Objective: The mechanisms involved in the dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, especially in the functioning of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) in depressed patients, are not well elucidated. The objective of this study was to conduct a systematic review of articles that assess the HPA axis activity from GR and MR in depressed patients and healthy controls with or without early life stress.

Methods: We conducted a systematic review of articles in PubMed, SCOPUS and SciELO published between 2000 and 2011, using the following search terms: child abuse, depression, HPA axis, dexamethasone, prednisolone, fludrocortisone and spironolactone. Thirty-four papers were selected for this review.

Results: Most studies identified in this review used the dexamethasone/corticotropin-releasing hormone test and dexamethasone suppression test. In these studies, hypercortisolaemia was associated with depression. We identified three studies with the Prednisolone suppression test, only one study with the use of fludrocortisone and one with spironolactone. This review found nine studies that evaluated the HPA axis in individuals with early life stress.

Conclusions: The majority of the studies assessed in this review show that early life stress leads to permanent changes in the HPA axis and may lead to development of depression in adults. The most consistent findings in the literature show increased activity of the HPA axis in depression associated with hypercortisolaemia and reduced inhibitory feedback. These findings suggest that this dysregulation of the HPA axis is partially attributable to an imbalance between GR and MR. Evidences have consistently showed that GR function is impaired in major depression, but few studies have assessed the activity of MR in depression and early life stress.

Four studies have found a smaller amygdalar volume in patients with borderline personality disorder (BPD) relative to controls, whereas four other studies have found similar amygdalar volume in BPD patients relative to controls. This study aims to compare amygdalar volumes of BPD patients with controls, and also to compare BPD patients with and without post-traumatic stress disorder (PTSD) with controls in order to determine whether PTSD can explain the heterogeneity of findings.

Systematic review and meta-analysis of magnetic resonance imaging studies that measured amygdalar volumes in BPD patients and healthy controls.

A significant reduction of amygdalar volumes in BPD patients was confirmed (p < .001). However, data from the studies that discriminated BPD patients with and without PTSD indicated that amygdalar volumes were significantly smaller in BPD patients without PTSD relative to controls (left: p = .02; right: p = .05), but not in BPD patients with PTSD relative to controls (left: p = .08; right: p = .20).

This meta-analysis suggests that amygdalar volumes are reduced in patients with BPD. This pattern is confirmed in BPD patients without PTSD, but not in BPD patients with PTSD, raising the possibility that reduced amygdalar volume in BPD patients cannot be explained by comorbid PTSD.