title: Neural signatures of the interaction between the 5-HTTLPR genotype and stressful life events in healthy women.
abstract: A change in neural connectivity of brain structures implicated in the memory of negative life events has been hypothesized to explain the enhancement of memory encoding during the processing of negative stimuli in depressed patients. Here, we investigated the effects of the interaction between negative life events and the 5-HTTLPR genotype - a polymorphism of the serotonin transporter gene - on the functional and structural connectivity of the hippocampal area in 34 healthy women. All participants were genotyped for the presence of the 5-HTTLPR short variant and for the A/G single-nucleotide polymorphism; they underwent clinical assessment including structured diagnostic interviews to exclude the presence of psychiatric disorders and to assess the presence of stressful life events. Resting state functional magnetic resonance imaging and diffusion tensor imaging scans were performed. We found significant interactions between stressful events and the 5-HTTLPR genotype in both the functional connectivity of the parahippocampus with the posterior cingulate cortex and the structural connectivity between the hippocampus and both the amygdala and the putamen. In addition, we found several genotype-related differences in the relationship between functional/structural connectivity of the hippocampal area and the ability to update expectations or stress-related phenotypes, such as anxiety symptoms. If confirmed by future studies, these mechanisms may clarify the role of the 5HTTLPR genotype as a risk factor for depression, in interaction with negative events.
authors.affiliation: Psychiatric Clinic, Department of Neurosciences, University of Padova, Via Giustiniani 3, 35128 Padova, Italy; Centro di Neuroscienze Cognitive, Università di Padova, Italy. Electronic address: angela.favaro@unipd.it.
authors.forename: Angela
authors.initials: A
authors.lastname: Favaro
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Italy; IRCCS Istituto San Camillo, Venezia, Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Manara
authors.affiliation: Laboratory of Epidemiology, Neuroimaging and Telemedicine - LENITEM, IRCCS Istituto Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Pievani
authors.affiliation: Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Clementi
authors.affiliation: Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Forzan
authors.affiliation: Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Bruson
authors.affiliation: Psychiatric Clinic, Department of Neurosciences, University of Padova, Via Giustiniani 3, 35128 Padova, Italy; Centro di Neuroscienze Cognitive, Università di Padova, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Tenconi
authors.affiliation: Psychiatric Clinic, Department of Neurosciences, University of Padova, Via Giustiniani 3, 35128 Padova, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Degortes
authors.affiliation: Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pinato
authors.affiliation: Psychiatric Clinic, Department of Neurosciences, University of Padova, Via Giustiniani 3, 35128 Padova, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Giannunzio
authors.affiliation: IRCCS Istituto San Camillo, Venezia, Italy; Memory Clinic and LANVIE - Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Battista Frisoni
authors.affiliation: Psychiatric Clinic, Department of Neurosciences, University of Padova, Via Giustiniani 3, 35128 Padova, Italy; Centro di Neuroscienze Cognitive, Università di Padova, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Santonastaso
mesh_terms: D000293:Adolescent; D000328:Adult; D000679:Amygdala / Q000502:physiology; D001007:Anxiety / Q000235:genetics; D001921:Brain / Q000502:physiology*; D003863:Depression / Q000235:genetics; D056324:Diffusion Tensor Imaging; D005260:Female; D005838:Genotype; D006179:Gyrus Cinguli / Q000502:physiology; D006624:Hippocampus / Q000502:physiology; D006801:Humans; D008016:Life Change Events; D008279:Magnetic Resonance Imaging; D009431:Neural Conduction; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D011699:Putamen / Q000502:physiology; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins
keywords: 5-HTTLPR; Depression; Diffusion tensor imaging; Iowa Gambling Task; Memory bias; Resting state fMRI