usefulness because diagnosis requires observation of pathology lasting 5 years. The present study tested the hypotheses that the two subtypes have significant overlap, but that retention of both classifications is nevertheless useful in the management of schizophrenia. 2. Methods 2.1. Subjects
M. Nakaya, K. Ohmori / Psychiatry Research 144 (2006) 221–225
223
Table 1 Demographic and clinical characteristics of Kraepelinian/non-Kraepelinian patients with and without deficit syndrome 4 subgroups (A–D)
One-way ANOVA
Scheffe´’s follow-up test
A: K(+)D(+) B: K(+)D( ) C: K( )D(+) D: K( )D( ) F value (n = 45)
(n = 11)
Age (years) 49.2(10.5) 49.2(6.7) Education (years) 10.3(2.9) 11.3(2.1) Age at onset (years) 24.5(7.2) 22.0(7.1) Months since onset 286.5(112.1) 325.7(112.0) No. hospitalizations 3.9(2.5) 5.9(4.4) Duration of hospitalization (months) 208.4(98.9) 185.0(100.4) EPRS 2.6(2.3) 1.9(1.6) AIMS 0.8(1.6) 0.2(0.6) PANSS Delusion/hallucination 12.8(4.1) 13.5(5.5) Thought disorder/disorganization 10.0(2.2) 8.8(2.6) Excitement 8.6(2.4) 8.7(2.8) Negative symptom 16.4(3.6) 11.4(1.7) Depressive symptom 7.2(3.0) 7.6(2.8) Gender (% male) Marital status (% single)
57.8% 77.8%
(n = 16)
(n = 31)
47.9(8.4) 10.8(1.7) 25.1(4.8) 264.1(111.5) 4.6(4.1) 94.8(78.5) 2.3(1.7) 0.8(1.6)
42.0(8.0) 11.9(2.2) 26.5(7.0) 189.1(76.8) 4.1(3.2) 38.3(52.3) 1.1(1.5) 0.2(0.7)
11.6(4.2) 8.9(1.7) 8.3(2.0) 15.8(3.0) 7.6(2.4)
11.5(3.9) 7.7(1.6) 8.4(2.1) 11.5(2.1) 8.4(2.7)
43.8% 75.0%
51.6% 70.2%
45.5% 81.8%
4.17 ( P b 0.01) 2.60 (NS) 1.26 (NS) 7.44 ( P b 0.001) 1.24 (NS) 27.36 ( P b 0.001) 1.35 (NS) 1.80 (NS)
A>D – – A & B>D – A > C & D; B > D – –
1.00 (NS) 8.19 ( P b0.001) 0.12 (NS) 21.68 ( P b 0.001) 1.06 (NS) Chi-square (d.f. = 3) 1.21 (NS) 2.34 (NS)
– A>D – A > B & D; C > B & D –
Data are presented as mean (S.D.) values. K(+)D(+), Kraepelinian schizophrenia with deficit syndrome; K(+)D( ), Kraepelinian schizophrenia without deficit syndrome; K( )D(+), nonKraepelinian schizophrenia with deficit syndrome; K( )D( ), non-Kraepelinian schizophrenia without deficit syndrome; EPRS, Simpson and Angus’ Extrapyramidal Rating Scale; AIMS, Abnormal Involuntary Movement Scale; PANSS, Positive and Negative Syndrome Scale.
