Aromatase ( CYP19A1 ) gene variants, sex steroid levels, and late‐life depression

Abstract

Background: Sex differences in psychiatric disorders are common and could involve sex steroids. Aromatase, the product of the CYP19A1 gene, is the key enzyme in the conversion of androgen to estrogen. Whether CYP19A1 variants could be associated with depression differently in men and women has not been examined.Methods: This population-based study included 405 men and 602 women aged ≥65 years. A clinical level of depression (DEP) was defined as having a score ≥16 on the Center for Epidemiology Studies Depression scale or a diagnosis of current major depression based on the Mini-International Neuropsychiatric Interview and according to DSM-IV criteria. Seven single-nucleotide polymorphisms (SNPs)spanning the CYP19A1 gene were genotyped and circulating levels of estradiol and testosterone were determined. Multivariable analyses were adjusted for age, body mass index, ischemic pathologies, cognitive impairment, and anxiety.Results: Five SNPs were associated with DEP in women specifically and this varied according to a history of major depression (p-values .01 to .0005). Three SNPs were associated with an increased risk of late-life DEP in women without a history of major depression, while two SNPs were associated with a decreased DEP risk in women with a history of major depression and were also associated with higher estradiol levels.Conclusions: Variants of the CYP19A1 gene appear to be susceptibility factors for late-life depression in a sex-specific manner. The polymorphisms decreasing the risk of recurrent depression in postmenopausal women also influence estradiol levels. K E Y W O R D Saromatase, elderly, estradiol, late-life depression, population-based study, sex difference

Solid-Phase Microextraction/Gas Chromatography–Time-of-Flight Mass Spectrometry Approach Combined with Network Pharmacology Analysis to Evaluate the Quality of Agarwood from Different Regions against Anxiety Disorder

“…In Figure 3 , the core genes with a degree value ≥ 20 included CYP19A1, AR, SHBG, UGT2B7, ESR1, and ESR2, which are all relevant to the regulation of estrogens [ 43 , 44 , 45 , 46 , 47 , 48 ]. It is well documented that estrogen might exert profound effects on anxiety and anxiety-like behaviors in humans and rodents [ 49 ].…”

Steroid 21-hydroxylase gene variants and late-life depression

“…In clinical studies, specific alterations in cortisol and sex steroid levels as well as psychiatric disorders were reported in women with 21-hydroxylase deficiency [ 13 ]. In our community-dwelling population of older adults, we have previously shown that variants of the CYP19A1 gene, which codes for aromatase, the key enzyme in the conversion of androgen to estrogen, were susceptibility factors for LLD in women specifically [ 29 ]. We also just reported that variants of the CYP11B1 gene coding for 11-β hydroxylase, the next enzymatic step after CYP21A2 in steroidogenesis pathway, were susceptibility factors for LLD in women [ 30 ].…”

Aromatase in the Human Brain

“…In this regard, it is relevant to mention that some single-nucleotide CYP19A1 polymorphisms increase the risk of late-life depression in women without a previous history of major depression, whereas other variants of the gene, associated with higher estradiol levels, decrease the risk of late-life depression in women with a history of major depression. 61 …”