title: Internalizing disorders and leukocyte telomere erosion: a prospective study of depression, generalized anxiety disorder and post-traumatic stress disorder.
abstract: There is evidence that persistent psychiatric disorders lead to age-related disease and premature mortality. Telomere length has emerged as a promising biomarker in studies that test the hypothesis that internalizing psychiatric disorders are associated with accumulating cellular damage. We tested the association between the persistence of internalizing disorders (depression, generalized anxiety disorder and post-traumatic stress disorder) and leukocyte telomere length (LTL) in the prospective longitudinal Dunedin Study (n=1037). Analyses showed that the persistence of internalizing disorders across repeated assessments from ages 11 to 38 years predicted shorter LTL at age 38 years in a dose-response manner, specifically in men (β=-0.137, 95% confidence interval (CI): -0.232, -0.042, P=0.005). This association was not accounted for by alternative explanatory factors, including childhood maltreatment, tobacco smoking, substance dependence, psychiatric medication use, poor physical health or low socioeconomic status. Additional analyses using DNA from blood collected at two time points (ages 26 and 38 years) showed that LTL erosion was accelerated among men who were diagnosed with internalizing disorder in the interim (β=-0.111, 95% CI: -0.184, -0.037, P=0.003). No significant associations were found among women in any analysis, highlighting potential sex differences in internalizing-related telomere biology. These findings point to a potential mechanism linking internalizing disorders to accelerated biological aging in the first half of the life course, particularly in men. Because internalizing disorders are treatable, the findings suggest the hypothesis that treating psychiatric disorders in the first half of the life course may reduce the population burden of age-related disease and extend health expectancy.
authors.affiliation: 1] Department of Psychology and Neuroscience, Duke University, Durham, NC, USA [2] Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA.
authors.forename: I
authors.initials: I
authors.lastname: Shalev
authors.affiliation: 1] Department of Psychology and Neuroscience, Duke University, Durham, NC, USA [2] Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA [3] Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA [4] Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College, London, UK.
authors.forename: T E
authors.initials: TE
authors.lastname: Moffitt
authors.affiliation: 1] Department of Pathology, School of Medicine, University of Otago, Dunedin, New Zealand [2] Children's Medical Research Institute, University of Sydney, Wentworthville, NSW, Australia.
authors.forename: A W
authors.initials: AW
authors.lastname: Braithwaite
authors.affiliation: 1] Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College, London, UK [2] Department of Child and Adolescent Psychiatry, Institute of Psychiatry, King's College London, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Danese
authors.affiliation: Department of Pathology, School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: N I
authors.initials: NI
authors.lastname: Fleming
authors.affiliation: 1] Department of Psychology and Neuroscience, Duke University, Durham, NC, USA [2] Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA.
authors.forename: S
authors.initials: S
authors.lastname: Goldman-Mellor
authors.affiliation: 1] Department of Psychology and Neuroscience, Duke University, Durham, NC, USA [2] Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA.
authors.forename: H L
authors.initials: HL
authors.lastname: Harrington
authors.affiliation: 1] Department of Psychology and Neuroscience, Duke University, Durham, NC, USA [2] Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Houts
authors.affiliation: 1] Department of Psychology and Neuroscience, Duke University, Durham, NC, USA [2] Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA.
authors.forename: S
authors.initials: S
authors.lastname: Israel
authors.affiliation: Dunedin Multidisciplinary Health and Development Research Unit, Department of Preventive and Social Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: R
authors.initials: R
authors.lastname: Poulton
authors.affiliation: Department of Paediatrics and Child Health, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: S P
authors.initials: SP
authors.lastname: Robertson
authors.affiliation: 1] Department of Psychology and Neuroscience, Duke University, Durham, NC, USA [2] Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA [3] Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA [4] Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College, London, UK.
authors.forename: K
authors.initials: K
authors.lastname: Sugden
authors.affiliation: 1] Department of Psychology and Neuroscience, Duke University, Durham, NC, USA [2] Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA [3] Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA [4] Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College, London, UK.
authors.forename: B
authors.initials: B
authors.lastname: Williams
authors.affiliation: 1] Department of Psychology and Neuroscience, Duke University, Durham, NC, USA [2] Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA [3] Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA [4] Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Caspi
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000235:genetics / Q000502:physiology; D001008:Anxiety Disorders / Q000235:genetics / Q000503:physiopathology*; D002648:Child; D003866:Depressive Disorder / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000502:physiology*; D008137:Longitudinal Studies; D008297:Male; D011446:Prospective Studies; D012727:Sex Characteristics; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics / Q000503:physiopathology*; D016615:Telomere / Q000378:metabolism*; D055815:Young Adult