drome (n = 45, 44%); Kraepelinian schizophrenia without deficit syndrome (n = 11; 11%); non-Kraepelinian schizophrenia with deficit syndrome (n = 16; 16%); and non-Kraepelinian schizophrenia without deficit syndrome (n = 31; 30%). Items from the PANSS were grouped into five domains as identified in previous investigations of latent structures underlying schizophrenic symptoms (Lindenmayer et al., 1994; Nakaya et al., 1999): delusions/hallucinations (delusion, hallucinatory behavior, grandiosity, suspiciousness and unusual thought content; PANSS item numbers P1, P3, P5, and G6, respectively); thought disorder/disorganization (conceptual disorganization, difficulty in abstract thinking and poor attention; P2, N5, and G11, respectively); excitement (excitement, hostility, tension and uncooperativeness; P4, P7, G4, and G8, respectively); negative symptoms (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, and lack of spontaneity and flow of conversation; N1, N2, N3, N4, and N6, respectively); and depressive symptoms (somatic concern, anxiety, guilt feelings and depression; G1, G2, G3, and G6, respectively). Marital status and gender in the four groups were compared using the chi-square test. Other sociodemographic data (age and highest level of education) and clinical characteristics (age at onset, duration of illness, number of hospitalizations, total duration of hospitalization, the
five symptom domains, and extrapyramidal side effects) were tested for the presence of significant differences between the groups using a one-way analysis of variance (ANOVA) with Scheffe´’s follow-up test for individual group differences. The significance level was set at alpha = 0.05. The overlap of the Kraepelinian classification with the deficit classification was also examined using the chi-square test. 3. Results Table 1 gives the mean scores (S.D.) for demographic characteristics (percentages for sex and marital status) and the clinical items in each of the four groups, together with the results of a one-way ANOVA and the Scheffe´ follow-up test comparing individual groups (chi-square for sex and marital status). Kraepelinian schizophrenia patients with deficit syndrome were significantly older than non-Kraepelinian schizophrenia patients without deficit. Kraepelinian patients with or without deficit had significantly longer duration of illness than non-Kraepelinian patients without deficit. Kraepelinian patients displayed significantly longer duration of illness and hospitalization than non-Kraepelinian patients, irrespective of deficit status. In the five symptom domains, Kraepelinian patients with deficit exhibited significantly more thought disorder/disorga-
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M. Nakaya, K. Ohmori / Psychiatry Research 144 (2006) 221–225
nization than non-Kraepelinian patients without deficit syndrome. Patients with deficit showed more negative symptoms than those without deficit syndrome, regardless of Kraepelinian subtype. No significant differences were identified between groups for the remaining three symptom domains, or for gender or marital status; nor were there significant differences between the groups in level of education, age at onset, number of hospitalizations, or extrapyramidal side effects. The classification of Kraepelinian subtype significantly overlapped with that of deficit subtype (v 2 = 22.7, df = 1, P b 0.001). 4. Discussion To our knowledge, the present study is the first to examine the relationship between the Kraepelinian subtype and deficit syndrome in schizophrenia. The two classifications did not always overlap with each other. There were 11 Kraepelinian patients without deficit syndrome (11%) and 16 non-Kraepelinian patients with deficit syndrome (16%). The comparisons of age, duration of illness, and duration of hospitalization between the groups were, on the whole, in accordance with the concept of the Kraepelinian subtype as reflecting deterioration features (Keefe et al., 1987). Interestingly, deficit syndrome was not significantly associated with duration of illness, regardless of Kraepelinian subtype, and this lack of a significant relationship with illness duration may result in patients being classified as Kraepelinian without deficit syndrome or nonKraepelinian with deficit syndrome. Deficit syndrome may represent a relatively cross-sectional and homogeneous subgroup, regardless of its definition of enduring negative symptoms lasting more than 12 months. Moreover, non-Kraepelinian patients in the present study, especially those without deficit, may be re-classified as Kraepelinian subtype later, given that their mean illness duration was the shortest of the four groups, while their deficit/non-deficit classification is likely to be stable hereafter. Thus, although the two classifications overlapped significantly, it is possible for them to be relatively independent of each other. No significant differences among the four groups were observed in the three symptom domains of delusion/hallucination; excitement; and depressive symptoms. For delusion/hallucination, this finding supports the results of previous studies of Kraepelinian (Keefe et al., 1987, 1996) and deficit patients (Carpenter et al., 1988; Spalletta et al., 1997). The finding has not been reported previously for excitement, but this symptom domain may have been included among positive symptoms in previous studies. Kilzieh et al. (2003) reported
