Differential Diagnosis of Major Depressive Disorder and Bipolar Disorder: Genetic and Hormonal Assessment and the Influence of Early-Life Stress

Abstract

Few studies have assessed biomarkers for the differentiation of major depressive disorder (MDD) and bipolar disorder (BD). However, some elements of depression such as hormones and receptors of the renin-angiotensin-adrenal system (RAAS), the hypothalamus-pituitary-adrenal (HPA) axis, and history of early-life stress (ELS) could be considered for differential diagnosis. Therefore, this study aimed to assess aldosterone and cortisol levels, MR and GR gene polymorphisms, and ELS as potential biomarkers for differentiating MDD and BD. This study presents a case-control design. Groups comprised samples for genetic, cortisol, and aldosterone analysis: healthy control (HC; n = 113/97/103), MDD (n = 78/69/67) and BD (n = 82/68/65) subjects. Furthermore, all subjects were assessed for diagnostic screening, the severity of depression, and history of ELS by applying MINI-PLUS, GRID-HDRS, and CTQ, respectively. In addition, genotype and allelic frequencies of GR (N363S, R22/23K and BclI) and MR (MI180V and -2G/C) polymorphisms were evaluated via PCR. Our findings demonstrate that basal aldosterone levels may be a biomarker for differentiating BD and MDD. Furthermore, ELS affects the HPA axis in BD, cortisol may be considered a biomarker for distinguishing BD and MDD, but only in the absence of ELS, and, finally, history of ELS and MR-2G/C variant alleles are factors that contribute to the severity of depressive symptoms in MDD and BD.

Keywords: aldosterone; biomarker; bipolar; cortisol; depression; early-life stress (ELS); glucocorticoid receptor (GR); mineralocorticoid receptor (MR); polymorphism (SNP).

Figure A1

Intensity of depressive symptoms assessed by GRID-HAM-D21. (a) Mean depressive symptoms score of MDD and BD groups, in the absence (white bars) or presence (gray bars) of ELS by intra and intergroup analysis; (b) Mean depressive symptoms score of MDD sample according to genotype (MR-2G/C). Error bars: 95% confidence interval; Note: ELS: early-life stress; GRID-HAM-D21: GRID–Hamilton Depression Rating Scale; * p < 0.05.

Figure 1

Hormonal levels presented in logarithmic scale (Y-axis). (a) Mean cortisol levels in HC, MDD and BD groups, in the presence (white bars) and absence (gray bars) of ELS; (b) mean aldosterone levels in HC, MDD, and BD groups; (c) Mean cortisol levels compared with BclI genotype. Note: BD: bipolar disorder; ELS: early-life stress; HC: health control; MDD: major depression disorder; * p < 0.05; error bars: +/−1 standard error.