Meals, Microbiota and Mental Health in Children and Adolescents (MMM-Study): A protocol for an observational longitudinal case-control study

Birna Asbjornsdottir, Bertrand Lauth, Alessio Fasano, Inga Thorsdottir, Ingibjorg Karlsdottir, Larus S Gudmundsson, Magnus Gottfredsson, Orri Smarason, Sigurveig Sigurdardottir, Thorhallur I Halldorsson, Viggo Thor Marteinsson, Valborg Gudmundsdottir, Bryndis Eva Birgisdottir, Birna Asbjornsdottir, Bertrand Lauth, Alessio Fasano, Inga Thorsdottir, Ingibjorg Karlsdottir, Larus S Gudmundsson, Magnus Gottfredsson, Orri Smarason, Sigurveig Sigurdardottir, Thorhallur I Halldorsson, Viggo Thor Marteinsson, Valborg Gudmundsdottir, Bryndis Eva Birgisdottir

Abstract

Recent studies indicate that the interplay between diet, intestinal microbiota composition, and intestinal permeability can impact mental health. More than 10% of children and adolescents in Iceland suffer from mental disorders, and rates of psychotropics use are very high. The aim of this novel observational longitudinal case-control study, "Meals, Microbiota and Mental Health in Children and Adolescents (MMM-Study)" is to contribute to the promotion of treatment options for children and adolescents diagnosed with mental disorders through identification of patterns that may affect the symptoms. All children and adolescents, 5-15 years referred to the outpatient clinic of the Child and Adolescent Psychiatry Department at The National University Hospital in Reykjavik, Iceland, for one year (n≈150) will be invited to participate. There are two control groups, i.e., sex-matched children from the same postal area (n≈150) and same parent siblings (full siblings) in the same household close in age +/- 3 years (n<150). A three-day food diary, rating scales for mental health, and multiple questionnaires will be completed. Biosamples (fecal-, urine-, saliva-, blood samples, and buccal swab) will be collected and used for 16S rRNA gene amplicon sequencing of the oral and gut microbiome, measurements of serum factors, quantification of urine metabolites and host genotype, respectively. For longitudinal follow-up, data collection will be repeated after three years in the same groups. Integrative analysis of diet, gut microbiota, intestinal permeability, serum metabolites, and mental health will be conducted applying bioinformatics and systems biology approaches. Extensive population-based data of this quality has not been collected before, with collection repeated in three years' time, contributing to the high scientific value. The MMM-study follows the "Strengthening the Reporting of Observational Studies in Epidemiology" (STROBE) guidelines. Approval has been obtained from the Icelandic National Bioethics Committee, and the study is registered with Clinicaltrials.gov. The study will contribute to an improved understanding of the links between diet, gut microbiota and mental health in children through good quality study design by collecting information on multiple components, and a longitudinal approach. Furthermore, the study creates knowledge on possibilities for targeted and more personalized dietary and lifestyle interventions in subgroups. Trial registration numbers: VSN-19-225 & NCT04330703.

Conflict of interest statement

The authors have declared that no competing intrests exist.

Figures

Fig 1. Meals, Microbiota, and Mental Health…
Fig 1. Meals, Microbiota, and Mental Health of Children and Adolescents study design.

References

    1. Asbjornsdottir B, Snorradottir H, Andresdottir E, Fasano A, Lauth B, Gudmundsson LS, et al.. Zonulin-Dependent Intestinal Permeability in Children Diagnosed with Mental Disorders: A Systematic Review and Meta-Analysis. Nutrients 2020;12:1982. doi: 10.3390/nu12071982
    1. Levy RL, Olden KW, Naliboff BD, Bradley LA, Francisconi C, Drossman DA, et al.. Psychosocial aspects of the functional gastrointestinal disorders. Gastroenterology 2006;130:1447–58. doi: 10.1053/j.gastro.2005.11.057
    1. Olden KW, Drossman DA. Psychologic and psychiatric aspects of gastrointestinal disease. Med Clin North Am 2000;84:1313–27. doi: 10.1016/s0025-7125(05)70288-1
    1. Rose DR, Yang H, Serena G, Sturgeon C, Ma B, Careaga M, et al.. Differential immune responses and microbiota profiles in children with autism spectrum disorders and co-morbid gastrointestinal symptoms. Brain, Behavior, and Immunity 2018;70:354–68. doi: 10.1016/j.bbi.2018.03.025
    1. Holzapfel WH, Haberer P, Snel J, Schillinger U, Huis in’t Veld JHJ. Overview of gut flora and probiotics. International Journal of Food Microbiology 1998;41:85–101. doi: 10.1016/s0168-1605(98)00044-0
    1. Fasano A. All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases. F1000Res 2020;9. 10.12688/F1000RESEARCH.20510.1.
    1. Esnafoglu E, Cırrık S, Ayyıldız SN, Erdil A, Ertürk EY, Daglı A, et al.. Increased Serum Zonulin Levels as an Intestinal Permeability Marker in Autistic Subjects. Journal of Pediatrics 2017;188:240–4. doi: 10.1016/j.jpeds.2017.04.004
    1. du Preez S, Corbitt M, Cabanas H, Eaton N, Staines D, Marshall-Gradisnik S. A systematic review of enteric dysbiosis in chronic fatigue syndrome/myalgic encephalomyelitis. Syst Rev 2018;7:241. doi: 10.1186/s13643-018-0909-0
    1. Alvarez-Mon MA, Gómez AM, Orozco A, Lahera G, Sosa MD, Diaz D, et al.. Abnormal Distribution and Function of Circulating Monocytes and Enhanced Bacterial Translocation in Major Depressive Disorder. Front Psychiatry 2019;10:812. doi: 10.3389/fpsyt.2019.00812
    1. Stevens BR, Goel R, Seungbum K, Richards EM, Holbert RC, Pepine CJ, et al.. Increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depression. Gut 2018;67:1555–7. 10.1136/gutjnl-2017-314759.
