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Metabolic and inflammatory markers: associations with individual depressive symptoms

Published online by Cambridge University Press:  11 September 2017

F. Lamers*
Affiliation:
Department of Psychiatry, Amsterdam Public Health Research Institute and Amsterdam Neuroscience research institute, VU University Medical Center/GGZ inGeest, Amsterdam, the Netherlands
Y. Milaneschi
Affiliation:
Department of Psychiatry, Amsterdam Public Health Research Institute and Amsterdam Neuroscience research institute, VU University Medical Center/GGZ inGeest, Amsterdam, the Netherlands
P. de Jonge
Affiliation:
Interdisciplinary Center Psychopathology and Emotion regulation (ICPE), University of Groningen, University Medical Center, Groningen, the Netherlands
E. J. Giltay
Affiliation:
Department of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands
B. W. J. H. Penninx
Affiliation:
Department of Psychiatry, Amsterdam Public Health Research Institute and Amsterdam Neuroscience research institute, VU University Medical Center/GGZ inGeest, Amsterdam, the Netherlands
*
Author for correspondence: F. Lamers, Ph.D., E-mail: f.lamers@vumc.nl

Abstract

Background

Literature has shown that obesity, metabolic syndrome and inflammation are associated with depression, however, evidence suggests that these associations are specific to atypical depression. Which of the atypical symptoms are driving associations with obesity-related outcomes and inflammation is unknown. We evaluated associations between individual symptoms of depression (both atypical and non-atypical) and body mass index (BMI), metabolic syndrome components and inflammatory markers.

Methods

We included 808 persons with a current diagnosis of depression participating in the Netherlands Study of Depression and Anxiety (67% female, mean age 41.6 years). Depressive symptoms were derived from the Composite International Diagnostic Interview and the Inventory of Depressive Symptomatology. Univariable and multivariable regression analyses adjusting for sex, age, educational level, depression severity, current smoking, physical activity, anti-inflammatory medication use, and statin use were performed.

Results

Increased appetite was positively associated with BMI, number of metabolic syndrome components, waist circumference, C-reactive protein and tumor necrosis factor-α. Decreased appetite was negatively associated with BMI and waist circumference. Psychomotor retardation was positively associated with BMI, high-density lipoprotein cholesterol and triglycerides, and insomnia with number of metabolic syndrome components.

Conclusion

Increased appetite – in the context of a depressive episode – was the only symptom that was associated with both metabolic as well as inflammatory markers, and could be a key feature of an immuno-metabolic form of depression. This immuno-metabolic depression should be considered in clinical trials evaluating effectiveness of compounds targeting metabolic and inflammatory pathways or lifestyle interventions.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2017 

