Neurological soft signs (NSS), minor and subtle neurological abnormalities in sensory integration and motor performance that are not part of a properly defined neurological syndrome, have been consistently observed in patients with schizophrenia. The prevalence estimates of NSS in patients with schizophrenia have been reported to be higher than in healthy subjects. Current evidence suggests that NSS are an integral part of the disease and cannot be fully explained by the exposure to antipsychotic medication, as they are already present in treatment-na?ve patients. NSS have been associated with cardinal features of the disorder such as cognitive impairment, psychopathological severity, or functional outcome. The increased prevalence of NSS and/or related motor precursors has been described at different stages of development (infancy, childhood, adolescence) in those subjects who later developed schizophrenia. Evidence from family and twin studies indicates that genetic factors play an important role in the emergence of NSS, and some authors have already suggested that such neurological anomalies are suitable endophenotypes for schizophrenia. Some genetic association studies based on a candidate gene approach have already reported the association of genetic variants with the severity of NSS. This non-systematic review describes the potential relevance of NSS 1) in the understanding of schizophrenia as a neurodevelopmental disorder, 2) as outcome predictors, 3) as biological markers during several stages of development, and 4) as a candidate (endo)phenotype for genetic analyses. Likewise, the possibilities afforded by the advances in high-throughput techniques in genomic analysis are also discussed.
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