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German Journal of Psychiatry

ISSN 1433-1055

Depressive Symptoms in Medicated Chronic Schizophrenics

Yasuhiro Kaneda1,2 Akira Fujii2, Masao Okura1, and Isao Nagamine1


1Department of Neuropsychiatry, The University of Tokushima School of Medicine, Tokushima 770-8503, Japan

2Department of Neuropsychiatry, Fujii Hospital, Anan 774-0017, Japan

Corresponding author: Yasuhiro Kaneda, M. D., Ph. D., Department of Neuropsychiatry, The University of Tokushima School of Medicine, 3-18-15 Kuramoto-Cho, Tokushima 770-8503, Japan, Tel.: +81-88-633-7130, Fax: +81-88-632-3214, E-mail: kaneday@clin.med.tokushima-u.ac.jp


Abstract


Objective: Depressive symptoms in regularly medicated chronic schizophrenics were evaluated by the Zung Self-Rating Depression Scale (SDS), and the relationships between depressive symptoms and psychotic symptoms and neuroleptics were investigated. Methods: The subjects for the present study included 109 schizophrenic inpatients meeting DSM-IV criteria for schizophrenia. Informed consent was obtained from all subjects involved in this study. Psychotic symptoms were assessed using the Brief Psychiatric Rating Scale. Results: 1) The mean total SDS score in the schizophrenics was significantly higher than that in the normal subjects. 2) Mean scores of eight SDS items were significantly higher in the schizophrenic patients than in the healthy controls. 3) There was no significant difference in the mean total SDS score between the schizophrenics medicated with haloperidol (HPD) and those without it. 4) There was a significant positive correlation between the total SDS scores and positive symptoms (POS), but no significant correlation between the total SDS scores and negative symptoms. 5) There was no significant correlation between the total SDS scores and HPD serum levels or neuroleptics dosage. Conclusion: Our results may indicate that depressive symptoms in medicated chronic schizophrenics are those of "secondary" depression associated with the POS (German J Psychiatry 1999; 2: 1-12).

Key words: depressive symptoms, schizophrenia, positive symptoms, negative symptoms, neuroleptics

Received: January 2, 1999 

Published: February 11, 1999

 

INTRODUCTION

 

Studies of comorbid psychiatric disorders have been stepped up, since these disorders may exert a significant influence on what is presumed to be the major or underlying psychiatric disorder (Coryell and Zimmerman, 1988). Moreover, clarification of the comorbidity has important clinical implications, particularly in choosing the best neuroleptics for the disease. Depressive features are well recognised within the context of schizophrenia (Miles, 1977; Roth, 1970). However, previous reports have contradictory findings of the associations between depressive symptoms and positive and negative symptoms. Whereas several studies have found a strong relationship between negative symptoms and depressive symptoms (Kulhara et al., 1989; Lindenmayer et al., 1992), others have found that some depressive symptoms are more strongly associated with positive versus negative symptoms (Barnes et al., 1989; Norman and Malla, 1994). Moreover, whether these findings reflect different manifestations of a similar underlying process or two independent processes with certain similar clinical features remains unclear. In addition to the above findings, "revealed depression" (Hirsch, 1982; Knights and Hirsch, 1981) or "pharmacogenic depression" (Galdi, 1983; Kapur and Mann, 1992) is reported to explain the presence of depression in schizophrenia. The present study investigated the relationships between depressive symptoms and neuroleptics and psychotic symptoms in schizophrenics, in 109 regularly medicated chronic schizophrenic inpatients.

 

MATERIAL AND METHODS

 

