•The polygenic risk score for educational attainment (PRS-EA), rather than psychopathological PRS (schizophrenia or bipolar disorder), was associated with lower risk and a later onset of ...relapse.•These results could indicate that the biological mechanisms beyond the risk of suffering a psychotic episode and the mechanisms of its prognosis could be independent.•The combination of polygenic scores and clinical data are potentially useful predictors of relapse.
Little is known about genetic predisposition to relapse. Previous studies have linked cognitive and psychopathological (mainly schizophrenia and bipolar disorder) polygenic risk scores (PRS) with clinical manifestations of the disease. This study aims to explore the potential role of PRS from major mental disorders and cognition on schizophrenia relapse. 114 patients recruited in the 2EPs Project were included (56 patients who had not experienced relapse after 3 years of enrollment and 58 patients who relapsed during the 3-year follow-up). PRS for schizophrenia (PRS-SZ), bipolar disorder (PRS-BD), education attainment (PRS-EA) and cognitive performance (PRS-CP) were used to assess the genetic risk of schizophrenia relapse.Patients with higher PRS-EA, showed both a lower risk (OR=0.29, 95% CI 0.11–0.73) and a later onset of relapse (30.96± 1.74 vs. 23.12± 1.14 months, p=0.007. Our study provides evidence that the genetic burden of neurocognitive function is a potentially predictors of relapse that could be incorporated into future risk prediction models. Moreover, appropriate treatments for cognitive symptoms appear to be important for improving the long-term clinical outcome of relapse.
This study investigated whether the risk of presenting antipsychotic (AP)-induced extrapyramidal symptoms (EPS) could be related to single-nucleotide polymorphisms (SNPs) in a naturalistic cohort of ...first episode psychosis (FEP) patients. Two hundred and two SNPs in 31 candidate genes (involved in dopamine, serotonin and glutamate pathways) were analyzed in the present study. One hundred and thirteen FEP patients (43 presenting EPS and 70 non-presenting EPS) treated with high-potency AP (amisulpride, paliperidone, risperidone and ziprasidone) were included in the analysis. The statistical analysis was adjusted by age, gender, AP dosage, AP combinations and concomitant treatments as covariates. Four SNPs in different genes (DRD2, SLC18A2, HTR2A and GRIK3) contributed significantly to the risk of EPS after correction for multiple testing (P<1 × 10(-4)). These findings support the involvement of dopamine, serotonin and glutamate pathways in AP-induced EPS.
Introduction
Recent studies support the identification of valid subtypes within schizophrenia and bipolar disorder using cluster analysis. Our aim was to identify meaningful biotypes of psychosis ...based on network properties of the electroencephalogram. We hypothesized that these parameters would be more altered in a subgroup of patients also characterized by more severe deficits in other clinical, cognitive, and biological measurements.
Methods
A clustering analysis was performed using the electroencephalogram‐based network parameters derived from graph‐theory obtained during a P300 task of 137 schizophrenia (of them, 35 first episodes) and 46 bipolar patients. Both prestimulus and modulation of the electroencephalogram were included in the analysis. Demographic, clinical, cognitive, structural cerebral data, and the modulation of the spectral entropy of the electroencephalogram were compared between clusters. Data from 158 healthy controls were included for further comparisons.
Results
We identified two clusters of patients. One cluster presented higher prestimulus connectivity strength, clustering coefficient, path‐length, and lower small‐world index compared to controls. The modulation of clustering coefficient and path‐length parameters was smaller in the former cluster, which also showed an altered structural connectivity network and a widespread cortical thinning. The other cluster of patients did not show significant differences with controls in the functional network properties. No significant differences were found between patients´ clusters in first episodes and bipolar proportions, symptoms scores, cognitive performance, or spectral entropy modulation.
Conclusion
These data support the existence of a subgroup within psychosis with altered global properties of functional and structural connectivity.
In this study, our aim was to contribute to a better understanding of the biological heterogeneity in psychoses. For this purpose, we conducted a cluster analysis to identify patients’ subgroups based on the characteristics of their functional network, assessed wit electroencephalogram (EEG) data and methods derived from graph‐theory. Our cluster analysis yielded a two‐cluster solution, where one cluster showed significant alterations in their functional network and a significantly altered structural connectivity network with a widespread cortical thinning, and the other cluster showed a normal functional network.
