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ORIGINAL ARTICLE
Year : 2019  |  Volume : 12  |  Issue : 3  |  Page : 227-232  

Neurological soft signs in positive and negative subtypes of schizophrenia


Department of Psychiatry, Dr. DY Patil Medical College, Hospital and Research Centre, Dr. DY Patil Vidyapeeth, Pune, Maharashtra, India

Date of Submission02-Feb-2018
Date of Acceptance04-Nov-2018
Date of Web Publication15-May-2019

Correspondence Address:
Suprakash Chaudhury
Department of Psychiatry, Dr. D. Y. Patil Medical College, Pimpri, Pune - 411 018, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mjdrdypu.mjdrdypu_26_18

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  Abstract 


Background: Schizophrenia, a heterogeneous clinical syndrome, has fascinated researchers since times immemorial. An increasing number of studies have implicated multiple brain regions, variations in the localization, and severity of brain impairments in schizophrenic patients that could ultimately lead to unraveling the etiopathogenesis of schizophrenia. A direct, easily administered, and inexpensive way of investigating brain dysfunction in schizophrenia is the study of neurological soft signs (NSS). Aim: To document the presence of NSS in positive and negative subtypes of schizophrenia and compare them with normal controls. Materials and Methods: The study was conducted on 52 schizophrenic patients diagnosed according to the International Classification of Diseases 10 Diagnostic Criteria for Research and 52 normal controls matched for age and education. All the patients gave written informed consent. NSS were assessed using Neurological Evaluation Scale (NES). Results: The prevalence of NSS in this study was estimated to be 77%. Statistically significant correlations were observed between the negative symptom subscale of Positive and Negative Syndrome Scale and the NES scores among the patients with schizophrenia. Conclusions: The comparison of the mean NES scores among cases and controls in this study reveals a very highly significant difference between the two groups studied. This suggests that NSS are highly prevalent among patients with schizophrenia.

Keywords: Neurological Evaluation Scale, neurological soft signs, positive and negative subtypes of schizophrenia, schizophrenia


How to cite this article:
Devabhaktuni S, Saldanha D, Chaudhury S, Sahu S. Neurological soft signs in positive and negative subtypes of schizophrenia. Med J DY Patil Vidyapeeth 2019;12:227-32

How to cite this URL:
Devabhaktuni S, Saldanha D, Chaudhury S, Sahu S. Neurological soft signs in positive and negative subtypes of schizophrenia. Med J DY Patil Vidyapeeth [serial online] 2019 [cited 2019 May 25];12:227-32. Available from: http://www.mjdrdypv.org/text.asp?2019/12/3/227/258209




  Introduction Top


Neurological soft signs (NSS) are defined as minor, nonlocalizable anomalies and are found on neurological examination in the absence of other fixed or fleeting features of the neurological disorder.[1] The study of these signs is a direct, easily administered, and inexpensive way of investigating brain dysfunction in schizophrenia. Abnormal neurodevelopment has been postulated to be the likely cause of the continued presence of NSS beyond adolescence, and these signs have been extensively studied in disorders believed to have a neurodevelopmental basis, such as schizophrenia.

Bender in 1947 gave the term soft neurological signs (SNS) when she studied a group of 100 children diagnosed with schizophrenia.[2] Research on neurological abnormalities evaluation in child psychiatry expanded as the concepts of “soft neurological signs” and “minimal brain dysfunction” became popular in the 1960s. This trend led to large pediatric studies, for conceptual and methodological clarification. Studies of NSS in adolescent and then adult psychiatric patients followed.[3] Neurological signs in schizophrenia have been investigated since the 1970s and in the 1980s, they were interpreted as an expression of the neurobiology of schizophrenia and have received consistent attention.[4],[5]