The subjects for the present study were 109 regularly medicated chronic schizophrenic inpatients (50 females and 59 males), meeting the DSM (Diagnostic and Statistical Manual of the American Psychiatric Association)-IV (American Psychiatric Association, 1994) diagnostic criteria for schizophrenia, and 47 normal subjects (31 females and 16 males). Informed consent was obtained from all subjects for the research involved in this study. Diagnosis of schizophrenia was made according to the formal criteria of DSM-IV. The inclusion criteria were confirmed by inspection of medical records. Patients were excluded if they presented with any organic central nervous system disorder, significant substance abuse, and mental retardation. Normal subjects had no neuropsychiatric history nor ongoing medication. Schizophrenics and normal subjects had respective ages of 49.7 years (SD = 11.5, range 18-76) and 49.2 years (SD = 11.7, range 23-60) (Table 1). Schizophrenics had been chronically treated for periods of 19.6 years (SD = 10.7, range 1-53). Psychiatric ratings were done using the Zung Self-Rating Depression Scale (SDS) (Zung and Durham, 1965) and the Brief Psychiatric Rating Scale (BPRS) (Overall and Gorham, 1962). The SDS is composed of 20-item scales constructed to measure depressive symptoms, using 4-point scales. The SDS scores were calculated for the complete 20-item measure. The BPRS provided a standardised method of assessing 18 psychiatric symptoms using operationally defined 7-point scales. Two symptoms, namely hallucinatory behaviour and unusual thought content, were derived from this scale as positive symptoms (POS) based on previous groupings of BPRS symptoms (Crow, 1985; Guy, 1976; Kitamura et al., 1989; Nicholson et al., 1995). The POS scores were formed using the sum of the ratings of the POS, and were 4.8 (SD = 2.9, range 2-14) (Table 1). Three symptoms, emotional withdrawal, motor retardation, and blunted affect, were derived from this scale as negative symptoms (NEG) (Crow, 1985; Guy, 1976; Nicholson et al., 1995). The NEG scores were formed using the sum of the ratings of the NEG, and were 6.7 (SD = 2.8, range 3-16) (Table 1). Each neuroleptic was converted to its haloperidol (HPD) equivalent using the dosage comparability table (Davis, 1976). The converted dosages were .21 mg/kg/day (SD = .22, range 0-1.44) (Table 1). Blood samples for HPD estimation were drawn from 47 out of 51 patients medicated with HPD between 0500 and 0600 h. Blood samples were prepared and stored at -20 centigrade until the time of analysis. HPD was assayed by a radioimmunoassay. Statistical analyses were done using parametric tests (e.g. t-test, Pearson product-moment correlations) if the data were normally distributed. Otherwise, nonparametric tests (e.g. Mann Whitney’s U-test, Spearman rank correlations) were used.

 

 

Table 1. Demographic characteristics, Brief Psychiatric Rating Scale (BPRS) scores, dosage, haloperidol serum levels

   

N

Age

Age of onset

BPRS

Dosage

HPD serum levels

     

(yr)

(yr)

POS scores

NEG scores

(mg/kg/day)

(ng/ml)

     

Mean SD

Mean SD

Mean SD

Mean SD

Mean SD

Mean SD

Schizophrenics Total

109

49.7 11.5

30.2 10.0

4.8 2.9

6.7 2.8

0.21 0.22

-

  HPD (+)

51

48.9 12.4

30.3 10.7

4.7 3.0

6.9 3.1

0.25 0.27

2.3 2.6 (N=47)

  HPD (-)

58

50.4 10.7

30.0 9.5

4.8 2.9

6.6 2.5

0.17 0.17

-

Healthy controls  

47

49.2 11.7

-

0

0

0

 -

HPD = haloperidol; BPRS = Brief Psychiatric Rating Scale; POS = positive syndrome; NEG = negative syndrome.

 

 

RESULTS

 

1. SDS scores in medicated schizophrenics and normal subjects

 

The mean total SDS scores in the medicated schizophrenics and normal subjects were 40.1 (SD = 9.5, range 20-69) and 34.5 (SD = 9.4, range 21-68), respectively (Table 2). The mean total SDS score in the medicated schizophrenics was significantly higher than that in the normal subjects (U-test, P < .001). The mean scores of the SDS item-1 (depressed affect), 4 (sleep disturbance), 7 (weight loss), 9 (tachycardia), 12 (psychomotor retardation), 13 (psychomotor agitation), 19 (suicidal rumination) and 20 (dissatisfaction) were significantly higher in the schizophrenics than in the normal subjects (U-test, P < .05, P < .001, P < .001, P < .01, P < .01, P < .001, P < .01 and P < .05, respectively) (Table 2). The mean total SDS scores in the schizophrenics medicated with HPD and those without it were 38.9 (SD = 10.1, range 20-69, N = 51) and 41.3 (SD = 8.9, range 26-64, N = 58), respectively (Table 1), and there was no significant difference between them.

