Lina Quteineh1, Martin Preisig2, Margarita Rivera3, Yuri Milaneschi4, Enrique Castelao2, Mehdi Gholam-Rezaee2, Frederik Vandenberghe1, Nuria Saigi-Morgui1, Aurélie Delacrétaz1, Jean-René Cardinaux5, Gonneke Willemsen6, Dorret I Boomsma6, Brenda W J H Penninx4, Ana Ching-López7, Philippe Conus8, Chin B Eap9. 1. Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland. 2. Centre of Psychiatric Epidemiology and Psychopathology, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland. 3. Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain; CIBERSAM-University of Granada and Institute of Neurosciences Federico Olóriz, Centro de Investigación Biomédica, University of Granada, Spain; MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom. 4. Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam, The Netherlands. 5. Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland; Child and Adolescent Psychiatric Clinic, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland. 6. Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands. 7. CIBERSAM-University of Granada and Institute of Neurosciences Federico Olóriz, Centro de Investigación Biomédica, University of Granada, Spain. 8. Service of General Psychiatry, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland. 9. Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland; School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland. Electronic address: chin.eap@chuv.ch.
Abstract
BACKGROUND: Psychiatric disorders have been hypothesized to share common etiological pathways with obesity, suggesting related neurobiological bases. We aimed to examine whether CRTC1 polymorphisms were associated with major depressive disorder (MDD) and to test the association of these polymorphisms with obesity markers in several large case-control samples with MDD. METHODS: The association between CRTC1 polymorphisms and MDD was investigated in three case-control samples with MDD (PsyCoLaus n1=3,362, Radiant n2=3,148 and NESDA/NTR n3=4,663). The effect of CRTC1 polymorphisms on obesity markers was then explored. RESULTS: CRTC1 polymorphisms were not associated with MDD in the three samples. CRTC1 rs6510997C>T was significantly associated with fat mass in the PsyCoLaus study. In fact, a protective effect of this polymorphism was found in MDD cases (n=1,434, β=-1.32%, 95% CI -2.07 to -0.57, p<0.001), but not in controls. In the Radiant study, CRTC1 polymorphisms were associated with BMI, exclusively in individuals with MDD (n=2,138, β=-0.75kg/m(2), 95% CI -1.30 to -0.21, p=0.007), while no association with BMI was found in the NESDA/NTR study. LIMITATIONS: Estimated fat mass using bioimpedance that capture more accurately adiposity was only present in the PsyCoLaus sample. CONCLUSIONS: CRTC1 polymorphisms seem to play a role with obesity markers in individuals with MDD rather than non-depressive individuals. Therefore, the weak association previously reported in the population-based samples was driven by cases diagnosed with lifetime MDD. However, CRTC1 seems not to be implicated directly in the development of psychiatric diseases.
BACKGROUND: Psychiatric disorders have been hypothesized to share common etiological pathways with obesity, suggesting related neurobiological bases. We aimed to examine whether CRTC1 polymorphisms were associated with major depressive disorder (MDD) and to test the association of these polymorphisms with obesity markers in several large case-control samples with MDD. METHODS: The association between CRTC1 polymorphisms and MDD was investigated in three case-control samples with MDD (PsyCoLaus n1=3,362, Radiant n2=3,148 and NESDA/NTR n3=4,663). The effect of CRTC1 polymorphisms on obesity markers was then explored. RESULTS: CRTC1 polymorphisms were not associated with MDD in the three samples. CRTC1 rs6510997C>T was significantly associated with fat mass in the PsyCoLaus study. In fact, a protective effect of this polymorphism was found in MDD cases (n=1,434, β=-1.32%, 95% CI -2.07 to -0.57, p<0.001), but not in controls. In the Radiant study, CRTC1 polymorphisms were associated with BMI, exclusively in individuals with MDD (n=2,138, β=-0.75kg/m(2), 95% CI -1.30 to -0.21, p=0.007), while no association with BMI was found in the NESDA/NTR study. LIMITATIONS: Estimated fat mass using bioimpedance that capture more accurately adiposity was only present in the PsyCoLaus sample. CONCLUSIONS: CRTC1 polymorphisms seem to play a role with obesity markers in individuals with MDD rather than non-depressive individuals. Therefore, the weak association previously reported in the population-based samples was driven by cases diagnosed with lifetime MDD. However, CRTC1 seems not to be implicated directly in the development of psychiatric diseases.
Authors: Kerstin Rohde; Maria Keller; Lars la Cour Poulsen; Torunn Rønningen; Michael Stumvoll; Anke Tönjes; Peter Kovacs; Annette Horstmann; Arno Villringer; Matthias Blüher; Yvonne Böttcher Journal: EBioMedicine Date: 2019-05-30 Impact factor: 8.143
Authors: Aurélie Delacrétaz; Anaïs Glatard; Céline Dubath; Mehdi Gholam-Rezaee; Jose Vicente Sanchez-Mut; Johannes Gräff; Armin von Gunten; Philippe Conus; Chin B Eap Journal: Clin Epigenetics Date: 2019-12-26 Impact factor: 6.551
Authors: Clara Rossetti; Daniel Sciarra; Jean-Marie Petit; Chin B Eap; Olivier Halfon; Pierre J Magistretti; Benjamin Boutrel; Jean-René Cardinaux Journal: Transl Psychiatry Date: 2017-12-08 Impact factor: 6.222