Treatment resistant schizophrenia and neurological soft signs may converge on the same pathology: Evidence from explanatory analysis on clinical, psychopathological, and cognitive variables

TRS had higher scores than SZ patients in total NES score and in almost all NES subscales, even after correction for duration of illness and antipsychotic dose (ANCOVA, p < 0.05). NSSs significantly correlated with multiple clinical, psychopathological, and cognitive variables (above all: duration of disease and negative symptoms) in TRS but not in SZ patients. Two-way ANOVA showed NSS-x-diagnosis interaction in determining outcomes on multiple cognitive performances, but not in other clinical variables. However, simple main effect analysis detected a significant relationship between high severity NSSs and TRS diagnosis on multiple clinical and cognitive outcomes. Hierarchical regression analysis showed that diagnosis was among a discrete number of predictors yielding significant increases in variance explained on NES total, Sensory Integration and Other Signs subscales' scores. NSSs, together with antipsychotic dose and disease severity, were found to be significantly predictive of TRS diagnosis in a binary logistic regression model. These results suggest a stringent association between NSSs and TRS diagnosis, and may imply that NSSs association with clinical, psychopathological, and cognitive variables may be in part mediated by TRS diagnosis.