that depressive symptoms are less prevalent in Kraepelinian patients than in non-Kraepelinian patients. However, a study by Bralet et al. (2002) did not replicate that result, and our findings concur with the latter study. A report by Kirkpatrick et al. (1994) described deficit patients as displaying significantly lower depressed mood than non-deficit patients, but this was not replicated in the present study. It is interesting that Kraepelinian status did not have a significant influence on severity of negative symptoms. Previous studies have reported that Kraepelinian subtype is associated with more severe negative symptoms than non-Kraepelinian subtype (Keefe et al., 1987, 1996), and this may be attributable to a lack of consideration of deficit subtype. The present study suggests that assessment under both classifications will be worthwhile in planning therapeutic strategies and psychosocial interventions, and that future research into schizophrenia, especially non-Kraepelinian subtype with deficit syndrome or Kraepelinian subtype without deficit syndrome, should examine both classifications. This study has a number of limitations. Firstly, the subjects included only inpatients with schizophrenia, and the findings may not be reproducible in outpatient samples. Secondly, the sample population (N = 103) was relatively small. Lastly, the classification of Kraepelinian and deficit status was not performed in a blinded manner. The relationship between these two schizophrenia subtypes requires further rigorous investigation. References American Psychiatric Association, 1994. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. APA, Washington, DC. Bralet, M.C., Loas, G., Marechal, V.Y.V., 2002. Clinical characteristics and risk factors for Kraepelinian subtype of schizophrenia: replication of previous findings and relation to summer birth. Psychiatry Research 111, 147 – 154. Brickman, A.M., Buchsbaum, M.S., Shihabuddin, L., Byne, W., Newmark, R.E., Brand, J., Ahmed, S., Mitelman, S.A., Hazlett, E.A., 2004. Thalamus size and outcome in schizophrenia. Schizophrenia Research 71, 473 – 484. Carpenter Jr., W.T., Heinrichs, D.W., Wagman, A.M.I., 1988. Deficit and nondeficit forms of schizophrenia: the concept. American Journal of Psychiatry 145, 578 – 583. Kay, S.R., Fiszbein, A., Opler, L.A., 1987. The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261 – 276. Keefe, R.S.E., Mohs, R.C., Losonczy, M.F., Davidson, M., Silverman, J.M., Kendler, K.S., Horvath, T.B., Nora, R., Davis, K.L., 1987. Characteristics of very poor outcome schizophrenia. American Journal of Psychiatry 144, 889 – 895. Keefe, R.S.E., Frescka, E., Apter, S.H., Davidson, M., Macaluso, J.M., Hirshowitz, J., Davis, K.L., 1996. Clinical characteristics of Kraepelinian schizophrenia: replication and extension of previous findings. American Journal of Psychiatry 153, 806 – 811.
M. Nakaya, K. Ohmori / Psychiatry Research 144 (2006) 221–225 Kilzieh, N., Wood, A.E., Erdmann, J., Raskind, M., Tapp, A., 2003. Depression in Kraepelinian schizophrenia. Comprehensive Psychiatry 44, 1 – 6. Kirkpatrick, B., Buchanan, R.W., McKenney, P.D., Alphs, L.D., Carpenter Jr., W.T., 1989. The Schedule for the Deficit Syndrome: an instrument for research in schizophrenia. Psychiatry Research 30, 119 – 123. Kirkpatrick, B., Buchanan, R.W., Breier, A., Carpenter Jr., W.T., 1994. Depressive symptoms and the deficit syndrome of schizophrenia. Journal of Nervous and Mental Disease 182, 452 – 455. Kirkpatrick, B., Castle, D., Murray, R.M., Carpenter Jr., W.T., 2000. Risk factors for the deficit syndrome of schizophrenia. Schizophrenia Bulletin 26, 233 – 242. Lindenmayer, J.P., Bernstein-Hyman, R., Grochowski, S., 1994. Fivefactor model of schizophrenia—initial validation. Journal of Nervous and Mental Disease 182, 631 – 638. Mitelman, S.A., Shihabuddin, L., Brickman, A.M., Hazlett, E.A., Buchsbaum, M.S., 2005. Volume of cingulate and outcome in schizophrenia. Schizophrenia Research 72, 91 – 108. Nakaya, M., Ohmori, K., Komahashi, T., Suwa, H., 1997. Depressive symptoms in acute schizophrenic inpatients. Schizophrenia Research 25, 131 – 139.