SNS are abnormalities reflecting a connection disorder among subcortical and cortical regions or between cortical regions. Unlike classical neurological signs, SNS are characterized by sensory, motor, and integrative functional dysfunctions, which do not reflect focal brain dysfunction.[6] NSS are commonly classified into clusters of coordination of motor acts, sensory integration, sequencing of complex motor acts, and primitive reflexes.[7] The high prevalence of these neurological abnormalities among patients with schizophrenia is well reported.[8] At least one sign has been found at the first presentation in nearly 90% of schizophrenic patients, and persons with schizophrenia have elevated rates of SNS compared with controls.[9] Even though NSS lack the potential to differentiate between schizophrenia and other psychiatric disorders, NSS may serve as markers of a disease process. Several studies have investigated the presence of NSS in persons with a family history of schizophrenia, most commonly unaffected siblings of probands, and concluded that such persons have elevated scores of NSS compared with healthy controls.[10],[11],[12],[13],[14] The above studies indicate a genetic component in the pathogenesis of soft signs, and higher levels of NSS are associated with an increased risk for schizophrenia.

NSS are closely related to psychopathology[15] and were found to be increased in acute illness and subsided with the treatment of symptoms. Similar findings were reported in a number of studies including patients with first-episode psychosis where high levels of NSS at first presentation are related to high levels of psychopathology at that stage.[16] Impairment in attention due to high levels of positive symptoms appears to increase NSS, which alleviate on the administration of antipsychotic medication. However, it has been observed that, in patients with predominantly negative symptoms, NSS persisted beyond the acute stage, indicating that NSS may be a function of these symptoms or possibly an independent factor to negative symptoms, cognitive impairment, and neurological function.[4] In this context, the present study was undertaken to document the presence of NSS in positive and negative subtypes of schizophrenia and compare them with normal controls.


  Materials and Methods Top


Consecutive patients diagnosed with schizophrenia as per the International Classification of Diseases (ICD) 10 Diagnostic Criteria for Research (DCR) criteria admitted in a tertiary care hospital with neuropsychiatry facility were compared with an equal number of age- and sex-matched normal adult volunteers (who were not on any known treatment or substance abuse) after their written consent over a period of 24 months. Institutional ethical clearance was taken before the conduct of the study. In addition, the following criteria were fulfilled before the patients were taken for the study. All the scales were applied by one of us (SS) who was blind to the clinical diagnosis of the patient.

Inclusion criteria (schizophrenia patients)

  1. Patients diagnosed according to the ICD-10 DCR for schizophrenia
  2. Both male and female patients aged between 18 and 60 years
  3. Patients who were drug naïve or drug free (drug free being defined as being off oral antipsychotic medications for 4 weeks and for long-acting antipsychotic, a period of 8 weeks)
  4. Those who gave written informed consent and agreed to participate in the study.


Exclusion criteria (schizophrenia patients)

  1. Known cases of head injury and seizure disorder
  2. Those who are already on psychotropic medications or have a past history of primary psychiatric illness.


Inclusion criteria (control group)

  1. Persons with no history of psychiatric illness and exposure to psychotropic medication
  2. Both male and female patients aged between 18 and 60 years
  3. Those who have given written consent and agreed to participate in the study.


Exclusion criteria (control group)

  1. Known cases of head injury and seizure disorder
  2. Persons below the age of 18 and above the age of 60 were not included in the study.


Tools

  1. Sociodemographic pro forma: A semi-structured pro forma was designed for the study to record information regarding sociodemographic data such as age, gender, education, marital status, occupation, and illness variables such as family history of schizophrenia, duration of illness, and handedness
  2. ICD-10: The ICD-10 diagnostic criteria for research were used. Patients who were diagnosed with schizophrenia as per the criteria of this manual were recruited into the study[17]
  3. Neurological Evaluation Scale (NES): Patients were evaluated for NSS using NES. This is a 26-item scale with ratings from 0 (absent) to 2 (extreme) for each item. The intensity of SNS is operationalized based on the NES scores from 0 (zero) to 2 (two) where 0 – absent, 1 – mild intensity, and 2 – high intensity. It takes about 40 min to administer this scale.[18]


The NSS total score (sum of scores on all items) and NSS component scores were calculated.