    1. Maes M, Sirivichayakul S, Kanchanatawan B, Vodjani A. Upregulation of the Intestinal Paracellular Pathway with Breakdown of Tight and Adherens Junctions in Deficit Schizophrenia. Molecular Neurobiology 2019;56:7056–73. doi: 10.1007/s12035-019-1578-2
    1. Barber GS, Sturgeon C, Fasano A, Cascella NG, Eaton WW, McMahon RP, et al.. Elevated zonulin, a measure of tight-junction permeability, may be implicated in schizophrenia. Schizophrenia Research 2019;211:111–2. doi: 10.1016/j.schres.2019.07.006
    1. Fasano A. Intestinal Permeability and Its Regulation by Zonulin: Diagnostic and Therapeutic Implications. Clinical Gastroenterology and Hepatology 2012;10:1096–100. doi: 10.1016/j.cgh.2012.08.012
    1. Fasano A. Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer 2011. 10.1152/physrev.00003.2008.
    1. Fasano A. Zonulin, regulation of tight junctions, and autoimmune diseases. Ann N Y Acad Sci 2012;1258:25–33. doi: 10.1111/j.1749-6632.2012.06538.x
    1. Fasano A. Leaky Gut and Autoimmune Diseases. Clinical Reviews in Allergy & Immunology 2012;42:71–8. doi: 10.1007/s12016-011-8291-x
    1. Sturgeon C, Fasano A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers 2016;4:e1251384. doi: 10.1080/21688370.2016.1251384
    1. Asmar R el, Panigrahi P, Bamford P, Berti I, Not T, Coppa G v., et al.. Host-dependent zonulin secretion causes the impairment of the small intestine barrier function after bacterial exposure. Gastroenterology 2002;123:1607–15. doi: 10.1053/gast.2002.36578
    1. Fiorentino M, Sapone A, Senger S, Camhi SS, Kadzielski SM, Buie TM, et al.. Blood–brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders. Molecular Autism 2016;7. 10.1186/s13229-016-0110-z.
    1. Yang B, Wei J, Ju P, Chen J. Effects of regulating intestinal microbiota on anxiety symptoms: A systematic review. General Psychiatry 2019;32:e100056. doi: 10.1136/gpsych-2019-100056
    1. Thapar A, Cooper M, Eyre O, Langley K. What have we learnt about the causes of ADHD? J Child Psychol Psychiatry 2013;54:3–16. doi: 10.1111/j.1469-7610.2012.02611.x
    1. Lesch K-P. Editorial: Illuminating the dark matter of developmental neuropsychiatric genetics—strategic focus for future research in child psychology and psychiatry. J Child Psychol Psychiatry 2014;55:201–3. doi: 10.1111/jcpp.12223
    1. Hansen BH, Oerbeck B, Skirbekk B, Petrovski BÉ, Kristensen H. Neurodevelopmental disorders: prevalence and comorbidity in children referred to mental health services. Nordic Journal of Psychiatry 2018;72:285–91. doi: 10.1080/08039488.2018.1444087
    1. Stein DJ, Szatmari P, Gaebel W, Berk M, Vieta E, Maj M, et al.. Mental, behavioral and neurodevelopmental disorders in the ICD-11: an international perspective on key changes and controversies. BMC Medicine 2020;18:21. doi: 10.1186/s12916-020-1495-2
    1. Mcginnity Á, Meltzer H, Ford T, Goodman R. Mental health of children and young people in Great Britain, 2004. 2005.
    1. National Institute of Mental Health. NIMH » Treatment of Children with Mental Illness n.d. .
    1. Kern JK, Geier DA, King PG, Sykes LK, Mehta JA, Geier MR. Shared Brain Connectivity Issues, Symptoms, and Comorbidities in Autism Spectrum Disorder, Attention Deficit/Hyperactivity Disorder, and Tourette Syndrome. Brain Connect 2015;5:321–35. doi: 10.1089/brain.2014.0324
    1. Caspi A, Houts RM, Ambler A, Danese A, Elliott ML, Hariri A, et al.. Longitudinal Assessment of Mental Health Disorders and Comorbidities Across 4 Decades Among Participants in the Dunedin Birth Cohort Study. JAMA Network Open 2020;3:e203221. doi: 10.1001/jamanetworkopen.2020.3221
    1. Dalsgaard S, Thorsteinsson E, Trabjerg BB, Schullehner J, Plana-Ripoll O, Brikell I, et al.. Incidence Rates and Cumulative Incidences of the Full Spectrum of Diagnosed Mental Disorders in Childhood and Adolescence. JAMA Psychiatry 2020;77:155–64. doi: 10.1001/jamapsychiatry.2019.3523
    1. Polanczyk G v Salum GA, Sugaya LS, Caye A, Rohde LA. Annual research review: A meta-analysis of the worldwide prevalence of mental disorders in children and adolescents. J Child Psychol Psychiatry 2015;56:345–65. doi: 10.1111/jcpp.12381
    1. Ogden CL, Carroll MD, Curtin LR, Lamb MM, Flegal KM. Prevalence of High Body Mass Index in US Children and Adolescents, 2007–2008. JAMA 2010;303:242. doi: 10.1001/jama.2009.2012
    1. Roper WL, Hamburg MA, King Holmes DK, Deborah Holtzman W, John Iglehart GK, Maki DG, et al.. Morbidity and Mortality Weekly Report Centers for Disease Control and Prevention Editorial and Production Staff. 2007.
