|Ahead of print
|Correlation of neurological soft signs with neuropsychological performance in persons with schizophrenia: A cross-sectional study from North-Eastern India
BS Sachin1, Kangkan Pathak2, Priyaranjan Avinash3, Vrinda Saxena4, Robin Victor5
1 Associate Professor, Department of Psychiatry, SDM College of Medical Sciences and Hospital, Dharwad, Karnataka, India
2 Professor, Department of Psychiatry, LGB Regional Institute of Mental Health, Tezpur, Assam, India
3 Associate Professor, Department of Psychiatry, Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India
4 Senior Resident, Department of Psychiatry, Government Doon Medical College, Dehradun, Uttarakhand, India
5 Assistant Professor, Department of Psychiatry, Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India
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|Date of Submission||26-Oct-2021|
|Date of Acceptance||17-Dec-2021|
|Date of Web Publication||04-Mar-2022|
Background: Neurological soft signs (NSS) are subtle motor and sensory deficits that are frequently found in various psychiatric disorders including schizophrenia. NSS in schizophrenia are frequently associated with impairment in cognitive abilities and deterioration in neuropsychological performance (NP).
Objective: We aimed to study the correlation between NSS and NP in persons with schizophrenia.
Methods: Sixty individuals of whom thirty had schizophrenia according to the International Classification of Diseases 10th Revision and the rest thirty were matched controls were selected based on inclusion and exclusion criteria. Demographic and clinical details were obtained and tests for the assessment of NSS and neuropsychological assessment were administered. Comparison based on scores obtained in these scales was made in both the groups.
Results: NSS were present in 100% of patients with schizophrenia and in 16.6% of controls in the control group. There was a statistically significant difference between the two groups in neuropsychological assessment. In Group 1, NSS showed a significant negative correlation with Tower of London, Stroop Color-Word Test, Digit Vigilance Test, and Digit Symbol Substitution Test. However, there was no correlation between NP and NSS in Group 2.
Conclusion: NSS were more in persons with schizophrenia compared to healthy normal controls. Furthermore, there is a negative correlation between NSS and NP in persons with schizophrenia, which is differing from the control group. We may conclude that the presence of NSS predicts the poor NP, and also contributes to poor cognitive abilities of persons with schizophrenia.
Keywords: Digit Symbol Substitution Test, motor sequencing, neurological performance, neuropsychological assessment, Stroop test, Tower of London
|How to cite this URL:|
Sachin B S, Pathak K, Avinash P, Saxena V, Victor R. Correlation of neurological soft signs with neuropsychological performance in persons with schizophrenia: A cross-sectional study from North-Eastern India. Arch Ment Health [Epub ahead of print] [cited 2022 Jun 26]. Available from: https://www.amhonline.org/preprintarticle.asp?id=339119
| Introduction|| |
Schizophrenia is a complex clinical syndrome. The presentation and psychopathology vary from cognitive, emotional, perceptual, and an array of various aspects of behavior. More than 100 years after Emil Kraepelin described dementia praecox (1896), the fundamental etiopathology is still unclear.
In the last three decades, various hypotheses have been discussed for its etiopathogenesis. One of the most robust ones is the neurodevelopmental hypothesis. Several longitudinal outcome studies demonstrated that considerable recovery was well within the bounds of schizophrenia, which further made the neurodevelopmental model more acceptable than the neurodegenerative one.,, Evidences supporting the neurodevelopmental origin of schizophrenia are the presence of neurological soft signs (NSS), minor physical anomalies, and cognitive neuropsychological deficits. Clinically visible and elicitable neurological abnormalities in patients with schizophrenia are usually known as “NSS.”
These are defined as abnormal motor or sensory findings, including involuntary movements, a variety of dyspraxia, difficulties in performing rapid alternating movements, difficulties in two-point discrimination, and graphesthesia in a person without a neurological disorder which can be determined as its focus. The term soft is used to indicate that there is no corresponding pathological lesion.,, Although the categorization of NSS as “soft” (example, frontal release and cerebellar signs), and the batteries used to measure them have varied, neurological abnormalities in schizophrenia seem to be localized to three main neurological domains: 
- Integrative sensory functions
- Motor coordination
- Motor sequencing.
