Characterization of neurological soft signs in a Brazilian sample of stable patients with schizophrenia

Caracterização de sinais neurológicos sutis em uma amostra brasileira de pacientes estáveis com esquizofrenia

Vinicius Sousa Pietra Pedroso Antônio Lúcio Teixeira João Vinícius Salgado About the authors

Abstract

Introduction:

Neurological soft signs (NSS) have been considered one of the target features and a potential endophenotype for schizophrenia. The present study aimed to characterize NSS in a sample of patients with chronic schizophrenia and to compare them with healthy control individuals.

Methods:

In this study, we evaluated the presence of NSS in a sample of stable patients (n = 24) diagnosed with schizophrenia according to DSM-IV criteria, recruited at the Schizophrenia Outpatient Clinic of Instituto Raul Soares, Belo Horizonte, state of Minas Gerais, southeastern Brazil. Assessment was made with the Brief Motor Scale (BMS), and extrapyramidal symptoms (EPS) were evaluated with the Simpson-Angus Scale (SAS) and the Abnormal Involuntary Movement Scale (AIMS). A control group (n = 21) was also submitted to the same battery of tests.

Results:

We observed a significant difference in relation to BMS and SAS scores (p < 0.0001), revealing that individuals with schizophrenia present more NSS and EPS than healthy ones. BMS total scores correlated positively with SAS scores (r = 0.495, p = 0.014), but not with AIMS scores, indicating that NSS could be influenced by the intensity of EPS. Nevertheless, we observed that this relationship remained only for motor coordination tasks (r = 0.550, p = 0.005), while motor sequencing tasks were not influenced by EPS (r = 0.313, p = 0.136).

Conclusion:

The results suggest that NSS are more frequent in patients with schizophrenia and that motor sequencing tasks could be more specific to the syndrome.

Keywords:
Neurological soft signs; schizophrenia; extrapyramidal symptoms

Resumo

Introdução:

Sinais neurológicos sutis (SNS) têm sido considerados características básicas e potenciais endofenótipos na esquizofrenia. O presente estudo procurou caracterizar os SNS em uma amostra de pacientes com esquizofrenia crônica e compará-los com indivíduos controles saudáveis.

Métodos:

Neste estudo, avaliamos a presença de SNS em uma amostra de pacientes estáveis (n = 24) com o diagnóstico de esquizofrenia de acordo com os critérios do DSM-IV, recrutados no Ambulatório de Esquizofrenia do Instituto Raul Soares, Belo Horizonte, MG, Brasil. A avaliação foi realizada com a Escala Motora Breve (BMS) e sinais extrapiramidais (SEP) foram observados com a Escala de Simpson-Angus (SAS) e a Escala de Movimentos Involuntários Anormais (AIMS). Um grupo controle (n = 21) também foi submetido à mesma bateria de testes.

Resultados:

Observamos uma diferença significativa em relação aos escores da BMS e da SAS (p < 0,0001), revelando que indivíduos com esquizofrenia apresentam mais SNS e SEP que indivíduos saudáveis. Os escores da BMS se correlacionaram positivamente com os da SAS (r = 0,495, p = 0,014), mas não com os da AIMS, indicando que os SNS podem ser influenciados pela intensidade de SEP. No entanto, observamos que essa relação permaneceu somente para as tarefas de coordenação motora (r = 0,550, p = 0,005), enquanto as tarefas de sequenciamento motor não foram influenciadas pelos SEP (r = 0,313, p = 0,136).

Conclusão:

Os resultados sugerem que os SNS são mais frequentes em pacientes com esquizofrenia e que tarefas de sequenciamento motor podem ser mais específicas na síndrome.

