Hyperprolactinaemia, a common side effect of some
antipsychotic drugs, is also present in drug-naïve psychotic patients and subjects at risk for
psychosis. Recent studies in non-psychiatric populations suggest that increased
prolactin may have negative effects on cognition. The aim of our study was to explore whether high plasma
prolactin levels are associated with poorer cognitive functioning in subjects with early
psychoses. We studied 107 participants: 29 healthy subjects and 78 subjects with an early
psychosis (55
psychotic disorders with <3 years of illness, 23 high-risk subjects). Cognitive assessment was performed with the MATRICS Cognitive Consensus Cognitive Battery, and
prolactin levels were determined as well as total
cortisol levels in plasma. Psychopathological status was assessed and the use of psychopharmacological treatments (
antipsychotics,
antidepressants,
benzodiazepines) recorded.
Prolactin levels were negatively associated with cognitive performance in processing speed, in patients with a
psychotic disorder and high-risk subjects. In the latter group, increased
prolactin levels were also associated with impaired reasoning and problem solving and poorer general cognition. In a multiple linear regression analysis conducted in both high-risk and psychotic patients, controlling for potential confounders,
prolactin and
benzodiazepines were independently related to poorer cognitive performance in the speed of processing domain. A mediation analysis showed that both
prolactin and
benzodiazepine treatment act as mediators of the relationship between
risperidone/
paliperidone treatment and speed of processing. These results suggest that increased
prolactin levels are associated with impaired processing speed in early
psychosis. If these results are confirmed in future studies, strategies targeting reduction of
prolactin levels may improve cognition in this population.