By Liisa Hantsoo, Ph.D.
During childhood, the prevalence of depressive disorders is similar in boys and girls. However, following puberty, the prevalence of depressive disorders in women is twice that of men (1,2). Reasons for this are complex, and likely include a combination of social and biological contributors (3–5). Is it possible that women experience a form of depression that is biologically distinct from “plain vanilla” major depression? Intriguingly, women are particularly vulnerable to depressive symptoms at times of sex steroid hormone fluctuation, including premenstrually, perinatally, and perimenopausally (6–8). Researchers have long been interested in the potential role of sex hormones, such as estrogen and progesterone, in depressive disorders in women. Some researchers propose that there may be biological subtypes of depression, each with its own signature. One of these subtypes, “reproductive related depression,” may affect women who are vulnerable to fluctuations in sex steroid hormones.
A recent review article looked at the hypothesis that a subset of women experience a biologically distinct form of depression related to fluctuations in sex steroid hormones (9). Specifically, the researchers were interested in whether neuroimaging data might support a unique signature of depression in women. The researchers reviewed functional neuroimaging (fMRI) studies of women experiencing depression at the pubertal transition, in the premenstruum, perinatally, and perimenopausally. The researchers compared brain activation patterns in these female-specific forms of depression with classic major depressive disorder (MDD). The researchers found that striatal deactivation was consistent across the reproductive subtypes of depression, which is also characteristic of MDD. Deactivation of the striatum may therefore be a marker of depression in general. However, the medial prefrontal cortex and insula activation patterns seen in premenstrual dysphoric disorder (PMDD) and perinatal depression (PD) were quite distinct from the typical MDD patterns. The amygdala also showed a dysregulated activation pattern in PMDD, and deactivation in PD. This may be because sex steroid hormone receptors are distributed differentially across the brain, with some regions having a higher density of these receptors than others. The researchers proposed that sex steroid hormones may influence function and connectivity of cortico-limbic, prefrontal, and striatal regions in a subgroup of hormone-sensitive women. The researchers concluded that there is some evidence suggesting a “female depression biotype,” but more research is needed to clarify whether these are indeed biologically distinct female-specific forms of depression, with biological underpinnings separate from those of MDD.
References
1. Bromet E, Andrade LH, Hwang I, et al. Cross-national epidemiology of DSM-IV major depressive episode. BMC Med. 2011;9:90. doi:10.1186/1741-7015-9-90
2. Burt VK, Stein K. Epidemiology of depression throughout the female life cycle. J Clin Psychiatry. 2002;63 Suppl 7:9-15.
3. Alloy LB, Hamilton JL, Hamlat EJ, Abramson LY. Pubertal Development, Emotion Regulatory Styles, and the Emergence of Sex Differences in Internalizing Disorders and Symptoms in Adolescence. Clin Psychol Sci. 2016;4(5):867-881. doi:10.1177/2167702616643008
4. Derry HM, Padin AC, Kuo JL, Hughes S, Kiecolt-Glaser JK. Sex Differences in Depression: Does Inflammation Play a Role? Curr Psychiatry Rep. 2015;17(10):78. doi:10.1007/s11920-015-0618-5
5. Nolen-Hoeksema S, Larson J, Grayson C. Explaining the gender difference in depressive symptoms. J Pers Soc Psychol. 1999;77(5):1061-1072.
6. Bromberger JT, Kravitz HM, Chang Y-F, Cyranowski JM, Brown C, Matthews KA. Major depression during and after the menopausal transition: Study of Women’s Health Across the Nation (SWAN). Psychol Med. 2011;41(9):1879-1888. doi:10.1017/S003329171100016X
7. 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(3):298-307. doi:10.4088/JCP.16m10662
8. Freeman EW, Sammel MD, Lin H, Nelson DB. Associations of hormones and menopausal status with depressed mood in women with no history of depression. Arch Gen Psychiatry. 2006;63(4):375-382. doi:10.1001/archpsyc.63.4.375
9. Stickel S, Wagels L, Wudarczyk O, et al. Neural correlates of depression in women across the reproductive lifespan - An fMRI review. J Affect Disord. 2018;246:556-570. doi:10.1016/j.jad.2018.12.133