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Mediation analyses further revealed the association between CLZ concentration and cognition to be partially mediated by changes in the CLZNDMC ratio. This is the first longitudinal analysis of the influence of CLZ concentration and CLZNDMC ratio on cognition. Our findings suggest that reduction of CLZ concentration and the CLZNDMC ratio might favorably affect cognition. Thus, the CLZNDMC ratio may represent a promising target for novel therapeutic strategies aiming to ameliorate cognitive impairment in clozapine-treated patients. V.BACK