Original Article
Neurologic soft signs (NSS) have been reported to be associated with schizophrenia, but some have argued that neuroleptics may play a role in the development of NSS. The objective of the present study is to examine the relationship between NSS and antipsychotic drugs, by evaluating the changes in NSS of first onset, neuroleptic-naïve schizophrenic patients, before and after one year of neuroleptic treatment. The subjects were 11 neuroleptic-naïve patients (male = 5, female = 6, mean age = 33.3 years) with schizophrenia or schizophreniform disorder. The presence of NSS was examined using the Neurological Evaluation Scale - Korean (NES-K) Version. All subjects were evaluated before the treatment was initiated and following one year of treatment. All scores on the NES-K and the subscores of the 'other' area significantly decreased following one year of treatment. Even though the results were not statistically significant, the scores of the other three functional categories were lower following one year of treatment. Our findings do not support the hypothesis that NSS in patients with schizophrenia are an epiphenomenon of the neuroleptic treatment. Also, our results indicate that some components of NSS observed in patients with schizophrenia are intrinsic to this illness and independent of the neuroleptic treatment.
Correspondence: Jeong-Ho Chae, MD, Department of Psychiatry, The Catholic
University of Korea, College of Medicine, St. Mary's Hospital, 62 Yoido-dong, Youngdeungpo-gu, Seoul 150-713, Korea
Tel: +82-2-3779-1250, Fax: +82-2-780-6577, E-mail: alberto@catholic.ac.kr
Neurologic soft signs (NSS) have been reported to be more prevalent in patients with schizophrenia than in patients with other psychiatric disorders or normal subjects1. However, these signs may be an epiphenomenon, related to the effects of neuroleptics, chronic institutionalization and other factors2.
Since Quikin et al3. argued that NSS are sometimes linked to neuroleptic effects, many studies have suggested that neuroleptics may play a pivotal role in the development of NSS.
Although exposure to neuroleptics may have contributed to the higher rate of NSS observed in the medicated schizophrenic group, no direct relationship between medication status and NSS has emerged in those studies that examined the effects of neuroleptic exposure4. There have been some reports on the presence of NSS in schizophrenic patients who had never received neuroleptics prior to the onset of schizophrenia5, but few longitudinal studies of NSS in patients with first episode,
neuroleptic-naïve schizophrenia after long term follow up with neuroleptic treatment have been published.
To elucidate the nature of NSS in patients with schizophrenia, a prospective study of patients who were
neuroleptic-naïve prior to the onset of schizophrenia according to the length of their subsequent neuroleptic treatment is needed6.
The aim of the present study is to examine the relationship between NSS and antipsychotic drugs by evaluating the changes in NSS of schizophrenic patients who had never received neuroleptic medication prior to diagnosis of schizophrenia, after one year of neuroleptic treatment.
Methods and Materials
Subjects
Eleven neuroleptic-naïve patients (male = 5, female = 6, mean age = 33.3 years) with schizophrenia or schizophreniform disorder who were recruited from The Keyo Mental Hospital, Korea were subjects in this study. Diagnosis was based on the DSM-IV criteria7 and subjects were excluded if they had any other serious medical or neurological illnesses or any other mental disorders, were over 50 or under 19 years old, or had a full-scale IQ of lower than 70. All of the patients were diagnosed using information collected according to the Schedule for Affective Disorders and Schizophrenia8. Patients diagnosed initially with schizophreniform disorder were followed up for up to one year, in order to confirm the diagnosis of schizophrenia. All of the subjects gave their informed consent prior to participating in the study.
Measures
Before treatment was initiated, the presence of NSS was examined using the Neurological Evaluation Scale - Korean (NES-K) Version9, which is a standardized translation of the original version10. This measure was repeated following one year of treatment.
Total scores and scores in the four functional subareas of the NES-K; 1) sensory integration [Audiovisual integration, Stereognosis, Graphesthesia, Extinction, Right-left confusion], 2) motor coordination [Tandem walk, Rapid alternating movement, Finger-thumb opposition, Finger-nose test], 3) sequencing of complex motor acts [Fist-ring, Fist-edge-palm, Ozeretski, Rhythm tapping test] and 4) others [Adventitious overflow test, Romberg test, Tremor, Memory, Rhythm tapping test, Mirror movement, Synkinesis, Convergence, Gaze impersistence, Glabellar reflex, Snout reflex, Grasp reflex, Suck reflex] at the baseline and one year follow-up assessments were compared using the Wilcoxon-matched pairs signed-ranks test.
