|Year : 2014 | Volume
| Issue : 3 | Page : 167-172
Neurological soft signs with respect to type of symptoms in patients with schizophrenia
Heba Fathy, Mohamed A Khalil
Department of Psychiatry, Faculty of Medicine, Cairo University, Cairo, Egypt
|Date of Submission||13-May-2014|
|Date of Acceptance||10-Jun-2014|
|Date of Web Publication||11-Nov-2014|
Department of Psychiatry, Faculty of Medicine, Cairo University, Cairo
Source of Support: None, Conflict of Interest: None
Neurological soft signs have been documented to occur in up to 60% of patients with schizophrenia and have been found even in neuroleptic-naive patients.
The aims of the study were to illustrate the presence of neurological soft signs among patients with schizophrenia and to show any relationship between neurological soft signs and type of symptoms.
Patients and methods
One hundred patients with schizophrenia were selected consecutively in a cross-sectional study. The patients were assessed using the Structured Clinical Interview for Diagnostic and statistical manual of mental disorders (DSM) Axis of Disorders, Positive and Negative Syndrome Scale, complete neurological examination, and Cambridge Neurological Inventory for soft sign examinations (primitive reflexes, repetitive movement, sensory integration), and Trail Making Test.
The main finding in this study indicates that the patients with schizophrenia have neurological impairment. There are positive correlations between soft neurological signs and positive symptoms in paranoid type, other types, and with the total; these indicate that neurological soft signs are more prominent in patients with positive symptoms than in those with negative symptoms.
Neurological Soft Signs (NSS) occur in a majority of the schizophrenia patient population and are largely distinct from symptomatic and cognitive features of the illness. Neurological signs in patients with schizophrenia are associated with prominent negative symptoms, relatively poor psychosocial performance, and significantly more cognitive impairment.
Keywords: Cambridge Neurological Inventory, cognitive impairment, neurological soft signs, schizophrenia
|How to cite this article:|
Fathy H, Khalil MA. Neurological soft signs with respect to type of symptoms in patients with schizophrenia. Egypt J Psychiatr 2014;35:167-72
| Introduction|| |
Patients with schizophrenia are characterized by the presence of neurological abnormalities that are not specific to the disease but are more prevalent in such patients than in persons with other mental illnesses and normal control individuals. These neurological abnormalities classically have been divided into 'hard' signs and 'soft' signs. The former are signs that are localizable to a specific brain area, whereas the latter are considered nonspecific and nonlocalizing. Patients with schizophrenia have been shown to have a greater prevalence of both soft and hard signs when compared with normal control individuals (Bombin et al., 2005).
Flashman et al. (1996) claimed that neurological soft signs have been documented to occur in up to 60% of patients with schizophrenia and have been found even in neuroleptic-naive patients with schizophrenia.
These signs do not appear to be attributable to either medication status or the presence of medication-induced neurological side effects. It has been argued that they represent a trait characteristic of the disorder (Bombin et al., 2005).
It is possible, then, that they are indicators of prior brain insults/injuries undetected in earlier life that predispose to schizophrenia or are modifying factors for the outcome of the disease; neurological soft signs have been investigated in correlation with different symptoms in patients with schizophrenia to evaluate their role as 'trait marker' for specific group of symptoms. In previous studies, these signs have been correlated with negative or deficit symptoms and lower psychosocial performance (Wong et al., 1997).
King et al. (1991) reported that NSS correlated positively with both negative and positive symptoms and there was a close relationship between NSS severity of psychopathology.
The correlations between NSS and clinical symptoms were relatively modest but significant. The correlation coefficients between NSS total and total positive and negative symptoms scores show a weak relationship between NSS and positive symptom severity. NSS are more prominent in patients with negative symptoms than in those with positive symptoms. NSS may serve as surrogate markers of the schizophrenic disease process with higher scores corresponding to a trait-like liability (Hembram et al., 2014).
The relationship between neurological signs and another important disease manifestation, cognitive impairment, has not received much attention in the past. Most but not all previous studies have found a correlation between general cognitive dysfunction and neurological signs (Chen et al., 1997).
