BackgroundRecent studies in patients with psychotic disorders or prolactinomas suggest that increased prolactin levels may have negative effects on cognition. Most previous studies including patients with psychotic disorders are cross-sectional, and longitudinal studies are lacking. We aimed to conduct an observational, prospective study to explore whether prolactin levels during the first year of treatment are associated with changes in cognitive tasks. Our hypothesis would be that those patients with increased prolactin levels would show a poorer cognitive outcome than those patients with lower prolactin levels.MethodsWe studied 60 patients (24.5 ± 6.8 years; 36% women) with a first episode psychosis (FEP) attending the Early Psychosis Programme from two institutions (Parc Taulí Hospital Universitari, Sabadell, Spain; Hospital Universitari Institut Pere Mata). Ethical approval was obtained from the local Ethics Committees of both institutions. Clinical diagnoses for a FEP were generated with the OPCRIT checklist v.4.0 after a semistructured interview by a psychiatrist. The MATRICS Consensus Cognitive Battery (MCCB) was administered to explore neuropsychological functioning at two-time points (baseline, 1 year). The MCCB contains 10 tests to measure cognitive performance in 7 cognitive domains. Three fasting blood samples (baseline, 6 months, 12 months) were obtained in the morning between 8:30 h and 9:30 h in resting conditions, to determine unstimulated plasma prolactin. Serum prolactin levels were determined with immunoassays standardized against the 3rd International Reference Standard 84/500. Statistical analyses were performed with SPSS version 21.0. As prolactin levels might be increased by stress, particularly at the onset of the FEP, we calculated mean prolactin levels over the follow-up period taking into account prolactin values at 6 and 12 months. A general linear model for repeated measures was performed in order to test whether longitudinal changes in cognitive tasks differed by mean prolactin levels. All analyses were adjusted for gender. A p value < 0.05 (two-tailed) was considered to be significant. For descriptive purposes, patients in the fourth quartile for serum prolactin (>47.8 ng/ml for men; >54.3 ng/ml for women) where compared with those with lower prolactin levels.ResultsPatients improved in all 10 MCCB cognitive tasks one year later (p<0.05 for all tasks). When exploring the interaction between time x prolactin in the GLM analyses, significant interactions were found for three cognitive tasks related with processing speed (BACS-SC [F= 5.9, p= 0.018]; Fluency [F= 5.6, p= 0.022]) and reasoning and problem solving (NAB mazes [F= 4.8, p= 0.033]). Percent change over the follow-up period in these cognitive tasks was greater for patients with lower prolactin levels, when compared to those in the highest quartile: BACS-SC (11.8% vs 0.6%), Fluency (8.5% vs -7.4%) and NAB mazes (10.7% vs -1.1%).DiscussionOur study is in accordance with previous cross-sectional studies reporting a negati...

Background Previous studies assessing the neurotoxicity of haloperidol, risperidone and paliperidone in cell culture suggest that paliperidone shows the strongest neuroprotective effect and a reduced apoptosis level. Other studies including patients with schizophrenia suggest that switching from risperidone long-acting injection (RLAI) to paliperidone palmitate (PP) may improve cognitive function in processing speed and attention. We aimed to study whether switching from risperidone to PP is associated with improved cognitive abilities at 3 or 6 months after the switch. Methods Our initial sample included 32 patients with schizophrenia attending to the Department of Mental Health from Parc Taulí Hospital (Sabadell, Barcelona). All patients were treated with oral risperidone or RLAI (at least two months of stable treatment in monotherapy) and had the indication to be switched to PP by their psychiatrists. Of all 32 patients, 24 (75%) had at least a follow-up visit at 3 months. Therefore, statistical analyses were conducted in a final sample of 24 patients (88% men; 35.6 ± 12.3 years; 63% were receiving RLAI at baseline visit). Ethical approval was obtained from the local Ethics Committee and all participants provided written informed consent. Clinical diagnoses for schizophrenia were generated with the OPCRIT checklist v.4.0. Three assessments were completed: 1) baseline (pre-switch), 2) 3 months post-switch, 3) 6 months post-switch. Cognitive assessment was conducted at each visit with the MATRICS Consensus Cognitive Battery, which includes 10 cognitive tests for assessing 7 cognitive domains. Statistical analyses were performed with SPSS v 23.0 (IBM, USA). A non-parametric paired test (Wilcoxon test) was used for comparing changes in cognitive function over time (baseline vs 3 months; baseline vs 6 months). Significance was set at p&lt;0.05. Results Significant improvements in cognitive function were found for two cognitive tasks dealing with processing speed (BACS-SC and TMT-A) and one task dealing with attention and vigilance (CPT-IP) at both 3 and 6 months. Although reasoning and problem solving (NAB Mazes) or spatial working memory (WMS-III-Spatial Span) did not improve at 3 months, significant improvements in these two cognitive tasks were found at 6 months. Verbal memory, visual memory and social cognition did not improve over time. Discussion In patients with schizophrenia, switching from risperidone to PP is associated with cognitive improvement in tasks dealing with processing speed, attention, working memory and reasoning and problem solving. Our findings are in accordance with previous studies that suggest a potential neuroprotective effect of paliperidone. Some limitations of our study include the lack of randomization (no control group) and the small sample size. The small number of female patients does not allow to explore potential sex differences in the improved cognitive outcome.