There is a higher rate of bilateral extinction, impaired audiovisual integration, agraphesthesia, and astereognosis among patients of schizophrenia which supports the theory of deficit in integrative sensory functioning., Deficits in motor coordination have been reported through tests of general coordination, intention tremor, finger thumb opposition, balance, and gait. Finally, poor performance in complex motor tasks (possibly resulting from a dysfunction of the frontal-basal ganglia circuit) has been reported in tests that involve repetitive-alternating hand positions, such as fist-edge-palm test, the fist-ring test, and Ozeretski test.
Abnormalities have also been reported in eye movements (pursuit and saccadic movements) and developmental reflexes, particularly in signs of frontal release. Other abnormalities, such as those of primary sensory function, have been less often described. The deficits in a broad range of cognitive functions, such as attention, abstraction, executive function, learning, and memory, have been demonstrated in schizophrenia.
Meta-analytic studies suggest moderate-to-severe impairments in the attention domain, in schizophrenia when compared to healthy controls. Set-shifting deficits in Wisconsin Card Sorting Test (WCST) performance have most consistently been reported in patients with schizophrenia., A meta-analysis by Weickert et al. 2000, also reported significant deficits in WCST scores in schizophrenia compared to healthy controls. Lack of increased interference time on Stroop paradigm (test for response inhibition) in patients with schizophrenia is reported by some studies., Two meta-analytic studies indicated that patients with schizophrenia show a significantly increased interference effect when compared with healthy controls. In several studies, patients with schizophrenia showed poor decision-making performance measured by gambling task compared to healthy controls.,,
Majority of the literature present suggests that the presence of NSS in schizophrenia is associated with poor cognitive abilities. However, studies highlighting the correlation between NSS and neuropsychological performance (NP) in patients with schizophrenia are rare more so from north-eastern part of India. The current study was planned to examine this correlation in patients with schizophrenia and understand the neurobiology of schizophrenia which will later help us evolve our approach toward the management of schizophrenia.
Aims and objectives
We aimed to study the correlation between NSS with NP in persons with schizophrenia.
| Methods|| |
The study was conducted in a tertiary care psychiatric teaching institute in Assam, India, after ethical and scientific approval from the institute. The study period was 1 year. A sample size of 60 individuals was included, of which thirty were cases of schizophrenia according to the International Classification of Diseases 10th Revision criteria (Group 1) and thirty were matched controls (Group 2). The matched controls were healthy individuals working in the institute in various capacities and were matched for age, gender, and comorbidities. The sample size was reached after considering the prevalence of schizophrenia in the area and the number of patients attending the outpatient department and inpatient department services of the institute. Appropriate consultation with the institute biostatistician was taken based on the database for sample size. Recruitment of the individuals was done after taking informed consent from the participants and was done by primary investigators. To avoid any bias, the study participants were randomly assigned to the investigators. All the scales were applied by the primary investigators in the original form. Scales were explained to the patient in their vernacular language. A semi-structured pro forma was applied to assess demographic and other clinical variables. The Mini-International Neuropsychiatric Interview (MINI) was used to rule out other psychiatric comorbidities (after obtaining the required permission). MINI was applied and interpreted by primary investigators who were well versed with using it. The Positive and Negative Syndrome Scale was used to assess the severity of symptoms. The Neurological Evaluation Scale (NES) was used (after obtaining the required permission) to measure NSS. It is a 30-item scale; each item is rated from 0 to 2 which includes the Annett's Handedness Questionnaire. It has been divided into four component subscores: sensory integration subscore, motor coordination subscore (MCS), sequential complex motor performance (SCMP) subscore, and primitive reflex subscore. Following this, neuropsychological tests were administered that included Token Test (TT), Stroop Color-Word Test (SCWT), Digit Vigilance Test (DVT), Digit Symbol Substitution Test (DSST), and Tower of London (TOL) test. These tests were applied in both the study group and the control group. Data were tabulated and appropriate statistical tools (mean, standard deviation (SD), t-test, and Pearson's correlation test) were used using IBM SPSS Statistics for Windows, version 22 (IBM Corp., Armonk, N.Y., USA). Descriptive statistics were used for continuous variables and Chi-square test was used to know the distribution of different variables between the two groups. Frequency table was used to know the frequency distribution of both continuous and categorical variables. Group comparison was done using the t-test, and finally, the correlation between the findings was assessed using Pearson's correlation test (appropriate assumptions met for using parametric test. The minimum sample for applying the test is 30 which were fulfilled by the number of study participants). Results were compared with the available literature in the area.
