Skip to main content

Advertisement

SpringerLink
Log in

An exploration of the associations of pregnancy and perinatal features with cytokines and tryptophan/kynurenine metabolism in children with attention-deficit hyperactivity disorder (ADHD)

  • Original Article
  • Published:
ADHD Attention Deficit and Hyperactivity Disorders

Abstract

Intra-individual variability of the characteristics of children with attention-deficit hyperactivity (ADHD) may reflect compromised glial energy supply in the synapse. We reported recently that while serum levels of a glial marker, the cytokine S100B, were not seriously altered, levels of other cytokines and tryptophan metabolites were related to symptoms, attention and variability. Here, we explore with a regression analysis whether levels of these substances were associated with features of the index pregnancy of potential aetiological significance. Serum was taken from 35 children with DSM-IV ADHD (14 on medication) and 21 typically developing controls to measure 8 cytokines (S100B, IL-2, IL-6, IL-10, IL-13, IL-16, TNF-α and IFN-γ) and 5 metabolites (Tryptophan, Kynurenine, Kynurenate [KA], 3-hydroxy-kynurenine [3HK] and 5-hydroxyindole acetic acid [5-HIAA]). The mothers received a 124-item questionnaire on features surrounding the pregnancy. (1) For children with ADHD, a shorter pregnancy and smaller birth weight were associated statistically with increased 3HK and IFN-γ and for obstetric problems with decreased TNF-α levels. (2) Maternal smoking related to decreasing kynurenine and increasing 3HK and S100B levels in ADHD children. Paternal smoking was associated with increased tryptophan in the controls and increased IL-6 levels in ADHD children. (3) The taking of supplements often related to decreasing TNF-α, increasing IL-10 and lower 5-HIAA levels in the ADHD children. Less 5-HIAA but more tryptophan was associated with earlier and later life events, respectively. (4) Increased IL-16 and 5-HIAA levels in the ADHD group related to reports of poorer infant health. Unexpectedly, more child care (seafood and time together) in ADHD than healthy families was implicated by lower tryptophan levels and an altered balance of pro-inflammatory cytokines. Across measures control families generally showed either non-significant associations or the opposite to those of the ADHD group. In ADHD children more than controls, the balance of potentially toxic or protective kynurenine metabolites and of pro- over anti-inflammatory cytokines may reflect the perinatal experience associated with stress, but not with maternal illness.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Notes

  1. The potential toxicity may result from the agonism of the 3HK metabolite quinolinic acid at NMDA receptors (Ribeiro et al. 2006). But, it may be noted that further metabolism to NAD(+) could in theory facilitate energy metabolism (Costantino 2009). The putative toxic or protective metabolic route is controlled by the indoleamine and tryptophan 2,3,-dioxygenases whose activity is modulated by the balance of pro-/anti-inflammatory cytokines (Myint et al. 2007).

Abbreviations

ADHD:

Attention-deficit/hyperactivity disorder

DSM-IV:

Diagnostic and Statistical Manual of the American Psychiatric Association, 4th edition

HI:

Hyperactive-impulsive

5-HIAA:

5-hydroxy-indoleacetic acid

IA:

Inattentive

IL:

Interleukin

IFN-γ:

Interferon gamma

KA:

Kynurenic acid

3HK:

3-hydroxy-kynurenine

NAD:

Nicotinamide adenine dinucleotide

NFκB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

SES:

Socio-economic scale

SD:

Standard deviation

TNF-α:

Tumour necrosis factor alpha

References

  • Amor LB, Grizenko N, Schwartz G et al (2005) Perinatal complications in children with attention deficit hyperactivity disorder and their unaffected siblings. J Psychiat Neurosci 30:120–126

    Google Scholar 

  • Ashdown H, Joita S, Luheshi GN et al (2008) Acute brain cytokine responses after global birth hypoxia in the rat. J Neurosci Res 86:3401–3409

    Article  PubMed  CAS  Google Scholar 

  • Azmitia EC (2001) Modern views on an ancient chemical: serotonin effects on cell proliferation, maturation, and apoptosis. Brain Res Bull 56:413–424

    Article  PubMed  CAS  Google Scholar 

  • Barkley RA, DuPaul GJ, McMurray MB (1990) Comprehensive evaluation of attention deficit disorder with and without hyperactivity as defined by research criteria. J Consult Clin Psychol 58:775–789