 

 

Table 2. Differences in SDS scores (Zung Self-Rating Depression Scale) between schizophrenics and healthy controls

   

Schizophrenics

Healthy controls

 
   

Mean SD

Mean SD

 
Total  

40.1 9.5

34.5 9.4

 
Item 1 Depressed affect

1.7 0.9

1.3 0.6

*
Item 2 Diurnal variation

2.3 1.3

2.6 1.2

 
Item 3 Crying spells

1.4 0.7

1.2 0.5

 
Item 4 Sleep disturbance

1.7 0.9

1.2 0.6

***
Item 5 Decreased appetite

1.5 0.9

1.4 0.8

 
Item 6 Decreased libido

3.2 1.0

3.0 1.0

 
Item 7 Weight loss

1.8 1.0

1.3 0.8

***
Item 8 Constipation

1.7 1.1

1.4 0.7

 
Item 9 Tachycardia

1.4 0.7

1.1 0.3

**
Item 10 Fatigue

2.0 1.0

1.9 0.9

 
Item 11 Confusion

2.2 1.2

2.1 1.2

 
Item 12 Psychomotor retardation

2.1 1.2

1.5 0.9

**
Item 13 Psychomotor agitation

1.8 1.0

1.1 0.4

***
Item 14 Hopelessness

3.0 3.9

2.3 1.2

 
Item 15 Irritability

1.5 0.8

1.4 0.6

 
Item 16 Indecisiveness

2.7 1.2

2.3 1.1

 
Item 17 Personal devaluation

2.5 1.2

2.3 1.1

 
Item 18 Emptiness

2.4 1.2

2.0 1.1

 
Item 19 Suicidal rumination

1.5 1.0

1.1 0.5

**
Item 20 Dissatisfaction

2.5 1.2

2.0 1.1

*

*p < .05, **p < .01 and ***p < .001 versus healthy controls by the Mann-Whitney U-test.

 

 

2. Relationships between depressive symptoms and neuroleptics and psychotic symptoms

 

There was a significant positive correlation between the total SDS scores and POS scores (Spearman’s r = .278, P < .01, N = 109) (Table 3). However, there was no significant correlation between the total SDS scores and NEG scores. There was no significant correlation between the total SDS scores and HPD serum levels or dosages of neuroleptic (Table 3).

Table 3. Correlations between depressive syndrome and positive syndrome, negative syndrome, haloperidol serum level, and dosage

 

r

p values

POS scores

0.278

p < .01

NEG scores

0.094

NS

HPD serum levels

0.169

NS

Dosage

0.175

NS

r= Spearman rank correlation with depressive syndrome; POS = positive syndrome; NEG = negative syndrome.

HPD = haloperidol;

 

DISCUSSION

 

In the present study, the mean total SDS score was significantly higher in the medicated schizophrenics than in the normal subjects. Moreover, the total SDS scores were significantly positively correlated with the POS scores, although there were no significant correlations between the total SDS scores and NEG scores, HPD serum levels or dosages of neuroleptics. These results are consistent with past investigations of Barnes et al. (Barnes et al., 1989), and Norman and Malla (Norman and Malla, 1994). These results seem to provide support for the idea that depressive symptoms in medicated chronic schizophrenics are those of "secondary" depression associated with the POS, but not for "pharmacogenic depression" or "revealed depression; depressive symptoms may represent an alternative expression of the underlying psychotic process or an integral part of the schizophrenic state" (Hirsch, 1982; Knights and Hirsch, 1981). And our results fit our impressions in clinical practices: many schizophrenics are suffering from their hallucinations and delusions, whether they have insight into the disease or not. However, the results may be applied only to the chronic schizophrenic sample, and other mechanisms might explain depression appearing at different stages of the disease. In our study, the self-rating scale was chosen, because most of the schizophrenic patients, except most severe ones, could express their feelings and complete them. In addition, sometimes, it remains difficult to clearly separate depressive symptoms from negative symptoms and extrapyramidal side-effects (Prosser et al., 1987). Since the effect of stress resulting from admission on SDS scores cannot be ruled out as a possible influence, further research with both in- and outpatients might be required to confirm our results.

 

CONCLUSIONS

 

In the present study, the mean total SDS score was significantly higher in the medicated chronic schizophrenics than in the normal subjects. Moreover, the total SDS scores were significantly positively correlated with the POS scores, although there were no significant correlations between the total SDS scores and NEG scores, HPD serum levels or dosages of neuroleptics. Our results may indicate that depressive symptoms in medicated chronic schizophrenics are those of "secondary" depression associated with the POS.

Acknowledgment: We appreciate the co-operation of colleagues in our department. Some of these results were presented at the 21st CINP (Collegium Internationale Neuro-Psychopharmacologicum) Congress, Glasgow, U.K., July, 1998.

 

References

 

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