    1. Baranne ML, Falissard B. Global burden of mental disorders among children aged 5–14 years. Child and Adolescent Psychiatry and Mental Health 2018;12:19. doi: 10.1186/s13034-018-0225-4
    1. Þórðarson Ó, Ævarsson FM, Helgadóttir S, Lauth B, Wessman I, Sigurjónsdóttir SA, et al.. Icelandic translation and reliability data on the DSM-5 version of the schedule for affective disorders and schizophrenia for school-aged children–present and lifetime version (K-SADS-PL). Nordic Journal of Psychiatry 2020;74:423–8. doi: 10.1080/08039488.2020.1733660
    1. Johannesdottir A. Tilvísanir á göngudeild og í bráðaþjónustu BUGL. University of Iceland, 2017.
    1. Bornstein RF. Toward a Multidimensional Model of Personality Disorder Diagnosis: Implications for DSM–5. Journal of Personality Assessment 2011;93:362–9. 10.1080/00223891.2011.577474.
    1. Kessler RC. The categorical versus dimensional assessment controversy in the sociology of mental illness. J Health Soc Behav 2002;43:171–88.
    1. Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium S, Ripke S, Wray NR, Lewis CM, Hamilton SP, Weissman MM, et al.. A mega-analysis of genome-wide association studies for major depressive disorder. Mol Psychiatry 2013;18:497–511. doi: 10.1038/mp.2012.21
    1. Power RA, Tansey KE, Buttenschøn HN, Cohen-Woods S, Bigdeli T, Hall LS, et al.. Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. Biological Psychiatry 2017;81:325–35. doi: 10.1016/j.biopsych.2016.05.010
    1. Common mental health problems: Common mental health problems: identification and path identification and pathwa ways to care ys to care 2011.
    1. Solomon CG, Feldman HM, Reiff MI. Attention Deficit–Hyperactivity Disorder in Children and Adolescents. N Engl J Med 2014;370:838–46. 10.1056/NEJMcp1307215.
    1. Galanter CA. Limited Support for the Efficacy of Nonpharmacological Treatments for the Core Symptoms of ADHD. American Journal of Psychiatry 2013;170:241–4. doi: 10.1176/appi.ajp.2012.12121561
    1. Ravid NL, Annunziato RA, Ambrose MA, Chuang K, Mullarkey C, Sicherer SH, et al.. Mental health and quality-of-life concerns related to the burden of food allergy. Psychiatr Clin North Am 2015;38:77–89. doi: 10.1016/j.psc.2014.11.004
    1. Hak E, de Vries TW, Hoekstra PJ, Jick SS. Association of childhood attention-deficit/hyperactivity disorder with atopic diseases and skin infections? A matched case-control study using the General Practice Research Database. Annals of Allergy, Asthma & Immunology 2013;111:102–106.e2. doi: 10.1016/j.anai.2013.05.023
    1. Dzidic M, Abrahamsson TR, Artacho A, Björkstén B, Collado MC, Mira A, et al.. Aberrant IgA responses to the gut microbiota during infancy precede asthma and allergy development. J Allergy Clin Immunol 2017;139:1017–1025.e14. doi: 10.1016/j.jaci.2016.06.047
    1. Chuang Y-C, Wang C-Y, Huang W-L, Wang L-J, Kuo H-C, Chen Y-C, et al.. Two meta-analyses of the association between atopic diseases and core symptoms of attention deficit hyperactivity disorder. Scientific Reports 2022;12:3377. doi: 10.1038/s41598-022-07232-1
    1. Singh RK, Chang H-W, Yan D, Lee KM, Ucmak D, Wong K, et al.. Influence of diet on the gut microbiome and implications for human health. Journal of Translational Medicine 2017;15:73. doi: 10.1186/s12967-017-1175-y
    1. Catinean A, Neag MA, Muntean DM, Bocsan IC, Buzoianu AD. An overview on the interplay between nutraceuticals and gut microbiota. PeerJ 2018;6:e4465. doi: 10.7717/peerj.4465
    1. Flint HJ, Duncan SH, Louis P. The impact of nutrition on intestinal bacterial communities. Current Opinion in Microbiology 2017;38:59–65. doi: 10.1016/j.mib.2017.04.005
    1. Logan AC, Jacka FN, Craig JM, Prescott SL. The Microbiome and Mental Health: Looking Back, Moving Forward with Lessons from Allergic Diseases. Clin Psychopharmacol Neurosci 2016;14:131–47. doi: 10.9758/cpn.2016.14.2.131
    1. Yoo BB, Mazmanian SK. The Enteric Network: Interactions between the Immune and Nervous Systems of the Gut. Immunity 2017;46:910–26. doi: 10.1016/j.immuni.2017.05.011
    1. Liu RT. The microbiome as a novel paradigm in studying stress and mental health. American Psychologist 2017;72:655–67. doi: 10.1037/amp0000058
    1. McIntyre RS, Subramaniapillai M, Shekotikhina M, Carmona NE, Lee Y, Mansur RB, et al.. Characterizing the gut microbiota in adults with bipolar disorder: a pilot study. Nutritional Neuroscience 2019:1–8. doi: 10.1080/1028415X.2019.1612555
    1. Dalile B, van Oudenhove L, Vervliet B, Verbeke K. The role of short-chain fatty acids in microbiota–gut–brain communication. Nature Reviews Gastroenterology & Hepatology 2019. doi: 10.1038/s41575-019-0157-3
    1. Hwang Y-H, Park S, Paik J-W, Chae S-W, Kim D-H, Jeong D-G, et al.. Efficacy and Safety of Lactobacillus Plantarum C29-Fermented Soybean (DW2009) in Individuals with Mild Cognitive Impairment: A 12-Week, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Nutrients 2019;11:305. doi: 10.3390/nu11020305
    1. Bear TLK, Dalziel JE, Coad J, Roy NC, Butts CA, Gopal PK. The Role of the Gut Microbiota in Dietary Interventions for Depression and Anxiety. Advances in Nutrition 2020. doi: 10.1093/advances/nmaa016
    1. Iddrisu I, Monteagudo-Mera A, Poveda C, Pyle S, Shahzad M, Andrews S, et al.. Malnutrition and Gut Microbiota in Children. Nutrients 2021;13. 10.3390/nu13082727.