| Results|| |
The mean age in both the groups was 31.53 years; a maximum (57%) number of samples in both the groups were that of 29–38 years' age group. In both the groups, 70% were male. Similarly, there was no significant difference in other sociodemographic variables between the two groups. More than half, 17 out of 30 cases, were with duration of illness between 1 and 4 years.
| Discussion|| |
We performed this cross-sectional study out to examine the presence of NSS and NP in persons with schizophrenia and to explore the correlation between the two. In our study, NSS were examined using NES and comparison was made between Groups 1 and 2 as shown in [Table 1]. Participants in Group 1 had NSS mean score 32.03 ± 5.05 on NES, whereas participants from Group 2 had NSS mean score 0.7 ± S. D = 1.7 on NES. A significant difference was found between the two groups on NSS score of NES (t = 32.17, df = 58, P < 0.001). These above results confirm that persons with schizophrenia have significantly more NSS when compared to the normal healthy control group. The findings of our study are similar that the findings of earlier studies.,, The findings of our study are supported strongly by earlier meta-analysis and other studies which used NES for assessing NSS and compared it among patients with schizophrenia and normal healthy controls.,,,, With the above observations, it is obvious from our study that the NSS were found more in the schizophrenic group in comparison to the control group.
|Table 1: Group differences of neurological soft signs among Group 1 (study group) and Group 2 (control group)|
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In our study, we found that persons with schizophrenia did significantly poor on all the domains of the neuropsychological test when compared to the controls which is shown in [Table 2]. In the present study, we found that TT performance which tests the verbal comprehension was found to be significantly poor in Group 1 (schizophrenia group) when compared to Group 2 (control group) (df = 58, t = 13.01, P < 0.001). Performance of Group 1 in TOL is significantly poor when compared to Group 2 (df = 58, t = 18.33, P < 0.001), which shows that persons with schizophrenia have poor planning abilities. This also indicates that persons with schizophrenia had deficits in executive functioning.
|Table 2: Group differences in neurological performance in Group 1 (study group) and Group 2 (control group)|
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Performance of participants from Group 1 on SCWT which tested the response inhibiting ability was significantly poor when compared to Group 2 (df = 58, t = 21.75, P < 0.001), indicating that persons with schizophrenia had poor ability in inhibiting two different types of responses, which is a function of the frontal lobe, and hence supporting the earlier hypothesis of hypofrontality.
Similarly, performance of the participants from Group 1 in DSST was found to be significantly poor when compared to Group 2 (df = 58, t = 9.21, P < 0.001), indicating that there is impairment in the sustained attention, visuomotor coordination, and response speed in persons with schizophrenia.
Likewise, performance of the participants from Group 1 in DVT was found to be significantly poor when compared to the controls (df = 58, t = 9.66, P < 0.001). This indicates that persons with schizophrenia had impairment in both sustained attention and psychomotor speed.
The above findings are similar to various other studies which have found poor NP in persons with schizophrenia when compared to normal persons.,,
In the present study, Pearson's correlation was used to find the correlation between the NSS and the NP among persons with schizophrenia (which is shown in [Table 3]). [Table 4] shows the co-relation between NES and NSS in control group and none of the finding was significant. We found that NSS showed a significant negative correlation with TOL, SCWT, DVT, and DSST. NSS – motor sequencing showed a significant negative correlation with TOL, DVT, and DSST. NSS – motor coordination showed a significant negative correlation with DVT and DSST. NSS – sensory integration showed a significant negative correlation with TT (P < 0.05, two-tailed).
|Table 3: Correlation of neurological soft signs and neurological performance in Group 1 (study group)|
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|Table 4: Correlation of neurological soft signs and neurological performance in Group 2 (control group)|
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The findings of the present study were well supported by the earlier studies which have reported that in persons suffering from schizophrenia, NSS were significantly correlated with NP and these individuals did poorly in the neuropsychological tests.,,,,,,
In our study, we used the control group which showed the magnitude of both neurological and cognitive impairments associated with persons with schizophrenia. This is clearly evident from lack of correlation between NSS and NP in the control group.
These above findings suggest that persons with schizophrenia who have NSS have poor NP, supporting the presence of neurological abnormalities and their potential influence on cognitive abilities of persons with schizophrenia.