Neurological signs have been correlated with markers of organicity such as lower IQ and impaired performance on the Mini-Mental State examination. It was also reported that seven 'frontal' neurological signs were correlated with poor cognitive testing performance (Cuesta et al., 1996).
Liddel (1987) and Whitty et al. (2003) assumed that there are three separate schizophrenic syndromes that could be distinguished by different symptoms clusters, and these syndromes reflect frontoparietal and frontotemporal abnormalities. He claimed that the frontoparietal abnormalities may lead to two different syndromes namely 'disorganization syndrome', which is characterized by the inappropriate affect, poverty of content of speech, and thought disorder, and 'psychomotor poverty syndrome', which is characterized by the poverty of speech, decreased spontaneous movement, and affective blunting. Liddel (1987) reported that the two syndromes were associated with NSS; meanwhile, the frontotemporal syndrome, which exhibit some positive symptoms - for example, delusions and/or hallucinations was not significantly associated with NSS.
In agreement with Liddel's (1987) assumptions, King et al. (1991) reported that NSS were strongly correlated with both positive and negative symptoms in patients with schizophrenia. In this study, we investigated the presence of soft neurological signs among patients with schizophrenia and showed whether there is any correlation between soft neurological signs, positive and negative symptoms, and cognitive functions.
| Patients and methods|| |
After taking approval from scientific and ethical committees in Kasr Al-Ainy Hospital, 100 patients having the diagnosis of schizophrenia according to the DSM-IV criteria were recruited consecutively from the Psychiatry Outpatient and Inpatient Department of Kasr Al-Ainy Psychiatric Hospital, Cairo University, with no sex preference. This was a cross-sectional study. All patients gave consent to participate in the study after explanation of procedures was provided. Patients in the study ranged from 18 to 50 years of age. Presence of organic or neurological brain diseases, history of substance abuse, and illiteracy would have excluded the patient from the study.
Patients were divided into two groups. The first group included patients who had a diagnosis of schizophrenia, paranoid type. Patients in the other group had a diagnosis of schizophrenia, any other type than paranoid type.
All participants were subjected to the following:
To assess personal data, positive family history, past history of neurological or psychiatric condition, scholastic achievement, duration of illness, electro-convulsive therapy (ECT), hospitalization, etc.
(2) Structured Clinical Interview for DSM-IV Axis I Disorders (SCID), schizophrenia section (First et al., 1996):
To diagnose patients and confirm their subtype.
(3) Psychometric tools:
(a) Positive and Negative Syndrome Scale (PANSS) (Kay et al., 1989):
It is used to assess the positive and negative symptoms of schizophrenia. It is a 30-item seven-point rating scale that evaluates positive, negative, and other symptoms dimensions. Operational criteria are provided for defining all 30 symptoms and for rating each item according to seven levels of severity covering a range from absent to extreme. Rating in general is based on totality of information from previous week; this is derived both from clinical interview and reports by primary care hospital staff or family members.
Of 30 items included in the PANSS, seven constitute a positive scale, seven a negative scale, and the remaining 16 a general psychopathology scale. The scores for these three scales are arrived at by summation of rating across component items (1: absent, 2: minimal, 3: mild, 4: moderate, 5: moderate severe, 6: severe, and 7: extreme).
(b) Trail making test (Reitan and Wolfson, 1985):
This is a quick and easily administered test of visuomotor tracking and of conceptualization and mental set-shifting. It is given in two parts, A and B. Part A consists of a series of circles enclosing numbers from 1 to 25, scattered at random on the page. The participant's task is to join the circles in numerical order as quickly as possible. Part B has both numbers and letters assayed in the random order. The participant must alternate between numbers and letters: 1 to A, 2 to B, 3 to C, and so on to 13 (Hodges, 1996).
(4) Neurological examination:
(a) Complete neurological examination.