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Nakaya, M., Suwa, H., Ohmori, K., 1999. Latent structures underlying schizophrenic symptoms: a five dimensional model. Schizophrenia Research 39, 39 – 50. National Institute of Mental Health, 1974. Abnormal Involuntary Movement Scale (AIMS). Department of Health, Education, and Welfare, Washington, DC. Roy, M.-A., Lehoux, C., Emond, C., Laplante, L., Bouchard, R.-H., Everett, J., Merette, C., Maziade, M., 2003. A pilot neuropsychological study of Kraepelinian and non-Kraepelinian schizophrenia. Schizophrenia Reseach 62, 155 – 163. Simpson, G.M., Angus, J.M.S., 1970. A rating scale for extrapyramidal side effects. Acta Psychiatrica Scandinavica 212 (Suppl 44), 11 – 19. Spalletta, G., Pasini, A., Angelis, F., Trosini, A., 1997. Patients with deficit, nondeficit, and negative symptom schizophrenia: do they differ during episodes of acute psychotic decompensation? Schizophrenia Research 24, 341 – 348. Tek, C., Kirkpatrick, B., Buchanan, R.W., 2001. A five-year follow up study of deficit and nondeficit schizophrenia. Schizophrenia Research 49, 253 – 260.
Brief report
Kraepelinian subtype and deficit syndrome in chronic schizophrenia Makoto Nakaya *, Kenich Ohmori Department of Psychiatry, Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi 321-0293, Japan Received 19 August 2004; received in revised form 7 March 2005; accepted 28 May 2005
Abstract The present study examined the clinical overlap between the Kraepelinian and deficit subtypes of schizophrenia. A total of 103 patients with schizophrenia were divided into four groups on the basis of the presence or absence of the two classifications, and the demographic and clinical characteristics of the groups were statistically compared. There was a significant overlap of Kraepelinian and deficit status, but nevertheless the retention of both classifications appears to be justified. D 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Positive symptoms; Negative symptoms; Depressive symptoms
1. Introduction In response to the heterogeneity of schizophrenia, numerous attempts have been made to define homogeneous subgroups within the disorder. Keefe et al. (1987) used longitudinal criteria to identify a subgroup of severely deteriorated schizophrenic patients, and postulated a subtype, Kraepelinian schizophrenia. This diagnosis is indicated if any one of the following criteria has been satisfied for the past 5 years: (1) continuous hospitalization or, if living outside the hospital, complete dependence on others for basic needs; (2) no gainful work or employment; or (3) no occurrence of complete remission of symptoms. Recent studies have suggested that the following characteristics distinguish Kraepelinian patients from non-Kraepelinian patients: more leftsided structural brain abnormalities; more severe negative symptoms and formal thought disorders; less severe affective symptoms; poorer premorbid sociosexual func* Corresponding author. Tel.: +81 28286 1111; fax: +81 28286 5187. E-mail address: [email protected] (M. Nakaya).
