Hostname: page-component-8448b6f56d-mp689 Total loading time: 0 Render date: 2024-04-19T12:14:11.410Z Has data issue: false hasContentIssue false

Maternal depression and inflammation during pregnancy

Published online by Cambridge University Press:  23 August 2019

Marius Lahti-Pulkkinen*
Affiliation:
Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland National Institute for Health and Welfare, Helsinki, Finland Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
Polina Girchenko
Affiliation:
Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
Rachel Robinson
Affiliation:
Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
Soili M. Lehto
Affiliation:
Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland Department of Psychiatry, Kuopio University Hospital, Kuopio, Finland Department of Psychiatry, Faculty of Medicine, University of Helsinki, Helsinki, Finland
Elena Toffol
Affiliation:
Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland National Institute for Health and Welfare, Helsinki, Finland
Kati Heinonen
Affiliation:
Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
Rebecca M. Reynolds
Affiliation:
Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
Eero Kajantie
Affiliation:
National Institute for Health and Welfare, Helsinki, Finland Children's Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, OuluFinland
Hannele Laivuori
Affiliation:
Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, University of Helsinki, Helsinki, Finland Medical and Clinical Genetics; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, Helsinki, Finland Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland Department of Obstetrics and Gynecology, Tampere University Hospital, Tampere, Finland
Pia M. Villa
Affiliation:
Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, University of Helsinki, Helsinki, Finland
Esa Hämäläinen
Affiliation:
Department of Clinical Chemistry, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Jari Lahti
Affiliation:
Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki, Finland Turku Institute for Advanced Studies, University of Turku, Turku, Finland
Katri Räikkönen
Affiliation:
Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
*
Author for correspondence: Marius Lahti-Pulkkinen, E-mail: marius.lahti-pulkkinen@helsinki.fi

Abstract

Background

Maternal depression during pregnancy increases the risk for adverse developmental outcomes in children. However, the underpinning biological mechanisms remain unknown. We tested whether depression was associated with levels of and change in the inflammatory state during pregnancy, if early pregnancy overweight/obesity or diabetes/hypertensive pregnancy disorders accounted for/mediated these effects, and if depression added to the inflammation that typically accompanies these conditions.

Methods

We analyzed plasma high-sensitivity C-reactive protein (hsCRP) and glycoprotein acetyls at three consecutive stages during pregnancy, derived history of depression diagnoses before pregnancy from Care Register for Healthcare (HILMO) (N = 375) and self-reports (N = 347) and depressive symptoms during pregnancy using the Center for Epidemiological Studies Depression Scale completed concurrently to blood samplings (N = 295). Data on early pregnancy body mass index (BMI) and diabetes/hypertensive pregnancy disorders came from medical records.

Results

Higher overall hsCRP levels, but not change, during pregnancy were predicted by history of depression diagnosis before pregnancy [HILMO: mean difference (MD) = 0.69 standard deviation (s.d.) units; 95% confidence interval (CI) 0.26–1.11, self-report: MD = 0.56 s.d.; 95% CI 0.17–0.94] and higher depressive symptoms during pregnancy (0.06 s.d. per s.d. increase; 95% CI 0.00–0.13). History of depression diagnosis before pregnancy also predicted higher overall glycoprotein acetyls (HILMO: MD = 0.52 s.d.; 95% CI 0.12–0.93). These associations were not explained by diabetes/hypertensive disorders, but were accounted for and mediated by early pregnancy BMI. Furthermore, in obese women, overall hsCRP levels increased as depressive symptoms during pregnancy increased (p = 0.006 for interaction).

Conclusions

Depression is associated with a proinflammatory state during pregnancy. These associations are mediated by early pregnancy BMI, and depressive symptoms during pregnancy aggravate the inflammation related to obesity.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2019

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.)

Footnotes

*

Dr Lahti-Pulkkinen and Dr Girchenko had equal contribution and are the joined first authors.