    1. Kim B, Choi H-N, Yim J-E. Effect of Diet on the Gut Microbiota Associated with Obesity. J Obes Metab Syndr 2019;28:216–24. doi: 10.7570/jomes.2019.28.4.216
    1. Greenhill C. Gut microbiota: Firmicutes and Bacteroidetes involved in insulin resistance by mediating levels of glucagon-like peptide 1. Nat Rev Endocrinol 2015;11:254. doi: 10.1038/nrendo.2015.40
    1. Mariat D, Firmesse O, Levenez F, Guimarăes V, Sokol H, Doré J, et al.. The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol 2009;9:123. doi: 10.1186/1471-2180-9-123
    1. Koliada A, Syzenko G, Moseiko V, Budovska L, Puchkov K, Perederiy V, et al.. Association between body mass index and Firmicutes/Bacteroidetes ratio in an adult Ukrainian population. BMC Microbiology 2017;17:120. doi: 10.1186/s12866-017-1027-1
    1. Wegh CAM, Schoterman MHC, Vaughan EE, Belzer C, Benninga MA. The effect of fiber and prebiotics on children’s gastrointestinal disorders and microbiome. Expert Rev Gastroenterol Hepatol 2017;11:1031–45. doi: 10.1080/17474124.2017.1359539
    1. Lai H-C, Young J, Lin C-S, Chang C-J, Lu C-C, Martel J, et al.. Impact of the gut microbiota, prebiotics, and probiotics on human health and disease. Biomedical Journal 2014;37:259. doi: 10.4103/2319-4170.138314
    1. Druart C, Alligier M, Salazar N, Neyrinck AM, Delzenne NM. Modulation of the Gut Microbiota by Nutrients with Prebiotic and Probiotic Properties. Advances in Nutrition: An International Review Journal 2014;5:624S–633S. 10.3945/an.114.005835.
    1. Hemarajata P, Versalovic J. Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation. Therap Adv Gastroenterol 2013;6:39–51. doi: 10.1177/1756283X12459294
    1. Lazar V, Ditu L-M, Pircalabioru GG, Picu A, Petcu L, Cucu N, et al.. Gut Microbiota, Host Organism, and Diet Trialogue in Diabetes and Obesity. Frontiers in Nutrition 2019;6:21. doi: 10.3389/fnut.2019.00021
    1. Bressan P, Kramer P. Bread and Other Edible Agents of Mental Disease. Frontiers in Human Neuroscience 2016;10:130. doi: 10.3389/fnhum.2016.00130
    1. Shah E, Rezaie A, Riddle M, Pimentel M. Psychological disorders in gastrointestinal disease: epiphenomenon, cause or consequence? Ann Gastroenterol 2014;27:224–30.
    1. Portincasa P, Lembo A, de Bari O, di Palo DM, Maggio A, Cataldo I, et al.. The role of dietary approach in irritable bowel syndrome. Current Medicinal Chemistry 2017;24:1–1. 10.2174/0929867324666170428102451.
    1. Jacka FN, Cherbuin N, Anstey KJ, Butterworth P. Does reverse causality explain the relationship between diet and depression? Journal of Affective Disorders 2015;175:248–50. doi: 10.1016/j.jad.2015.01.007
    1. Firth J, Marx W, Dash S, Carney R, Teasdale SB, Solmi M, et al.. The Effects of Dietary Improvement on Symptoms of Depression and Anxiety: A Meta-Analysis of Randomized Controlled Trials. Psychosom Med 2019;81:265–80. doi: 10.1097/PSY.0000000000000673
    1. LaChance LR, Ramsey D. Antidepressant foods: An evidence-based nutrient profiling system for depression. World J Psychiatry 2018;8:97–104. doi: 10.5498/wjp.v8.i3.97
    1. Holton KF, Nigg JT. The Association of Lifestyle Factors and ADHD in Children. J Atten Disord 2016. doi: 10.1177/1087054716646452
    1. Cagigal C, Silva T, Jesus M, Silva C. Does Diet Affect the Symptoms of ADHD? Current Pharmaceutical Biotechnology 2019;20:130–6. doi: 10.2174/1389201019666180925140733
    1. Watanabe N, Matsuoka Y, Kumachi M, Hamazaki K, Horikoshi M, Furukawa TA. Omega-3 fatty acids for a better mental state in working populations—Happy Nurse Project: A 52-week randomized controlled trial. Journal of Psychiatric Research 2018;102:72–80. doi: 10.1016/j.jpsychires.2018.03.015
    1. Ólason DT, Sighvatsson MB, Smári J. Psychometric properties of the Multidimensional Anxiety Scale for Children (MASC) among Icelandic schoolchildren. Scandinavian Journal of Psychology 2004;45:429–36. doi: 10.1111/j.1467-9450.2004.00424.x
    1. Ghasemi Fard S, Wang F, Sinclair AJ, Elliott G, Turchini GM. How does high DHA fish oil affect health? A systematic review of evidence. Critical Reviews in Food Science and Nutrition 2018;8398:1–44. 10.1080/10408398.2018.1425978.
