Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Sep 8;12(9):e0184382.
doi: 10.1371/journal.pone.0184382. eCollection 2017.

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

Basar Cenik  1 , Can Cenik  2 , Michael P Snyder  2 , E Sherwood Brown  1
Affiliations

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

Basar Cenik et al. PLoS One. .

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.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Dr. Brown has been funded by the NIH, the Stanley Medical Research Institute and Dreyfus Health Foundation and received an honorarium from Genentech. Dr. Snyder is co-founder and a member of the scientific advisory board (SAB) of Personalis and a member of the SAB of Genapsys. Dr. B. Cenik and Dr. C. Cenik report no financial conflicts of interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Pre-specified data analysis flowchart.
The models S, D, and F are further specified in Table 4. QIDS, Quick Inventory of Depressive Symptomatology-Self Report.
Fig 2
Fig 2. Unbiased feature selection using a recursive elimination method.
A total of 34 sterol concentration measurements and 9 demographic parameters were used to predict QIDS-SR16 scores from 3117 subjects. A repeated cross-validation approach is used such that data is partitioned into test and training sets via resampling. Performance as measured by percent variation explained as a function of the number of features used in training the RFM is shown.
Fig 3
Fig 3. Nineteen variables comprising Model F.
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.
Fig 4
Fig 4. Correlation of QIDS-SR16 scores with 7-DHC and desmosterol concentrations.
(a), 7-DHC; (b), desmosterol. Blue dashed line indicates QIDS-SR16 score of 10.5, red dashed line indicates 95th percentile for 7-DHC and 5th percentile for desmosterol concentrations. Each gray circle indicates one data point.
Fig 5
Fig 5. Hypothetical model of sterol derangements in depression.
Arrows summarize main findings of the study (Table 6): Desmosterol concentrations are negatively correlated with depressive symptoms and low (<5th percentile) desmosterol concentrations predict moderate to severe depressive symptoms. 7-DHC concentrations above the 95th 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 p values for multiple comparisons).
See this image and copyright information in PMC

References

    1. Moussavi S, Chatterji S, Verdes E, Tandon A, Patel V, Ustun B. Depression, chronic diseases, and decrements in health: results from the World Health Surveys. Lancet. 2007;370(9590):851–8. doi: 10.1016/S0140-6736(07)61415-9 . - DOI - PubMed
    1. Hasler G. Pathophysiology of depression: do we have any solid evidence of interest to clinicians? World Psychiatry. 2010;9(3):155–61. ; PubMed Central PMCID: PMCPMC2950973. - PMC - PubMed
    1. Huang TL, Lin CC. Advances in biomarkers of major depressive disorder. Advances in clinical chemistry. 2015;68:177–204. doi: 10.1016/bs.acc.2014.11.003 . - DOI - PubMed
    1. Beasley CL, Honer WG, Bergmann K, Falkai P, Lutjohann D, Bayer TA. Reductions in cholesterol and synaptic markers in association cortex in mood disorders. Bipolar disorders. 2005;7(5):449–55. doi: 10.1111/j.1399-5618.2005.00239.x . - DOI - PubMed
    1. Boscarino JA, Erlich PM, Hoffman SN. Low serum cholesterol and external-cause mortality: potential implications for research and surveillance. Journal of psychiatric research. 2009;43(9):848–54. doi: 10.1016/j.jpsychires.2008.11.007 . - DOI - PubMed