PT  - JOURNAL ARTICLE
AU  - Marie-Laure Ancelin
AU  - Joanna Norton
AU  - Karen Ritchie
AU  - Isabelle Chaudieu
AU  - Joanne Ryan
TI  - 11β-Hydroxylase (<em>CYP11B1</em>) gene variants and new-onset depression in later life
AID  - 10.1503/jpn.190177
DP  - 2021 Jan 01
TA  - Journal of Psychiatry and Neuroscience
PG  - E147--E153
VI  - 46
IP  - 1
4099  - http://jpn.ca/content/46/1/E147.short
4100  - http://jpn.ca/content/46/1/E147.full
SO  - JPN2021 Jan 01; 46
AB  - 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 sex-specific 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.