Emotional intelligence (EI) and neurocognition (NC) impairments are common in first-episode psychosis (FEP), yet their evolution over time remains unclear. This study identified patient profiles in ...EI and NC performance in FEP. 98 adult FEP patients and 128 healthy controls (HCs) were tested on clinical, functional, EI, and NC variables at baseline and two-year follow-up (FUP). A repeated-measures ANOVA compared the effects of group (patients and HCs) and time on EI. Significant EI improvements were observed in both groups. Four groups were created based on NC and EI performance at baseline and FUP in patients: impairment in NC and EI, impairment in NC only, impairment in EI only, and no impairment. At FUP, patients impaired in NC and EI showed less cognitive reserve (CR), greater negative and positive symptoms, and poorer functional outcomes. At FUP, three group trajectories were identified: (I) maintain dual impairment (II) maintain no impairment or improve, (III) maintain sole impairment or worsen. The maintain dual impairment group had the lowest levels of CR. EI and NC impairments progress differently in FEP. Greater CR may protect against comorbid EI/NC impairment. Identifying these patient characteristics could contribute to the development of personalised interventions.
Deficits in psychosocial functioning are present in the early stages of psychosis. Several factors, such as premorbid adjustment, neurocognitive performance, and cognitive reserve (CR), potentially ...influence functionality. Sex differences are observed in individuals with psychosis in multiple domains. Nonetheless, few studies have explored the predictive factors of poor functioning according to sex in first-episode psychosis (FEP). This study aimed to explore sex differences, examine changes, and identify predictors of functioning according to sex after onset.
The initial sample comprised 588 individuals. However, only adults with non-affective FEP (
= 247, 161 males and 86 females) and healthy controls (
= 224, 142 males and 82 females) were included. A comprehensive assessment including functional, neuropsychological, and clinical scales was performed at baseline and at 2-year follow-up. A linear regression model was used to determine the predictors of functioning at 2-year follow-up.
FEP improved their functionality at follow-up (67.4% of both males and females). In males, longer duration of untreated psychosis (β = 0.328,
= 0.003) and worse premorbid adjustment (β = 0.256,
= 0.023) were associated with impaired functioning at 2-year follow-up, while in females processing speed (β = 0.403,
= 0.003), executive function (β = 0.299,
= 0.020) and CR (β = -0.307,
= 0.012) were significantly associated with functioning.
Our data indicate that predictors of functioning at 2-year follow-up in the FEP group differ according to sex. Therefore, treatment and preventative efforts may be adjusted taking sex into account. Males may benefit from functional remediation at early stages. Conversely, in females, early interventions centered on CR enhancement and cognitive rehabilitation may be recommended.
Abstract Risperidone (R) is the most prescribed antipsychotic drug for patients with a first episode of psychosis (FEP). In a naturalistic cohort of chronic psychiatric inpatients, we demonstrated ...that clinicians adjust R dosage by CYP2D6 activity, despite being blinded to the genotype, which we described as an “intuitive pharmacogenetic” process. The aim of the present study is to replicate our previous findings of intuitive pharmacogenetic in a cohort of FEP patients using CYP2D6 phenotype extrapolated from genotypes. 70 FEP patients, under baseline treatment with R monotherapy were genotyped using the iPLEX® ADME PGx multiplex panel and TaqMan® Genotyping and Copy Number Assays. Plasma concentrations of R and its metabolite, 9-hydroxyrisperidone (9-OH), were determined. The predictive properties of those variables associated with R dosage were tested using a multiple linear regression model as well as regression trees. Significant differences in the mean daily dosage of R among CYP2D6 phenotypes were observed (Kruskal-Wallis test p=0.02): PM (4.00±2.3 mg/mL), IM (4.56±2.44), EM (6.22±4.0 mg/day) and UM (10.20±4.91 mg/day). However, non-significant differences were observed in the R/9-OH ratio or in the Concentration/Dose ratio. Regression tree provided better estimations of R dosage than the multiple linear regression model (MAE=0.958 and R2 =0.871). We confirm the “intuitive pharmacogenetic” dosing of R according to the CYP2D6 phenotype in a FEP cohort. The results presented provides a rationale for the clinical use of CYP2D6 genotyping in personalized medicine.
