Biomedical subjects

Sergi Papiol

Publications and source records attributed to Sergi Papiol.

4 recordsLinked to original sources

PubMed2026

Polygenic risk score for neurodevelopmental disorders and cognitive impairment at long-term follow-up of first-episode psychosis.

BACKGROUND: One of the most outstanding contributions to the understanding of the etiopathogenesis of schizophrenia spectrum disorders (SSD) was the neurodevelopmental hypothesis. SSD and neurodevelopmental disorders (NDD) share pathogenetic mechanisms and overlapping clinical and cognitive impairment features. METHODS: We investigated whether polygenic risk scores (PRSs) for NDD are associated with cognitive performance in patients with first-episode psychosis (FEP). The sample comprised 127 patients with FEP who were followed up for a mean of 20.9 years. Cognitive examination was performed using the MoCA test at follow-up. Pearson coefficient correlations and multiple regression analyses were performed to examine the contribution of the three PRSs for rare neurodevelopmental conditions (PRSNDD), attention-deficit hyperactivity disorder (PRSADHD) and autism spectrum disorder (PRSASD) to cognitive impairment after allowing for the effect of covariates. Furthermore, we examined the interconnections between the PRS for NDD and cognitive impairment using network analysis (NA), including core premorbid variables. RESULTS: PRSNDD showed significant associations with impairment on visuospatial/executive, attention, and language MoCA subtests, after allowing for the influence of covariates. PRSNDD and PRSADHD, but not PRSASD, were significantly associated with worse performance on the total MoCA score. Moreover, in the network analysis, the relationships between PRSs for NDD and cognitive impairment were highly interconnected with premorbid variables and PRSs for schizophrenia and educational attainment. CONCLUSIONS: These results provide evidence for a possible direct genetic effect on cognitive performance for the PRS of common genetic variations related to neurodevelopment and attention deficit hyperactivity disorder in patients with FEP.

Cognitive impairment↗

PubMed2026

Effects of quetiapine on cognitive functioning in schizophrenia: evidence for the remyelination hypothesis?

Postmortem findings, neuroimaging data, and in-vitro models suggest a decrease in number and density of oligodendrocytes is driving cognitive deficits in schizophrenia (SCZ). Second-generation antipsychotics are discussed to improve oligodendrocyte dysfunction with most conclusive evidence available for quetiapine (QET). We postulate that sustained QET treatment leads to cognitive improvement in SCZ, particularly, in tests with high demands for working memory function. We further hypothesize that these effects are moderated by polygenic factors associated with hippocampus-related brain volumes, general white matter integrity, and/or oligodendroglia-related SCZ risk. Using data of the prospective PsyCourse study, we identified 166 patients with SCZ spectrum disorder receiving QET at one or two consecutive visits plus 166 matched patients without QET. Polygenic scores were calculated for subcortical brain volumes, measures of white matter integrity, and for cell type-specific genetic SCZ risks. QET treatment was consistently associated with improved cognitive function independent of time, specifically, in tests with high, but not with low to medium working memory load. Polygenic analyses did not reveal significant moderation effects. In contrary, low genetic SCZ risk specific for genes related to human oligodendrocyte function was associated with higher cognitive performance independent from QET. While we observed improved cognitive performance under QET in high working memory tests, we did not find evidence that polygenic factors associated with hippocampus-related brain volumes, white matter integrity, or oligodendroglia-related SCZ risk moderate this association. Thus, our tentative findings do not provide evidence for the hypothesis that polygenic estimates of hippocampal remyelination capacities influence the association between QET and cognitive performance in SCZ.

Humans↗

PubMed2025

Genetic Susceptibility to the Environment Moderates the Impact of Childhood Experiences on Psychotic, Depressive, and Anxiety Dimensions.

BACKGROUND AND HYPOTHESIS: Gene-by-environment (GxE) studies in psychosis have exclusively focused on negative exposures. However, evidence supports the resilience-enhancing effect of positive factors on psychosis outcome. The Differential Susceptibility (DS) model proposes that common genetic variants may confer not only disproportionate responsiveness to negative environments, but also greater sensitivity to positive, resilience-enhancing conditions. This study is the first to apply the DS model to the expression of subclinical psychosis, employing polygenic risk scores of environmental sensitivity (PRS-ES). PRS-ES were hypothesized to moderate, in a DS manner, associations between childhood adversity and psychosis, affective, and anxiety dimensions in young adults. An exploratory goal examined whether PRS for psychotic-like experiences (PRS-PLE) also showed DS patterns. STUDY DESIGN: PRS, schizotypy, PLE, depression, anxiety, and childhood adversity ratings were obtained for 197 nonclinical young adults. LEGIT software for testing competitive-confirmatory GxE models was employed. STUDY RESULTS: Results largely supported DS: Individuals high on PRS-ES showed increased subclinical psychosis, depression, and anxiety if they had experienced elevated childhood adversity, and lower symptoms if exposed to low levels of adversity as compared with those with low PRS-ES. Similarly, PRS-PLE moderated the effect of adversity on PLE, positive schizotypy, and depression following the DS model, but only PRS-ES moderation on PLE survived statistical correction. CONCLUSIONS: Our results suggest that genetic DS to the environment is relevant to psychosis, depression, and anxiety. Current debates on reconceptualization of genetic "risk" and resilience may benefit from this insight that support optimistic views on preventative efforts for early detection and intervention.

Humans↗

PubMed2025

Genetic Differences in Reactivity to the Environment Impact Psychotic-Like and Affective Reactivity in Daily Life.

BACKGROUND AND HYPOTHESIS: Consistent with diathesis-stress models, psychosis research has focused on genetic moderation of adverse environmental exposures. In contrast, the Differential Susceptibility (DS) model suggests that the same genetic variants that increase risk-inducing effects of adverse experiences also enhance beneficial effects from positive experiences. This study examined whether individuals with high genetic susceptibility to the environment showed differential psychotic-like and affective reactivity in response to positive and negative events in daily life. STUDY DESIGN: Experience sampling methodology assessed context (positive and stressful) and momentary levels of paranoia, psychotic-like experiences (PLE), and positive (PA) and negative affect (NA) in 217 non-clinical adults oversampled for schizotypy. Linear mixed models examined whether Polygenic Risk Scores of Environmental Sensitivity (PRS-ES) moderated the impact of current context on subsequent experiences. STUDY RESULTS: PRS-ES moderated positive, but not stressful, context on subsequent levels of momentary paranoia, NA, and PA, but not PLE. Genetic and environmental (G × E) interactions indicated diathesis-stress at lower thresholds of PRS-ES, but a DS model at the highest threshold of the PRS-ES. Participants with elevated PRS-ES showed increased paranoia and NA and decreased PA in subsequent assessments when reporting low levels of positive situations, but also decreased paranoia and NA and increased PA when rating contexts as positive. CONCLUSIONS: Findings support the influence of genetic sensitivity to the environment on psychotic-like and affective reactivity in daily life, particularly in response to positive contexts. This highlights the transdiagnostic protective role of positive experiences and informs ecological momentary interventions.

Humans↗