Neurological soft signs in schizophrenia - The past, the present and the future

Clinical neurological abnormalities in patients with schizophrenia have been generally called "Neurological Soft Signs" (NSS). Studies have consistently shown increased NSS in patients with schizophrenia as compared to healthy persons. Early studies were limited by possible confounds of prior neuroleptic medications and illness chronicity. Studies in first episode never treated schizophrenia patients have addressed these confounds. The clinical significance of these findings and the correlation with cognitive dysmetria is the focus of the current review. Relevant literature was obtained using PUBMED and MEDLINE search (1980-2008) and a direct search of reference list of pertinent journal articles. In a 2003 study, neuroleptic-naive schizophrenia patients had significantly more NSS than controls. Patients who were more neurologically impaired had more negative symptoms. Higher NSS scores in treatment-naive schizophrenia patients and the absence of correlation between NSS and illness duration lends support to a neurodevelopmental pathogenesis for schizophrenia. The finding of incoordination and cerebellar signs in most studies also supports the "cognitive dysmetria" explanatory model for schizophrenia. A significant subgroup of patients with schizophrenia may have more neuropathological abnormalities, which predisposes them for a more severe and chronic course of illness. These patients may potentially be identified by clinical neurological examination, which might be very important for prognostication and evolving better methods of treatment for these patients. NSS, by themselves or as a composite index with other neurobiological parameters, hold potential as a candidate endophenotype for schizophrenia.