    1. Su KP, Tseng PT, Lin PY, Okubo R, Chen TY, Chen YW, et al.. Association of Use of Omega-3 Polyunsaturated Fatty Acids With Changes in Severity of Anxiety Symptoms: A Systematic Review and Meta-analysis. JAMA Netw Open 2018;1. doi: 10.1001/jamanetworkopen.2018.2327
    1. Kim S, Arora M, Fernandez C, Landero J, Caruso J, Chen A. Lead, mercury, and cadmium exposure and attention deficit hyperactivity disorder in children. Environmental Research 2013;126:105–10. doi: 10.1016/j.envres.2013.08.008
    1. von Schacky C. Importance of EPA and DHA Blood Levels in Brain Structure and Function. Nutrients 2021;13:1074. doi: 10.3390/nu13041074
    1. Gabbay V, Freed RD, Alonso CM, Senger S, Stadterman J, Davison BA, et al.. A Double-Blind Placebo-Controlled Trial of Omega-3 Fatty Acids as a Monotherapy for Adolescent Depression. J Clin Psychiatry 2018;79. doi: 10.4088/JCP.17m11596
    1. McNamara RK, Strimpfel J, Jandacek R, Rider T, Tso P, Welge JA, et al.. Detection and Treatment of Long-Chain Omega-3 Fatty Acid Deficiency in Adolescents with SSRI-Resistant Major Depressive Disorder. PharmaNutrition 2014;2:38–46. doi: 10.1016/j.phanu.2014.02.002
    1. Fristad MA, Vesco AT, Young AS, Healy KZ, Nader ES, Gardner W, et al.. Pilot Randomized Controlled Trial of Omega-3 and Individual-Family Psychoeducational Psychotherapy for Children and Adolescents With Depression. J Clin Child Adolesc Psychol 2019;48:S105–18. doi: 10.1080/15374416.2016.1233500
    1. T J, H Z, B F, V M, W I, G I, et al.. Emulsified omega-3 fatty-acids modulate the symptoms of depressive disorder in children and adolescents: a pilot study. Child Adolesc Psychiatry Ment Health 2017;11. 10.1186/S13034-017-0167-2.
    1. Ginty AT, Conklin SM. Short-term supplementation of acute long-chain omega-3 polyunsaturated fatty acids may alter depression status and decrease symptomology among young adults with depression: A preliminary randomized and placebo controlled trial. Psychiatry Res 2015;229:485–9. doi: 10.1016/j.psychres.2015.05.072
    1. Nemets H, Nemets B, Apter A, Bracha Z, Belmaker RH. Omega-3 treatment of childhood depression: a controlled, double-blind pilot study. Am J Psychiatry 2006;163:1098–100. doi: 10.1176/ajp.2006.163.6.1098
    1. Smith B, Rogers SL, Blissett J, Ludlow AK. The relationship between sensory sensitivity, food fussiness and food preferences in children with neurodevelopmental disorders. Appetite 2020;150:104643. doi: 10.1016/j.appet.2020.104643
    1. Koponen KK, Salosensaari A, Ruuskanen MO, Havulinna AS, Männistö S, Jousilahti P, et al.. Associations of healthy food choices with gut microbiota profiles. The American Journal of Clinical Nutrition 2021;114:605–16. doi: 10.1093/ajcn/nqab077
    1. Rosenfeld CS. Microbiome Disturbances and Autism Spectrum Disorders. Drug Metab Dispos 2015;43:1557–71. doi: 10.1124/dmd.115.063826
    1. Tomova A, Husarova V, Lakatosova S, Bakos J, Vlkova B, Babinska K, et al.. Gastrointestinal microbiota in children with autism in Slovakia. Physiol Behav 2015;138:179–87. doi: 10.1016/j.physbeh.2014.10.033
    1. Wang L, Conlon MA, Christophersen CT, Sorich MJ, Angley MT. Gastrointestinal microbiota and metabolite biomarkers in children with autism spectrum disorders. Biomarkers in Medicine 2014;8:331–44. doi: 10.2217/bmm.14.12
    1. Pärtty A, Kalliomäki M, Wacklin P, Salminen S, Isolauri E. A possible link between early probiotic intervention and the risk of neuropsychiatric disorders later in childhood: a randomized trial. Pediatr Res 2015;77:823–8. doi: 10.1038/pr.2015.51
    1. Zhang M, Ma W, Zhang J, He Y, Wang J. Analysis of gut microbiota profiles and microbe-disease associations in children with autism spectrum disorders in China. Sci Rep 2018;8:13981. doi: 10.1038/s41598-018-32219-2
    1. Buie T. Potential Etiologic Factors of Microbiome Disruption in Autism. Clin Ther 2015;37:976–83. doi: 10.1016/j.clinthera.2015.04.001
    1. Lacorte E, Gervasi G, Bacigalupo I, Vanacore N, Raucci U, Parisi P. A Systematic Review of the Microbiome in Children With Neurodevelopmental Disorders. Frontiers in Neurology 2019;10:727. doi: 10.3389/fneur.2019.00727
    1. McGuinness AJ, Davis JA, Dawson SL, Loughman A, Collier F, O’Hely M, et al.. A systematic review of gut microbiota composition in observational studies of major depressive disorder, bipolar disorder and schizophrenia. Molecular Psychiatry 2022:1–16. 10.1038/s41380-022-01456-3.
    1. Jin D, Wu S, Zhang Y, Lu R, Xia Y, Dong H, et al.. Lack of Vitamin D Receptor Causes Dysbiosis and Changes the Functions of the Murine Intestinal Microbiome. Clinical Therapeutics 2015;37:996–1009.e7. doi: 10.1016/j.clinthera.2015.04.004
    1. Levy M, Thaiss CA, Elinav E. Metagenomic cross-talk: the regulatory interplay between immunogenomics and the microbiome. Genome Med 2015;7:120. doi: 10.1186/s13073-015-0249-9
    1. Shapiro H, Thaiss CA, Levy M, Elinav E. The cross talk between microbiota and the immune system: metabolites take center stage. Current Opinion in Immunology 2014;30:54–62. doi: 10.1016/j.coi.2014.07.003
    1. Thaiss CA, Levy M, Suez J, Elinav E. The interplay between the innate immune system and the microbiota. Curr Opin Immunol 2014;26:41–8. doi: 10.1016/j.coi.2013.10.016
    1. Nichols RG, Davenport ER. The relationship between the gut microbiome and host gene expression: a review. Hum Genet 2021;140:747–60. doi: 10.1007/s00439-020-02237-0
    1. Thaiss CA, Elinav E. Exploring New Horizons in Microbiome Research. Cell Host & Microbe 2014;15:662–7. 10.1016/J.CHOM.2014.05.016.
