Yoko Tomioka1, Esther Jiménez1, Estela Salagre1, Bárbara Arias2, Marina Mitjans3, Victoria Ruiz4, Pilar Sáiz5, María Paz García-Portilla5, Lorena de la Fuente6, Susana Patricia Gomes-da-Costa1, Julio Bobes5, Eduard Vieta7, Antoni Benabarre1, Iria Grande8. 1. Bipolar Disorders Unit, Hospital Clinic, Institute of Neurosciences, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain. 2. Departament Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, CIBERSAM, Barcelona, Spain. 3. Departament Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, CIBERSAM, Barcelona, Spain; Clinical Neuroscience, Max Planck Institute of Experimen tal Medicine, Göttingen, Germany. 4. Institut Clinic de Neurociencies, Hospital Clinic, Barcelona, Catalonia, Spain. 5. Department of Psychiatry, School of Medicine, University of Oviedo, CIBERSAM Instituto de Neurociencias del Principado de Asturias, INEUROPA, Oviedo, Spain; Servicio de Salud del Principado de Asturias (SESPA), Oviedo, Spain. 6. Department of Psychiatry, School of Medicine, University of Oviedo, CIBERSAM Instituto de Neurociencias del Principado de Asturias, INEUROPA, Oviedo, Spain. 7. Bipolar Disorders Unit, Hospital Clinic, Institute of Neurosciences, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain. Electronic address: evieta@clinic.ub.es. 8. Bipolar Disorders Unit, Hospital Clinic, Institute of Neurosciences, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain. Electronic address: igrande@clinic.ub.es.
Abstract
INTRODUCTION: The age at onset of bipolar disorder (BD) has significant implications for severity, duration of affective episodes, response to treatment, and psychiatric comorbidities. It has been suggested that early-onset BD (EO-BD) could represent a clinically distinct subtype with probable genetic risk factors different from those of late-onset BD (LO-BD). To date, several genes have been associated with BD risk but few studies have investigated the genetic differences between EO-BD and LO-BD. The aim of this study was to evaluate if variants of the gene coding for myo-inositol monophosphatase (IMPA2) are linked to age at onset of BD. METHOD: 235 bipolar patients were recruited and assessed. The final sample consisting of 192 euthymic individuals, was compared according to the age at onset. Polymorphisms were genotyped in the IMPA2 gene (rs669838, rs1020294, rs1250171, and rs630110). Early-onset was defined by the appearance of a first affective episode before the age of 18. RESULTS: The analyses showed that in the genotype distribution rs1020294 (p = .01) and rs1250171 (p = .01) were associated with the age at onset. The significant effect remained only in the rs1020294 SNP in which G carriers were more likely to debut later compared to patients presenting the AA genotype (p = .002; OR = 9.57, CI95%[2.37-38.64]). The results also showed that EO-BD tended to experience more alcohol misuse (p = .003; OR = .197, CI95%[.07-.58]) compared to LO-BD. CONCLUSIONS: Our results provide evidence for genetic differences between EO-BD and LO-BD at the IMPA2 gene as well as clinical differences between subgroups with therapeutic implications.
INTRODUCTION: The age at onset of bipolar disorder (BD) has significant implications for severity, duration of affective episodes, response to treatment, and psychiatric comorbidities. It has been suggested that early-onset BD (EO-BD) could represent a clinically distinct subtype with probable genetic risk factors different from those of late-onset BD (LO-BD). To date, several genes have been associated with BD risk but few studies have investigated the genetic differences between EO-BD and LO-BD. The aim of this study was to evaluate if variants of the gene coding for myo-inositol monophosphatase (IMPA2) are linked to age at onset of BD. METHOD: 235 bipolarpatients were recruited and assessed. The final sample consisting of 192 euthymic individuals, was compared according to the age at onset. Polymorphisms were genotyped in the IMPA2 gene (rs669838, rs1020294, rs1250171, and rs630110). Early-onset was defined by the appearance of a first affective episode before the age of 18. RESULTS: The analyses showed that in the genotype distribution rs1020294 (p = .01) and rs1250171 (p = .01) were associated with the age at onset. The significant effect remained only in the rs1020294 SNP in which G carriers were more likely to debut later compared to patients presenting the AA genotype (p = .002; OR = 9.57, CI95%[2.37-38.64]). The results also showed that EO-BD tended to experience more alcohol misuse (p = .003; OR = .197, CI95%[.07-.58]) compared to LO-BD. CONCLUSIONS: Our results provide evidence for genetic differences between EO-BD and LO-BD at the IMPA2 gene as well as clinical differences between subgroups with therapeutic implications.
Authors: Kan Zhang; Lei Liu; Min Wang; Min Yang; Xianping Li; Xiaomeng Xia; Jingjing Tian; Shan Tan; Lingli Luo Journal: Cell Death Dis Date: 2020-05-14 Impact factor: 8.469