(b) Cambridge Neurological Inventory (Chen and Shaleske, 1995):
It was constructed for standardized neurological assessment of psychiatric patients. Part 2 of the inventory was designed for soft sign examinations (primitive reflexes, repetitive movement, sensory integration).
Coded data were analyzed statistically using the statistical package for the social sciences (SPSS, version 16; SPSS Inc., Chicago, Illinois, USA).
| Results|| |
(1) Sociodemographic data: No significant differences were found between both groups as shown in [Table 1].
(2) Trail making test: Differences were borderline significant between two groups, P = 0.052 for both Trail A and Trail B. In Trail A, the mean score for group A was higher than that for group B. The main for group A was 114.51 ± 29.709 and for group B it was 102.54 ± 27.639. In contrast, in Trail B the mean score for group A was higher than that for group B. The mean for group A was 264.29 ± 16.675 and for group B it was 262.00 ± 28.306.
(3) Soft neurological sign in both groups:
(a) Differences were statistically not significant between two groups, P = 0.415 for right, P = 0.800 for left, and P = 0.351 for total.
(4) Sex difference:
(a) With respect to Trail A, the main score for men was higher than that for women. The main for men was 107.47 ± 31.548 and for female it was 105.96 ± 25.957. In contrast, in Trail B the main score for women was higher than that for men. The main for women was 263.63 ± 22.343 and for men it was 262.00 ± 27.138. Differences were statistically not significant between two groups, P = 0.162 for Trail A and P = 0.885 for Trail B (P > 0.05).
(b) With respect to soft neurological signs, right sign mean score for women was higher than that for men. The mean for women was 6.88 ± 1.495 and for men it was 6.78 ± 1.701. However, in the left soft neurological sign test, the mean score for men was higher than that for women. The mean for men was 7.24 ± 1.505 and for women it was 7.18 ± 1.799. In contrast, in total soft neurological sign test the mean score for women was slightly higher than that for men. The mean for women was 19.39 ± 2.532 and for men it was 19.04 ± 3.218. Differences were statistically not significant between two groups, P = 0.569 for right and P = 0.067 for left and P = 0.638 for total (P > 0.05).
(1) Correlative data of all cases are summarized in [Table 2].
Important significant correlations were positive correlation between positive part of PANSS and NSS in the left side (P = 0.035), positive correlation between right, left, and total NSS and Trail B. Negative correlation was found significant between Trail A and both left and total NSS.
(2) Correlative data of paranoid cases are summarized in [Table 3].
Positive part of PANSS positively correlated with both left and total NSS.
Trail B was positively correlated with right, left, and total NSS.
(3) Correlative data of nonparanoid cases are summarized in [Table 4].
Trail B positively correlated with both positive and negative parts of PANSS.
| Discussion|| |
This study was applied to demonstrate the presence of soft neurological signs among patients with schizophrenia and to show correlation between soft neurological signs and presence of positive and negative symptoms and cognitive functions. It is a cross-sectional study of 100 patients meeting DSM-IV criteria of schizophrenia, who were recruited from Psychiatry Outpatient and Inpatient Department of both Kasr Al-Ainy Hospital, Cairo University, with no sex preference. Sixty-five patients had paranoid type of schizophrenia, whereas 35 patients were nonparanoid type.
