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

<div><p>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.</p></div

Correlation of QIDS-SR₁₆ scores with 7-DHC and desmosterol concentrations.

<p>(a), 7-DHC; (b), desmosterol. Blue dashed line indicates QIDS-SR₁₆ score of 10.5, red dashed line indicates 95^th percentile for 7-DHC and 5^th percentile for desmosterol concentrations. Each gray circle indicates one data point.</p

Nineteen variables comprising Model F.

<p>Parameters selected from a pool of 43 demographic or general health variables and sterol concentrations by a feature selection algorithm based on explained variation in QIDS-SR16 scores is shown, ranked by importance judged by the percent increase in mean squared error metric.</p

Hypothetical model of sterol derangements in depression.

<p>Arrows summarize main findings of the study (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0184382#pone.0184382.t006" target="_blank">Table 6</a>): Desmosterol concentrations are negatively correlated with depressive symptoms and low (<5^th percentile) desmosterol concentrations predict moderate to severe depressive symptoms. 7-DHC concentrations above the 95^th percentile also predict moderate to severe depressive symptoms. 14-Desmethyl lanosterol concentrations trend towards a negative correlation with depressive symptoms (not statistically significant after correction of <i>p</i> values for multiple comparisons).</p

Summary of random forest models.

<p>Summary of random forest models.</p

Pre-specified data analysis flowchart.

<p>The models S, D, and F are further specified in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0184382#pone.0184382.t004" target="_blank">Table 4</a>. QIDS, Quick Inventory of Depressive Symptomatology-Self Report.</p

Characteristics of study population.

<p>Characteristics of study population.</p

Mean scores and standard deviations for 9 items comprising the QIDS-SR₁₆.

<p>Mean scores and standard deviations for 9 items comprising the QIDS-SR₁₆.</p

Odds ratios and correlation coefficients for six of the 13 sterols picked by feature selection.

<p>Odds ratios and correlation coefficients for six of the 13 sterols picked by feature selection.</p

34 plasma sterols and lipoproteins investigated in this study.

<p>34 plasma sterols and lipoproteins investigated in this study.</p