Towards a major methodological shift in depression research by assessing continuous scores of recurrence of illness, lifetime and current suicidal behaviors and phenome features.

<title>Abstract</title> Background The binary major depressive disorder (MDD) diagnosis is inadequate and should never be used in research. Aims The study's objective is to explicate our novel precision nomothetic strategy for constructing depression models based on adverse childhood experiences (ACEs), lifetime and current phenome, and biomarker (atherogenicity indices) scores. Methods This study assessed recurrence of illness (ROI: namely recurrence of depressive episodes and suicidal behaviors), lifetime and current suicidal behaviors and the phenome of depression, neuroticism, dysthymia, anxiety disorders, and lipid biomarkers (including ApoA, ApoB, free cholesterol and cholesteryl esters, triglycerides, high density lipoprotein cholesterol) in 67 normal controls and 66 MDD patients. We computed atherogenic and reverse cholesterol transport indices. Results We were able to extract one factor from a) the lifetime phenome of depression comprising ROI, and traits such as neuroticism, dysthymia and anxiety disorders, and b) the phenome of the acute phase (based on depression, anxiety and quality of life scores). PLS analysis showed that 55.7% of the variance in the lifetime + current phenome factor was explained by increased atherogenicity, neglect and sexual abuse, while atherogenicity partially mediated the effects of neglect. Cluster analysis generated a cluster of patients with major dysmood disorder, which was externally validated by increased atherogenicity and characterized by increased scores of all clinical features. Conclusions The outcome of depression should not be represented as a binary variable (MDD or not), but rather as multiple dimensional scores based on biomarkers, ROI, subclinical depression traits, and lifetime and current phenome scores including suicidal behaviors.