References

Alam, R, Abdolmaleky, HM and Zhou, JR (2017) Microbiome, inflammation, epigenetic alterations, and mental diseases. American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics 174, 651660.CrossRefGoogle ScholarPubMed
Anthony, M and Lin, F (2018) A systematic review for functional neuroimaging studies of cognitive reserve across the cognitive aging spectrum. Archives of Clinical Neuropsychology 33, 937948.CrossRefGoogle ScholarPubMed
Azar, R and Mercer, D (2013) Mild depressive symptoms are associated with elevated C-reactive protein and proinflammatory cytokine levels during early to midgestation: a prospective pilot study. Journal of Women's Health 22, 385389.CrossRefGoogle ScholarPubMed
Barnes, J, Mondelli, V and Pariante, CM (2017) Genetic contributions of inflammation to depression. Neuropsychopharmacology 42, 8198.CrossRefGoogle ScholarPubMed
Berggren, EK, Roeder, HA, Boggess, KA, Moss, K, Offenbacher, S, Campbell, E and Grotegut, CA (2015) First-trimester maternal serum C-reactive protein as a predictor of third-trimester impaired glucose tolerance. Reproductive Sciences 22, 9093.CrossRefGoogle ScholarPubMed
Blackmore, ER, Moynihan, JA, Rubinow, DR, Pressman, EK, Gilchrist, M and O'Connor, TG (2011) Psychiatric symptoms and proinflammatory cytokines in pregnancy. Psychosomatic Medicine 73, 656663.CrossRefGoogle ScholarPubMed
Boggero, IA, Hostinar, CE, Haak, EA, Murphy, MLM and Segerstrom, SC (2017) Psychosocial functioning and the cortisol awakening response: meta-analysis, P-curve analysis, and evaluation of the evidential value in existing studies. Biological Psychology 129, 207230.CrossRefGoogle ScholarPubMed
Cassidy-Bushrow, AE, Peters, RM, Johnson, DA and Templin, TN (2012) Association of depressive symptoms with inflammatory biomarkers among pregnant African-American women. Journal of Reproductive Immunology 94, 202209.CrossRefGoogle ScholarPubMed
Cheng, CY and Pickler, RH (2014) Perinatal stress, fatigue, depressive symptoms, and immune modulation in late pregnancy and one month postpartum. TheScientificWorldJournal 2014, 652630.CrossRefGoogle ScholarPubMed
Choi, J, Joseph, L and Pilote, L (2013) Obesity and C-reactive protein in various populations: a systematic review and meta-analysis. Obesity Reviews 14, 232244.CrossRefGoogle ScholarPubMed
Christian, LM, Franco, A, Glaser, R and Iams, JD (2009) Depressive symptoms are associated with elevated serum proinflammatory cytokines among pregnant women. Brain, Behavior, and Immunity 23, 750754.CrossRefGoogle ScholarPubMed
Copeland, WE, Shanahan, L, Worthman, C, Angold, A and Costello, EJ (2012) Cumulative depression episodes predict later C-reactive protein levels: a prospective analysis. Biological Psychiatry 71, 1521.CrossRefGoogle ScholarPubMed
Cox, AJ, West, NP and Cripps, AW (2015) Obesity, inflammation, and the gut microbiota. The Lancet Diabetes & Endocrinology 3, 207215.CrossRefGoogle ScholarPubMed
Fenton, WS and Stover, ES (2006) Mood disorders: cardiovascular and diabetes comorbidity. Current Opinion in Psychiatry 19, 421427.CrossRefGoogle ScholarPubMed
Flanigan, C, Sheikh, A, DunnGalvin, A, Brew, BK, Almqvist, C and Nwaru, BI (2018) Prenatal maternal psychosocial stress and offspring's asthma and allergic disease: a systematic review and meta-analysis. Clinical & Experimental Allergy 48, 403414.CrossRefGoogle ScholarPubMed
