Hostname: page-component-8448b6f56d-xtgtn Total loading time: 0 Render date: 2024-04-23T12:08:40.256Z Has data issue: false hasContentIssue false
  • English
  • Français

Major depressive disorder: a possible typisation according to serotonin, inflammation, and metabolic syndrome

Published online by Cambridge University Press:  10 September 2021

Ante Silić ,
Jakša Vukojević Open the ORCID record for Jakša Vukojević [Opens in a new window] ,
Vjekoslav Peitl ,
Marc De Hert  and
Dalibor Karlović
Ante Silić
Affiliation:
Department of Psychiatry, University Hospital Center Sestre Milosrdnice, Zagreb, Croatia School of Medicine, Catholic University of Croatia, Zagreb, Croatia
Jakša Vukojević
Affiliation:
Department of pharmacology, University of Zagreb, Zagreb, Croatia
Vjekoslav Peitl*
Affiliation:
Department of Psychiatry, University Hospital Center Sestre Milosrdnice, Zagreb, Croatia School of Medicine, Catholic University of Croatia, Zagreb, Croatia
Marc De Hert
Affiliation:
University Psychiatric Centre, KU Leuven, Leuven, Belgium Department of neurosciences, Clinical Psychiatry, KU Leuven, Leuven, Belgium AHLEC, Antwerp University, Antwerp, Belgium
Dalibor Karlović
Affiliation:
Department of Psychiatry, University Hospital Center Sestre Milosrdnice, Zagreb, Croatia School of Medicine, Catholic University of Croatia, Zagreb, Croatia
*
Author for correspondence: Vjekoslav Peitl, Email: vjekoslav.peitl@gmail.com
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective:

Major depressive disorder (MDD) is closely related to obesity, inflammation, and insulin resistance, all together being etiologically linked to metabolic syndrome (MetS) development. The depressive disorder has a neuroendocrinological component, co-influencing the MetS, while MetS is characterised by increased cytokine levels, which are known to cause a depressed mood. This study aimed to establish biological subtypes of the depressive disorder based on researched clinical, laboratory, and anthropometric variables.

Methods:

We performed a cross-sectional study on a sample of 293 subjects (145 suffering from a depressive disorder and 148 healthy controls). Results were analysed with multivariate statistical methods as well as with cluster and discriminant analysis. In order to classify depressive disorder on the grounds of laboratory, anthropometric, and clinical parameters, we performed cluster analysis, which resulted in three clusters.

Results:

The first cluster is characterised by low platelet serotonin, high cortisol levels, high blood glucose levels, high triglycerides levels, high Hamilton Depression Rating Scale score, high waist circumference, high C-Reactive Protein values, and a high number of previous depressive episodes, was named Combined (Metabolic) depression. The inflammatory depression cluster is defined with average platelet serotonin values, normal cortisol, and all other parameter levels, except for increased IL-6 levels. The serotoninergic depression cluster is characterised by markedly low platelet serotonin, and all other parameters are within the normal range.

Conclusions:

From a biological point of view, depressive disorder is not uniform, and as such, these findings suggest potential clinically useful and generalisable biological subtypes of depressive disorder.

Keywords

MDDdepressionmetabolic syndromeserotonininflammation
Type
Original Article
Information
Acta Neuropsychiatrica , Volume 34 , Issue 1 , February 2022 , pp. 15 - 23
Check for updates
Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of Scandinavian College of Neuropsychopharmacology

