Perinatal depression (PD) affects 10–20 % of pregnant women, with variable recurrence rates in subsequent pregnancies (Stevens et al., 2019, Peindl et al., 2004, Woody et al., 2017). PD incurs major socio-economic costs (Luca et al., 2020) and predicts adverse long-term consequences for the mother, child and family (Capron et al., 2015, Stein et al., 2014). The mechanisms underlying PD remain poorly understood, however both environmental and genetic risk factors have been implicated (Halbreich, 2005, Payne and Maguire, 2019).

The perinatal period involves major adaptations across almost all biological systems (Aghaeepour et al., 2017, Hoekzema et al., 2017). Notably, this period is marked by substantial fluctuations in steroid hormones, which influence affective states, and may trigger psychiatric disorders in individuals with latent susceptibility. This is supported by experimental evidence highlighting the impact of sex steroid fluctuations on symptoms of depression (Bloch et al., 2000, Frokjaer et al., 2013). Dynamic processes regulating genomic function, including DNA methylation and gene expression, can capture perinatal adaptations and may provide insight into both healthy and pathological states (McKenna et al., 2021, Mehta et al., 2014).

There is an emerging body of research describing functional genomic signatures of PD (Mehta et al., 2014, Luo et al., 2023, Standeven et al., 2020). However, a systematic overview of functional genomic signatures of PD is currently lacking. To address this, we performed a scoping review to describe the current state of knowledge in the field. We focused our review on biomarker studies in peripheral blood for several reasons: 1) blood sampling is minimally invasive and routinely performed in perinatal care; 2) blood-based biomarkers are scalable; 3) peripheral blood enables early risk profiling and better reflects maternal health status compared to placenta or cord-blood (Nemoda et al., 2015, Ponder et al., 2011), which are of fetal origin and only available post-partum; and 4) peripheral blood provides a window on immune function with emerging evidence linking immune dysregulation and depression in non-pregnant cohorts (Milaneschi et al., 2020).

In this scoping review, we describe and synthesize current knowledge on functional genomic signatures of PD as measured in peripheral blood samples. We discuss insights into potential disease mechanisms and evaluate the clinical potential of molecular signatures as biomarkers of PD. Finally, we outline future research directions to advance the field.