Descritores:
Sinais neurológicos sutis; esquizofrenia; sinais extrapiramidais

Introduction

Schizophrenia is usually conceptualized as a disorder characterized by positive, negative and cognitive symptoms. However, ever since the first descriptions were published, most patients with schizophrenia have been reported to also display a wide range of symptoms characterized by aberrant motor functioning. Such symptoms include catatonic features, extrapyramidal signs, psychomotor slowing, reduced motor activity, and motor neurological soft signs (NSS). 1Pedroso VSP, Salgado JV, Teixeira AL. Neurological soft signs: a review. J Bras Psiquiatr. 2010;59:233-7. The latter refer to subtle neurological abnormalities comprising deficits in motor coordination and sequencing of complex motor acts. NSS have been considered one of the target features and a potential endophenotype for schizophrenia. To qualify as an endophenotype, a marker must be reliably associated with the illness, demonstrate state-dependent cosegregation, and reveal heritable familial association. 2Morrens M, Docx L, Walther S. Beyond boundaries: in search of an integrative view on motor symptoms in schizophrenia. Front Psychiatry. 2014;5:145. Indeed, evidence has shown that NSS are a stable trait in patients with schizophrenia, are not secondary to the use of medication, and tend to be more frequent in unaffected relatives. 1Pedroso VSP, Salgado JV, Teixeira AL. Neurological soft signs: a review. J Bras Psiquiatr. 2010;59:233-7.,3Bachmann S, Degen C, Geider FJ, Schröder J. Neurological soft signs in the clinical course of schizophrenia: results of a meta-analysis. Front Psychiatry. 2014;5:185. Besides, studies have yielded significant associations between NSS, negative symptoms and a wide range of neurocognitive dysfunctions, which are often manifested in schizophrenia spectrum disorders and are sensitive to the development of psychosis. 1Pedroso VSP, Salgado JV, Teixeira AL. Neurological soft signs: a review. J Bras Psiquiatr. 2010;59:233-7.4Chan RC, Dai S, Lui SS, Ho KK, Hung KS, Wang Y, et al. Re-visiting the nature and relationships between neurological signs and neurocognitive functions in first-episode schizophrenia: An invariance model across time. Sci Rep. 2015;5:11850. Nevertheless, NSS literature is still limited, especially in Brazil. The present study aimed to characterize NSS in a sample of patients with chronic schizophrenia and to compare them with healthy control individuals.

Methods

For the purpose of this study, a sample of stable patients (n = 24) diagnosed with schizophrenia according to criteria from the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) was recruited at the Schizophrenia Outpatient Clinic of Instituto Raul Soares, Belo Horizonte, state of Minas Gerais, southeastern Brazil. Stability was defined as a score < 19 on the Positive and Negative Syndrome Scale (PANSS) – positive scale, scores ≤ 3 on each one of the positive subscale items, and no intercurrence recorded in the 3 months prior to the evaluation. 5Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13:261-76. Exclusion criteria for controls were the same general criteria used for patients, i.e., presence of neurological disease, history of drug abuse, diagnosis of other axis I disorder, and age under 18 or over 65 years. Both patients and controls underwent a structured interview with the Mini-International Neuropsychiatric Interview-Plus (MINI-Plus). 6Amorim P. Mini International Neuropsychiatric Interview (MINI): validação de entrevista breve para diagnóstico de transtornos mentais. Rev Bras Psiquiatr. 2000;22:106-15.

In order to evaluate the presence of NSS, patients were assessed with the Brief Motor Scale (BMS), composed of 10 tasks divided into two subscales of motor coordination (MOCO) and motor sequencing (MOSE) tests. 7Jahn T, Cohen R, Hubmann W, Mohr F, Köhler I, Schlenker R, et al. The Brief Motor Scale (BMS) for the assessment of motor soft signs in schizophrenic psychoses and other psychiatric disorders. Psychiatry Res. 2006;142:177-89. The occurrence of extrapyramidal symptoms (EPS) was evaluated with the Simpson-Angus Scale (SAS) and the Abnormal Involuntary Movement Scale (AIMS). 8Simpson GM, Angus JW. A rating scale for extrapyramidal side effects. Acta Psychiatr Scand Suppl. 1970;212:11-9.,9Guy W. Abnormal involuntary movement scale (AIMS). In: Guy W. ECDEU Assessment Manual for Psychopharmacology. Rockville: US Department of Health, Education and Welfare, Public Health Service, Alcohol, Drug Abuse and Mental Health Administration, NIMH, Psychopharmacology Research Branch, Division of Extramural Research Programs; 1976. p. 534-7. The control group (n = 21) was also submitted to the same battery of tests. Analysis was made with the Mann-Whitney test, chi-square test, and the Spearman correlation test.