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Alshehri, T, Mook-Kanamori, DO, van Dijk, KW, Dinga, R, Penninx, BWJH, Rosendaal, FR, le Cessie, S and Milaneschi, Y (2021) Metabolomics dissection of depression heterogeneity and related cardiometabolic risk. Psychological Medicine 1–10. doi: 10.1017/S0033291721001471.CrossRefGoogle ScholarPubMed
Balkau, B, Valensi, P, Eschwège, E and Slama, G (2007) A review of the metabolic syndrome. Diabetes & Metabolism 33, 405–413.10.1016/j.diabet.2007.08.001CrossRefGoogle ScholarPubMed
Baune, BT, Stuart, M, Gilmour, A, Wersching, H, Arolt, V and Berger, K (2012) Moderators of the relationship between depression and cardiovascular disorders: a systematic review. General Hospital Psychiatry 34, 478–492.CrossRefGoogle ScholarPubMed
Bot, M, Milaneschi, Y, Al-Shehri, T, Amin, N, Garmaeva, S, Onderwater, GLJ, Pool, R, Thesing, CS, Vijfhuizen, LS and Vogelzangs, N (2020) Metabolomics profile in depression: a pooled analysis of 230 metabolic markers in 5283 cases with depression and 10,145 controls. Biological Psychiatry 87, 409–418.10.1016/j.biopsych.2019.08.016CrossRefGoogle ScholarPubMed
Breznoscakova, D, Palova, E, Dragasek, J and Moscovic, P (2007) The comorbidity depression and coronary disease – the differences between male and female. European Psychiatry 22, S225–S226.CrossRefGoogle Scholar
Capuron, L, Su, S, Miller, AH, Bremner, JD, Goldberg, J, Vogt, GJ, Maisano, C, Jones, L, Murrah, NV and Vaccarino, V 2008. Depressive symptoms and metabolic syndrome: is inflammation the underlying link? Biological Psychiatry 64, 896–900.CrossRefGoogle ScholarPubMed
Chan, KL, Cathomas, F and Russo, SJ (2019) Central and peripheral inflammation link metabolic syndrome and major depressive disorder. Physiology 34, 123–133.CrossRefGoogle ScholarPubMed
De Hert, M, Detraux, J and Vancampfort, D (2018) The intriguing relationship between coronary heart disease and mental disorders. Dialogues in Clinical Neuroscience 20, 31.Google ScholarPubMed
Dowlati, Y, Herrmann, N, Swardfager, W, Liu, H, Sham, L, Reim, EK and Lanctôt, KL (2010) A meta-analysis of cytokines in major depression. Biological Psychiatry 67, 446–457.CrossRefGoogle ScholarPubMed
Dunbar, JA, Reddy, P, Davis-Lameloise, N, Philpot, B, Laatikainen, T, Kilkkinen, A, Bunker, SJ, Best, JD, Vartiainen, E and Lo, SK (2008) Depression: an important comorbidity with metabolic syndrome in a general population. Diabetes Care 31, 2368–2373.10.2337/dc08-0175CrossRefGoogle Scholar
Eckel, RH, Alberti, KGMM, Grundy, SM and Zimmet, PZ (2010) The metabolic syndrome. Lancet (London, England) 375, 181–183.10.1016/S0140-6736(09)61794-3CrossRefGoogle ScholarPubMed
Elenkov, IJ, Iezzoni, DG, Daly, A, Harris, AG and Chrousos, GP (2005) Cytokine dysregulation, inflammation and well-being. Neuroimmunomodulation 12, 255–269.10.1159/000087104CrossRefGoogle ScholarPubMed
Elhwuegi, AS (2004) Central monoamines and their role in major depression. Progress in Neuro-Psychopharmacology & Biological Psychiatry 28, 435–451.CrossRefGoogle ScholarPubMed
Fried, EI and Nesse, RM (2015) Depression is not a consistent syndrome: an investigation of unique symptom patterns in the STAR*D study. Journal of Affective Disorders 172, 96–102.CrossRefGoogle Scholar
García-Toro, M, Vicens-Pons, E, Gili, M, Roca, M, Serrano-Ripoll, MJ, Vives, M, Leiva, A, Yáñez, AM, Bennasar-Veny, M and Oliván-Blázquez, B (2016) Obesity, metabolic syndrome and Mediterranean diet: impact on depression outcome. Journal of Affective Disorders 194, 105–108.CrossRefGoogle ScholarPubMed
Goldberg, D (2011) The heterogeneity of “major depression”. World Psychiatry 10, 226–228.CrossRefGoogle ScholarPubMed
Han, TS, Sattar, N, Williams, K, Gonzalez-Villalpando, C, Lean, MEJ and Haffner, SM (2002) Prospective study of C-reactive protein in relation to the development of diabetes and metabolic syndrome in the Mexico City Diabetes Study. Diabetes Care 25, 2016–2021.CrossRefGoogle Scholar
