title: Associations between serotonin transporter and behavioral traits and diagnoses related to anxiety.
abstract: The role of the serotonin transporter promoter-linked polymorphism (5-HTTLPR) in psychiatric disease remains unclear. Behavioral traits could serve as alternative outcomes that are stable, precede psychopathology, and capture more sub-clinical variation. We test associations between 5-HTTLPR and (1) behavioral traits and (2) clinical diagnoses of anxiety and depression. Second and third generation participants (N=203, 34.2±13.8 years, 54% female) at high- or low- familial risk for depression (where risk was defined by the presence of major depression in the 1st generation) were assessed longitudinally using the Schedule for Affective Disorders and Schizophrenia-lifetime interview, Barratt Impulsiveness Scale-11, Buss-Perry Aggression Questionnaire, and the NEO-Five Factor Inventory. High (but not low)-risk offspring with two risk (short, s) alleles had higher impulsivity (+13%), hostility (+31%) and neuroticism (+23%). SS was associated higher rates of panic (OR=7.05 [2.44, 20.38], p=0.0003) and phobic (OR=2.68[1.04, 6.93], p=0.04), but not other disorders. Impulsivity accounted for 16% of associations between 5-HTTLPR and panic, and 52% of association between 5-HTTLPR and phobias. We show that 5-HTTLPR predicts higher impulsivity, hostility, and neuroticism, and that impulsivity could serve as a useful independent outcome or intermediary phenotype in genetic studies of anxiety.
authors.affiliation: Department of Psychiatry, Columbia University Medical Center, New York, NY, USA; Division of Epidemiology, New York State Psychiatric Institute, New York, NY, USA; Sackler Institute for Developmental Psychobiology, Columbia University, New York, NY, USA. Electronic address: talatia@nyspi.columbia.edu.
authors.forename: Ardesheer
authors.initials: A
authors.lastname: Talati
authors.affiliation: Division of Epidemiology, New York State Psychiatric Institute, New York, NY, USA. Electronic address: zdodgerel@yahoo.com.
authors.forename: Zagaa
authors.initials: Z
authors.lastname: Odgerel
authors.affiliation: Department of Psychiatry, Columbia University Medical Center, New York, NY, USA; Division of Epidemiology, New York State Psychiatric Institute, New York, NY, USA; Departments of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA. Electronic address: wickramp@nyspi.columbia.edu.
authors.forename: Priya J
authors.initials: PJ
authors.lastname: Wickramaratne
authors.affiliation: Department of Psychiatry, Columbia University Medical Center, New York, NY, USA. Electronic address: Norcini@nyspi.columbia.edu.
authors.forename: Andrea
authors.initials: A
authors.lastname: Norcini-Pala
authors.affiliation: Division of Epidemiology, New York State Psychiatric Institute, New York, NY, USA. Electronic address: skipper@nyspi.columbia.edu.
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Skipper
authors.affiliation: Department of Psychiatry, Columbia University Medical Center, New York, NY, USA; Division of Epidemiology, New York State Psychiatric Institute, New York, NY, USA; Departments of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA. Electronic address: jag46@columbia.edu.
authors.forename: Jay A
authors.initials: JA
authors.lastname: Gingrich
authors.affiliation: Department of Psychiatry, Columbia University Medical Center, New York, NY, USA; Division of Epidemiology, New York State Psychiatric Institute, New York, NY, USA; Departments of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA; Sackler Institute for Developmental Psychobiology, Columbia University, New York, NY, USA. Electronic address: mmw3@columbia.edu.
authors.forename: Myrna M
authors.initials: MM
authors.lastname: Weissman
mesh_terms: D000293:Adolescent; D000328:Adult; D000374:Aggression; D000483:Alleles; D001007:Anxiety / Q000235:genetics*; D001008:Anxiety Disorders / Q000235:genetics*; D002648:Child; D003863:Depression / Q000235:genetics; D003865:Major Depressive Disorder / Q000235:genetics; D005190:Family / Q000523:psychology*; D005260:Female; D005838:Genotype; D006791:Hostility; D006801:Humans; D007175:Impulsive Behavior; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins