Evolution of metabolic risk factors over a two-year period in a cohort of first episodes of psychosis
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
References (44)
- et al.
The metabolic syndrome - a new worldwide definition
Lancet
(2005) - et al.
Outcome in early-onset schizophrenia revisited: findings from the early psychosis prevention and intervention centre long-term follow-up study
Schizophr. Res.
(2011) - et al.
A comparison of schizophrenia outpatients treated with antipsychotics with and without metabolic syndrome: findings from the CLAMORS study
Schizophr. Res.
(2008) - et al.
What have we learned from research into first-episode psychosis?
Rev Psiquiatr Salud Ment
(2014) - et al.
Assessing clinical and functional outcomes in a gene-environment interaction study in first episode of psychosis (PEPs)
Rev Psiquiatr Salud Ment
(2013) - et al.
Modelling gene-environment interaction in first episodes of psychosis
Schizophr. Res.
(2017) - et al.
Abnormal glycemic homeostasis at the onset of serious mental illnesses: a common pathway
Psychoneuroendocrinology
(2016) - et al.
Metabolic syndrome or glucose challenge in first episode of psychosis?
Eur. Psychiatry
(2017) - et al.
Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): initial reliability and validity data
J. Am. Acad. Child Adolesc. Psychiatry
(1997) - et al.
Early insulin resistance predicts weight gain and waist circumference increase in first-episode psychosis—a one year follow-up study
Schizophr. Res.
(2015)
Cholesterol and triglycerides in antipsychotic-naive patients with nonaffective psychosis
Psychiatry Res.
Lipid profile disturbances in antipsychotic-naive patients with first-episode non-affective psychosis: A systematic review and meta-analysis
Schizophr. Res.
Metabolic profiles of second-generation antipsychotics in early psychosis: findings from the CAFE study
Schizophr. Res.
Characterizing and dating the onset of symptoms in psychotic illness: the symptom onset in schizophrenia (SOS) inventory
Schizophr. Res.
The association between first-episode psychosis and abnormal glycaemic control: systematic review and meta-analysis
Lancet Psychiatry
The effects of atypical antipsychotics on visceral fat distribution in first episode, drug-naive patients with schizophrenia
Life Sci.
Interventions to reduce antipsychotic polypharmacy: a systematic review
Schizophr. Res.
Cardiometabolic risk in first-episode schizophrenia (FES) patients with the earliest stages of both illness and antipsychotic treatment
Schizophr. Res.
DSM-IV: Diagnostic and Statistical Manual of Mental Disorders
Antipsychotic polypharmacy in a regional health service: a population-based study
BMC Psychiat.
A pharmacovigilance study in first episode of psychosis: psychopharmacological interventions and safety profiles in the PEPs project
Int. J. Neuropsychopharmacol.
School performance in finnish children and later development of schizophrenia: a population-based longitudinal study
Arch. Gen. Psychiatry
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- 1
The second and the third authors (MPG-P, CG-R) contributed equally to this work.
- 2
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 Usall, Anna Butjosa, Salvador Sarró, Ramón Landín-Romero,
Ángela Ibáñez, Manuel J Cuesta and Vicent Balanzá-Martínez.