tioning; relative non-responsiveness to haloperidol treatment (Keefe et al., 1987, 1996); association with summer birth (Bralet et al., 2002); greater impairment of fine motor dexterity and executive functioning (Roy et al., 2003); greater thalamic reduction of ventral–dorsal volumes (Brickman et al., 2004); and reduced gray matter in the posterior cingulate (Mitelman et al., 2005). Additionally, biological relatives exhibit a greater morbid risk for schizophrenia spectrum disorders (Keefe et al., 1987). The concept of a deficit syndrome in schizophrenia has also been introduced to describe a relatively homogeneous subgroup of patients characterized by the presence of the following enduring negative symptoms: restricted affect; diminished emotional range; poverty of speech; curbing of interests; lack of a sense of purpose; and diminished social drive. Deficit syndrome is rated as present if two of these enduring negative symptoms are primary and stable (Carpenter et al., 1988). It is suggested that compared with non-deficit patients, patients with deficit syndrome display poorer premorbid adjustment, carry a greater genetic load for schizophrenia, and more frequently suffer an insidious
0165-1781/$ - see front matter D 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.psychres.2005.05.021
222
M. Nakaya, K. Ohmori / Psychiatry Research 144 (2006) 221–225
The subjects were 106 consecutive patients with schizophrenia admitted to a long-stay psychiatric unit associated with Dokkyo University School of Medicine. All patients were formally diagnosed with schizophrenia using DSM-IV criteria (American Psychiatric Association, 1994). The diagnosis of schizophrenia was independently confirmed in a diagnostic interview conducted by the two research psychiatrists. Patients with evidence of organic brain disorders (e.g. brain injury), mental retardation, severe abuse of alcohol or other drugs, illness duration b72 months, or age N 65 years were excluded, as were three patients who declined to participate in the study. Onset of illness was defined as time of the first psychotic episode. Data from 103 patients were available for analysis. All subjects gave written informed consent to their participation in the study. The patient sample included chronic inpatients at various stages after acute flare-up (n = 5) and in the stable stage of illness (n = 98). At the time of the study, all subjects were hospitalized in the unit and were undergoing neuroleptic treatment. Typical neuroleptics commonly used were haloperidol, chlorpromazine, levomepromazine, and perphenazine; other typical neuroleptics were administered to only a very small number of patients. Six patients were treated using only atypical neuroleptics (risperidone: range, 6–12 mg/day).
care, history of gainful work or employment, and remission of symptoms was obtained from interviews with psychiatrists and other mental health professionals who had treated the patients and had been in long-term contact with them. All medical records were reviewed to verify and supplement information gathered in the interviews. The validity of the assessment of Kraepelinian status using this methodology is inferior to that obtained in a prospective study. The subjects were divided into two clinical groups, Kraepelinian; and non-Kraepelinian, on the basis of the criteria prescribed by Keefe et al. (1987). Two independent investigators determined the Kraepelinian status of the 103 subjects on the basis of all the clinical information gathered. Most patients diagnosed as Kraepelinian met the criteria by virtue of having been hospitalized for N 5 years in psychiatric hospitals. Conversely, regardless of recent chronic status, non-Kraepelinian patients had shorter durations of past hospitalization and some periods after onset in which they cared for themselves. Kraepelinian status was determined with a high degree of reliability, and no disagreements between raters occurred. All subjects were also diagnosed as deficit or nondeficit subtype in accordance with the Schedule for the Deficit Syndrome (SDS; Kirkpatrick et al., 1989). The schedule provides for specific categorization of schizophrenia patients into deficit and non-deficit subtypes on the basis of a differentiation between primary and enduring negative symptoms and secondary or transient negative symptoms. Two researchers conducted joint practice interviews before the commencement of the study, and joint ratings (n = 30) were made at intervals during the process of classification to monitor interrater agreement on deficit subtype. Inter-rater reliability for deficit categorization was 0.98 (Cohen’s kappa). Additional information was obtained from clinicians in long-term contact with the patient and from family members, as needed. Schizophrenic symptoms were assessed by one of the researchers using the Positive and Negative Syndrome Scale (PANSS; Kay et al., 1987). In our previous study of another patient population (Nakaya et al., 1997), interrater reliability for PANSS items ranged from 0.65 to 0.95. The Simpson–Angus Extrapyramidal Rating Scale (EPRS; Simpson and Angus, 1970) and the Abnormal Involuntary Movement Scale (AIMS; National Institute of Mental Health, 1974) were also administered.