Even though our study sample size was less compared to the above studies, we found that the presence of NSS had influenced poor performance in the neuropsychological tests in schizophrenia patients. They influenced planning, inhibition, sustained attention, psychomotor speed, and visuomotor coordination in persons with schizophrenia.
| Conclusion|| |
From the findings of our study, we conclude that NSS were more in persons with schizophrenia compared to healthy normal controls. The NP of the persons with schizophrenia was poor compared to the normal healthy control group, suggesting that schizophrenia patients have cognitive deficits. Furthermore, there is a negative correlation between NSS and NP in persons with schizophrenia, which is differing from the control group. We conclude that the presence of NSS is associated with poor NP, and also contributes to poor cognitive abilities of persons with schizophrenia.
Limitations of the study
Sample being small was a major limitation, also majority of the participants in the study group were male (which might be a confounding factor), and hence the results of the study cannot be generalized. Literature suggested that exposure to neuroleptic drugs can have an adverse effect on the NP of persons with schizophrenia; in this study, we did not have control over the neuroleptic medication, so this could have influenced some of the findings.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Varambally S, Venkatasubramanian G, Gangadhar BN. Neurological soft signs in schizophrenia – The past, the present and the future. Indian J Psychiatry 2012;54:73-80. [Full text]
Venkatasubramanian G, Latha V, Gangadhar BN, Janakiramaiah N, Subbakrishna DK, Jayakumar PN, et al
. Neurological soft signs in never-treated schizophrenia. Acta Psychiatr Scand 2003;108:144-6.
Chan RC, Xu T, Heinrichs RW, Yu Y, Wang Y. Neurological soft signs in schizophrenia: A meta-analysis. Schizophr Bull 2010;36:1089-104.
Tosato S, Dazzan P. The psychopathology of schizophrenia and the presence of neurological soft signs: A review. Curr Opin Psychiatry 2005;18:285-8.
Quitkin F, Rifkin A, Klein DF. Neurologic soft signs in schizophrenia and character disorders. Organicity in schizophrenia with premorbid asociality and emotionally unstable character disorders. Arch Gen Psychiatry 1976;33:845-53.
Chan RC, Wang Y, Wang L, Chen EY, Manschreck TC, Li ZJ, et al
. Neurological soft signs and their relationships to neurocognitive functions: A re-visit with the structural equation modeling design. PLoS One 2009;4:e8469.
Smith RC, Kadewari RP, Rosenberger JR, Bhattacharyya A. Nonresponding schizophrenia: Differentiation by neurological soft signs and neuropsychological tests. Schizophr Bull 1999;25:813-25.
Flashman LA, Flaum M, Gupta S, Andreasen NC. Soft signs and neuropsychological performance in schizophrenia. Am J Psychiatry 1996;153:526-32.
Heinrichs RW, Zakzanis KK. Neurocognitive deficit in schizophrenia: A quantitative review of the evidence. Neuropsychology 1998;12:426-45.
Fioravanti M, Carlone O, Vitale B, Cinti ME, Clare L. A meta-analysis of cognitive deficits in adults with a diagnosis of schizophrenia. Neuropsychol Rev 2005;15:73-95.
Dickinson D, Ramsey ME, Gold JM. Overlooking the obvious: A meta-analytic comparison of digit symbol coding tasks and other cognitive measures in schizophrenia. Arch Gen Psychiatry 2007;64:532-42.
Braff DL, Heaton R, Kuck J, Cullum M, Moranville J, Grant I, et al
. The generalized pattern of neuropsychological deficits in outpatients with chronic schizophrenia with heterogeneous Wisconsin Card Sorting Test results. Arch Gen Psychiatry 1991;48:891-8.
Weickert TW, Goldberg TE, Gold JM, Bigelow LB, Egan MF, Weinberger DR. Cognitive impairments in patients with schizophrenia displaying preserved and compromised intellect. Arch Gen Psychiatry 2000;57:907-13.
Johnson-Selfridge M, Zalewski C. Moderator variables of executive functioning in schizophrenia: meta-analytic findings. Schizophr Bull 2001;27:305-16.
Barch DM, Carter CS, Perlstein W, Baird J, Cohen JD, Schooler N. Increased stroop facilitation effects in schizophrenia are not due to increased automatic spreading activation. Schizophr Res 1999;39:51-64.
Barch DM, Carter CS, Hachten PC, Usher M, Cohen JD. The “benefits” of distractibility: Mechanisms underlying increased Stroop effects in schizophrenia. Schizophr Bull 1999;25:749-62.
