Genetic analysis; personnalized medicine; psychotropic drugs; pharmacogenetics; pharmacogenomics; metabolic syndrome; psychiatry; weight gain
Saigi-Morgui Nuria, Vandenberghe Frederik, Delacrétaz Aurélie, Quteineh Lina, Choong Eva, Gholamrezaee Mehdi, Magistretti Pierre, Aubry Jean-Michel, von Gunten Armin, Preisig Martin, Castelao Enrique, Vollenweider Peter, Waeber Gerard, Kutalik Zoltan, Conus Philippe, Eap Chin B (2015), Association of PCK1 with Body Mass Index and Other Metabolic Features in Patients with Psychotropic Treatments, in Journal of Clinical Psychopharmacology
, 35(5), 544-552.
Vandenberghe Frederik, Guidi Monia, Choong Eva, von Gunten Armin, Conus Philippe, Csajka Chantal, Eap Chin B (2015), Genetics-Based Population Pharmacokinetics and Pharmacodynamics of Risperidone in a Psychiatric Cohort, in Clinical Pharmacokinetics
, 54(12), 1259-1272.
Quteineh Lina, Vandenberghe Frederik, Saigi Morgui Nuria, Delacrétaz Aurélie, Choong Eva, Gholamrezaee Mehdi, Magistretti Pierre, Bondolfi Guido, Von Gunten Armin, Preisig Martin, Castelao Enrique, Vollenweider Peter, Waeber Gerard, Bochud Murielle, Kutalik Zoltán, Conus Philippe, Eap Chin B. (2015), Impact of HSD11B1 polymorphisms on BMI and components of the metabolic syndrome in patients receiving psychotropic treatments, in Pharmacogenetics and Genomics
, 25(5), 246-258.
Vandenberghe Frederik, Gholam-Rezaee Mehdi, Saigi-Morgui Nuria, Delacrétaz Aurélie, Choong Eva, Solida-Tozzi Alessandra, Kolly Stéphane, Thonney Jacques, Fassassi Gallo Sylfa, Hedjal Ahmed, Ambresin Anne-Emmanuelle, von Gunten Armin, Conus Philippe, Eap Chin B (2015), Importance of early weight changes to predict long-term weight gain during psychotropic drug treatment, in The Journal of Clinical Psychiatry
, 76(11), e1417-e1423.
Delacrétaz Aurélie, Preisig Martin, Vandenberghe Frederik, Saigi Morgui Nuria, Quteineh Lina, Choong Eva, Gholamrezaee Mehdi, Kutalik Zoltan, Magistretti Pierre, Aubry Jean-Michel, von Gunten Armin, Castelao Enrique, Vollenweider Peter, Waeber Gerard, Conus Philippe, Eap Chin B (2015), Influence of MCHR2 and MCHR2-AS1 Genetic Polymorphisms on Body Mass Index in Psychiatric Patients and in Population-Based Subjects with Present or Past Atypical Depression, in Plos One
, 10(10), e0139155.