2.2. Procedures
2.3. Statistical analysis
Information on the subjects regarding the number and duration of hospitalizations, ability to administer self-
The subjects were allocated to one of four groups (Table 1): Kraepelinian schizophrenia with deficit syn-
onset of the illness; they show a similar severity of productive symptoms and a lower severity of dysphoria, more frequently are resistant to antipsychotic treatment, and have a worse long-term outcome (Carpenter et al., 1988; Kirkpatrick et al., 1994; Tek et al., 2001); and there is a significant correlation with summer birth (Kirkpatrick et al., 2000). It can be seen that there is a partial overlap in the definitions of these two schizophrenia subtypes. However, the extent of the overlap remains unclear. If they fully overlap, the postulated Kraepelinian subtype is inferior in practical usefulness because diagnosis requires observation of pathology lasting 5 years. The present study tested the hypotheses that the two subtypes have significant overlap, but that retention of both classifications is nevertheless useful in the management of schizophrenia. 2. Methods 2.1. Subjects
M. Nakaya, K. Ohmori / Psychiatry Research 144 (2006) 221–225
223
Table 1 Demographic and clinical characteristics of Kraepelinian/non-Kraepelinian patients with and without deficit syndrome 4 subgroups (A–D)
One-way ANOVA
Scheffe´’s follow-up test
A: K(+)D(+) B: K(+)D( ) C: K( )D(+) D: K( )D( ) F value (n = 45)
(n = 11)
Age (years) 49.2(10.5) 49.2(6.7) Education (years) 10.3(2.9) 11.3(2.1) Age at onset (years) 24.5(7.2) 22.0(7.1) Months since onset 286.5(112.1) 325.7(112.0) No. hospitalizations 3.9(2.5) 5.9(4.4) Duration of hospitalization (months) 208.4(98.9) 185.0(100.4) EPRS 2.6(2.3) 1.9(1.6) AIMS 0.8(1.6) 0.2(0.6) PANSS Delusion/hallucination 12.8(4.1) 13.5(5.5) Thought disorder/disorganization 10.0(2.2) 8.8(2.6) Excitement 8.6(2.4) 8.7(2.8) Negative symptom 16.4(3.6) 11.4(1.7) Depressive symptom 7.2(3.0) 7.6(2.8) Gender (% male) Marital status (% single)
57.8% 77.8%
(n = 16)
(n = 31)
47.9(8.4) 10.8(1.7) 25.1(4.8) 264.1(111.5) 4.6(4.1) 94.8(78.5) 2.3(1.7) 0.8(1.6)
42.0(8.0) 11.9(2.2) 26.5(7.0) 189.1(76.8) 4.1(3.2) 38.3(52.3) 1.1(1.5) 0.2(0.7)
11.6(4.2) 8.9(1.7) 8.3(2.0) 15.8(3.0) 7.6(2.4)
11.5(3.9) 7.7(1.6) 8.4(2.1) 11.5(2.1) 8.4(2.7)
43.8% 75.0%
51.6% 70.2%
45.5% 81.8%
4.17 ( P b 0.01) 2.60 (NS) 1.26 (NS) 7.44 ( P b 0.001) 1.24 (NS) 27.36 ( P b 0.001) 1.35 (NS) 1.80 (NS)
A>D – – A & B>D – A > C & D; B > D – –
1.00 (NS) 8.19 ( P b0.001) 0.12 (NS) 21.68 ( P b 0.001) 1.06 (NS) Chi-square (d.f. = 3) 1.21 (NS) 2.34 (NS)
– A>D – A > B & D; C > B & D –
Data are presented as mean (S.D.) values. K(+)D(+), Kraepelinian schizophrenia with deficit syndrome; K(+)D( ), Kraepelinian schizophrenia without deficit syndrome; K( )D(+), nonKraepelinian schizophrenia with deficit syndrome; K( )D( ), non-Kraepelinian schizophrenia without deficit syndrome; EPRS, Simpson and Angus’ Extrapyramidal Rating Scale; AIMS, Abnormal Involuntary Movement Scale; PANSS, Positive and Negative Syndrome Scale.
drome (n = 45, 44%); Kraepelinian schizophrenia without deficit syndrome (n = 11; 11%); non-Kraepelinian schizophrenia with deficit syndrome (n = 16; 16%); and non-Kraepelinian schizophrenia without deficit syndrome (n = 31; 30%). Items from the PANSS were grouped into five domains as identified in previous investigations of latent structures underlying schizophrenic symptoms (Lindenmayer et al., 1994; Nakaya et al., 1999): delusions/hallucinations (delusion, hallucinatory behavior, grandiosity, suspiciousness and unusual thought content; PANSS item numbers P1, P3, P5, and G6, respectively); thought disorder/disorganization (conceptual disorganization, difficulty in abstract thinking and poor attention; P2, N5, and G11, respectively); excitement (excitement, hostility, tension and uncooperativeness; P4, P7, G4, and G8, respectively); negative symptoms (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, and lack of spontaneity and flow of conversation; N1, N2, N3, N4, and N6, respectively); and depressive symptoms (somatic concern, anxiety, guilt feelings and depression; G1, G2, G3, and G6, respectively). Marital status and gender in the four groups were compared using the chi-square test. Other sociodemographic data (age and highest level of education) and clinical characteristics (age at onset, duration of illness, number of hospitalizations, total duration of hospitalization, the
five symptom domains, and extrapyramidal side effects) were tested for the presence of significant differences between the groups using a one-way analysis of variance (ANOVA) with Scheffe´’s follow-up test for individual group differences. The significance level was set at alpha = 0.05. The overlap of the Kraepelinian classification with the deficit classification was also examined using the chi-square test. 3. Results Table 1 gives the mean scores (S.D.) for demographic characteristics (percentages for sex and marital status) and the clinical items in each of the four groups, together with the results of a one-way ANOVA and the Scheffe´ follow-up test comparing individual groups (chi-square for sex and marital status). Kraepelinian schizophrenia patients with deficit syndrome were significantly older than non-Kraepelinian schizophrenia patients without deficit. Kraepelinian patients with or without deficit had significantly longer duration of illness than non-Kraepelinian patients without deficit. Kraepelinian patients displayed significantly longer duration of illness and hospitalization than non-Kraepelinian patients, irrespective of deficit status. In the five symptom domains, Kraepelinian patients with deficit exhibited significantly more thought disorder/disorga-
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nization than non-Kraepelinian patients without deficit syndrome. Patients with deficit showed more negative symptoms than those without deficit syndrome, regardless of Kraepelinian subtype. No significant differences were identified between groups for the remaining three symptom domains, or for gender or marital status; nor were there significant differences between the groups in level of education, age at onset, number of hospitalizations, or extrapyramidal side effects. The classification of Kraepelinian subtype significantly overlapped with that of deficit subtype (v 2 = 22.7, df = 1, P b 0.001). 4. Discussion To our knowledge, the present study is the first to examine the relationship between the Kraepelinian subtype and deficit syndrome in schizophrenia. The two classifications did not always overlap with each other. There were 11 Kraepelinian patients without deficit syndrome (11%) and 16 non-Kraepelinian patients with deficit syndrome (16%). The comparisons of age, duration of illness, and duration of hospitalization between the groups were, on the whole, in accordance with the concept of the Kraepelinian subtype as reflecting deterioration features (Keefe et al., 1987). Interestingly, deficit syndrome was not significantly associated with duration of illness, regardless of Kraepelinian subtype, and this lack of a significant relationship with illness duration may result in patients being