Heiskanen, TH, Niskanen, LK, Hintikka, JJ, Koivumaa-Honkanen, HT, Honkalampi, KM, Haatainen, KM and Viinamäki, HT (2006) Metabolic syndrome and depression: a cross-sectional analysis. Journal of Clinical Psychiatry 67, 1422–1427.10.4088/JCP.v67n0913CrossRefGoogle ScholarPubMed
Herrera-Marquez, R, Hernandez-Rodriguez, J, Medina-Serrano, J, Boyzo-Montes de Oca, A and Manjarrez-Gutierrez, G (2011) Association of metabolic syndrome with reduced central serotonergic activity. Metabolic Brain Disease 26, 29–35.CrossRefGoogle ScholarPubMed
Hildrum, B, Mykletun, A, Midthjell, K, Ismail, K and Dahl, AA (2009) No association of depression and anxiety with the metabolic syndrome: the Norwegian HUNT study. Acta Psychiatrica Scandinavica 120, 14–22.CrossRefGoogle ScholarPubMed
Jernej, B, Banović, M, Cicin-Sain, L, Hranilović, D, Balija, M, Oresković, D and Folnegović-Smalc, V (2000) Physiological characteristics of platelet/circulatory serotonin: study on a large human population. Psychiatry Research 94, 153–162.10.1016/S0165-1781(00)00129-3CrossRefGoogle Scholar
Juruena, MF, Cleare, AJ, Papadopoulos, AS, Poon, L, Lightman, S and Pariante, CM (2006) Different responses to dexamethasone and prednisolone in the same depressed patients. Psychopharmacology (Berlin) 189, 225–235.10.1007/s00213-006-0555-4CrossRefGoogle ScholarPubMed
Khandaker, GM, Zuber, V, Rees, JMB, Carvalho, L, Mason, AM, Foley, CN, Gkatzionis, A, Jones, PB and Burgess, S (2020) Shared mechanisms between coronary heart disease and depression: findings from a large UK general population-based cohort. Molecular Psychiatry 25, 1477–1486.CrossRefGoogle ScholarPubMed
Khassawneh, AH, Alzoubi, A, Khasawneh, AG, Abdo, N, Abu-Naser, D, Al-Mistarehi, A, Albattah, MF and Kheirallah, KA (2020) The relationship between depression and metabolic control parameters in type 2 diabetic patients: a cross-sectional and feasibility interventional study. International Journal of Clinical Practice e13777.Google ScholarPubMed
Koponen, H, Jokelainen, J, Keinänen-Kiukaanniemi, S, Kumpusalo, E and Vanhala, M (2008) Metabolic syndrome predisposes to depressive symptoms: a population-based 7-year follow-up study. Journal of Clinical Psychiatry 69, 178–182.CrossRefGoogle ScholarPubMed
Kubaszek, A, Pihlajamäki, J, Komarovski, V, Lindi, V, Lindström, J, Eriksson, J, Valle, TT, Hämäläinen, H, Ilanne-Parikka, P, Keinänen-Kiukaanniemi, S, Tuomilehto, J, Uusitupa, M and Laakso, M (2003) Promoter polymorphisms of the TNF-alpha (G-308A) and IL-6 (C-174G) genes predict the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study. Diabetes 52, 1872–1876.CrossRefGoogle ScholarPubMed
Lamers, F, Vogelzangs, N, Merikangas, KR, de Jonge, P, Beekman, ATF and Penninx, BWJH (2013) Evidence for a differential role of HPA-axis function, inflammation and metabolic syndrome in melancholic versus atypical depression. Molecular Psychiatry 18, 692–699.CrossRefGoogle ScholarPubMed
Lecrubier, Y, Sheehan, DV, Weiller, E, Amorim, P, Bonora, I, Sheehan, KH, Janavs, J and Dunbar, GC (1997) The Mini International Neuropsychiatric Interview (MINI). A short diagnostic structured interview: reliability and validity according to the CIDI. European Psychiatry 12, 224–231.10.1016/S0924-9338(97)83296-8CrossRefGoogle Scholar
Lucki, I (1998) The spectrum of behaviors influenced by serotonin. Biological Psychiatry 44, 151–162.CrossRefGoogle ScholarPubMed
Lux, V, Kendler, KS, Payerle, G, Team, RC, Payerle, G, Dolnicar, S, Chapple, A, Pastuszak, AW and Wang, R (2015) Deconstructing major depression: a validation study of the DSM-IV symptomatic criteria. Annals of Tourism Research 3, 45.Google Scholar
Maes, M (2011) Depression is an inflammatory disease, but cell-mediated immune activation is the key component of depression. Progress in Neuro-Psychopharmacology & Biological Psychiatry 35, 664–675.CrossRefGoogle ScholarPubMed
Maes, M, Kubera, M, Mihaylova, I, Geffard, M, Galecki, P, Leunis, JC and Berk, M (2013) Increased autoimmune responses against auto-epitopes modified by oxidative and nitrosative damage in depression: implications for the pathways to chronic depression and neuroprogression. Journal of Affective Disorders 149, 23–29.CrossRefGoogle ScholarPubMed
