Marie-Laure Ancelin, PhD; Joanna Norton, PhD; Karen Ritchie, PhD; Isabelle Chaudieu, PhD; Joanne Ryan, PhD
Background: Cumulative exposure to high glucocorticoid levels is detrimental for the brain and may have particular implications in later life. A feature of late-life depression is increased cortisol secretion. Variants in the CYP11B1 gene, which codes for the enzyme responsible for cortisol synthesis, could influence risk of late-life depression, but this hypothesis has not been examined. We investigated the associations between variants in the CYP11B1 gene and late-life depression, taking into account history of depression and potential sexspecific effects.
Methods: We assessed depression in 1007 community-dwellers aged 65 years or older (60% women) at baseline and over a 14-year follow-up. A clinical level of depression was defined as a score of ≥ 16 on the Centre for Epidemiology Studies Depression scale or a diagnosis of current major depression based on the Mini-International Neuropsychiatric Interview and according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV). We examined incident and recurrent depression in participants without or with a history of major depression, respectively. We genotyped 5 single-nucleotide polymorphisms (SNPs) spanning CYP11B1. We used multivariable analyses to adjust for age, body mass index, cardiovascular ischemic pathologies, hypertension, cognitive impairment and anxiety.
Results: In women, rs6471580 and rs7016924 were associated with a 50% lower rate of incident (new-onset) late-life depression, and rs11783855 was associated with a 2.4-fold higher rate of late-life depression. These associations remained after correction for multiple testing, but we found no associations for recurrent depression in women or men.
Limitations: This study focused on the major gene involved in corticosteroid biosynthesis, but other genes may also be implicated in this pathway.
Conclusion: Variants of the CYP11B1 gene appear to be susceptibility factors for late-life depression in a sex-specific manner.
Submitted Oct. 24, 2019; Revised Jun. 11, 2020; Accepted Jul. 11, 2020; Early-released Nov. 26, 2020
Affiliations: From Inserm, Université Montpellier, Neuropsychiatry: Epidemiological and Clinical Research, Montpellier, France (Ancelin, Norton, Ritchie, Chaudieu, Ryan); the Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom (Ritchie); and the Biological Neuropsychiatry and Dementia Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia (Ryan).
Competing interests: No competing interests declared.
Contributors: M. Ancelin designed the study. M. Ancelin and K. Ritchie acquired the data, which M. Ancelin, J. Norton, I. Chaudieu and J. Ryan analyzed. M. Ancelin wrote the article, which J. Norton, K. Ritchie, I. Chaudieu and J. Ryan reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.
Funding: The ESPRIT project is financed by the regional government of Languedoc-Roussillon, the Agence Nationale de la Recherche (ANR) Project 07 LVIE 004, and an unconditional grant from Novartis. Joanne Ryan is funded by a Dementia Research Leader fellowship [APP1135727] from the National Health & Medical Research Council (NHMRC), Australia. The funders had no role in the design and conduct of the study; in data collection, management, analysis, interpretation of the data; or writing the report preparation, review, or approval of the manuscript.
Content licence: This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY-NC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is non-commercial (i.e. research or educational use), and no modifications or adaptations are made. See: https://creativecommons.org/licenses/by-nc-nd/4.0/
Correspondence to: M.L. Ancelin, Inserm U1061, Hôpital La Colombière, 39 avenue Flahault, BP 34493, 34093 Montpellier Cedex 5, France; firstname.lastname@example.org