    1. Sullivan PF, Daly MJ, O’Donovan M. Genetic architectures of psychiatric disorders: the emerging picture and its implications. Nat Rev Genet 2012;13:537–51. doi: 10.1038/nrg3240
    1. Rogers GB, Keating DJ, Young RL, Wong M-L, Licinio J, Wesselingh S. From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways. Molecular Psychiatry 2016;21:738–48. doi: 10.1038/mp.2016.50
    1. Mörkl S, Wagner-Skacel J, Lahousen T, Lackner S, Holasek SJ, Bengesser SA, et al.. The Role of Nutrition and the Gut-Brain Axis in Psychiatry: A Review of the Literature. Neuropsychobiology 2020;79:80–8. 10.1159/000492834.
    1. Chen LL, Abbaspour A, Mkoma GF, Bulik CM, Rück C, Djurfeldt D. Gut Microbiota in Psychiatric Disorders: A Systematic Review. Psychosomatic Medicine 2021;83:679–92. doi: 10.1097/PSY.0000000000000959
    1. Lima-Ojeda JM, Rupprecht R, Baghai TC. “I am i and my bacterial circumstances”: Linking gut microbiome, neurodevelopment, and depression. Frontiers in Psychiatry 2017. 10.3389/fpsyt.2017.00153.
    1. Skonieczna-Żydecka K, Marlicz W, Misera A, Koulaouzidis A, Łoniewski I. Microbiome—The Missing Link in the Gut-Brain Axis: Focus on Its Role in Gastrointestinal and Mental Health. Journal of Clinical Medicine 2018;7:521. doi: 10.3390/jcm7120521
    1. Deans E. Microbiome and mental health in the modern environment. J Physiol Anthropol 2016;36:1. doi: 10.1186/s40101-016-0101-y
    1. O’Mahony SM, Clarke G, Dinan TG, Cryan JF. Early-life adversity and brain development: Is the microbiome a missing piece of the puzzle? Neuroscience 2017;342:37–54. doi: 10.1016/j.neuroscience.2015.09.068
    1. Brown K, DeCoffe D, Molcan E, Gibson DL. Diet-induced dysbiosis of the intestinal microbiota and the effects on immunity and disease. Nutrients 2012;4:1095–119. doi: 10.3390/nu4081095
    1. Maitre Y, Micheneau P, Delpierre A, Mahalli R, Guerin M, Amador G, et al.. Did the Brain and Oral Microbiota Talk to Each Other? A Review of the Literature. J Clin Med 2020;9. 10.3390/jcm9123876.
    1. Wingfield B, Lapsley C, McDowell A, Miliotis G, McLafferty M, O’Neill SM, et al.. Variations in the oral microbiome are associated with depression in young adults. Sci Rep 2021;11:15009. doi: 10.1038/s41598-021-94498-6
    1. Qing Y, Xu L, Cui G, Sun L, Hu X, Yang X, et al.. Salivary microbiome profiling reveals a dysbiotic schizophrenia-associated microbiota. NPJ Schizophr 2021;7:51. doi: 10.1038/s41537-021-00180-1
    1. Granero R. Role of Nutrition and Diet on Healthy Mental State. Nutrients 2022;14:750. doi: 10.3390/nu14040750
    1. Marx W, Moseley G, Berk M, Jacka F. Nutritional psychiatry: the present state of the evidence. Proc Nutr Soc 2017;76:427–36. doi: 10.1017/S0029665117002026
    1. Ma J, Li Z, Zhang W, Zhang C, Zhang Y, Mei H, et al.. Comparison of gut microbiota in exclusively breast-fed and formula-fed babies: a study of 91 term infants. Scientific Reports 2020;10:15792. doi: 10.1038/s41598-020-72635-x
    1. Dinan TG, Cryan JF. Melancholic microbes: a link between gut microbiota and depression? Neurogastroenterology & Motility 2013;25:713–9. doi: 10.1111/nmo.12198
    1. Luna RA, Foster JA. Gut brain axis: Diet microbiota interactions and implications for modulation of anxiety and depression. Current Opinion in Biotechnology 2015;32:35–41. doi: 10.1016/j.copbio.2014.10.007
    1. Simpson CA, Schwartz OS, Eliby D, Butler CA, Huang K, O’Brien-Simpson N, et al.. Bugs and Brains, the Gut and Mental Health Study: a mixed-methods study investigating microbiota composition and function in anxiety, depression and irritable bowel syndrome. BMJ Open 2021;11:e043221. doi: 10.1136/bmjopen-2020-043221
    1. Nikolova VL, Hall MRB, Hall LJ, Cleare AJ, Stone JM, Young AH. Perturbations in Gut Microbiota Composition in Psychiatric Disorders. JAMA Psychiatry 2021;78:1343. 10.1001/jamapsychiatry.2021.2573.