Girchenko, P, Lahti, M, Tuovinen, S, Savolainen, K, Lahti, J, Binder, EB, Reynolds, RM, Entringer, S, Buss, C, Wadhwa, PD, Hamalainen, E, Kajantie, E, Pesonen, AK, Villa, PM, Laivuori, H and Raikkonen, K (2017) Cohort Profile: Prediction and prevention of preeclampsia and intrauterine growth restriction (PREDO) study. International Journal of Epidemiology 46, 13801381, g.Google ScholarPubMed
Glover, V (2015) Prenatal stress and its effects on the fetus and the child: possible underlying biological mechanisms. Advances in Neurobiology 10, 269283.CrossRefGoogle ScholarPubMed
Gustafsson, HC, Sullivan, EL, Nousen, EK, Sullivan, CA, Huang, E, Rincon, M, Nigg, JT and Loftis, JM (2018) Maternal prenatal depression predicts infant negative affect via maternal inflammatory cytokine levels. Brain, Behavior, and Immunity 73, 470481.CrossRefGoogle ScholarPubMed
Haeri, S, Baker, AM and Ruano, R (2013) Do pregnant women with depression have a pro-inflammatory profile? Journal of Obstetrics and Gynaecology Research 39, 948952.CrossRefGoogle ScholarPubMed
Herzog, R, Álvarez-Pasquin, MJ, Díaz, C, Del Barrio, JL, Estrada, JM and Gil, Á (2013) Are healthcare workers’ intentions to vaccinate related to their knowledge, beliefs and attitudes? A systematic review. BMC Public Health 13, 154.CrossRefGoogle ScholarPubMed
Hotamisligil, GS (2006) Inflammation and metabolic disorders. Nature 444, 860.CrossRefGoogle ScholarPubMed
Huang, M, Su, S, Goldberg, J, Miller, AH, Levantsevych, OM, Shallenberger, L, Pimple, P, Pearce, B, Bremner, JD and Vaccarino, V (2019) Longitudinal association of inflammation with depressive symptoms: A 7-year cross-lagged twin difference study. Brain, Behavior, and Immunity 75, 200207.CrossRefGoogle ScholarPubMed
Ironson, G, Banerjee, N, Fitch, C and Krause, N (2018) Positive emotional well-being, health Behaviors, and inflammation measured by C-Reactive protein. Social Science & Medicine 197, 235243.CrossRefGoogle ScholarPubMed
Jarde, A, Morais, M, Kingston, D, Giallo, R, MacQueen, GM, Giglia, L, Beyene, J, Wang, Y and McDonald, SD (2016) Neonatal outcomes in women with untreated antenatal depression compared with women without depression: a systematic review and meta-analysis. JAMA Psychiatry 73, 826837.CrossRefGoogle ScholarPubMed
Kohler, O, Petersen, L, Mors, O, Mortensen, PB, Yolken, RH, Gasse, C and Benros, ME (2017) Infections and exposure to anti-infective agents and the risk of severe mental disorders: a nationwide study. Acta Psychiatrica Scandinavica 135, 97105.CrossRefGoogle ScholarPubMed
Kumpulainen, SM, Girchenko, P, Lahti-Pulkkinen, M, Reynolds, RM, Tuovinen, S, Pesonen, AK, Heinonen, K, Kajantie, E, Villa, PM, Hamalainen, E, Laivuori, H and Raikkonen, K (2018) Maternal early pregnancy obesity and depressive symptoms during and after pregnancy. Psychological Medicine 48, 23532363.CrossRefGoogle ScholarPubMed
Ladwig, KH, Marten-Mittag, B, Lowel, H, Doring, A and Koenig, W (2003) Influence of depressive mood on the association of CRP and obesity in 3205 middle aged healthy men. Brain, Behavior, and Immunity 17, 268275.CrossRefGoogle ScholarPubMed
Lahti, M, Savolainen, K, Tuovinen, S, Pesonen, AK, Lahti, J, Heinonen, K, Hamalainen, E, Laivuori, H, Villa, PM, Reynolds, RM, Kajantie, E and Raikkonen, K (2017) Maternal depressive symptoms during and after pregnancy and psychiatric problems in children. Journal of the American Academy of Child & Adolescent Psychiatry 56, 3039, e7.CrossRefGoogle ScholarPubMed
