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.

In a study published online in Journal of Psychiatric Research, Dr. Raymond Chan from the Neuropsychology and Applied Cognitive Neuroscience Laboratory, CAS Key Laboratory of Mental Health, Institute of Psychology of the Chinese Academy of Sciences and his collaborators, conducted a longitudinal study to specifically the prediction of NSS upon treatment-resistant in first-episode schizophrenia.

The researchers recruited 206 patients with first-episode schizophrenia who entered at baseline and followed them up to five years. They 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.

The 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.

This study provides 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.