classified as Kraepelinian without deficit syndrome or nonKraepelinian with deficit syndrome. Deficit syndrome may represent a relatively cross-sectional and homogeneous subgroup, regardless of its definition of enduring negative symptoms lasting more than 12 months. Moreover, non-Kraepelinian patients in the present study, especially those without deficit, may be re-classified as Kraepelinian subtype later, given that their mean illness duration was the shortest of the four groups, while their deficit/non-deficit classification is likely to be stable hereafter. Thus, although the two classifications overlapped significantly, it is possible for them to be relatively independent of each other. No significant differences among the four groups were observed in the three symptom domains of delusion/hallucination; excitement; and depressive symptoms. For delusion/hallucination, this finding supports the results of previous studies of Kraepelinian (Keefe et al., 1987, 1996) and deficit patients (Carpenter et al., 1988; Spalletta et al., 1997). The finding has not been reported previously for excitement, but this symptom domain may have been included among positive symptoms in previous studies. Kilzieh et al. (2003) reported
that depressive symptoms are less prevalent in Kraepelinian patients than in non-Kraepelinian patients. However, a study by Bralet et al. (2002) did not replicate that result, and our findings concur with the latter study. A report by Kirkpatrick et al. (1994) described deficit patients as displaying significantly lower depressed mood than non-deficit patients, but this was not replicated in the present study. It is interesting that Kraepelinian status did not have a significant influence on severity of negative symptoms. Previous studies have reported that Kraepelinian subtype is associated with more severe negative symptoms than non-Kraepelinian subtype (Keefe et al., 1987, 1996), and this may be attributable to a lack of consideration of deficit subtype. The present study suggests that assessment under both classifications will be worthwhile in planning therapeutic strategies and psychosocial interventions, and that future research into schizophrenia, especially non-Kraepelinian subtype with deficit syndrome or Kraepelinian subtype without deficit syndrome, should examine both classifications. This study has a number of limitations. Firstly, the subjects included only inpatients with schizophrenia, and the findings may not be reproducible in outpatient samples. Secondly, the sample population (N = 103) was relatively small. Lastly, the classification of Kraepelinian and deficit status was not performed in a blinded manner. The relationship between these two schizophrenia subtypes requires further rigorous investigation. References American Psychiatric Association, 1994. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. APA, Washington, DC. Bralet, M.C., Loas, G., Marechal, V.Y.V., 2002. Clinical characteristics and risk factors for Kraepelinian subtype of schizophrenia: replication of previous findings and relation to summer birth. Psychiatry Research 111, 147 – 154. Brickman, A.M., Buchsbaum, M.S., Shihabuddin, L., Byne, W., Newmark, R.E., Brand, J., Ahmed, S., Mitelman, S.A., Hazlett, E.A., 2004. Thalamus size and outcome in schizophrenia. Schizophrenia Research 71, 473 – 484. Carpenter Jr., W.T., Heinrichs, D.W., Wagman, A.M.I., 1988. Deficit and nondeficit forms of schizophrenia: the concept. American Journal of Psychiatry 145, 578 – 583. Kay, S.R., Fiszbein, A., Opler, L.A., 1987. The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261 – 276. Keefe, R.S.E., Mohs, R.C., Losonczy, M.F., Davidson, M., Silverman, J.M., Kendler, K.S., Horvath, T.B., Nora, R., Davis, K.L., 1987. Characteristics of very poor outcome schizophrenia. American Journal of Psychiatry 144, 889 – 895. Keefe, R.S.E., Frescka, E., Apter, S.H., Davidson, M., Macaluso, J.M., Hirshowitz, J., Davis, K.L., 1996. Clinical characteristics of Kraepelinian schizophrenia: replication and extension of previous findings. American Journal of Psychiatry 153, 806 – 811.
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