Lahti-Pulkkinen, M, Cudmore, MJ, Haeussner, E, Schmitz, C, Pesonen, AK, Hamalainen, E, Villa, PM, Mehtala, S, Kajantie, E, Laivuori, H, Reynolds, RM, Frank, HG and Raikkonen, K (2018) Placental morphology is associated with maternal depressive symptoms during pregnancy and toddler psychiatric problems. Scientific Reports 8, 791.CrossRefGoogle ScholarPubMed
Lai, JS, Hiles, S, Bisquera, A, Hure, AJ, McEvoy, M and Attia, J (2014) A systematic review and meta-analysis of dietary patterns and depression in community-dwelling adults. American Journal of Clinical Nutrition 99, 181197.CrossRefGoogle ScholarPubMed
Lai, HM, Cleary, M, Sitharthan, T and Hunt, GE (2015) Prevalence of comorbid substance use, anxiety and mood disorders in epidemiological surveys, 1990–2014: a systematic review and meta-analysis. Drug and Alcohol Dependence 154, 113.CrossRefGoogle ScholarPubMed
Leff-Gelman, P, Mancilla-Herrera, I, Flores-Ramos, M, Cruz-Fuentes, C, Reyes-Grajeda, JP, Garcia-Cuetara Mdel, P, Bugnot-Perez, MD and Pulido-Ascencio, DE (2016) The immune system and the role of inflammation in perinatal depression. Neuroscience Bulletin 32, 398420.CrossRefGoogle ScholarPubMed
Li, Y, Zhong, X, Cheng, G, Zhao, C, Zhang, L, Hong, Y, Wan, Q, He, R and Wang, Z (2017) Hs-CRP and all-cause, cardiovascular, and cancer mortality risk: a meta-analysis. Atherosclerosis 259, 7582.CrossRefGoogle ScholarPubMed
Liukkonen, T, Rasanen, P, Jokelainen, J, Leinonen, M, Jarvelin, MR, Meyer-Rochow, VB and Timonen, M (2011) The association between anxiety and C-reactive protein (CRP) levels: results from the Northern Finland 1966 birth cohort study. European Psychiatry 26, 363369.CrossRefGoogle ScholarPubMed
Lund-Sorensen, H, Benros, ME, Madsen, T, Sorensen, HJ, Eaton, WW, Postolache, TT, Nordentoft, M and Erlangsen, A (2016) A nationwide cohort study of the association between hospitalization with infection and risk of death by suicide. JAMA Psychiatry 73, 912919.CrossRefGoogle ScholarPubMed
Luppino, FS, de Wit, LM, Bouvy, PF, Stijnen, T, Cuijpers, P, Penninx, BW and Zitman, FG (2010) Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Archives of General Psychiatry 67, 220229.CrossRefGoogle ScholarPubMed
Mahajan, GJ, Vallender, EJ, Garrett, MR, Challagundla, L, Overholser, JC, Jurjus, G, Dieter, L, Syed, M, Romero, DG, Benghuzzi, H and Stockmeier, CA (2018) Altered neuro-inflammatory gene expression in hippocampus in major depressive disorder. Progress in Neuro-Psychopharmacology & Biological Psychiatry 82, 177186.CrossRefGoogle ScholarPubMed
Milaneschi, Y, Simmons, WK, van Rossum, EFC and Penninx, BW (2019) Depression and obesity: evidence of shared biological mechanisms. Molecular Psychiatry 29, 2433.Google Scholar
Molyneaux, E, Poston, L, Ashurst-Williams, S and Howard, LM (2014) Pre-pregnancy obesity and mental disorders during pregnancy and postpartum: a systematic review and meta-analysis. Pregnancy Hypertension 4, 236.CrossRefGoogle ScholarPubMed
Osborne, S, Biaggi, A, Chua, TE, Du Preez, A, Hazelgrove, K, Nikkheslat, N, Previti, G, Zunszain, PA, Conroy, S and Pariante, CM (2018) Antenatal depression programs cortisol stress reactivity in offspring through increased maternal inflammation and cortisol in pregnancy: The Psychiatry Research and Motherhood – Depression (PRAM-D) Study. Psychoneuroendocrinology 98, 211236.CrossRefGoogle ScholarPubMed