    Article  PubMed  CAS  Google Scholar 

  • Barry S, Clarke G, Scully P et al (2009) Kynurenine pathway in psychosis: evidence of increased tryptophan degradation. J Psychopharmacol 23:287–294

    Article  PubMed  CAS  Google Scholar 

  • Bergman K, Sarkar P, O’Connor TG et al (2007) Maternal stress during pregnancy predicts cognitive ability and fearfulness in infancy. J Am Acad Child Adolesc Psychiat 46:1454–1463

    Article  Google Scholar 

  • Biederman J (2005) Attention-deficit/hyperactivity disorder: a selective overview. Biol Psychiatry 57:1215–1220

    Article  PubMed  Google Scholar 

  • Blank R, Remschmidt H (1994) Hyperkinetic syndrome: the role of allergy among psychological and neurological factors. Eur Child Adolesc Psychiatry 3:220–228

    Article  Google Scholar 

  • Bock J, Braun K (2011) The impact of perinatal stress on the functional maturation of prefronto-cortical synaptic circuits: implications for the pathophysiology of ADHD? Prog Brain Res 189:155–169

    Article  PubMed  Google Scholar 

  • Boksa P (2010) Effects of prenatal infection on brain development and behavior: a review of findings from animal models. Brain Behav Immun 24:881–887

    Article  PubMed  Google Scholar 

  • Bourgeois JP, Rakic P (1993) Changes of synaptic density in the primary visual cortex of the macaque monkey from fetal to adult stage. J Neurosci 13:2801–2820

    PubMed  CAS  Google Scholar 

  • Brauns H, Haun D, Steinmann S (1997) The construction of an internationally comparable classification by class. Erwerbsstatistische Besonderheiten am Beispiel von Labour Force Surveys der Bundesrepublik Deutschland, Frankreichs, Großbritanniens und Ungarns, Mannheim

    Google Scholar 

  • Castellanos FX, Tannock R (2002) Neuroscience of attention-deficit/hyperactivity disorder: the search for endophenotypes. Nat Rev Neurosci 3:617–628

    PubMed  CAS  Google Scholar 

  • Cerresoli-Borroni G, Guidetti P, Amori L et al (2007) Perinatal kynurenine 3-hydroxylase inhibition in rodents: pathophysiological implications. J Neurosci Res 85:845–854

    Article  Google Scholar 

  • Chen W, Taylor EA (2006) Parental account of children’s symptoms (PACS), ADHD phenotypes and its application to molecular genetic studies. In: Oades RD (ed) Attention-deficit/hyperactivity disorder and the hyperkinetic syndrome: Current ideas and ways forward. Nova Science Publishing Inc., Hauppauge, vol 11788, pp 3–20

  • Chen W, Asherson P, Taylor EA (2005) Gene-environment interaction questionnaire. Kings College, University of London, London

    Google Scholar 

  • Condray R, Dougherty GG, Keshavan MS et al. (2011) 3-Hydroxykynurenine and clinical symptoms in first-episode neuroleptic-naive patients with schizophrenia. Int J Neuropsychopharmacol 14:756–767

    Google Scholar 

  • Conners CK (2002) Manual for Conners’ rating scales. Revised edn. Multi-Health Systems Inc., N.Tonoawanda

    Google Scholar 

  • Connor TJ, Starr N, O’Sullivan JB et al (2008) Induction of indoleamine 2, 3-dioxygenase and kynurenine 3-monooxygenase in rat brain following a systemic inflammatory challenge: a role for IFN-γ? Neurosci Lett 441:29–34

    Article  PubMed  CAS  Google Scholar 

  • Costantino G (2009) New promises for manipulation of kynurenine pathway in cancer and neurological diseases. Expert Opin Ther Targets 13:247–258

    Article  PubMed  CAS  Google Scholar 

  • Das Banerjee T, Middleton F, Faraone SV (2007) Environmental risk factors for attention-deficit hyperactivity disorder. Acta Paediatr 96:1269–1274

    Article  Google Scholar 

  • Deverman BE, Patterson PH (2009) Cytokines and CNS development. Neuron 64:61–78

    Article  PubMed  CAS  Google Scholar 

  • Djuardi Y, Wibowo H, Supali T et al (2009) Determinants of the relationship between cytokine production in pregnant women and their infants. PLoS ONE 4:e7711

