Almost 20% of women are affected by minor or major depression during pregnancy and the first three months postpartum (PP) (O'Hara & Wisner, 2014), which is often accompanied by severe anxiety (American Psychiatric Association, 2013). Perinatal depression (PND) and anxiety represent significant complications of pregnancy and the PP period (O'Hara & Wisner, 2014), since they are associated with adverse birth outcomes including preterm birth and low birth weight, unfavorable infant health outcomes (Dadi et al., 2022), delayed cognitive and behavioral child development as well as a risk for maternal suicide (Van Niel & Payne, 2020). First-line treatment for pregnant or lactating mothers with less severe depression or anxiety are nonpharmacological approaches including cognitive behavioral or interpersonal psychotherapy (Robakis & Williams, 2013). In more severe cases nonpharmacological approaches can be complemented by pharmacotherapy, however remission/response rates to commonly used anti-depressants, such as serotonin reuptake inhibitors (SRIs), but also more novel pharmaceutical substances including γ-aminobutyric acid sub-type A receptor modulator range around 40-80% in postpartum depression (PPD), suggesting that they are not sufficiently effective in a considerable proportion of patients (Deligiannidis et al., 2021, Gerbasi et al., 2021, Robakis and Williams, 2013). This need for alternative therapy options gives rise to more in-depth examinations of the understanding of perinatal depression and anxiety. Several risk factors for PND were identified, such as inflammation, estrogen excess, progesterone resistance, absence of breastfeeding, skin-to-skin contact or social contact (Levin & Ein-Dor, 2023). However, most importantly, a precipitant for PND that was even included into the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DMS-5) definition was the presence of stressful life events (American Psychiatric Association, 2013).

The World Health Organization defines stress as a “state of worry or mental tension caused by a difficult situation” (Organization, 2023). It is a vital reaction of the body to danger with the hypothalamic-pituitary-adrenal (HPA) axis as its key regulatory pathway (Russell & Lightman, 2019). Activation of the HPA axis starts with the secretion of corticotropin-releasing factor (CRF) from the hypothalamus inducing adrenocorticotropic hormone (ACTH) excretion from the anterior pituitary, which in turn stimulates release of glucocorticoids, including most importantly cortisol, from the zona fasciculata of the adrenal cortex into the blood (James et al., 2023). Cortisol inhibits CRF and ACTH secretion from the central nervous system, thus the HPA axis functions in a negative feedback manner (James et al., 2023) but is also modulated by other factors such as oxytocin, which is released by the hypothalamus and pituitary as well and able to suppress the HPA axis (Takayanagi & Onaka, 2021). Although stress from an evolutionary point of view is crucial to respond to threats, it can affect body and mind negatively, especially when persisting for a long period of time (Ernst, 2022). Chronic stress leads to abnormal regulatory mechanisms involving hypothalamic, pituitary and adrenal activity resulting in long-term non-physiological levels of cortisol causing poor cognitive, metabolic and immune functions (Russell & Lightman, 2019). Accordingly, measurement of stress can be performed based on the biological perspective on stress, by assessing the activation of the physiological systems involved in the stress response (Lee, 2012). However, in addition stress can be classified based on two additional perspectives: From the environmental perspective on stress research focuses on stressors or stressful life events (SLE), while from the psychological perspective stress is assessed by examining subjective stress appraisal and affective reactions (Lee, 2012) most commonly using the “Perceived Stress Scale (PSS)” (Cohen et al., 1983).

Although stress was identified as a crucial risk factor for PND and numerous studies were performed examining its role in the development and maintenance of perinatal depression and anxiety, their results have not been systematically brought together and evaluated in order to create an overview of the literature. Thus, in this systematic review we aimed to include all relevant research articles to illustrate the role of biological as well as environmental and psychological stress in perinatal depression and anxiety as well as to identify gaps in current knowledge to foster further research.