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. 2023 Jun 10;13(1):198.
doi: 10.1038/s41398-023-02484-5.

Metabolomics signatures of depression: the role of symptom profiles

Hilde de Kluiver  1   2 , Rick Jansen  1   2   3 , Brenda W J H Penninx  1   2   3 , Erik J Giltay  4 , Robert A Schoevers  5 , Yuri Milaneschi  6   7   8
Affiliations

Metabolomics signatures of depression: the role of symptom profiles

Hilde de Kluiver et al. Transl Psychiatry. .

Abstract

Depression shows a metabolomic signature overlapping with that of cardiometabolic conditions. Whether this signature is linked to specific depression profiles remains undetermined. Previous research suggested that metabolic alterations cluster more consistently with depressive symptoms of the atypical spectrum related to energy alterations, such as hyperphagia, weight gain, hypersomnia, fatigue and leaden paralysis. We characterized the metabolomic signature of an "atypical/energy-related" symptom (AES) profile and evaluated its specificity and consistency. Fifty-one metabolites measured using the Nightingale platform in 2876 participants from the Netherlands Study of Depression and Anxiety were analyzed. An 'AES profile' score was based on five items of the Inventory of Depressive Symptomatology (IDS) questionnaire. The AES profile was significantly associated with 31 metabolites including higher glycoprotein acetyls (β = 0.13, p = 1.35*10-12), isoleucine (β = 0.13, p = 1.45*10-10), very-low-density lipoproteins cholesterol (β = 0.11, p = 6.19*10-9) and saturated fatty acid levels (β = 0.09, p = 3.68*10-10), and lower high-density lipoproteins cholesterol (β = -0.07, p = 1.14*10-4). The metabolites were not significantly associated with a summary score of all other IDS items not included in the AES profile. Twenty-five AES-metabolites associations were internally replicated using data from the same subjects (N = 2015) collected at 6-year follow-up. We identified a specific metabolomic signature-commonly linked to cardiometabolic disorders-associated with a depression profile characterized by atypical, energy-related symptoms. The specific clustering of a metabolomic signature with a clinical profile identifies a more homogenous subgroup of depressed patients at higher cardiometabolic risk, and may represent a valuable target for interventions aiming at reducing depression's detrimental impact on health.

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Conflict of interest statement

BWJHP has received research funding (unrelated to the work reported here) from Jansen Research and Boehringer Ingelheim and declare no competing interests. HdK, RJ, EJG, RS, and YM declare no competing interests.

Figures

Fig. 1
Fig. 1. Baseline associations of 51 metabolomic markers with the atypical, energy symptom profile and with the other-IDS symptoms severity.
Standardized estimates and 95% confidence intervals from linear regression models. Red: atypical, energy-related symptom profile; blue: other-IDS symptoms severity. Filled indicators indicate significant associations at False Discovery Rate <5%.
Fig. 2
Fig. 2. Associations between individual atypical, energy-related symptoms and 31 metabolomic markers.
Standardized estimates from linear regression models. Five left columns: individual atypical, energy-related symptoms; right column: atypical, energy-related symptom profile.
Fig. 3
Fig. 3. Metabolite levels difference of depressed cases with low and high atypical, energy-related symptom profiles versus healthy controls.
Estimated mean differences and 95% confidence intervals of metabolite levels from general linear model. Reference group: healthy controls. Depressed cases stratified in high (purple indicators) and low (orange indicators) atypical, energy-related symptom profile scores. Filled indicators indicate a significant difference (p < .05) from healthy controls.
Fig. 4
Fig. 4. Six-year follow-up associations of 31 metabolomic markers with the atypical, energy symptom related profile and with the other-IDS symptoms severity.
Standardized estimates and 95% confidence intervals from linear regression models. Red: atypical, energy-related symptom profile; blue: other-IDS items symptoms severity. Filled indicators indicate significant associations at False Discovery Rate <5%.
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References

    1. Vancampfort D, Mitchell AJ, De Hert M, Sienaert P, Probst M, Buys R, et al. Type 2 diabetes in patients with major depressive disorder: a meta-analysis of prevalence estimates and predictors. Depress Anxiety. 2015;32:763–73. doi: 10.1002/da.22387. - DOI - PubMed
    1. Milaneschi Y, Simmons WK, van Rossum EFC, Penninx BW. Depression and obesity: evidence of shared biological mechanisms. Mol Psychiatry. 2019;24:18–33. doi: 10.1038/s41380-018-0017-5. - DOI - PubMed
    1. Penninx BWJH. Depression and cardiovascular disease: epidemiological evidence on their linking mechanisms. Neurosci Biobehav Rev. 2017;74:277–86. doi: 10.1016/j.neubiorev.2016.07.003. - DOI - PubMed
    1. Bot M, Milaneschi Y, Al-Shehri T, Amin N, Garmaeva S, Onderwater GLJ, et al. Metabolomics profile in depression: a pooled analysis of 230 metabolic markers in 5283 cases with depression and 10,145 controls. Biol Psychiatry. 2020;87:409–18. doi: 10.1016/j.biopsych.2019.08.016. - DOI - PMC - PubMed
    1. Ahola-Olli AV, Mustelin L, Kalimeri M, Kettunen J, Jokelainen J, Auvinen J, et al. Circulating metabolites and the risk of type 2 diabetes: a prospective study of 11,896 young adults from four Finnish cohorts. Diabetologia. 2019;62:2298–309. doi: 10.1007/s00125-019-05001-w. - DOI - PMC - PubMed

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