Saigi-Morgui Nuria, Vandenberghe Frederik, Delacrétaz Aurélie, Quteineh Lina, Gholamrezaee Mehdi, Aubry Jean-Michel, von Gunten Armin, Kutalik Zoltan, Conus Philippe, Eap Chin B, Association of Genetic Risk Scores (GRS) with Body Mass Index in Swiss Psychiatric Cohorts, in Pharmacogenetics and Genomics
Quteineh Lina, Bochud Pierre-Yves, Golshayan Dela, Crettol Severine, Venetz Jean-Pierre, Manuel Oriol, Kutalik Zoltan, Treyer Andrea, Lehmann Roger, Mueller Nicolas, Binet Isabelle, van Delden Christian, Steiger Jurg, Mohacsi Paul, Dufour Jean François, Soccal Paola, Pascual Manuel, Eap Chin Bin, The Swiss Transplant Cohort Study, CRTC2 polymorphism as a risk factor for the incidence of metabolic syndrome in patients with solid organ transplantation, in Pharmacogenomics Journal
This SNF project constitutes the continuation of our previous SNF project (320030-120686). Weight gain and metabolic complications are major side effects induced by some psychotropic drugs, and increase the risk of cardiovascular events and long term morbidity and mortality in psychiatric populations. Our Department of Psychiatry has therefore implemented an internal guideline requiring that patients being prescribed atypical antipsychotics must be followed up for side-effects. For the purpose of the previous project, informed consents were obtained from 800 patients in routine clinical monitoring, with DNA available. A very important feature of this cohort is that plasma levels have been measured for all psychotropic drugs of interest, which allows to study the relationship between the clinical variables and the plasma levels, and to exclude false negatives, i.e. absence of side-effects due to poor or non-compliance. Very interesting clinical as well as genetic results (in particular influence of CRTC1 genetic polymorphism on weight have been obtained during the previous project). A very large data base has thus been collected (initial weight and weight gain during treatment; variables from the metabolic syndrome i.e waist measurement, triglycerides and cholesterol levels, blood pressure, fasting glucose; UKU rating scales for extra pyramidal symptoms; Clinical Global Impression (CGI) rating scales). The first major aim of the present project is to perform a thorough analysis of genetic factors possibly associated with all collected clinical variables, in a cohort of 1000 patients (800 already included plus 200 first future patients to be included in the present project). Associations will first be continued to be searched on between genetic factors and weight as well as weight gain during treatment. In addition, other abovementioned clinical variables, in particular those associated with metabolic syndrome, will also be examined. In genetic and pharmacogenetic studies, it is of major importance to obtain large cohorts of patients, to increase the power of the study as well as to validate the results. The majority of published studies were performed with small or moderate number of patients, which can also contribute to the fact that original positive results are not confirmed in subsequent studies. The second major aim of the present SNF project is therefore to continue the inclusions of patients during the next 3 years and to include 700 more patients (total number: 1500 patients) hence allowing to increase the power of the study. The last 500 patients included in the present project will be used in particular to confirm positive results found in the first group of 1000 patients. Weight gain during antipsychotic treatment, with drugs such as clozapine, olanzapine, risperidone or quetiapine is the rule rather than the exception. However, a small proportion of patients appear to be protected against this side-effect despite a good compliance. It would be extremely interesting to determine whether some genetic factors can be shown to be associated with a protection against weight gain during treatment and/or against other variables of the metabolic syndrome. The first minor aim of this project is to include 75 patients with such a phenotype. They will be age, gender, diagnostic, type and duration of treatment matched with 225 patients who presented a major weight gain during their treatment (> 15% of initial weight during the first 3 months of treatment). These 300 patients with be analyzed with the Illumina Cardiometabochip, which contains more than 200’000 SNPs in relation with cardio metabolic diseases identified through genome wide association studies. The second minor aim is to analyze drug levels using a population pharmacokinetic approach in order to quantify variability in drug levels, to identify genetic and non-genetic sources of variability and to explore concentration-effect and toxicity relationships. The third minor aim is to analyze the prevalence, intensity and evolution of side effects (weight gain, BMI change, abdominal fat, deterioration of lipid and glycemic profile, hypertension, hyperprolactinemia, extrapyramidal symptoms) in the whole cohort of 1500 psychiatric patients, with a follow-up of up to one year. During the previous project, this analysis has been performed in a group of 197 adult psychiatric patients and the present project is intended to obtain results in a much larger cohort, including children, adolescents and old aged patients. Because of the experience acquired during the previous project, thanks to the implications of the heads of our Department of Psychiatry, the feasibility of the present project seems excellent, as shown by the number of patients included in the previous project as planned. In addition, a collaboration was established with the main investigators from the CoLaus study which will be continued. CoLaus is a population-based sample with over 5300 subjects who have been extensively clinically characterized for variables of the metabolic syndrome, and with genome wide analysis data. Thus, if any gene is found to influence weight and/or other variables of the metabolic syndrome in psychiatric patients, it will be determined whether this is also the case in a general population, thus widening the implication of the findings.