Westerhausen R, Kompus K, Hugdahl K. Impaired cognitive inhibition in schizophrenia: A meta-analysis of the Stroop interference effect. Schizophr Res 2011;133:172-81.
Beninger RJ, Wasserman J, Zanibbi K, Charbonneau D, Mangels J, Beninger BV. Typical and atypical antipsychotic medications differentially affect two nondeclarative memory tasks in schizophrenic patients: A double dissociation. Schizophr Res 2003;61:281-92.
Ritter LM, Meador-Woodruff JH, Dalack GW. Neurocognitive measures of prefrontal cortical dysfunction in schizophrenia. Schizophr Res 2004;68:65-73.
Shurman B, Horan WP, Nuechterlein KH. Schizophrenia patients demonstrate a distinctive pattern of decision-making impairment on the Iowa Gambling Task. Schizophr Res 2005;72:215-24.
IBM SPSS Statistics for Windows, version 22 (IBM Corp., Armonk, N.Y., USA).
Brébion G, Smith MJ, Gorman JM, Malaspina D, Sharif Z, Amador X. Memory and schizophrenia: Differential link of processing speed and selective attention with two levels of encoding. J Psychiatr Res 2000;34:121-7.
Woods BT, Kinney DK, Yurgelun-Todd D. Neurologic abnormalities in schizophrenic patients and their families. I. Comparison of schizophrenic, bipolar, and substance abuse patients and normal controls. Arch Gen Psychiatry 1986;43:657-63.
Murray RM, O'Callaghan E, Castle DJ, Lewis SW. A neurodevelopmental approach to the classification of schizophrenia. Schizophr Bull 1992;18:319-32.
Yazici AH, Demir B, Yazici KM, Göğüş A. Neurological soft signs in schizophrenic patients and their nonpsychotic siblings. Schizophr Res 2002;58:241-6.
Kinney DK, Yurgelun-Todd DA, Woods BT. Neurological hard signs in schizophrenia and major mood disorders. J Nerv Ment Dis 1993;181:202-4.
Woods BT, Kinney DK, Yurgelun-Todd DA. Neurological “hard” signs and family history of psychosis in schizophrenia. Biol Psychiatry 1991;30:806-16.
Simpson GM, Angus JW. A rating scale for extrapyramidal side effects. Acta Psychiatr Scand Suppl 1970;212:11-9.
Simpson GM, Lee JH, Zoubok B, Gardos G. A rating scale for tardive dyskinesia. Psychopharmacology (Berl) 1979;64:171-9.
Harvey PD, Bowie CR, Friedman JI. Cognition in schizophrenia. Curr Psychiatry Rep 2001;3:423-8.
Harvey PD. Cognitive and functional impairments in elderly patients with schizophrenia: A review of the recent literature. Harv Rev Psychiatry 2001;9:59-68.
Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry 1996;153:321-30.
Dazzan P, Morgan KD, Chitnis X, Suckling J, Morgan C, Fearon P, et al
. The structural brain correlates of neurological soft signs in healthy individuals. Cereb Cortex 2006;16:1225-31.
Schröder J, Essig M, Baudendistel K, Jahn T, Gerdsen I, Stockert A, et al
. Motor dysfunction and sensorimotor cortex activation changes in schizophrenia: A study with functional magnetic resonance imaging. Neuroimage 1999;9:81-7.
Chan RC, Chen EY, Cheung EF, Cheung HK. Executive dysfunctions in schizophrenia. Relationships to clinical manifestation. Eur Arch Psychiatry Clin Neurosci 2004;254:256-62.
Bersani G, Clemente R, Gherardelli S, Pancheri P. Deficit of executive functions in schizophrenia: Relationship to neurological soft signs and psychopathology. Psychopathology 2004;37:118-23.
Lal N, Tiwari SC, Srivastava S, Khalid A, Siddhartha, Kohli N. Neurological soft signs, cognitive dysfunction and ventricular brain ration in schizophrenics. Indian J Psychiatry 1998;40:180-5.
] [Full text]
Andreasen NC, Grove WM, Shapiro RW, Keller MB, Hirschfeld RM, McDonald-Scott P. Reliability of lifetime diagnosis. A multicenter collaborative perspective. Arch Gen Psychiatry 1981;38:400-5.
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[Table 1], [Table 2], [Table 3], [Table 4]
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