Ovesen, P, Rasmussen, S and Kesmodel, U (2011) Effect of prepregnancy maternal overweight and obesity on pregnancy outcome. Obstetrics & Gynecology 118, 305312.CrossRefGoogle ScholarPubMed
Pantham, P, Aye, IL and Powell, TL (2015) Inflammation in maternal obesity and gestational diabetes mellitus. Placenta 36, 709715.CrossRefGoogle ScholarPubMed
Pariante, CM (2017) Why are depressed patients inflamed? A reflection on 20 years of research on depression, glucocorticoid resistance and inflammation. European Neuropsychopharmacology 27, 554559.CrossRefGoogle ScholarPubMed
Plant, DT, Pawlby, S, Sharp, D, Zunszain, PA and Pariante, CM (2016) Prenatal maternal depression is associated with offspring inflammation at 25 years: a prospective longitudinal cohort study. Translational Psychiatry 6, e936.CrossRefGoogle ScholarPubMed
Radloff, LS (1977) The CES-D scale: a self-report depression scale for research in the general population. Applied Psychological Measurement 1, 385401.CrossRefGoogle Scholar
Raikkonen, K, Pesonen, AK, O'Reilly, JR, Tuovinen, S, Lahti, M, Kajantie, E, Villa, P, Laivuori, H, Hamalainen, E, Seckl, JR and Reynolds, RM (2015) Maternal depressive symptoms during pregnancy, placental expression of genes regulating glucocorticoid and serotonin function and infant regulatory behaviors. Psychological Medicine 45, 32173226.CrossRefGoogle ScholarPubMed
Rebelo, F, Schlussel, MM, Vaz, JS, Franco-Sena, AB, Pinto, TJ, Bastos, FI, Adegboye, AR and Kac, G (2013) C-reactive protein and later preeclampsia: systematic review and meta-analysis taking into account the weight status. Journal of Hypertension 31, 1626.CrossRefGoogle ScholarPubMed
Reynolds, RM, Pesonen, AK, O'Reilly, JR, Tuovinen, S, Lahti, M, Kajantie, E, Villa, PM, Laivuori, H, Hamalainen, E, Seckl, JR and Raikkonen, K (2015) Maternal depressive symptoms throughout pregnancy are associated with increased placental glucocorticoid sensitivity. Psychological Medicine 45, 20232030.CrossRefGoogle ScholarPubMed
Ritchie, SC, Würtz, P, Nath, AP, Abraham, G, Havulinna, AS, Fearnley, LG, Sarin, A-P, Kangas, AJ, Soininen, P, Aalto, K, Seppälä, I, Raitoharju, E, Salmi, M, Maksimow, M, Männistö, S, Kähönen, M, Juonala, M, Ripatti, S, Lehtimäki, T, Jalkanen, S, Perola, M, Raitakari, O, Salomaa, V, Ala-Korpela, M, Kettunen, J and Inouye, M (2015) The biomarker GlycA is associated with chronic inflammation and predicts long-term risk of severe infection. Cell Systems 1, 293301.CrossRefGoogle ScholarPubMed
Scrandis, DA, Langenberg, P, Tonelli, LH, Sheikh, TM, Manogura, AC, Alberico, LA, Hermanstyne, T, Fuchs, D, Mighty, H, Hasday, JD, Boteva, K and Postolache, TT (2008) Prepartum depressive symptoms correlate positively with C-reactive protein levels and negatively with tryptophan levels: a preliminary report. International Journal of Child Health and Human Development: IJCHD 1, 167174.Google ScholarPubMed
Simmonds, M, Llewellyn, A, Owen, CG and Woolacott, N (2016) Predicting adult obesity from childhood obesity: a systematic review and meta-analysis. Obesity Reviews 17, 95107.CrossRefGoogle ScholarPubMed
