title: 5-HTTLPR, anxiety and gender interaction moderates right amygdala volume in healthy subjects.
abstract: Genetic variants within the serotonin transporter gene (5-HTTLPR) impact the neurobiology and risk for anxiety-related behaviours. There are also gender differences in the prevalence of anxiety-related behaviours. Although numerous studies have investigated the influence of 5-HTTLPR genotype on the neural systems involved in emotional regulation, none have investigated how these effects are modulated by gender and anxiety. We investigated this issue using two complementary region of interest-based structural neuroimaging approaches (voxel-based morphometry and Freesurfer) in 138 healthy individuals categorized into 'no anxiety' and 'subclinical anxiety' groups based on the Hamilton Rating Scale for Anxiety (HAM-A). Preliminarily, using anxiety as a continuous variable, we found a significant interaction effect of genotype by gender on anxiety. Females homozygous for the Short allele showed the highest HAM-A scores and males the lowest. In addition, a three-way significant interaction among genotype, gender and anxiety category was found for the right amygdala volume. Post hoc tests revealed that homozygous females carrying the Short variant with a subclinical anxiety condition had larger volume. The reported interaction effects demonstrate that gender strongly modulates the relationship between 5-HTTLPR genotype and subclinical expression of anxiety acting on amygdala, one region of the emotional neural network specifically involved in the anxiety-like behaviours.
authors.affiliation: Neuroimaging Research Unit, Institute of Neurological Sciences, National Research Council, 88100 - Catanzaro, Institute of Neurology, University 'Magna Graecia', 88100 - Catanzaro, Neuropsychiatry Laboratory and Clinical and Behavioural Neurology Laboratory, IRCCS Santa Lucia Foundation, Via Ardeatina, 306 - 00179 - Rome, Institute of Neurological Sciences, National Research Council, 88100 - Catanzaro, Ne.S.M.O.S. Department, 'Sapienza' University, II Faculty of Medicine, 00189 - Rome and Department of Neuroscience, Tor 'Vergata' University, 00133 - Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cerasa
authors.affiliation: Neuroimaging Research Unit, Institute of Neurological Sciences, National Research Council, 88100 - Catanzaro, Institute of Neurology, University 'Magna Graecia', 88100 - Catanzaro, Neuropsychiatry Laboratory and Clinical and Behavioural Neurology Laboratory, IRCCS Santa Lucia Foundation, Via Ardeatina, 306 - 00179 - Rome, Institute of Neurological Sciences, National Research Council, 88100 - Catanzaro, Ne.S.M.O.S. Department, 'Sapienza' University, II Faculty of Medicine, 00189 - Rome and Department of Neuroscience, Tor 'Vergata' University, 00133 - Rome, Italy Neuroimaging Research Unit, Institute of Neurological Sciences, National Research Council, 88100 - Catanzaro, Institute of Neurology, University 'Magna Graecia', 88100 - Catanzaro, Neuropsychiatry Laboratory and Clinical and Behavioural Neurology Laboratory, IRCCS Santa Lucia Foundation, Via Ardeatina, 306 - 00179 - Rome, Institute of Neurological Sciences, National Research Council, 88100 - Catanzaro, Ne.S.M.O.S. Department, 'Sapienza' University, II Faculty of Medicine, 00189 - Rome and Department of Neuroscience, Tor 'Vergata' University, 00133 - Rome, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Quattrone
authors.affiliation: Neuroimaging Research Unit, Institute of Neurological Sciences, National Research Council, 88100 - Catanzaro, Institute of Neurology, University 'Magna Graecia', 88100 - Catanzaro, Neuropsychiatry Laboratory and Clinical and Behavioural Neurology Laboratory, IRCCS Santa Lucia Foundation, Via Ardeatina, 306 - 00179 - Rome, Institute of Neurological Sciences, National Research Council, 88100 - Catanzaro, Ne.S.M.O.S. Department, 'Sapienza' University, II Faculty of Medicine, 00189 - Rome and Department of Neuroscience, Tor 'Vergata' University, 00133 - Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Piras
authors.affiliation: Neuroimaging Research Unit, Institute of Neurological Sciences, National Research Council, 88100 - Catanzaro, Institute of Neurology, University 'Magna Graecia', 88100 - Catanzaro, Neuropsychiatry Laboratory and Clinical and Behavioural Neurology Laboratory, IRCCS Santa Lucia Foundation, Via Ardeatina, 306 - 00179 - Rome, Institute of Neurological Sciences, National Research Council, 88100 - Catanzaro, Ne.S.M.O.S. Department, 'Sapienza' University, II Faculty of Medicine, 00189 - Rome and Department of Neuroscience, Tor 'Vergata' University, 00133 - Rome, Italy.