    1. Cao X, Lin P, Jiang P, Li C. Characteristics of the gastrointestinal microbiome in children with autism spectrum disorder: a systematic review. Shanghai Arch Psychiatry 2013;25:342–53. doi: 10.3969/j.issn.1002-0829.2013.06.003
    1. Grimes DA, Schulz KF. Compared to what? Finding controls for case-control studies. Lancet 2005. doi: 10.1016/S0140-6736(05)66379-9
    1. Rigby AS, Robinson MB. Statistical methods in epidemiology. IV. Confounding and the matched pairs odds ratio. Disabil Rehabil 2000;22:259–65. doi: 10.1080/096382800296719
    1. Eysteinsdottir T, Thorsdottir I, Gunnarsdottir I, Steingrimsdottir L. Assessing validity of a short food frequency questionnaire on present dietary intake of elderly Icelanders. Nutrition Journal 2012;11:12. doi: 10.1186/1475-2891-11-12
    1. Walter Willett. Nutritional epidemiology. Oxford University Press; 2013.
    1. Baber KF, Anderson J, Puzanovova M, Walker LS. Rome II versus Rome III classification of functional gastrointestinal disorders in pediatric chronic abdominal pain. J Pediatr Gastroenterol Nutr 2008;47:299–302. doi: 10.1097/MPG.0b013e31816c4372
    1. Caplan A, Walker L, Rasquin A. Development and preliminary validation of the questionnaire on pediatric gastrointestinal symptoms to assess functional gastrointestinal disorders in children and adolescents. J Pediatr Gastroenterol Nutr 2005;41:296–304. doi: 10.1097/01.mpg.0000172748.64103.33
    1. Hyams JS, di Lorenzo C, Saps M, Shulman RJ, Staiano A, van Tilburg M. Childhood functional gastrointestinal disorders: Child/adolescent. Gastroenterology 2016. 10.1053/j.gastro.2016.02.015.
    1. Keil T, McBride D, Grimshaw K, Niggemann B, Xepapadaki P, Zannikos K, et al.. The multinational birth cohort of EuroPrevall: Background, aims and methods. Allergy: European Journal of Allergy and Clinical Immunology 2010;65:482–90. doi: 10.1111/j.1398-9995.2009.02171.x
    1. Sigurdardottir ST, Jonasson K, Clausen M, Lilja Bjornsdottir K, Sigurdardottir SE, Roberts G, et al.. Prevalence and early-life risk factors of school-age allergic multimorbidity: The EuroPrevall-iFAAM birth cohort. Allergy 2021;76:2855–65. doi: 10.1111/all.14857
    1. Grabenhenrich L, Trendelenburg V, Bellach J, Yürek S, Reich A, Fiandor A, et al.. Frequency of food allergy in school-aged children in eight European countries-The EuroPrevall-iFAAM birth cohort. Allergy 2020;75:2294–308. doi: 10.1111/all.14290
    1. Barkley RA, Murphy KR. Attention-deficit hyperactivity disorder: a clinical workbook. Guilford Press; 2006.
    1. Magnússon P, Smári J, Grétarsdóttir H, Prándardóttir H. Attention-Deficit/Hyperactivity symptoms in Icelandic schoolchildren: assessment with the Attention Deficit/Hyperactivity Rating Scale-IV. Scand J Psychol 1999;40:301–6. doi: 10.1111/1467-9450.404130
    1. Magnusson P, Smári J, Sigurðardóttir D, Baldursson G, Sigmundsson J, Kristjánsson K, et al.. Validity of Self-Report and Informant Rating Scales of Adult ADHD Symptoms in Comparison With a Semistructured Diagnostic Interview. Journal of Attention Disorders 2006;9:494–503. doi: 10.1177/1087054705283650
    1. Child Behavior Checklist/4-18. University Associates in Psychiatry; 1991.
    1. Jensen PS, Watanabe HK, Richters JE, Roper M, Hibbs ED, Salzberg AD, et al.. Scales, diagnoses, and child psychopathology: II. Comparing the CBCL and the DISC against external validators. J Abnorm Child Psychol 1996;24:151–68. doi: 10.1007/BF01441482
    1. Hannesdóttir H, Einarsdóttir S. The Icelandic child mental health study. An epidemiological study of Icelandic children 2–18 years of age using the Child Behavior Checklist as a screening instrument. European Child & Adolescent Psychiatry 1995;4:237–48. 10.1007/BF01980488.
    1. Hannesdottir Helga, Andre Sourander ASJPASJP. Comparison of behavioral problems between two samples of 2- to 3-year-old children in Finland and Iceland. Nordic Journal of Psychiatry 2000;54:13–7. 10.1080/080394800427528.
    1. Ehlers S, Gillberg C, Wing2 L. A Screening Questionnaire for Asperger Syndrome and Other High-Functioning Autism Spectrum Disorders in School Age Children. Journal of Autism and Developmental Disorders 1999;29.
    1. Constantino J. N. & Gruber CP. Social Responsiveness Scale. Western Psychological Services 2005. .
    1. Social Responsiveness Scale (SRS) SRS Total Score Results n.d.
    1. Magnússon P. An Evaluation of the Psychometric Properties of the Social Responsiveness Scale in Two Groups of Children in Iceland. International Meeting for Autism Research, Reykjavik: 2008.
    1. Constantino JN, Davis SA, Todd RD, Schindler MK, Gross MM, Brophy SL, et al.. Validation of a brief quantitative measure of autistic traits: comparison of the social responsiveness scale with the autism diagnostic interview-revised. J Autism Dev Disord 2003;33:427–33. doi: 10.1023/a:1025014929212
    1. Kovacs M. The Children’s Depression, Inventory (CDI). Psychopharmacol Bull 1985;21:995–8.
    1. Kovacs M. Childrens Depression Inventory (CDI) manual. New-York: 1992.
    1. Kazdin AE. Childhood depression. J Child Psychol Psychiatry 1990;31:121–60. doi: 10.1111/j.1469-7610.1990.tb02276.x
    1. Craighead WE, Curry JF IS. Relationship of children´s depression inventory factors to major depression among adolescents. Psychological Assessment 1995;7:171–6.