Abstract
The main objective of the present study was to investigate the association between several epigenetic clocks, covering different aspects of aging, with schizophrenia relapse evaluated over a ...3-year follow-up period in a cohort of ninety-one first-episode schizophrenia patients. Genome-wide DNA methylation was profiled and four epigenetic clocks, including epigenetic clocks of chronological age, mortality and telomere length were calculated. Patients that relapsed during the follow-up showed epigenetic acceleration of the telomere length clock (
p
= 0.030). Shorter telomere length was associated with cognitive performance (working memory,
r
= 0.31
p
= 0.015; verbal fluency,
r
= 0.28
p
= 0.028), but no direct effect of cognitive function or symptom severity on relapse was detected. The results of the present study suggest that epigenetic age acceleration could be involved in the clinical course of schizophrenia and could be a useful marker of relapse when measured in remission stages.
Background
Obstetric complications (OCs) are key contributors to psychosis risk. However, it is unclear whether they increase psychosis vulnerability independently of genetic risk, in interaction ...with it, or are a manifestation of psychosis proneness. We examined the role of distinct types of OCs in terms of psychosis risk and tested whether they interact differently with genetic vulnerability, whilst accounting for other known environmental risk factors.
Study Design
405 participants (219 first episode psychosis patients and 186 healthy volunteers) underwent a comprehensive assessment of OCs, measured using the Lewis‐Murray scale and divided into complications of pregnancy, abnormalities of foetal growth and development, and complications of delivery. Participants were compared in terms of history of OCs, polygenic risk score for schizophrenia (PRS‐SZ) and interactions between these.
Results
Both complications of pregnancy and abnormalities of foetal growth were significantly associated with case–control status (p = 0.02 and 0.03, respectively), whereas complications of delivery were not. PRS‐SZ showed a significant association with psychosis (p = 0.04), but there were no significant interactions between genetic risk for schizophrenia and OCs, either when these were considered globally or separated based on their timeframe.
Conclusions
We observed no significant interaction between genetic and obstetric vulnerability, yet distinct types of OCs may have a different impact on psychosis risk, based on their nature and timeframe. Examining their differential role might clarify their relative contributions to this risk.
There is high prevalence of cigarette smoking in individuals with first-episode psychosis (FEP) prior to psychosis onset. The purpose of the study was to determine the impact of previous tobacco use ...with or without cannabis on first psychotic experiences in FEP and the impact of this use on age of onset of symptoms, including prodromes.
Retrospective analyses from the naturalistic, longitudinal, multicentre, “Phenotype-Genotype and Environmental Interaction. Application of a Predictive Model in First Psychotic Episodes (PEPs)” Study. The authors analysed sociodemographic/clinical data of 284 FEP patients and 231 matched healthy controls, and evaluated first psychotic experiences of patients using the Symptom Onset in Schizophrenia Inventory.
FEP patients had significantly higher prevalence of tobacco, cannabis, and cocaine use than controls. The FEP group with tobacco use only prior to onset (N = 56) had more sleep disturbances (42.9% vs 18.8%, P = 0.003) and lower prevalence of negative symptoms, specifically social withdrawal (33.9% vs 58%, P = 0.007) than FEP with no substance use (N = 70), as well as lower prevalence of ideas of reference (80.4% vs 92.4%, P = 0.015), perceptual abnormalities (46.4% vs 67.4%, P = 0.006), hallucinations (55.4% vs 71.5%, P = 0.029), and disorganised thinking (41.1% vs 61.1%, P = 0.010) than FEP group with previous tobacco and cannabis use (N = 144). FEP patients with cannabis and tobacco use had lower age at first prodromal or psychotic symptom (mean = 23.73 years SD = 5.09) versus those with tobacco use only (mean = 26.21 SD = 4.80) (P = 0.011).
The use of tobacco alone was not related to earlier age of onset of a first psychotic experience, but the clinical profile of FEP patients is different depending on previous tobacco use with or without cannabis.
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