The study was approved by the local research ethics committee. All individuals included in the study provided written consent.

Results

As can be seen in Table 1 , groups did not differ with respect to age, gender, or AIMS scores. However, we observed a significant difference in relation to BMS and SAS scores (p < 0.0001), revealing that individuals with schizophrenia present more NSS and EPS than healthy ones. BMS total scores correlated positively with SAS scores (r = 0.581, p = 0.002), but not with AIMS scores, indicating that NSS could be influenced by the intensity of EPS. Nevertheless, when we considered the MOCO and MOSE subscales of the BMS separately, we observed that MOCO still correlated positively with SAS (r = 0.582, p = 0.002), while MOSE did not (r = 0.375, p = 0.065). Finally, we evaluated correlations between the presence of NSS and the intensity of symptoms measured by PANSS. We did not observe any significant association, except for a specific correlation between MOSE and the negative symptoms subscale (r = 0.423, p = 0.039).

Table 1
Characterization of the study sample

Discussion

The intensity of NSS in patients with schizophrenia is higher in comparison to unaffected individuals. Most studies have demonstrated a prevalence of 50 to 65% in these patients, in contrast to approximately 5% in control populations. 10Dazzan P, Murray RM. Neurological soft signs in first-episode psychosis: a systematic review. Br J Psychiatry. 2002;43:s50-7.

According to the literature, patients with schizophrenia present NSS related to sensory integrative function, motor coordination and sequencing of complex motor tasks, as well as primitive reflexes. 11Hui CL, Wong GH, Chiu CP, Lam MM, Chen EY. Potential endophenotype for schizophrenia: neurological soft signs. Ann Acad Med Singapore. 2009;38:408-13. Evaluations focused on motor signs only are widely used. This strategy was emphasized by Manschreck & Ames 12Manschreck TC, Ames D. Neurologic features and psychopathology in schizophrenic disorders. Biol Psychiatry. 1984;19:703-19. and Woods et al., 13Woods 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. because it is believed that specific motor signals, such as dysdiadochokinesia, can be valid indicators of neurointegrative deficits in schizophrenia and because of the greater reliability in the reproduction of motor tests.

Taken together, our results suggest that motor NSS are more frequent in patients with schizophrenia than in unaffected individuals and that motor sequencing tasks, as evaluated by MOSE, could be more specific to the syndrome, in the sense of revealing traits that are independent from the use of medication – since MOSE did not correlate with SAS. In this sense, it is interesting to note that MOSE also correlated with the intensity of negative symptoms measured by the PANSS negative scale.

A meta-analysis conducted by Bachmann et al. concluded that NSS scores decrease in the clinical course of schizophrenia, with remission of psychopathological symptoms, but not to the levels observed in healthy individuals. The authors provided an indication that this effect is more pronounced in patients with a remitting course than in those with non-remitting schizophrenia. 3Bachmann S, Degen C, Geider FJ, Schröder J. Neurological soft signs in the clinical course of schizophrenia: results of a meta-analysis. Front Psychiatry. 2014;5:185. NSS in schizophrenia are more closely related to morphological changes and abnormal neural activity in pre- and postcentral, inferior frontal, parietal, thalamic, striatal, and cerebellar structures. 14Hirjak D, Thomann PA, Kubera KM, Wolf ND, Sambataro F, Wolf RC. Motor dysfunction within the schizophrenia-spectrum: a dimensional step towards an underappreciated domain. Schizophr Res. 2015;169:217-33. Unfortunately, we could not find studies in the Brazilian literature that have evaluated to date the presence of NSS in patients with schizophrenia.