authors.forename: Graziella
authors.initials: G
authors.lastname: Mangone
authors.affiliation: Neuroimaging Research Unit, Institute of Neurological Sciences, National Research Council, 88100 - Catanzaro, Institute of Neurology, University 'Magna Graecia', 88100 - Catanzaro, Neuropsychiatry Laboratory and Clinical and Behavioural Neurology Laboratory, IRCCS Santa Lucia Foundation, Via Ardeatina, 306 - 00179 - Rome, Institute of Neurological Sciences, National Research Council, 88100 - Catanzaro, Ne.S.M.O.S. Department, 'Sapienza' University, II Faculty of Medicine, 00189 - Rome and Department of Neuroscience, Tor 'Vergata' University, 00133 - Rome, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Magariello
authors.affiliation: Neuroimaging Research Unit, Institute of Neurological Sciences, National Research Council, 88100 - Catanzaro, Institute of Neurology, University 'Magna Graecia', 88100 - Catanzaro, Neuropsychiatry Laboratory and Clinical and Behavioural Neurology Laboratory, IRCCS Santa Lucia Foundation, Via Ardeatina, 306 - 00179 - Rome, Institute of Neurological Sciences, National Research Council, 88100 - Catanzaro, Ne.S.M.O.S. Department, 'Sapienza' University, II Faculty of Medicine, 00189 - Rome and Department of Neuroscience, Tor 'Vergata' University, 00133 - Rome, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Fagioli
authors.affiliation: Neuroimaging Research Unit, Institute of Neurological Sciences, National Research Council, 88100 - Catanzaro, Institute of Neurology, University 'Magna Graecia', 88100 - Catanzaro, Neuropsychiatry Laboratory and Clinical and Behavioural Neurology Laboratory, IRCCS Santa Lucia Foundation, Via Ardeatina, 306 - 00179 - Rome, Institute of Neurological Sciences, National Research Council, 88100 - Catanzaro, Ne.S.M.O.S. Department, 'Sapienza' University, II Faculty of Medicine, 00189 - Rome and Department of Neuroscience, Tor 'Vergata' University, 00133 - Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Girardi
authors.affiliation: Neuroimaging Research Unit, Institute of Neurological Sciences, National Research Council, 88100 - Catanzaro, Institute of Neurology, University 'Magna Graecia', 88100 - Catanzaro, Neuropsychiatry Laboratory and Clinical and Behavioural Neurology Laboratory, IRCCS Santa Lucia Foundation, Via Ardeatina, 306 - 00179 - Rome, Institute of Neurological Sciences, National Research Council, 88100 - Catanzaro, Ne.S.M.O.S. Department, 'Sapienza' University, II Faculty of Medicine, 00189 - Rome and Department of Neuroscience, Tor 'Vergata' University, 00133 - Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Muglia
authors.affiliation: Neuroimaging Research Unit, Institute of Neurological Sciences, National Research Council, 88100 - Catanzaro, Institute of Neurology, University 'Magna Graecia', 88100 - Catanzaro, Neuropsychiatry Laboratory and Clinical and Behavioural Neurology Laboratory, IRCCS Santa Lucia Foundation, Via Ardeatina, 306 - 00179 - Rome, Institute of Neurological Sciences, National Research Council, 88100 - Catanzaro, Ne.S.M.O.S. Department, 'Sapienza' University, II Faculty of Medicine, 00189 - Rome and Department of Neuroscience, Tor 'Vergata' University, 00133 - Rome, Italy Neuroimaging Research Unit, Institute of Neurological Sciences, National Research Council, 88100 - Catanzaro, Institute of Neurology, University 'Magna Graecia', 88100 - Catanzaro, Neuropsychiatry Laboratory and Clinical and Behavioural Neurology Laboratory, IRCCS Santa Lucia Foundation, Via Ardeatina, 306 - 00179 - Rome, Institute of Neurological Sciences, National Research Council, 88100 - Catanzaro, Ne.S.M.O.S. Department, 'Sapienza' University, II Faculty of Medicine, 00189 - Rome and Department of Neuroscience, Tor 'Vergata' University, 00133 - Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Caltagirone
authors.affiliation: Neuroimaging Research Unit, Institute of Neurological Sciences, National Research Council, 88100 - Catanzaro, Institute of Neurology, University 'Magna Graecia', 88100 - Catanzaro, Neuropsychiatry Laboratory and Clinical and Behavioural Neurology Laboratory, IRCCS Santa Lucia Foundation, Via Ardeatina, 306 - 00179 - Rome, Institute of Neurological Sciences, National Research Council, 88100 - Catanzaro, Ne.S.M.O.S. Department, 'Sapienza' University, II Faculty of Medicine, 00189 - Rome and Department of Neuroscience, Tor 'Vergata' University, 00133 - Rome, Italy g.spalletta@hsantalucia.it.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Spalletta
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000679:Amygdala / Q000473:pathology*; D000704:Analysis of Variance; D001007:Anxiety / Q000235:genetics* / Q000473:pathology; D016009:Chi-Square Distribution; D005260:Female; D007839:Functional Laterality / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012727:Sex Characteristics; D013223:Statistics as Topic; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins
keywords: 5-HTTLPR genotype; amygdala; anterior cingulate cortex; anxiety; cortical thickness; gender