Maes, M, Leonard, BE, Myint, AM, Kubera, M and Verkerk, R (2011) The new “5-HT” hypothesis of depression: cell-mediated immune activation induces indoleamine 2,3-dioxygenase, which leads to lower plasma tryptophan and an increased synthesis of detrimental tryptophan catabolites (TRYCATs), both of which contribute to t. Progress in Neuro-Psychopharmacology & Biological Psychiatry 35, 702–721.CrossRefGoogle Scholar
Majd, M, Saunders, EFH and Engeland, CG (2020) Inflammation and the dimensions of depression: a review. Frontiers in Neuroendocrinology 56, 100800.10.1016/j.yfrne.2019.100800CrossRefGoogle ScholarPubMed
Malhi, GS and Mann, JJ (2018) Depression. Lancet (London, England) 392, 2299–2312.CrossRefGoogle ScholarPubMed
Mannan, M, Mamun, A, Doi, S and Clavarino, A (2016) Prospective associations between depression and obesity for adolescent males and females–a systematic review and meta-analysis of longitudinal studies. PLoS One 11, e0157240.CrossRefGoogle ScholarPubMed
Milaneschi, Y, Lamers, F, Peyrot, WJ, Abdellaoui, A, Willemsen, G, Hottenga, JJ, Jansen, R, Mbarek, H, Dehghan, A, Lu, C, Boomsma, DI and Penninx, BWJH (2016) Polygenic dissection of major depression clinical heterogeneity. Molecular Psychiatry 21, 516–522.CrossRefGoogle ScholarPubMed
Milton, DC, Ward, J, Ward, E, Lyall, DM, Strawbridge, RJ, Smith, DJ and Cullen, B (2021) The association between C-reactive protein, mood disorder, and cognitive function in UK Biobank. European Psychiatry 64, e14.CrossRefGoogle ScholarPubMed
Moller, DE and Kaufman, KD (2005) Metabolic syndrome: a clinical and molecular perspective. Annual Review of Medicine 56, 45–62.CrossRefGoogle ScholarPubMed
Pan, A, Keum, N, Okereke, OI, Sun, Q, Kivimaki, M, Rubin, RR and Hu, FB (2012) Bidirectional association between depression and metabolic syndrome: a systematic review and meta-analysis of epidemiological studies. Diabetes Care 35, 1171–1180.CrossRefGoogle ScholarPubMed
Penninx, BWJH and Lange, SMM (2018) Metabolic syndrome in psychiatric patients: overview, mechanisms, and implications. Dialogues in Clinical Neuroscience 20, 63–73.Google ScholarPubMed
Perlis, RH (2013) A clinical risk stratification tool for predicting treatment resistance in major depressive disorder. Biological Psychiatry 74, 7–14.CrossRefGoogle ScholarPubMed
Pitharouli, MC, Hagenaars, SP, Glanville, KP, Coleman, JRI, Hotopf, M, Lewis, CM and Pariante, CM (2021) Elevated C-reactive protein in patients with depression, independent of genetic, health, and psychosocial factors: results from the UK Biobank. American Journal of Psychiatry. doi: 10.1176/appi.ajp.2020.20060947.CrossRefGoogle ScholarPubMed
Schiepers, OJG, Wichers, MC and Maes, M (2005) Cytokines and major depression. Progress in Neuro-Psychopharmacology & Biological Psychiatry 29, 201–217.10.1016/j.pnpbp.2004.11.003CrossRefGoogle ScholarPubMed
Seppälä, J, Vanhala, M, Kautiainen, H, Eriksson, J, Kampman, O, Mäntyselkä, P, Oksa, H, Ovaskainen, Y, Viikki, M and Koponen, H (2012) Prevalence of metabolic syndrome in subjects with melancholic and non-melancholic depressive symptoms. A Finnish population-based study. Journal of Affective Disorders 136, 543–549.10.1016/j.jad.2011.10.032CrossRefGoogle ScholarPubMed
Sjöberg, L, Karlsson, B, Atti, AR, Skoog, I, Fratiglioni, L and Wang, HX (2017) Prevalence of depression: comparisons of different depression definitions in population-based samples of older adults. Journal of Affective Disorders 221, 123–131.CrossRefGoogle ScholarPubMed
Vaccarino, V, McClure, C, Johnson, BD, Sheps, DS, Bittner, V, Rutledge, T, Shaw, LJ, Sopko, G, Olson, MB and Krantz, DS (2008) Depression, the metabolic syndrome and cardiovascular risk. Psychosomatic Medicine 70, 40–48.CrossRefGoogle ScholarPubMed
Supplementary material: File

Silić et al. supplementary material

Silić et al. supplementary material 1

Download Silić et al. supplementary material(File)
File 14.6 KB
Supplementary material: File

Silić et al. supplementary material

Silić et al. supplementary material 2

Download Silić et al. supplementary material(File)
File 13.2 KB