The impact of early life stress on the hypothalamic-pituitary-adrenal axis in unipolar major depression: A systematic review.

BACKGROUND

Patients with major depressive disorder (MDD) tend to have abnormal hypothalamic-pituitary-adrenal axis (HPA) characterized by hypo- or hyperactivity, and early life stress (ELS) events influence the HPA axis, resulting in a heightened risk of depression. We conducted a systematic review evaluating the existing literature to summarise whether the HPA axis abnormalities in MDD are associated with ELS.

METHODS

This review was conducted following the PRISMA framework. In April 2024, searching was conducted on Ovid MEDLINE, Global Health, and APA PsycINFO. Keywords were based on three clusters of constructs: "HPA axis," "MDD," and "ELS." Studies comparing the HPA axis activity in participants with and without unipolar depression and ELS were included. Quality assessment was conducted with the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool.

RESULTS

Among the 17 included studies, 6 examined the naturalistic HPA axis activity, 7 conducted functional tests, and 4 performed psychosocial stress tests. The hypo- and hyperactive HPA axis was observed in most studies in depressed patients with ELS. Depressed patients with ELS and abused controls also manifested abnormal HPA axis activity compared to healthy controls.

CONCLUSION

HPA axis abnormality is associated with depressive pathology, and ELS has an independent effect on the HPA axis. Posttraumatic stress disorder (PTSD) is associated with HPA axis hypoactivity either alone or as an MDD comorbidity. HPA axis hyperactivity in MDD with or without ELS may dampen over time, and an imbalance may implicate HPA axis abnormalities in depressed patients with ELS in the negative feedback.