    1. Arnarson EÖ, Smari J, Einarsdóttir H JE. The Prevalence of Depressive Symptoms in Pre-adolescent School Children in Iceland. Scand J Behav Ther 1994;23:121–30.
    1. MARCH JS, PARKER JDA, SULLIVAN K, STALLINGS P, CONNERS CK. The Multidimensional Anxiety Scale for Children (MASC): Factor Structure, Reliability, and Validity. Journal of the American Academy of Child & Adolescent Psychiatry 1997;36:554–65. 10.1097/00004583-199704000-00019.
    1. Anderson ER, Jordan JA, Smith AJ, Inderbitzen-Nolan HM. An examination of the MASC social anxiety scalein a non-referred sample of adolescents. Journal of Anxiety Disorders 2009;23:1098–105. doi: 10.1016/j.janxdis.2009.07.013
    1. DIERKER LC, ALBANO AM, CLARKE GN, HEIMBERG RG, KENDALL PC, MERIKANGAS KR, et al.. Screening for Anxiety and Depression in Early Adolescence. Journal of the American Academy of Child & Adolescent Psychiatry 2001;40:929–36. doi: 10.1097/00004583-200108000-00015
    1. Ivarsson T. Normative data for the Multidimensional Anxiety Scale for Children (MASC) in Swedish adolescents. Nordic Journal of Psychiatry 2006;60:107–13. doi: 10.1080/08039480600588067
    1. van Gastel W, Ferdinand RF. Screening capacity of the Multidimensional Anxiety Scale for Children (MASC) for DSM-IV anxiety disorders. Depression and Anxiety 2008;25:1046–52. doi: 10.1002/da.20452
    1. Skarphedinsson G, Villabø MA, Lauth B. Screening efficiency of the self-report version of the Multidimensional Anxiety Scale for Children in a highly comorbid inpatient sample. Nordic Journal of Psychiatry 2015;69:613–20. doi: 10.3109/08039488.2015.1026841
    1. Bolyen E, Rideout JR, Dillon MR, Bokulich NA, Abnet CC, Al-Ghalith GA, et al.. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat Biotechnol 2019;37:852–7. doi: 10.1038/s41587-019-0209-9
    1. Paulson JN, Stine OC, Bravo HC, Pop M. Differential abundance analysis for microbial marker-gene surveys. Nat Methods 2013;10:1200–2. doi: 10.1038/nmeth.2658
    1. McMurdie PJ, Holmes S. Phyloseq: a bioconductor package for handling and analysis of high-throughput phylogenetic sequence data. Pac Symp Biocomput 2012:235–46.
    1. Friedman J, Alm EJ. Inferring Correlation Networks from Genomic Survey Data. PLoS Computational Biology 2012;8:e1002687. doi: 10.1371/journal.pcbi.1002687
    1. Estaki M, Jiang L, Bokulich NA, McDonald D, González A, Kosciolek T, et al.. QIIME 2 Enables Comprehensive End‐to‐End Analysis of Diverse Microbiome Data and Comparative Studies with Publicly Available Data. Current Protocols in Bioinformatics 2020;70:e100. doi: 10.1002/cpbi.100
    1. Li J, Jia H, Cai X, Zhong H, Feng Q, Sunagawa S, et al.. An integrated catalog of reference genes in the human gut microbiome. Nat Biotechnol 2014;32:834–41. doi: 10.1038/nbt.2942
    1. Xia J, Sinelnikov I v., Han B, Wishart DS. MetaboAnalyst 3.0—making metabolomics more meaningful. Nucleic Acids Research 2015;43:W251–7. 10.1093/nar/gkv380.
    1. Pedersen HK, Forslund SK, Gudmundsdottir V, Petersen AØ, Hildebrand F, Hyötyläinen T, et al.. A computational framework to integrate high-throughput ‘-omics’ datasets for the identification of potential mechanistic links. Nature Protocols 2018;13:2781–800. doi: 10.1038/s41596-018-0064-z
    1. Knight R, Vrbanac A, Taylor BC, Aksenov A, Callewaert C, Debelius J, et al.. Best practices for analysing microbiomes. Nature Reviews Microbiology 2018;16:410–22. doi: 10.1038/s41579-018-0029-9
    1. Chong J, Xia J. Computational Approaches for Integrative Analysis of the Metabolome and Microbiome. Metabolites 2017;7. doi: 10.3390/metabo7040062
    1. Wykes T, Haro JM, Belli SR, Obradors-Tarragó C, Arango C, Ayuso-Mateos JL, et al.. Mental health research priorities for Europe. The Lancet Psychiatry 2015;2:1036–42. doi: 10.1016/S2215-0366(15)00332-6
    1. WHO | WHO calls for stronger focus on adolescent health. WHO; 2014. .
    1. Kranzler HR, Kadden RM, Babor TF, Rounsaville BJ. Longitudinal, expert, all data procedure for psychiatric diagnosis in patients with psychoactive substance use disorders. J Nerv Ment Dis 1994;182:277–83. doi: 10.1097/00005053-199405000-00005
    1. Haro JM, Ayuso-Mateos JL, Bitter I, Demotes-Mainard J, Leboyer M, Lewis SW, et al.. ROAMER: roadmap for mental health research in Europe. Int J Methods Psychiatr Res 2014;23 Suppl 1:1–14. doi: 10.1002/mpr.1406
    1. Fiorillo A, Luciano M, del Vecchio V, Sampogna G, Obradors-Tarragó C, Maj M. Priorities for mental health research in Europe: A survey among national stakeholders’ associations within the ROAMER project. World Psychiatry 2013. doi: 10.1002/wps.20052

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