The four component scores include:

  1. NSS motor co-ordination subscore is the sum of:


    • Tandem walk
    • Rapid alternating movements
    • Finger–thumb opposition
    • Finger-to-nose test.


  2. NSS sequential complex motor performance subscore is the sum of:


    • Fist-ring test
    • Fist-edge-palm test
    • Ozeretski test
    • Rhythm tapping production test.


  3. NSS sensory integration subscore is the sum of:


    • Audio–visual integration
    • Stereognosis
    • Graphesthesia
    • Extinction
    • Right–left confusion.


  4. Primitive reflex subscore is the sum of all the primitive reflexes added together.


  5. Positive and Negative Syndrome Scale (PANSS): Patients were screened with PANSS to analyze the severity of schizophrenia for positive and negative symptoms.[19]


Statistical analysis

Final qualitative and quantitative analysis was carried out as per the protocols laid down by the questionnaire, and data thus availed were computed and statistically analyzed using SPSS software (IBM, USA). Descriptive statistics in terms of percentage were used for categorical variables. Statistical tests such as Student's unpaired t-test, Chi-square test, analysis of variance, and Spearman's correlation coefficient were used to compute the data.


  Results Top


A cross-sectional analytical study was carried out on 52 patients with schizophrenia and compared with an equal number of normal controls. Majority of the cases (64%) were in the age group of 18–30 years, predominantly of male gender (52%), were Hindu by religion (84.6%) with an education between fifth to tenth standard (55.8%), the majority of whom were unemployed (48%). Most of them were unmarried (53.87%), living in an urban area (52%) [Table 1]. Out of the 52 patients, 54% were drug naïve, while 46% were drug free. Group statistics [Table 2], correlation between total NES scores and PANSS scores (Spearman) [Table 3] and [Table 4], and comparison of NSS in the study and control groups [Table 5] and [Table 6] were discussed.
Table 1: Demographic characteristics of patients with schizophrenia (n=52) and controls (n=52)

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Table 2: Scores on the Positive and Negative Syndrome Scale and the Neurological Evaluation Scale of patients with schizophrenia (n=52) and controls (n=52)

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Table 3: Correlation between total Neurological Evaluation Scale scores and total duration of illness

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Table 4: Correlation between total Neurological evaluation scale scores and Positive and Negative Syndrome Scale scores obtained by schizophrenic patients

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Table 5: Comparison of neurological soft signs in schizophrenic patients and controls

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Table 6: Comparison of neurological soft signs in positive and negative symptom group

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  Discussion Top


In the recent years, growing interest in motor symptoms, particularly the SNS, has been the focus of research. The present study is driven by this renewed interest in studying the subtle motor symptoms associated with schizophrenia and their use as a diagnostic and prognostic tool. In this study, an attempt is made to find a relationship between NSS and various manifestations of schizophrenia through the use of relevant instruments such as NES and PANSS. Studies conducted on NSS in schizophrenia are confounded by prior treatment with neuroleptics. To avoid this confounding factor, the present study included only drug-free or drug-naive patients. Studies of drug-naive patients have found that NSS are found even in the drug-naive group, and their presence in this group is more than that seen in the normal population.[20],[21]

Prevalence of neurological soft signs in schizophrenia

In this study, the prevalence of NSS was 77%. Previous studies have reported prevalence rates ranging from 20% to 96.9%.[22],[23] Ninety-two percent prevalence of NSS was reported in schizophrenic patients as compared to 52% in affective disorders and 5% in normal individuals.[3] Another study reported the prevalence of SNS in schizophrenic patients to be between 50% and 65% as compared to 5% observed in controls.[18]

The mean NES score was found to be 12.27 in the study group with a standard deviation (SD) of 9.2. In two earlier studies, the mean (±SD) NES scores were 15 (±11)[24] and 16 (±8).[22] Another study compared NSS in patients of schizophrenia and obsessive-compulsive disorder and healthy controls. The study reported the mean NES score in patients of Schizophrenia and obsessive-compulsive disorder to be 10(±3) and 5(±4) with a statistically significant difference.[25] The comparison of the mean NES scores among cases and controls in this study reveals a very highly significant difference between the two groups. This suggests that NSS are highly prevalent among patients with schizophrenia.

