Elsevier

Schizophrenia Research

Volume 193, March 2018, Pages 188-196
Schizophrenia Research

Evolution of metabolic risk factors over a two-year period in a cohort of first episodes of psychosis

https://doi.org/10.1016/j.schres.2017.06.032Get rights and content

Abstract

Patients with a first episode of psychosis (FEP) display a broad range of metabolic risk factors related to the development of diverse medical comorbidities. Initial stages of these disorders are essential in understanding the increased vulnerability of developing cardiometabolic disturbances, associated with a reduced life expectancy. This study aimed to evaluate the metabolic profile of a cohort of patients with a FEP and its evolution during a two year follow-up, as well as the factors that influence the changes in their metabolic status.

16 participating centers from the PEPs Project recruited 335 subjects with a FEP and 253 matched healthy controls, aged 9–35 years. We investigated a set of anthropometric measures, vital signs and laboratory data obtained from each participant over two years in a prospective, naturalistic study.

From the beginning of the study the FEP group showed differences in the metabolic profile compared to the control group, together with a progressive worsening in the major part of the analyzed variables during the follow-up period, with higher rates of obesity and metabolic syndrome. Certain risk factors were related to determinate clinical variables such as male gender, the presence of affective symptoms or an early onset or to treatment variables such as the use of antipsychotic polypharmacy, antidepressants or mood stabilizers.

Our results highlight the extremely high risk of patients at early phases of schizophrenia and other psychotic disorders of developing cardiovascular comorbidity and the fast worsening of the metabolic profile during the first two years.

Introduction

Patients with a first episode of psychosis (FEP) display a wide array of metabolic disturbances (Fleischhacker et al., 2013), which over time might predict the development of diverse medical conditions, such as metabolic syndrome (MetS) or cardiovascular diseases (CVD). Those medical co-morbidities seem to underlie the increased mortality in those patients detected even at the onset of a mental disorder (Laursen et al., 2013, Nordentoft et al., 2013). Part of this increased risk might also be related to the metabolic side effects of antipsychotics, already present after few weeks of treatment (Fernandez-Egea et al., 2011, Tek et al., 2016).

Initial stages of psychotic disorders are essential in understanding the increased risk of developing metabolic disturbances (Fernandez-Egea et al., 2009, Perez-Iglesias et al., 2014). Two meta-analyses reflect that the risk for MetS is low in FEP but increases over time (Mitchell et al., 2013, Mitchell et al., 2011), with high prevalence in chronic patients (Arango et al., 2008). The determination of MetS rates at initial stages might underscore the risk of developing CVD, so further analysis must be implemented (Garcia-Rizo et al., 2017). At initial stages, glucose abnormalities are the most replicated findings (Rajkumar et al., 2017, Garcia-Rizo et al., 2016, Greenhalgh et al., 2016, Perry et al., 2016, Pillinger et al., 2017, Ryan et al., 2003, Spelman et al., 2007). Besides, other CVD risk factors have been assessed: (i) blood pressure, through increased pulse pressure (Fernandez-Egea et al., 2009); (ii) lipid profile has been reported to be altered (Keinanen et al., 2015) or subclincal (Misiak et al., 2017), while other studies did not find differences(Kirkpatrick et al., 2010); and (iii) abdominal obesity (Ryan et al., 2004), but other studies failed to replicate (Fernandez-Egea et al., 2009, Keinanen et al., 2015). In this context, the study of the population with a FEP is of great interest because it avoids the effect of confounding variables, such as somatic comorbidities, prolonged antipsychotic treatment or chronicity (Bernardo and Bioque, 2014, Bernardo et al., 2013).

The PEPs Project was a multicenter, prospective, longitudinal, naturalistic study, conducted in 16 research sites in Spain designed to follow a cohort of 335 subjects with a FEP, matched with 253 healthy controls (Bernardo et al., 2013, Bioque et al., 2016). The aim of the present study was to evaluate the metabolic profile of patients at the FEP and its evolution during the two year follow-up, aiming to identify the factors that influence in these early changes. This study offers a unique opportunity to extend previous research by investigating the prevalence of metabolic abnormalities in a real-world cohort of patient with a FEP treated with commonly-used drugs during a follow-up of two years.

Section snippets

Subjects

During the recruitment period (2009–2012), every patient who met the inclusion criteria that was attended at the PEPs project participating sites facilities was invited to participate in the study, either inpatient or outpatient. The rationale and the complete clinical protocol used in the PEPs project were previously published (Bernardo et al., 2013) (free text available both in English and Spanish).

The inclusion criteria for patients were: presence of a FEP in the last 12 months, age between 7

Baseline clinical characteristics, anthropometric, vital signs and metabolic measures

335 patients with a FEP and 253 healthy controls completed the baseline visit. 57 (17,6%) patients and 32 (12.6%) controls were underage. Demographic and clinical characteristics and baseline metabolic measures are presented in Table 1.

At baseline, the FEP group presented statistically significant higher total and LDL cholesterol and lower HDL cholesterol mean levels (Table 1). At this point, patients and control showed differences in two of the five IDF MetS criteria (glucose and HDL

Discussion

These results highlight the extremely high risk of patients at early phases of schizophrenia and other psychotic disorders of developing CVD risk factors and the rapid worsening of the metabolic profile during two years period. From the beginning of the study, the FEP group showed differences in metabolic parameters compared to the control group (Table 1). After two years of follow-up, the metabolic status of the FEP group clearly worsened compared to the control group in almost all metabolic

Contributors

MBi collected the biological samples and the clinical data, managed and analyzed the clinical data and wrote the first version of the paper; MPG-P and CGR collected the biological samples and the clinical data and wrote the first version of the paper; MBe coordinated the PEPs study. All the authors contributed to the final version of the paper.

Funding

This study was supported by Ministerio de Economía y Competitividad (ref. ISCIII 2009–2011: PEPs study PI 080208); Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional, Unión Europea, “Un manera de hacer Europa”; Centro de Investigación Biomédica en Red de salud Mental, CIBERSAM, by the CERCA Programme/Generalitat de Catalunya and Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement (2014SGR441).

Conflicts of interest

M Bioque has been a consultant for, received grant/research support and honoraria from, and been on the speakers/advisory board of Adamed, Ferrer, Janssen-Cilag, Lundbeck, Otsuka, and Pfizer.

MP García-Portilla has been a consultant to and/or has received honoraria/grants from Alianza Otsuka-Lundbeck, CIBERSAM, European Comission, Instituto de Salud Carlos III, Janssen-Cilag, Lilly, Lundbeck, Otsuka, Pfizer, Servier, Roche, and Rovi.

C Carcía-Rizo has received honoraria/travel support from

Acknowledgements

PEPs GROUP: Ana Meseguer, Sílvia Amoretti, Carmen Moreno, Mara Parellada, Anna Alonso-Solís, Mireia Rabella, Mónica Martínez- Cengotitabengoa, Itxaso González-Ortega, José Luis Díaz, Mª Fe Barcones, Maria Jose Escarti, Carlos Cañete, Purificación Salgado, Iris Cáceres, Carla Torrent, Ivette Morilla, Inmaculada Baeza, Elena de la Serna, Fernando Contreras, Auria Albacete, Leticia García-Alvarez, Lorena de la Fuente, José Ignacio Eguiluz, Rafael Segarra, Isabel Morales-Muñoz, Iosune Torio, Judith

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