Simpson, W, Steiner, M, Coote, M and Frey, BN (2016) Relationship between inflammatory biomarkers and depressive symptoms during late pregnancy and the early postpartum period: a longitudinal study. Brazilian Journal of Psychiatry 38, 190196.CrossRefGoogle ScholarPubMed
Soininen, P, Kangas, AJ, Wurtz, P, Suna, T and Ala-Korpela, M (2015) Quantitative serum nuclear magnetic resonance metabolomics in cardiovascular epidemiology and genetics. Circulation: Cardiovascular Genetics 8, 192206.Google ScholarPubMed
Stetler, C and Miller, GE (2011) Depression and hypothalamic-pituitary-adrenal activation: a quantitative summary of four decades of research. Psychosomatic Medicine 73, 114126.CrossRefGoogle ScholarPubMed
Stubbs, B, Vancampfort, D, Firth, J, Schuch, FB, Hallgren, M, Smith, L, Gardner, B, Kahl, KG, Veronese, N, Solmi, M, Carvalho, AF and Koyanagi, A (2018) Relationship between sedentary behavior and depression: a mediation analysis of influential factors across the lifespan among 42469 people in low- and middle-income countries. Journal of Affective Disorders 229, 231238.CrossRefGoogle ScholarPubMed
Tuovinen, S, Lahti-Pulkkinen, M, Girchenko, P, Lipsanen, J, Lahti, J, Heinonen, K, Reynolds, RM, Hamalainen, E, Kajantie, E, Laivuori, H, Pesonen, AK, Villa, PM and Raikkonen, K (2018) Maternal depressive symptoms during and after pregnancy and child developmental milestones. Depression and Anxiety 35, 732741.CrossRefGoogle ScholarPubMed
Valkanova, V, Ebmeier, KP and Allan, CL (2013) CRP, IL-6 and depression: a systematic review and meta-analysis of longitudinal studies. Journal of Affective Disorders 150, 736744.CrossRefGoogle ScholarPubMed
Van den Bergh, BRH, van den Heuvel, MI, Lahti, M, Braeken, M, de Rooij, SR, Entringer, S, Hoyer, D, Roseboom, T, Raikkonen, K, King, S and Schwab, M (2017) Prenatal developmental origins of behavior and mental health: the influence of maternal stress in pregnancy. Neuroscience and Biobehavioral Reviews. doi: 10.1016/j.neubiorev.2017.07.003.CrossRefGoogle ScholarPubMed
Walker, DJ and Spencer, KA (2018) Glucocorticoid programming of neuroimmune function. Genetic and Comparative Endocrinology 256, 8088.CrossRefGoogle ScholarPubMed
Wang, Q, Würtz, P, Auro, K, Mäkinen, V-P, Kangas, AJ, Soininen, P, Tiainen, M, Tynkkynen, T, Jokelainen, J, Santalahti, K, Salmi, M, Blankenberg, S, Zeller, T, Viikari, J, Kähönen, M, Lehtimäki, T, Salomaa, V, Perola, M, Jalkanen, S, Järvelin, M-R, Raitakari, OT, Kettunen, J, Lawlor, DA and Ala-Korpela, M (2016) Metabolic profiling of pregnancy: cross-sectional and longitudinal evidence. BMC Medicine 14, 205.CrossRefGoogle ScholarPubMed
Wells, G, Shea, B, O'Connell, D, Peterson, J, Welch, V, Losos, M and Tugwell, P (2014a) Newcastle-Ottawa quality assessment form for cohort studies. pp. E17E18. Available at http://www.ncbi.nlm.nih.gov/books/NBK115843/bin/appe-fm3.pdf.Google Scholar
Wells, G, Shea, B, O'Connell, D, Peterson, J, Welch, V, Losos, M and Tugwell, P (2014b) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Available at http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.Google Scholar
WHO (2000) Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organization Technical Report Series, 894, i-xii, pp. 1-253.Google Scholar
Wirtz, DC, Heller, KD, Miltner, O, Zilkens, KW and Wolff, JM (2000) Interleukin-6: a potential inflammatory marker after total joint replacement. International Orthopaedics 24, 194196.CrossRefGoogle ScholarPubMed