The main finding in this study indicates that the patients with schizophrenia have neurological impairment. There are positive correlations between soft neurological signs and positive symptoms in paranoid type, other types, and with the total; these indicate that neurological soft signs are more prominent in patients with positive symptoms than in those with negative symptoms. Tiryaki et al. (2003) found that the patients with the negative subtype show a significant higher neurological impairment than those with the positive subtype, which is in disagreement with the result of our study. In addition, Addington et al. (2007) suggested that neurological soft signs were not associated with positive symptoms as might be expected; there were several significant associations between negative symptoms and neurological soft signs. These are inconsistent with the studies by Brazo et al. (2005), Tosato and Dazzan (2005), Whitty et al. (2006), Hui et al. (2009), and Smit et al. (2012), who found that negative symptoms and disorganization but not hallucinations and delusions are associated with poor performance on neurological function. Ruiz-Veguilla et al. (2008) found a correlation between negative symptoms of schizophrenia and the presence of neurological soft signs. Hembram et al.0 (2014) found positive relationship between soft neurological impairment and severity of negative symptoms in patients with schizophrenia. Cvetiζ et al. (2009) found also that the patient with schizophrenia have soft neurological impairment and that patients with negative symptoms show significantly higher soft neurological impairment than those with positive symptoms. Twelve studies of the negative subtypes of schizophrenia showed that these patients have significantly soft neurological impairment (Heinrichs, 2005); in addition, many studies report the connection between negative symptoms and neurological signs (Varambally et al., 2006). Also, Chan et al. (2004, 2010) found that neurological soft signs are more prominent in patients with negative symptoms than in those with positive symptoms; King et al. (1991) reported that neurological soft signs correlated positively with both negative and positive symptoms.
In this study, the score of Trail Making A was higher in group A (114.51) than in group B (102.54); in addition, a score of Trail Making B was higher in group A (264.29) than in group B (262.00). The differences were borderline significant between two groups, P = 0.052 for both Trail A and Trail B; this means that group B showed worse performance on both subtest A and B more than group A. This was consistent with the result of Gruzelier et al. (1988) who found that the paranoid group showed a better performance on most of cognitive functions. Nuechterlein et al. (2004) indicated that paranoid patients had more intact cognitive function. Patients with paranoid disorder have better cognitive function than patients with other forms of schizophrenia; this result is also consistent with the result of Seltzer (1997).
This is inconsistent with the result of Chan et al. (2004), who found that the paranoid schizophrenia performed worse on cognitive functions than nonparanoid patients. Zalewski et al. (1998) found that several studies suggest that the paranoid subtype is associated with higher performance on tests of cognitive functions; in addition, there are positive correlations between Trail A, B, and negative soft neurological signs [Table 2]. These findings are inconsistent with the result of Das et al. (2004), who found no significant correlations between cognitive measure and neurological soft signs.
In our study, there were no correlations between sex difference and the neuropsychological performance in both groups, and, even when the differences were present, they did not reach statistical significance. This finding was inconsistent with the finding of Moriarty et al. (2001), who reported that male patients would have more impairment in cognitive functions, explaining this with the early onset and more chronic course. In addition, Han et al. (2012) found that male patients had significant lower cognitive functions than female patients; Julia et al. (2010) found that female patients show less cognitive impairment than male patients. A number of authors have demonstrated that men score worse in attention, language, and executive function than women (Goldstein et al., 1994, 1998; Seidman et al., 1997; Hoff et al., 1998); in addition, Vaskinn et al. (2011) suggested better functioning in neuropsychological performance in women than in men, except in the category of attention.
The differences are statistically not significant between sex and soft neurological signs in both groups. Lewine and Meltzer (1984) found that female patients had higher neurological signs score than male patients; this may be due to factors other than sex difference, as most of female patients were older, with prolonged hospitalization and longer duration of illness. These factors have been shown to be correlated with neurological signs (NS). McGlashan and Fenton (1992) reported that sex differences appeared at moderate frequency in the direction of more NS among men. This finding was consistent with the finding of Hochman and Lewine (2004). Goldberg et al. (1995), Tiryaki et al. (2003), Cvetic et al. (2009), and El Rakhawy (1998) found also that there are no sex differences in the presence and severity of soft neurological signs.
| Conclusion|| |
(1) NSS occur in patients with schizophrenia and are largely distinct from symptomatic and cognitive features of the illness.
(2) Neurological signs in patients with schizophrenia are associated with prominent negative symptoms, relatively poor psychosocial performance, and significantly more cognitive impairment.
(3) Patients with schizophrenia may have impairment in some domains of executive functions.
| Acknowledgements|| |
| References|| |
Addington J, Cadenhead K, Cannon T (2007). North American Prodrome Longitudinal Study: a collaborative multisite approach to prodromal schizophrenia research. Schizophr Bull 33:665-672.
