Antipsychotic medications: linking receptor antagonist properties to neuropsychological functioning

Antipsychotic medications are thought to contribute to neuropsychological impairments associated with schizophrenia, but specific links with pharmacology are not well established. This study investigated associations of specific medication properties with neuropsychological and psychiatric symptoms in a first-episode psychosis sample. Medication doses and indices of receptor antagonism were used to estimate dopamine antagonist, serotonergic antagonist, and anticholinergic loads (i.e., impact of participants’ medications on those receptors). Results indicated higher anticholinergic load was associated with poorer verbal long-term memory and higher D2 load was associated with poorer motor functioning. Additional exploratory analyses indicated that in non-smokers, higher D1 load was associated with more severe negative symptoms, whereas higher 5-HT2A load was associated with less severe negative symptoms. In smokers, higher 5-HT2A load was associated with poorer verbal working memory. These results support the validity of estimating medication receptor loads to elucidate specific and dissociable effects of antipsychotic medication properties.