Wium-Andersen, MK, Orsted, DD and Nordestgaard, BG (2014) Elevated C-reactive protein, depression, somatic diseases, and all-cause mortality: a Mendelian randomization study. Biological Psychiatry 76, 249257.CrossRefGoogle ScholarPubMed
Woody, CA, Ferrari, AJ, Siskind, DJ, Whiteford, HA and Harris, MG (2017) A systematic review and meta-regression of the prevalence and incidence of perinatal depression. Journal of Affective Disorders 219, 8692.CrossRefGoogle ScholarPubMed
Wray, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Adams, MJ, Agerbo, E, Air, TM, Andlauer, TMF, Bacanu, SA, Baekvad-Hansen, M, Beekman, AFT, Bigdeli, TB, Binder, EB, Blackwood, DRH, Bryois, J, Buttenschon, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, TK, Coleman, JIR, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Crowley, CA, Dashti, HS, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Direk, N, Dolan, CV, Dunn, EC, Eley, TC, Eriksson, N, Escott-Price, V, Kiadeh, FHF, Finucane, HK, Forstner, AJ, Frank, J, Gaspar, HA, Gill, M, Giusti-Rodriguez, P, Goes, FS, Gordon, SD, Grove, J, Hall, LS, Hannon, E, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, JJ, Hougaard, DM, Hu, M, Hyde, CL, Ising, M, Jansen, R, Jin, F, Jorgenson, E, Knowles, JA, Kohane, IS, Kraft, J, Kretzschmar, WW, Krogh, J, Kutalik, Z, Lane, JM, Li, Y, Li, Y, Lind, PA, Liu, X, Lu, L, MacIntyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, McGrath, P, McGuffin, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milaneschi, Y, Milani, L, Mill, J, Mondimore, FM, Montgomery, GW, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, O'Reilly, PF, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, Posthuma, D, Purcell, SM, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Saeed Mirza, S, Saxena, R, Schoevers, R, Schulte, EC, Shen, L, Shi, J, Shyn, SI, Sigurdsson, E, Sinnamon, GBC, Smit, JH, Smith, DJ, Stefansson, H, Steinberg, S, Stockmeier, CA, Streit, F, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thomson, PA, Thorgeirsson, TE, Tian, C, Traylor, M, Treutlein, J, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, Van der Auwera, S, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Witt, SH, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Baune, BT, Berger, K, Boomsma, DI, Cichon, S, Dannlowski, U, de Geus, ECJ, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Grabe, HJ, Hamilton, SP, Hayward, C, Heath, AC, Hinds, DA, Kendler, KS, Kloiber, S, Lewis, G, Li, QS, Lucae, S, Madden, PFA, Magnusson, PK, Martin, NG, McIntosh, AM, Metspalu, A, Mors, O, Mortensen, PB, Muller-Myhsok, B, Nordentoft, M, Nothen, MM, O'Donovan, MC, Paciga, SA, Pedersen, NL, Penninx, B, Perlis, RH, Porteous, DJ, Potash, JB, Preisig, M, Rietschel, M, Schaefer, C, Schulze, TG, Smoller, JW, Stefansson, K, Tiemeier, H, Uher, R, Volzke, H, Weissman, MM, Werge, T, Winslow, AR, Lewis, CM, Levinson, DF, Breen, G, Borglum, AD and Sullivan, PF (2018) Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nature Genetics 50, 668681.CrossRefGoogle ScholarPubMed
Supplementary material: File

Lahti-Pulkkinen et al. supplementary material

Lahti-Pulkkinen et al. supplementary material 1

Download Lahti-Pulkkinen et al. supplementary material(File)
File 5.1 MB