Bombin I, Arango C, Buchanan R (2005). Significance and meaning of neurological signs in schizophrenia: two decades later. Schizophr Bull 31:962-977.
Brazo P, Delamillieure P, Morello R, et al.
(2005). Impairments of executive/attentional functions in schizophrenia with primary and secondary negative symptoms. Psychiatry Res 133:45-55.
Chan M, Yip J, Lee T (2004). Differential impairment on measures of attention in patients with paranoid and non paranoid schizophrenia. J Psychiatr Res 38:145-152.
Chan RCK, Xu T, Heinrichs RW et al.
(2010). Neurological soft signs in schizophrenia: a meta-analysis. Schizophr Bull 36:1089-1104.
Chen EY, Shaleske J (1995). The Cambridge Neurological Inventory: a clinical instrument for assessment of soft neurological signs in psychiatric patients. Psychiatry Res 56:183-204.
Chen E, Lam L, Chen R, et al.
(1997). Cognitive correlates of soft signs in schizophrenia. Schizophr Res 24:100.
Cuesta MJ, Peralta V, de Leon J (1996). Neurological frontal signs and neuropsychological deficits in schizophrenic patients. Schizophr Res 20:15-20.
Cvetiæ T, Vukoviæ O, Britviæ D, et al.
(2009). Comparative analysis of soft neurological signs in positive and negative subtype of schizophrenia. Psychiatr Danub 21:174-178.
Das M, Kutnari V, Soni M, et al.
(2004). Neurological soft signs and their relationship to cognitive and clinical efficacy of atypical antipsychotics in schizophrenia. Schizophr Bull 30:241-253.
El Rakhawy M. (1998): Gender difference in schizophrenia. M.D thesis supervised by Prof. Mahmoud Abdel Gawad, Prof. Emad Hamdy, Mohsen Askar, Prof. Mahmoud El Batrawy. Faculty of medicine. Cairo University.
Flashman LA, Flaum M, Gupta S (1996). Soft signs and neuropsychological performance in schizophrenia. Am J Psychiatry 153:526-532.
First, Michael B., Spitzer, et al.
(1996) Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version (SCID-CV). Washington, D.C.: American Psychiatric Press, Inc.
Goldberg TE, Gold JM, Torrey EF, et al.
(1995). Lack of sex differences in the neuropsychological performance of patients with schizophrenia. Am J Psychiatry 152:883-888.
Goldstein JM, Seidman L, Santangelo S, et al.
(1994). Are schizophrenic men at higher risk for developmental deficits than schizophrenic women? Implications for adult neuropsychological functions. J Psychiatr Res 28:483-498.
Goldstein JM, Seidman L, Goodman J, et al.
(1998). Are there sex differences in neuropsychological functions among patients with schizophrenia? Am J Psychiatry 155:1358-1364.
Gruzelier J, Seymour K, Wilson L, et al.
(1988). Impairments on neuropsychologic tests of temporohippocampal and frontohippocampal functions and word fluency in remitting schizophrenia and affective disorders. Arch Gen Psychiatry 45:623-629.
Han M, Huang XF, Chen da C, et al.
(2012). Gender differences in cognitive function of patients with chronic schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 39:358-363.
Heinrichs P (2005). The primacy of cognition in schizophrenia Am Psychol 60:229-242.
Hembram M, Simlai J, Biswas P (2014). First rank symptoms and neurological soft signs in schizophrenia). Psychiatry J 2014:931014.
Hochman KM, Lewine RR (2004). Age of menarche and schizophrenia onset in women. Schizophr Res 69:183-188.
Hoff M, Wieneke W, Faustman O, et al.
(1998). Sex differences in neuropsychological functioning of first-episode and chronically III schizophrenic patients Am J Psychiatry 155:1437-1439.
Hodges JR (2002). Cognitive assessment for clinicians
. Oxford, UK: Oxford University Press.
Hui C, Wong G, Chiu C, et al.
(2009). Potential endophenotype for schizophrenia: neurological soft signs. Ann Acad Med 38:408-413.
