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Original Research

Association of Adverse Childhood Environment and 5-HTTLPR Genotype With Late-Life Depression

Karen Ritchie, PhD; Isabelle Jaussent, MSc; Robert Stewart, MD, PhD; Anne-Marie Dupuy, MD, PhD; Philippe Courtet, MD, PhD; Marie-Laure Ancelin, PhD; and Alain Malafosse, MD, PhD

Published: June 30, 2009

Article Abstract

Objective: Neurobiological and clinical studies suggest that childhood maltreatment may result in functional and structural nervous system changes that predispose the individual to depression. This vulnerability appears to be modulated by a polymorphism in the serotonin gene-linked promoter region (5-HTTLPR). Little is known, however, about the persistence of this vulnerability across the life span, although clinical studies of adult populations suggest that gene-environment interaction may diminish with aging.

Method: Depressive symptomatology and adverse and protective childhood events were examined in a population of 942 persons aged 65 years and older, taking into account sociodemographic characteristics and proximal competing causes of depression (widowhood, recent life events, vascular and neurologic disorder, and disability). Subjects were recruited between March 1999 and February 2001 and were diagnosed as depressed if they met 1 of 3 criteria: a diagnosis of major depression on the Mini-International Neuropsychiatric Interview, a score higher than 16 on the Center for Epidemiologic Studies-Depression Scale, or current treatment with an antidepressant.

Results: Exposure to traumatic events in childhood doubled the risk of late-life depression and increased the risk of repeated episodes. Not all events were found to be pathogenic; significant risk was associated with excessive sharing of parental problems, poverty or financial difficulties, mental disorder in parents, excessive physical punishment, verbal abuse from parents, humiliation, and mistreatment by an adult outside the family. Interactions were observed between the 5-HTTLPR long (L) allele, poverty, and excessive sharing of parental problems.

Conclusions: Certain types of childhood trauma continue to constitute risk factors for depression in old age, outweighing more proximal causes. Gene environment vulnerability interaction is linked in older age to the L-carrying genotype, modulating the effects of general environmental conditions rather than aggressive acts on the individual, perhaps due to increased cardiac reactivity.

Submitted: July 1, 2008; accepted September 15, 2008.

Online ahead of print: June 30, 2009.

Corresponding author: Karen Ritchie, PhD, Inserm U888 Pathologies of the Nervous System, La Colombière Hospital, 39 Avenue Flahault, BP 34493, 34093 Montpellier Cedex 5, France (

Volume: 70

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