Neurological soft signs (NSS) have been considered among the target features a potential endophenotype for schizophrenia. The investigation of NSS has provided important information in the search for the aetiology of the illness. Despite the substantial number of studies on NSS in the past decades, several issues remain unresolved. One of the most important criteria of a potential endophenotype is its stability across the different stages of the illness. The aforementioned studies were all limited by their cross-sectional design. It is still not clear how the prevalence and nature of NSS evolve and change over the course of illness. This gap in knowledge highlights the need for a prospective longitudinal study. Another unresolved issue is the relationship between NSS and the symptomatology of schizophrenia. It is especially unclear how NSS associate with negative symptoms throughout the course of the illness.

Dr. CHAN Raymond from the Institute of Psychology of Chinese Academy of Sciences and his collaborators have conducted a longitudinal study to examine the course of NSS in patients with first-episode schizophrenia and its relationship with negative symptoms and cognitive functions. More importantly, they would like to track and compare the changes in NSS between patients with and without prominent negative symptoms within one year of illness onset.

Researchers recruited 145 patients (29 were classified as prominent with negative symptoms) with first-episode schizophrenia from the early psychosis programme and 62 healthy controls from the community. They administered the NSS and neuropsychological assessment to all participants and follow them up at six-month intervals for up to a year. Patients with prominent negative symptoms were found to demonstrate significantly more motor coordination signs and poorer working memory than those patients without negative symptoms. Longitudinal data analysis further suggested that two distinct subtypes of first-episode patients could be distinguished by NSS and prominent negative symptoms. The patients with prominent negative symptoms showed persistent poorer motor coordination and higher levels of NSS, and poorer working memory than patients without prominent negative symptoms.

These findings suggest that NSS may be more sensitive in detecting the underlying clinical and neurological manifestations of schizophrenia. Substantial evidence suggests that clinical features and neurological signs share many similarities, or may even be equivalent in characterizing the different stages of the schizophrenic illness both behaviourally and morphologically. The present findings are consistent with the recent reformulation of schizophrenia as a neurodevelopmental illness characterized by different stages with specific markers for early detection and intervention. The ease of assessment and sensitivity of NSS lends itself as a potentially useful tool for early detection and identification of schizophrenia.

This study was supported by grants from the National Science Fund China Outstanding Investigator Award, the Beijing Training Project for the Leading Talents in Science and Technology, and the CAS/SAFEA International Partnership Program for Creative Research Teams.

This paper is now available online in Scientific Reports .