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References

Angst, J, Gamma, A, Benazzi, F, Silverstein, B, Ajdacic-Gross, V, Eich, D et al. (2006) Atypical depressive syndromes in varying definitions. European Archives of Psychiatry and Clinical Neuroscience 256, 4454.CrossRefGoogle ScholarPubMed
Anisman, H, Ravindran, AV, Griffiths, J and Merali, Z (1999) Endocrine and cytokine correlates of major depression and dysthymia with typical or atypical features. Molecular Psychiatry 4, 182188.CrossRefGoogle ScholarPubMed
Cizza, G, Ronsaville, DS, Kleitz, H, Eskandari, F, Mistry, S, Torvik, S et al. (2012) Clinical subtypes of depression are associated with specific metabolic parameters and circadian endocrine profiles in women: the power study. PLoS ONE 7, e28912.CrossRefGoogle ScholarPubMed
Craig, CL, Marshall, AL, Sjostrom, M, Bauman, AE, Booth, ML, Ainsworth, BE et al. (2003) International physical activity questionnaire: 12-country reliability and validity. Medicine and Science in Sports and Exercise 35, 13811395.CrossRefGoogle ScholarPubMed
Dashti, HS, Follis, JL, Smith, CE, Tanaka, T, Cade, BE, Gottlieb, DJ et al. (2015) Habitual sleep duration is associated with BMI and macronutrient intake and may be modified by CLOCK genetic variants. American Journal of Clinical Nutrition 101, 135143.CrossRefGoogle ScholarPubMed
Dowlati, Y, Herrmann, N, Swardfager, W, Liu, H, Sham, L, Reim, EK et al. (2010) A meta-analysis of cytokines in major depression. Biological Psychiatry 67, 446457.CrossRefGoogle ScholarPubMed
Eyre, HA, Air, T, Proctor, S, Rositano, S and Baune, BT (2015) A critical review of the efficacy of non-steroidal anti-inflammatory drugs in depression. Progress in Neuro-psychopharmacol and Biological Psychiatry 57, 1116.CrossRefGoogle ScholarPubMed
Gecici, O, Kuloglu, M, Atmaca, M, Tezcan, AE, Tunckol, H, Emul, HM et al. (2005) High serum leptin levels in depressive disorders with atypical features. Psychiatry and Clinical Neurosciences 59, 736738.CrossRefGoogle ScholarPubMed
Ghanizadeh, A and Hedayati, A (2013) Augmentation of fluoxetine with lovastatin for treating major depressive disorder, a randomized double-blind placebo controlled-clinical trial. Depression & Anxiety 30, 10841088.CrossRefGoogle ScholarPubMed
Glaus, J, Vandeleur, CL, von Känel, R, Lasserre, AM, Strippoli, MP, Gholam-Rezaee, M et al. (2014) Associations between mood, anxiety or substance use disorders and inflammatory markers after adjustment for multiple covariates in a population-based study. Journal of Psychiatric Research 58, 3645.CrossRefGoogle ScholarPubMed
Grundy, SM, Cleeman, JI, Daniels, SR, Donato, KA, Eckel, RH, Franklin, BA et al. (2005) Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 112, 27352752.CrossRefGoogle ScholarPubMed
Haghighi, M, Khodakarami, S, Jahangard, L, Ahmadpanah, M, Bajoghli, H, Holsboer-Trachsler, E et al. (2014) In a randomized, double-blind clinical trial, adjuvant atorvastatin improved symptoms of depression and blood lipid values in patients suffering from severe major depressive disorder. Journal of Psychiatric Research 58, 109114.CrossRefGoogle Scholar
Hasler, G, Pine, DS, Gamma, A, Milos, G, Ajdacic, V, Eich, D et al. (2004) The associations between psychopathology and being overweight: a 20-year prospective study. Psychological Medicine 34, 10471057.CrossRefGoogle ScholarPubMed
Hickman, RJ, Khambaty, T and Stewart, JC (2014) C-reactive protein is elevated in atypical but not nonatypical depression: data from the National Health and Nutrition Examination Survey (NHANES) 1999–2004. Journal of Behavioral Medicine 37, 621629.CrossRefGoogle Scholar
Hiles, SA, Baker, AL, de Malmanche, T and Attia, J (2012) A meta-analysis of differences in IL-6 and IL-10 between people with and without depression: exploring the causes of heterogeneity. Brain, Behavior, and Immunity 26, 11801188.CrossRefGoogle ScholarPubMed
Howren, MB, Lamkin, DM and Suls, J (2009) Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosomatic Medicine 71, 171186.CrossRefGoogle ScholarPubMed
Hung, CF, Rivera, M, Craddock, N, Owen, MJ, Gill, M, Korszun, A et al. (2014) Relationship between obesity and the risk of clinically significant depression: Mendelian randomisation study. British Journal of Psychiatry 205, 2428.CrossRefGoogle ScholarPubMed
Insel, T, Cuthbert, B, Garvey, M, Heinssen, R, Pine, DS, Quinn, K et al. (2010) Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. American Journal of Psychiatry 167, 748751.CrossRefGoogle Scholar
