title: Effect of early stress on hippocampal gray matter is influenced by a functional polymorphism in EAAT2 in bipolar disorder.
abstract: Current views on the pathogenesis of psychiatric disorders focus on the interplay between genetic and environmental factors, with individual variation in vulnerability and resilience to hazards being part of the multifactorial development of illness. The aim of the study is to investigate the effect of glutamate transporter polymorphism SLC1A2-181A>C and exposure to Adverse Childhood Experiences (ACE) on hippocampal gray matter volume of patients with bipolar disorder (BD). Patients exposed to higher levels of ACE reported lower gray matter volume. The effect of SLC1A2-181A>C revealed itself only among patients exposed to lower levels of ACE, with T/T homozygotes showing the lowest, and G/G the highest, gray matter volume. The greatest difference between high and low exposures to ACE was observed in carriers of the G allele. Since the mutant G allele has been associated with a reduced transcriptional activity and expression of the transporter protein, we could hypothesize that after exposure to highest levels of ACE G/G homozygotes are more vulnerable to stress reporting the highest brain damage as a consequence of an excess of free glutamate.
authors: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy. Electronic address: poletti.sara@hsr.it.
authors: Sara
authors: S
authors: Poletti
authors: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy.
authors: Clara
authors: C
authors: Locatelli
authors: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy.
authors: Daniele
authors: D
authors: Radaelli
authors: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy.
authors: Cristina
authors: C
authors: Lorenzi
authors: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy.
authors: Enrico
authors: E
authors: Smeraldi
authors: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy.
authors: Cristina
authors: C
authors: Colombo
authors: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy.
authors: Francesco
authors: F
authors: Benedetti
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics* / Q000473:pathology*; D027342:Excitatory Amino Acid Transporter 2; D005260:Female; D005838:Genotype; D050491:Glutamate Plasma Membrane Transport Proteins / Q000235:genetics*; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D012189:Retrospective Studies; D013315:Stress, Psychological / Q000473:pathology* / Q000523:psychology; D011795:Surveys and Questionnaires
chemical_list: D027342:Excitatory Amino Acid Transporter 2; D050491:Glutamate Plasma Membrane Transport Proteins; C493397:SLC1A2 protein, human
keywords: Adverse childhood experiences; Bipolar disorder; EAAT2; Glutamate; Hippocampus