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Neurological Soft Signs Predict Treatment-resistant in Patients with Schizophrenia
Author: Dr. Raymond CHAN      Update time: 2021/05/20
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Neurological soft signs (NSS) have long been defined as non-localizable motor and sensory neurological abnormalities in psychosis have recently been re-orientated to be sensitive and specific biomarker of schizophrenia with hard evidence of brain structural and functional connectivity. The extant literature further suggests that NSS could predict end-point diagnosis and treatment response in first-episode schizophrenia. However, it is still not clear whether NSS could discriminate treatment-responsive and treatment-resistant first-episode schizophrenia patients.

To address such as unresolved issue, Dr. Raymond Chan from the Neuropsychology and Applied Cognitive Neuroscience Laboratory, CAS Key Laboratory of Mental Health, Institute of Psychology and his collaborators have conducted a longitudinal study to specifically the prediction of NSS upon treatment-resistant in first-episode schizophrenia. They recruited 206 patients with first-episode schizophrenia who entered at baseline and followed them up to 5 years, they then identified 29 treatment-responsive and 23 treatment-resistant for this study. The treatment-resistant group was operationally defined as those patients having been started on clozapine, after failing to response to two trials of non-clozapine antipsychotics of adequate dose and duration All participants were assessed at baseline, sixth month and the fifth year. They administered the abridged version of the Cambridge Neurological Inventory to assess motor coordination, sensory integration and disinhibition domains of NSS.

Their findings showed that treatment-responsive and treatment-resistant groups differed significantly in the trajectories of NSS amid these two groups exhibited comparable NSS at the baseline. In particular, the treatment-resistant group showed a worsening trajectory of NSS over time. These findings provide further support for the clinical utility of NSS in identifying treatment resistance in first-episode schizophrenia. NSS progression in treatment-resistant schizophrenia patients may reflect the development of neuropathology. Nevertheless, given the relatively small sample size of the present study, further research using large sample of treatment-resistant schizophrenia patients is needed in the Chinese population.

The study was a joint collaboration between the Department of Psychiatry, the University of Hong Kong and Castle Peak Hospital. It was supported by the Philip K.H. Wong Foundation to Castle Peak Hospital.

The paper is now published online in Journal of Psychiatric Research on May 8 2021.

Lui, S. S. Y.#*, Yip, S. S. L.#, Wang, Y., Hung, K. S. Y., Ho, K. K. Y., Tsang, K. C. M., Yeung, H. K. H., Cheung, E. F. C., Chan, R. C. K.* (2021). Different trajectories of neurological soft signs progression between treatment-responsive and treatment-resistant schizophrenia patients. Journal of Psychiatric Research, 138, 607-614. https://doi.org/10.1016/j.jpsychires.2021.05.018

Related papers

Chan, R.C.K.*, Gottesman, I.I., 2008. Neurological soft signs as candidate endophenotypes for schizophrenia: A shooting star or a Northern star? Neuroscience and Biobehavioral Reviews. 32(5), 957–971.
Chan, R.C.K.*, Wang, Y., Wang, L., Chen, E.Y.H., Manschreck, T.C., Li, Z.J., et al., 2009. Neurological soft signs and their relationships to neurocognitive functions: a re-visit with the structural equation modeling design. PLoS One 4(12), e8469.
Chan, R.C.K.*, Wang, Y., Zhao, Q., Yan, C., Xu, T., Gong, Q.Y., Manschreck, T.C., 2010a. Neurological soft signs in individuals with schizotypal personality features. Australian New Zealand Journal of Psychiatry. 44(9), 800-804.
Chan, R.C.K.*, Xu, T., Heinrichs, R.W., Yu, Y., et al., 2010b. Neurological soft signs in non-psychotic first-degree relatives of patients with schizophrenia: a systematic review and meta-analysis. Neuroscience and Biobehavioral Reviews. 34(6), 889-896.
Chan, R.C.K.*, Dai, S., Lui, S.S.Y., Ho, K.K.Y., Hung, K.S.Y., Wang, Y., Geng, F., Li, Z., ...et al., 2015a. Re-visiting the nature and relationships between neurological signs and neurocognitive functions in first-episode schizophrenia: An invariance model across time. Scientific Reports. 5(1), 1-9.
Chan, R.C.K.*, Geng, F., Lui, S.S.Y., Wang, Y., Ho, K.K.Y., Hung, K.S.Y., …et al., 2015b. Course of neurological soft signs in first-episode schizophrenia: relationship with negative symptoms and cognitive performances. Scientific Reports. 5, 11053.
Chan, R.C.K.*, Xie, W., Geng, F.L., Wang, Y., Lui, S.S.Y., Wang, C.Y., Yu, X., Cheung, E.F., Rosenthal, R., 2016. Clinical Utility and Lifespan Profiling of Neurological Soft Signs in Schizophrenia Spectrum Disorders. Schizophrenia Bulletin. 42(3), 560-70.
Chan, R.C.K.*, Cui, H.R., Chu, M.Y., Zhang, T.H., Wang, Y., Wang, Y., Li, Z., et al.., 2018. Neurological soft signs precede the onset of schizophrenia: a study of individuals with schizotypy, ultra-high-risk individuals, and first-onset schizophrenia. European Archives of Psychiatry and Clinical Neuroscience, 268(1), 49-56.

LIU Chen
Institute of Psychology
Chinese Academy of Sciences
Beijing 100101, China.
E-mail: liuc@psych.ac.cn

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