Jansen, R, Penninx, BW, Madar, V, Xia, K, Milaneschi, Y, Hottenga, JJ et al. (2016) Gene expression in major depressive disorder. Molecular Psychiatry 21, 339347.CrossRefGoogle ScholarPubMed
Jokela, M, Virtanen, M, Batty, GD and Kivimaki, M (2016) Inflammation and specific symptoms of depression. JAMA Psychiatry 73, 8788.CrossRefGoogle ScholarPubMed
Kaestner, F, Hettich, M, Peters, M, Sibrowski, W, Hetzel, G, Ponath, G et al. (2005) Different activation patterns of proinflammatory cytokines in melancholic and non-melancholic major depression are associated with HPA axis activity. Journal of Affective Disorder 87, 305311.CrossRefGoogle ScholarPubMed
Karlovic, D, Serretti, A, Vrkic, N, Martinac, M and Marcinko, D (2012) Serum concentrations of CRP, IL-6, TNF-alpha and cortisol in major depressive disorder with melancholic or atypical features. Psychiatry Research, 198, 7480.CrossRefGoogle ScholarPubMed
Kohler, O, Benros, ME, Nordentoft, M, Farkouh, ME, Iyengar, RL, Mors, O et al. (2014) Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials. JAMA Psychiatry 17, 13811391.CrossRefGoogle Scholar
Korte, SM, Prins, J, Krajnc, AM, Hendriksen, H, Oosting, RS, Westphal, KG et al. (2015) The many different faces of major depression: it is time for personalized medicine. European Journal of Pharmacology 753, 88104.CrossRefGoogle ScholarPubMed
Lamers, F, Bot, M, Jansen, R, Chan, MK, Cooper, JD, Bahn, S et al. (2016) Serum proteomic profiles of depressive subtypes. Translational Psychiatry 6, e851.CrossRefGoogle ScholarPubMed
Lamers, F, de Jonge, P, Nolen, WA, Smit, JH, Zitman, FG, Beekman, AT et al. (2010) Identifying depressive subtypes in a large cohort study: results from the Netherlands Study of Depression and Anxiety (NESDA). Journal of Clinical Psychiatry 71, 15821589.CrossRefGoogle Scholar
Lamers, F, Vogelzangs, N, Merikangas, KR, de Jonge, P, Beekman, AT and Penninx, BW (2013) Evidence for a differential role of HPA-axis function, inflammation and metabolic syndrome in melancholic versus atypical depression. Molecular Psychiatry 18, 692699.CrossRefGoogle ScholarPubMed
Lasserre, AM, Glaus, J, Vandeleur, CL, Marques-Vidal, P, Vaucher, J, Bastardot, F et al. (2014) Depression with atypical features and increase in obesity, body mass index, waist circumference, and fat mass: a prospective, population-based study. JAMA Psychiatry 71, 880888.CrossRefGoogle ScholarPubMed
Lasserre, AM, Strippoli, MF, Glaus, J, Gholam-Rezaee, M, Vandeleur, CL, Castelao, E et al. (2017) Prospective associations of depression subtypes with cardio-metabolic risk factors in the general population. Molecular Psychiatry 22, 10261034.CrossRefGoogle ScholarPubMed
Levitan, RD, Davis, C, Kaplan, AS, Arenovich, T, Phillips, DI and Ravindran, AV (2012) Obesity comorbidity in unipolar major depressive disorder: refining the core phenotype. Journal of Clinical Psychiatry 73, 11191124.CrossRefGoogle ScholarPubMed
Licht, CM, Vreeburg, SA, van Reedt Dortland, AK, Giltay, EJ, Hoogendijk, WJ, DeRijk, RH et al. (2010) Increased sympathetic and decreased parasympathetic activity rather than changes in hypothalamic-pituitary-adrenal axis activity is associated with metabolic abnormalities. Journal of Clinical Endocrinology and Metabolism 95, 24582466.CrossRefGoogle ScholarPubMed
Luppino, FS, de Wit, LM, Bouvy, PF, Stijnen, T, Cuijpers, P, Penninx, BW et al. (2010) Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Archives of General Psychiatry 67, 220229.CrossRefGoogle ScholarPubMed
McIntyre, RS, Soczynska, JK, Konarski, JZ, Woldeyohannes, HO, Law, CW, Miranda, A et al. (2007) Should depressive syndromes be reclassified as ‘Metabolic Syndrome Type II’? Annals of Clinical Psychiatry 19, 257264.CrossRefGoogle Scholar
Milaneschi, Y, Lamers, F, Bot, M, Drent, ML and Penninx, BW (2017) Leptin dysregulation is specifically associated with major depression with atypical features: evidence for a mechanism connecting obesity and depression. Biological Psychiatry, 81, 807814.CrossRefGoogle ScholarPubMed
Milaneschi, Y, Lamers, F, Mbarek, H, Hottenga, JJ, Boomsma, DI and Penninx, BW (2014) The effect of FTO rs9939609 on major depression differs across MDD subtypes. Molecular Psychiatry 19, 960962.CrossRefGoogle ScholarPubMed
Milaneschi, Y, Lamers, F, Peyrot, WJ, Abdellaoui, A, Willemsen, G, Hottenga, JJ et al. (2016) Polygenic dissection of major depression clinical heterogeneity. Molecular Psychiatry 21, 516522.CrossRefGoogle ScholarPubMed
Mostafavi, S, Battle, A, Zhu, X, Potash, JB, Weissman, MM, Shi, J et al. (2014) Type I interferon signaling genes in recurrent major depression: increased expression detected by whole-blood RNA sequencing. Molecular Psychiatry 19, 12671274.CrossRefGoogle ScholarPubMed