Since researchers have proposed that NSS and conventional neurocognitive tests capture the same underlying brain functions in schizophrenia spectrum disorders, the brevity of NSS assessment (less than 10 minutes) could make it feasible for clinicians to screen for neurocognitive dysfunction in patients with schizophrenia. 14Hirjak D, Thomann PA, Kubera KM, Wolf ND, Sambataro F, Wolf RC. Motor dysfunction within the schizophrenia-spectrum: a dimensional step towards an underappreciated domain. Schizophr Res. 2015;169:217-33.,15Chan RC, Xie W, Geng FL, Wang Y, Lui SS, Wang CY, et al. Clinical utility and lifespan profiling of neurological soft signs in schizophrenia spectrum disorders. Schizophr Bull. 2016;42:560-70.

The major limitations of this study are the size of the sample and its cross-sectional design. Studies including a larger number of patients and that can longitudinally assess the manifestation of NSS may assist in understanding the significance of these markers in schizophrenia.

References

  • Pedroso VSP, Salgado JV, Teixeira AL. Neurological soft signs: a review. J Bras Psiquiatr. 2010;59:233-7.
  • Morrens M, Docx L, Walther S. Beyond boundaries: in search of an integrative view on motor symptoms in schizophrenia. Front Psychiatry. 2014;5:145.
  • Bachmann S, Degen C, Geider FJ, Schröder J. Neurological soft signs in the clinical course of schizophrenia: results of a meta-analysis. Front Psychiatry. 2014;5:185.
  • Chan RC, Dai S, Lui SS, Ho KK, Hung KS, Wang Y, et al. Re-visiting the nature and relationships between neurological signs and neurocognitive functions in first-episode schizophrenia: An invariance model across time. Sci Rep. 2015;5:11850.
  • Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13:261-76.
  • Amorim P. Mini International Neuropsychiatric Interview (MINI): validação de entrevista breve para diagnóstico de transtornos mentais. Rev Bras Psiquiatr. 2000;22:106-15.
  • Jahn T, Cohen R, Hubmann W, Mohr F, Köhler I, Schlenker R, et al. The Brief Motor Scale (BMS) for the assessment of motor soft signs in schizophrenic psychoses and other psychiatric disorders. Psychiatry Res. 2006;142:177-89.
  • Simpson GM, Angus JW. A rating scale for extrapyramidal side effects. Acta Psychiatr Scand Suppl. 1970;212:11-9.
  • Guy W. Abnormal involuntary movement scale (AIMS). In: Guy W. ECDEU Assessment Manual for Psychopharmacology. Rockville: US Department of Health, Education and Welfare, Public Health Service, Alcohol, Drug Abuse and Mental Health Administration, NIMH, Psychopharmacology Research Branch, Division of Extramural Research Programs; 1976. p. 534-7.
  • Dazzan P, Murray RM. Neurological soft signs in first-episode psychosis: a systematic review. Br J Psychiatry. 2002;43:s50-7.
  • Hui CL, Wong GH, Chiu CP, Lam MM, Chen EY. Potential endophenotype for schizophrenia: neurological soft signs. Ann Acad Med Singapore. 2009;38:408-13.
  • Manschreck TC, Ames D. Neurologic features and psychopathology in schizophrenic disorders. Biol Psychiatry. 1984;19:703-19.
  • 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.
  • Hirjak D, Thomann PA, Kubera KM, Wolf ND, Sambataro F, Wolf RC. Motor dysfunction within the schizophrenia-spectrum: a dimensional step towards an underappreciated domain. Schizophr Res. 2015;169:217-33.
  • Chan RC, Xie W, Geng FL, Wang Y, Lui SS, Wang CY, et al. Clinical utility and lifespan profiling of neurological soft signs in schizophrenia spectrum disorders. Schizophr Bull. 2016;42:560-70.

Publication Dates

  • Publication in this collection
    17 Sept 2018
  • Date of issue
    Jul-Sep 2018

History

  • Received
    01 Aug 2017
  • Accepted
    25 Sept 2017
Associação de Psiquiatria do Rio Grande do Sul Av. Ipiranga, 5311/202, 90610-001 Porto Alegre RS/ Brasil, Tel./Fax: (55 51) 3024 4846 - Porto Alegre - RS - Brazil
E-mail: trends@aprs.org.br