Plasma sterols and depressive symptom severity in a population-based cohort

Abstract

Convergent evidence strongly suggests major depressive disorder is heterogeneous in its etiology and clinical characteristics. Depression biomarkers hold potential for identifying etiological subtypes, improving diagnostic accuracy, predicting treatment response, and personalization of treatment. Human plasma contains numerous sterols that have not been systematically studied. Changes in cholesterol concentrations have been implicated in suicide and depression, suggesting plasma sterols may be depression biomarkers. Here, we investigated associations between plasma levels of 34 sterols (measured by mass spectrometry) and scores on the Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR16) scale in 3117 adult participants in the Dallas Heart Study, an ethnically diverse, population-based cohort. We built a random forest model using feature selection from a pool of 43 variables including demographics, general health indicators, and sterol concentrations. This model comprised 19 variables, 13 of which were sterol concentrations, and explained 15.5% of the variation in depressive symptoms. Desmosterol concentrations below the fifth percentile (1.9 ng/mL, OR 1.9, 95% CI 1.2–2.9) were significantly associated with depressive symptoms of at least moderate severity (QIDS-SR16 score ≥10.5). This is the first study reporting a novel association between plasma concentrations cholesterol precursors and depressive symptom severity.

Plasma nesfatin-1 level is associated with severity of depression in Chinese depressive patients

“…However, there are no commonly accepted depression biomarkers to improve diagnostic accuracy or to evaluate severity ratings [ 3 ]. Although the cellular and molecular mechanisms underlying the pathophysiology of depression are not been fully elucidated, there have been increasing interests in associations between depression and changes in various biochemical pathways, including inflammatory, neurotrophic and hypothalamic-pituitary-adrenal (HPA) axis alterations [ 4 , 5 ].…”

Desmosterol and 7-dehydrocholesterol concentrations in post mortem brains of depressed people: The role of trazodone

“…Subject characteristics are summarized in Table 1 . Sample size was estimated based on the effect size we had observed in plasma samples in a previous study [ 15 ]. Collection of postmortem brains by the Dallas Brain Collection was approved by UT Southwestern Institutional Review Board.…”

“…Additionally, a putative association between low plasma cholesterol and depression or suicide has been suggested by several lines of investigation [ 9 – 14 ]. In light of these findings, we previously investigated associations between plasma sterols and depressive symptoms in a large, population-based cohort, as potential biomarkers [ 15 ]. We found that lower concentrations of the cholesterol precursor desmosterol and higher concentrations of another precursor, 7-dehydrocholesterol (7DHC), were predictive of moderate to severe depressive symptoms.…”

Medication effects on developmental sterol biosynthesis

“…While endogenous cholesterol synthesis is essential for brain development, intact cholesterol metabolism is also critical for normal functioning of the adult brain ( 19 ). In the elderly, high brain cholesterol is associated with better memory function, while low cholesterol is associated with an increased risk for depression ( 20 , 21 ). Dysfunction of the cholesterol biosynthesis pathways and/or metabolism might contribute to a number of psychiatric and neurodegenerative disorders including major depression, bipolar disorder, schizophrenia, Huntington’s disease, and Alzheimer’s disease ( 22 – 25 ).…”