Na, KS, Lee, KJ, Lee, JS, Cho, YS and Jung, HY (2014) Efficacy of adjunctive celecoxib treatment for patients with major depressive disorder: a meta-analysis. Progress in Neuro-psychopharmacol and Biological Psychiatry 48, 7985.CrossRefGoogle ScholarPubMed
Pan, A, Keum, N, Okereke, OI, Sun, Q, Kivimaki, M, Rubin, RR et al. (2012) Bidirectional association between depression and metabolic syndrome: a systematic review and meta-analysis of epidemiological studies. Diabetes Care 35, 11711180.CrossRefGoogle ScholarPubMed
Penninx, BWJH, Beekman, ATF, Smit, JH, Zitman, FG, Nolen, WA, Spinhoven, P et al. (2008) The Netherlands Study of Depression and Anxiety (NESDA): rationale, objectives and methods. International Journal of Methods in Psychiatric Research 17, 121140.CrossRefGoogle ScholarPubMed
Punjabi, NM (2008) The epidemiology of adult obstructive sleep apnea. Proceedings of the American Thoracic Society 5, 136143.CrossRefGoogle ScholarPubMed
Rahe, C, Baune, BT, Unrath, M, Arolt, V, Wellmann, J, Wersching, H et al. (2015) Associations between depression subtypes, depression severity and diet quality: cross-sectional findings from the BiDirect study. BMC Psychiatry 15, 38.CrossRefGoogle ScholarPubMed
Raison, CL, Capuron, L and Miller, AH (2006) Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends in Immunology 27, 2431.CrossRefGoogle Scholar
Raison, CL, Rutherford, RE, Woolwine, BJ, Shuo, C, Schettler, P, Drake, DF et al. (2013) A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. Archives of General Psychiatry 70, 3141.Google ScholarPubMed
Rudolf, S, Greggersen, W, Kahl, KG, Huppe, M and Schweiger, U (2014) Elevated IL-6 levels in patients with atypical depression but not in patients with typical depression. Psychiatry Research 217, 3438.CrossRefGoogle Scholar
Rush, AJ, Trivedi, MH, Ibrahim, HM, Carmody, TJ, Arnow, B, Klein, DN et al. (2003) The 16-item quick inventory of depressive symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biological Psychiatry 54, 573583.CrossRefGoogle ScholarPubMed
Samaan, Z, Lee, YK, Gerstein, HC, Engert, JC, Bosch, J, Mohan, V et al. (2015) Obesity genes and risk of major depressive disorder in a multiethnic population: a cross-sectional study. Journal of Clinical Psychiatry, 76, e1611e1618.CrossRefGoogle Scholar
Santoro, A, Mattace, RG and Meli, R (2015) Drug targeting of leptin resistance. Life Sciences 140, 6474.CrossRefGoogle ScholarPubMed
Seppala, J, Vanhala, M, Kautiainen, H, Eriksson, J, Kampman, O, Mantyselka, P et al. (2012) Prevalence of metabolic syndrome in subjects with melancholic and non-melancholic depressive symptoms. A Finnish population-based study. Journal of Affective Disorders 136, 543549.CrossRefGoogle ScholarPubMed
Simmons, WK, Burrows, K, Avery, JA, Kerr, KL, Bodurka, J, Savage, CR et al. (2016) Depression-Related Increases and Decreases in Appetite: Dissociable Patterns of Aberrant Activity in Reward and Interoceptive Neurocircuitry. The American Journal of Psychiatry 173, 418428.CrossRefGoogle ScholarPubMed
Singh, M (2014) Mood, food, and obesity. Frontiers in Psychology 5, 925.CrossRefGoogle Scholar
Stubbs, B, Vancampfort, D, Veronese, N, Solmi, M, Gaughran, F, Manu, P et al. (2016) The prevalence and predictors of obstructive sleep apnea in major depressive disorder, bipolar disorder and schizophrenia: a systematic review and meta-analysis. Journal of Affective Disorders 197, 259267.CrossRefGoogle ScholarPubMed
Sullivan, PF, Prescott, CA and Kendler, KS (2002) The subtypes of major depression in a twin registry. Journal of Affective Disorders 68, 273284.CrossRefGoogle Scholar
Vogelzangs, N, Beekman, AT, Boelhouwer, IG, Bandinelli, S, Milaneschi, Y, Ferrucci, L et al. (2011) Metabolic depression: a chronic depressive subtype? Findings from the InCHIANTI study of older persons. Journal of Clinical Psychiatry 72, 598604.CrossRefGoogle ScholarPubMed
Vogelzangs, N, Comijs, HC, Oude Voshaar, RC, Stek, ML and Penninx, BW (2014) Late-life depression symptom profiles are differentially associated with immunometabolic functioning. Brain Behavior and Immunity 41, 109115.CrossRefGoogle ScholarPubMed
World Health Organization (1997) Composite International Diagnostic Interview, Core Version 2.1: Interviewer's Manual Sydney. Australia: World Health Organization.Google Scholar
Yoon, HK, Kim, YK, Lee, HJ, Kwon, DY and Kim, L (2012) Role of cytokines in atypical depression. Nordic Journal of Psychiatry, 66, 183188.CrossRefGoogle ScholarPubMed
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