By Chiara Ghetti, MD

Associate Professor, Obstetrics and Gynecology, Division of Female Pelvic Medicine and Reconstructive Surgery, Washington University School of Medicine, St. Louis

Dr. Ghetti reports no financial relationships relevant to this field of study.

SYNOPSIS: The number and timing of adverse childhood experiences in relation to puberty affect the risk of incident major depressive disorder in menopausal transition.

SOURCE: Epperson CN, Sammel MD, Bale TL, et al. Adverse childhood experiences and risk for first-episode major depression during the menopause transition. J Clin Psychiatry 2017;78:e298-e307.

The objective of this study was to determine the effect of early-life stress on the risk of having a first episode of major depressive disorder (MDD) during the menopause transition (incident depression) among participants in the Penn Ovarian Aging Study (POAS). In addition, the study authors explored whether the timing of adverse childhood experiences (ACEs) in relationship to puberty affects the risk of lifetime MDD and incident MDD at time of the menopausal transition. This was a cohort study of the POAS group, which is a population-based longitudinal set of cycling premenopausal women between the ages of 35 and 47 years. The cohort initially was identified by random-digit dialing in Philadelphia County, PA, in 1996-1997, and was stratified to obtain equal numbers of white and African-American women. Exclusion criteria included hysterectomy, the use of hormonal contraception or psychotropic medication, the presence of a serious health problem, or alcohol or drug abuse in the previous year. The initial cohort consisted of 436 women. The current study is the analysis of 293 women who remained active in the cohort between June 2012 and August 2012. The main outcomes included: menopausal status obtained by menstrual diaries; ACE, measured using the ACE-Q questionnaire; and history of major depression diagnosis and depressive symptoms, as measured by Center for Epidemiologic Studies Depression (CES-D) scale scores.

The ACE-Q focuses on three general categories of childhood adversity (abuse, neglect, and household/family dysfunction), which are divided into subcategories that include physical, sexual, and emotional abuse; emotional and physical neglect; parental separation; household violence; parental substance abuse or psychiatric disorders; and household member in prison. A CES-D score of 16 corresponds to a clinically meaningful level of depressive symptoms, while a score of 25 is suggestive of a clinical diagnosis of MDD. Of the women active in the POAS in the cohort, 243 had completed ACE-Q data. The mean age of these women was 41.6 years, and 47% were African American, with the remainder Caucasian. Forty percent of women had not experienced an ACE, 22% had experienced one ACE, and 38% had experienced two or more ACEs. Most ACEs occurred in the prepubertal window. Groups with high vs. low ACEs differed by race, with African-American women more likely to be in the high ACE group. Women with two or more postpubertal ACEs were significantly more likely to exhibit baseline CES-D scores 16 or 25 and body mass index (BMI) 30 kg/m2. Of the women at risk for incident menopause MDD, 22.4% were diagnosed with MDD during premenopause, while 20.7% had incident menopause MDD. In logistic regression models adjusted for race, smoking, BMI 30 kg/m2, and employment status, subjects with two or more ACEs, compared to subjects with no ACE, were two times more likely to experience a lifetime MDD and incident menopause MDD. Women with two or more postpubertal ACEs were at greater risk of incident menopause MDD but not lifetime MDD when compared to those with no postpubertal ACEs. Women who reported one ACE had significantly reduced MDD risk compared to women who reported two or more ACEs.


Major depression is very prevalent and is a leading cause for disability. The World Health Organization has ranked depression the fourth leading cause of disability worldwide, estimating that it will be the second leading cause by 2020.1,2 Lifetime prevalence estimates vary worldwide and are estimated to be 16.9% but are as high as 21% in the United States.1,2,3 Women are at higher risk for MDD and are more susceptible during certain reproductive milestones. Obstetricians may be most familiar with postpartum depression. However, depression also is common in young women and in women during the menopausal transition. Women with no prior history of depression are two to three times more likely to experience a first episode of depression during perimenopause and early menopause.4,5 Although a role of childhood adversity has been established in mood disorders, this is the first study of the role of childhood adversity and the onset of MDD during the menopausal transition.

Chapman et al found that exposure to ACEs was associated with an increased risk of adult depressive disorders and established the role of childhood adversity in major depression.6 In their study, the most commonly reported adverse experiences were household substance, physical, and sexual abuse, with emotional abuse posing the largest risk for lifetime or recent depression among women. Limitations include the inability to provide more details about specific ACEs. This study includes some data points that may be influenced by recall bias. In addition, Chapman et al were not able to explore the relationships between depression, ACE, and hormone therapy.

Epperson et al built on prior work and established a link between childhood adversity and increased risk of depression in women experiencing the menopausal transition decades after the ACEs. This provides another window into the relationship of depression, stress, and hormonal fluctuations. Although they did not discuss the clinical management of depression, the discussion further underscores the lasting effect of childhood trauma and its role in adult depression, even during the menopausal transition.7,8,9 As clinicians, awareness of the relationship between trauma and depression may aid us to better care for women with depression throughout the lifespan.


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