Julia L, Dwight D, Daniel R et al.
(2010). Cognitive differences between men and women: a comparison of patients with schizophrenia and healthy volunteers. Schizophr Res 120:234-235.
Kay S, Opler L, Lindenmayer J (1989). The Positive and Negative Syndrome Scale (PANSS): rationale and standardisation. Br J Psychiatry Suppl 7: 59-67.
King D, Wilson A, Cooper S, et al.
(1991). The clinical correlate of neurological soft signs in chronic schizophrenia. Br J Psychiatry 158:770-775.
Lewine R, Meltzer H (1984). Negative symptoms and platelet monoamine oxidase activity in male schizophrenic patients. Psychiatry Res 12:99-109.
Liddel PF (1987). Schizophrenic syndrome, cognitive performance and neurological dysfunction. Psychol Med 17:49-57.
McGlashan T, Fenton WS (1992). The positive-negative distinction in schizophrenia - review of natural history validators. Arch Gen Psychiatry 49:63-72.
Moriarty PJ, Lieber D, Bennett A et al.
(2001). Gender difference in poor outcome patients with life long schizophrenia. Schizophr Bull 27:103-113.
Nuechterlein K, Barch K, Gold J et al.
(2004). Identification of separable cognitive factors in schizophrenia. Schizophr Res 72:29-39.
Reitan R, Wolfson D. (1985). The Halstead-Reitan neuropsychological test battery: Theory and clinical interpretation. Tucson, AZ: Neuropsychology Press.
Ruiz-Veguilla M, Cervilla J, Barringón M, et al.
(2008). Neurodevelopmental markers in different psychopathological dimensions of first episode psychoses: the ESPIGAS study. Eur Psychiatry 23:533-540.
Seidman LJ, Goldstein JM, Goodman JM et al.
(1997). Sex differences in olfactory identification and Wisconsin card sorting performance in schizophrenia: relationship to attention and verbal ability. Biol Psychiatry 42:104-115.
Seltzer J, Conrad C, Cassens G. (1997). Neuropsychological profiles in schizophrenia: Paranoid versus undifferentiated distinctions. Schizophrenia Research, 23:131-138.
Smit L, Koen DJH, Niehaus E, et al.
(2012). Neurological soft signs as an endophenotype in an African schizophrenia population - a pilot study. Afr J Psychiatry 15:124-127.
Tiryaki A, Yazici M, Anil A, et al.
(2003). Reexamination of the characteristics of the deficit schizophrenia patients. Eur Arch Psychiatry Clin Neurosci 253:221-227.
Tosato S, Dazzan P (2005). The psychopathology of schizophrenia and the presence of neurological soft signs: a review. Curr Opin Psychiatry 18:285-288.
Varambally S, Venkatasubramanian G, Thirthalli J, et al.
(2006). Cerebellar and other neurological soft signsinantipsychotic-naive schizophrenia. Acta Psychiatr Scand 114:352-356.
Vaskinn K, Sundet C, Simonsen T, et al.
(2011). Sex differences in neuropsychological performance and social functioning in schizophrenia and bipolar disorder. Neuropsychology 25:499-510.
Whitty P, Clarke M, Browne S, et al.
(2003). Prospective evaluation of neurological soft signs in first-episode schizophrenia in relation to psychopathology: state versus trait phenomena. Psychol Med 33: 1479-1484.
Whitty P, Clarke M, McTigue O, et al.
(2006). Diagnostic specificity and predictors of neurological soft signs in schizophrenia, bipolar disorder and other psychoses over the first 4 years of illness. Schizophr Res 86: 110-117.
Wong A, Voruganti L, Heslegrave R, et al.
(1997). Neurocognitive deficits and neurological signs in schizophrenia. Schizophr Res 23:139-146.
Zalewski M, Johnsori S, Steven O, et al.
(1998). A review of neuropsychological differences between paranoid and nonparanoid schizophrenia patients. Schizophr Bull 24:127-145.
[Table 1], [Table 2], [Table 3], [Table 4]