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OBJECTIVE: Neurological soft signs are frequently found in schizophrenia. They are indicators of both genetic liability and psychopathological symptoms. To further differentiate “trait” and “state” relations the authors compared the 1-year course of neurological soft signs in schizophrenia patients and comparison subjects. METHOD: Thirty-nine patients with first-episode schizophrenia spectrum disorders were examined after remission of acute symptoms and 14 months later. Established instruments assessed diagnoses, psychopathological symptoms, predictors of outcome, handedness, and neurological soft signs. Twenty-two age- and gender-matched comparison subjects were also examined twice. RESULTS: Neurological soft sign scores in patients were significantly elevated relative to comparison subjects at both measurement points. Whereas neurological soft signs remained stable in comparison subjects (time 1: mean=4.8, SD=3.3; time 2: mean=4.6, SD=3.9), they significantly decreased in patients (time 1: mean=15.7, SD=7.1; time 2: mean=10.1, SD=7.9). This effect was more pronounced in patients with a favorable versus a chronic course and was mainly accounted for by motor signs. Predictors of follow-up neurological soft sign scores were neurological soft sign levels at remission and compliance with treatment. CONCLUSIONS: Although neurological soft signs are intrinsic to schizophrenia, their level varies with the clinical course. Thus, neurological soft signs may correspond to both genetic liability and the activity of the disease process and may be considered as potential predictors of outcome.