Neurological Evaluation Scale scores on sociodemographic variables

Age

This study showed the highest mean NES scores in the 31–40 years' age group followed by the 51–60 years' age group. As the ages of the patients increase, the mean NES scores also show an increasing trend with a decrease noted in the 41–50 years' age group. While Buchanan and Heinrichs have shown that the relationship between SNS and age is inconclusive,[18] several studies have also reported of no correlation with the age of the patient.[26],[27] However, a comparison of the mean NES scores between the different age groups did not show any statistically significant difference. Some studies have reported an increase in NSS with increasing age of the patient.[28],[29] In our study, we have not found a significant relation between SNS and age.

Gender

In this study, the mean NES scores were found to be higher among males as compared to females. However, an analysis between the two gender groups did not show any statistically significant difference between them. Variation in NSS based on sex differences had been reported across various studies. Some studies have reported an increase in NSS in males as compared to females.[3] One study has shown more NSS in females with a family history of schizophrenia.[30] However, majority of the studies have failed to show any association between NSS and gender.[26],[28],[29] The present study found no variance between gender and severity of NSS in patients with schizophrenia, which is consistent with previously reported findings.

Educational status

NSS were found to be highest among the patients educated up to graduation, followed by patients educated up to the higher primary level of schooling. Analysis between the four groups did not show any statistically significant difference in the mean NES scores according to the educational qualifications of the patients. Though a few studies have found an inverse correlation between education and neurological impairment,[26],[31],[32] this has not been replicated in other studies.[33] The present study has not found any association between NSS and educational status in patients with schizophrenia, and this finding appears to be consistent with previously reported studies.

Relationship of family history with neurological soft signs in schizophrenia

Positive family history of schizophrenia was present in 35% of our study participants. When NSS were compared between cases with and without family history, it was found that there was a statistically significant difference among both the groups. Similar findings were reported by few studies[34],[35] though other studies failed to reach this conclusion.[36],[37]

Duration of illness

The mean duration of illness in this study was 3.37 years. This study did not find an increasing trend in the mean NES scores of patients with schizophrenia with an increase in the duration of illness. This finding may have been due to fewer number of patients with duration of illness >10 years in the study population. The results of this study are consistent with few previous studies,[38],[39] though other studies described NSS as features characteristic of chronicity in schizophrenia.[40],[41],[42]

Neurological Evaluation Scale scores and correlation with Positive and Negative Syndrome Scale

On comparing the NSS in the positive and negative subtypes of schizophrenia in this study, all the subscales except sequencing complex motor acts yielded very highly significant statistical difference. The results suggest that the total and subscales of NSS are highly represented in the negative subtype of schizophrenia. As mentioned earlier, the study by Cvetić et al.[43] which compared the NSS in patients with positive and negative signs of schizophrenia showed that the total score of the NES was significantly higher in the negative subtype group, indicating higher neurological impairment in patients with negative symptoms. Though this has not been a consistent finding, a study done by Tiryaki et al. found that the subscore of sequencing of complex motor acts is an important predictor of deficit state, which is the negative subtype of schizophrenia.[35] Results of the study by Cvetić et al. showed that the scores on sequencing of complex motor acts subscales, although highly significantly different, were not the highest among the subscales.[43] Similar results were also reported in a study by Prikryl et al. who found that the PANSS scale for negative symptom score correlated positively with the “Others” NES subscore and the total score of NES.[44] A study done by Varambally et al. examined the cerebellar signs along with other NSS and reported a significant correlation between cerebellar soft signs and negative symptom scores.[45]

Limitations

The limitations of the study include small sample size and hospital-based study design which may limit its generalizability. Another control group of different types of psychiatric disorders should have been included. Inclusion of first-degree relatives of patients with schizophrenia would have given additional information.


  Conclusions Top


NSS are highly prevalent in schizophrenia. NSS are significantly associated with negative symptoms of schizophrenia and a positive family history.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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