Severity of psychopathology in patients was assessed using the Positive and Negative Syndrome Scale for schizophrenia11 and the changes were analyzed using the Wilcoxon-matched pairs signed-ranks test. Spearman ranked correlation test was used to analyze the relationship between NSS, psychopathology in patients with schizophrenia, and dosage of neuroleptics.
Results
Clinical characteristics including status of neuroleptic treatment of subjects are summarized in Table 111. Following one year of treatment, severity of psychopathology of subjects improved significantly, positive symptom (Z = -2.94, P = 0.003), negative symptoms (Z = -2.63, P = 0.009), and general psychopathology (Z = -2.94, P = 0.003), respectively. Total scores of the NES-K and the subscores of the 'other' area decreased significantly following one year of treatment (Table 2). An increase in total scores of the NES-K was observed in only two subjects (Figure 1). Even though the decrease was not statistically significant, the scores of "sensory integration", "motor coordination" and "sequencing of complex motor acts" categories were lower after one year of treatment. There was no correlation between NSS, degree of psychopathology and dosage of neuroleptics.
Discussion
The findings of this study indicate that some NSS are usually present in patients with schizophrenia prior to neuroleptic treatment. This result is in accordance with those of previous studies that reported the presence of neurologic abnormalities in
neuroleptic-naïve schizophrenic patients6,12. Although many studies have suggested that neuroleptics may play a role in the development of NSS, the results of this study showed a decrease in some NSS in
drug-naïve schizophrenic patients following their treatment with neuroleptics for one year.
Many studies have reported that NSS are more prevalent in schizophrenic patients than in controls, and that the patients appear to be affected by neuroleptic treatment. However, most of the findings of these studies were obtained by simple comparison between
neuroleptic-naïve and neuroleptic-treated groups. Consequently, this design suffers from certain draw-backs associated confounding variables such as age, gender, previous pharmacological treatment, institutionalization, and various individual differences.
Among the few studies performed in a long-term prospective design examining NSS in
neuroleptic-naïve schizophrenic patients, Whitman et al13 showed that there was significant improvement in overall neurological function, primarily in motor-related and cortical signs, which were associated with improvement in psychopathology in a prospective study of 97 patients with first-episode schizophrenia assessing NSS and psychopathology at presentation and at 6 month follow-up for 73 cases. In their findings, motor and cortical signs decreased in accordance with clinical improvement, these results, however, were not observed in this study. They suggested that "harder" signs were more static and unrelated to improvement in psychopathology, suggesting trait-like characteristics13. While on the other, in the present study, the items of "other" NSS, which significantly decreased after one year of treatment, are thought to consist mainly of primitive reflexes and mirror movements that are actually "harder" signs compared with the other NES-K subcategories. However, it is difficult to draw any conclusions because NSS were compared in group not individual items. Since NSS in schizophrenia are heterogenous, it is difficult to differentiate using simple a comparison of the summation of individual items. Further studies with larger sample sizes and with multiple rating scales to assess NSS, psychopathology, and side effects of the neuroleptic are needed to confirm the different findings of this study.
Several limitations should be considered when interpreting the results of this study. First, due to the small sample size, the results are preliminary. Second, some possible confounding variables such as the doses and kinds of neuroleptics and the severity of the symptoms were not completely controlled for. Third, because the neurologic examination was conducted by a clinician who was not blinded to the subject's condition, there is some possibility of rater bias. Fourth, we did not measure symptoms of neuroleptic-induced parkinsonism, akathisia, and dyskinesia. Since it is very important to distinguish between neuroleptic-induced movement symptoms and NSS, a complete assessment of movement ratings would be crucial in future studies. Finally, the learning effect of the examinee in the examination was not controlled for.
In conclusion, our findings do not support the hypothesis that NSS in patients with schizophrenia are an epiphenomenon of neuroleptic treatment. Also, our results indicate that some components of NSS observed in patients with schizophrenia are intrinsic to this illness and independent of the neuroleptic treatment. Since this study was performed in using patient with typical antipsychotics, it would also be useful to replicate the present findings, in which the subject were treated with atypical antipsychotics, which have minimum neurologic side effects profiles.
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