    Article  PubMed  Google Scholar 

  • Entringer S, Kumsta R, Nelson EL et al (2008) Influence of prenatal psychosocial stress on cytokine production in adult women. Dev Psychobiol 50:579–587

    Article  PubMed  CAS  Google Scholar 

  • Fatemi SH, Sidwel R, Kist D et al (1998) Differential expression of synaptosome-associated protein 25 kDa [SNAP-25] in hippocampi of neonatal mice following exposure to human influenza virus in utero. Brain Res 800:1–9

    Article  PubMed  CAS  Google Scholar 

  • Gabbay V, Coffey BJ, Guttman LE et al (2009) A cytokine study in children and adolescents with Tourette’s disorder. Prog Neuropsychopharmacol Biol Psychiatry 33:967–971

    Article  PubMed  CAS  Google Scholar 

  • Gallagher CN, Carpenter KLH, Grice P et al (2009) The human brain utilizes lactate via the tricarboxylic acid cycle: a 13C-labelled microdialysis and high-resolution nuclear magnetic resonance study. Brain 132:2839–2849

    Article  PubMed  Google Scholar 

  • Godfrey KM, Barker DJ (2001) Fetal programming and adult health. Public Health Nutr 4:611–624

    Article  PubMed  CAS  Google Scholar 

  • Graciarena M, Depino AM, Pitossi FJ (2010) Prenatal inflammation impairs adult neurogenesis and memory related behavior through persistent hippocampal TGFβ1 downregulation. Brain Behav Immun 24:1301–1309

    Google Scholar 

  • Grizenko N, Shayan YR, Polotskaia A et al (2008) Relation of maternal stress during pregnancy to symptom severity and response to treatment in children with ADHD. J Psychiat Neurosci 33:10–16

    Google Scholar 

  • Gustafsson P, Källen K (2010) Perinatal, maternal, and fetal characteristics of children diagnosed with attention-deficit-hyperactivity disorder: results from a population-based study utilizing the Swedish Medical Birth Register. Dev Med Child Neurol 53:269–274

    Google Scholar 

  • Harding D, Brull D, Humphries SE et al (2005) Variation in the interleukin-6 gene is associated with impaired cognitive development in children born prematurely: a preliminary study. Pediatr Res 58:117–120

    Google Scholar 

  • Himeda T, Watanabe Y, Tounai H et al (2006) Time dependent alterations of co-localization of S100ß and GFAP in the MPTP-treated mice. J Neural Transm 113:1887–1894

    Article  PubMed  CAS  Google Scholar 

  • Holtze M, Asp L, Schwieler L et al (2008) Induction of the kynurenine pathway by neurotropic influenza a virus infection. J Neurosci Res 86:3674–3683

    Article  PubMed  CAS  Google Scholar 

  • Hsiao EY, Patterson PH (2011) Activation of the maternal immune system induces endocrine changes in the placenta via IL-6. Brain Behav Immun 25:604–615

    Google Scholar 

  • Huttenlocher PR (1984) Synapse elimination and plasticity in developing human cerebral cortex. Am J Ment Defic Res 88:488–496

    CAS  Google Scholar 

  • Kaufman AS, Kaufman NL (2001) Kaufman-assessment battery for children. 5th edn. transl. Melchers P, Preuß U. Swets & Zeitlinger, Frankfurt am Main

  • King S, St-Hilaire A, Heidkamp D (2010) Prenatal factors in schizophrenia. Curr Dir Psychol Sci 19:209

    Article  Google Scholar 

  • Kiss C, Ceresoli-Borroni G, Guidetti P et al (2003) Kynurenate production by cultured human astrocytes. J Neural Transm 110:1–14

    PubMed  CAS  Google Scholar 

  • Klein C, Wendling K, Huettner P et al (2006) Intra-subject variability in attention-deficit hyperactivity disorder (ADHD). Biol Psychiatry 60:1088–1097

    Article  PubMed  Google Scholar 

  • Knopik VS, Sparrow EP, Madden PAF (2005) Contributions of parental alcoholism, prenatal substance exposure, and genetic transmission to child ADHD risk: a female twin study. Psychol Med 35:625–635

    Article  PubMed  Google Scholar 

  • Knopik VS, Heath AC, Buchholz KK et al (2009) Genetic and environmental influences on externalizing behavior and alcohol problems in adolescence: a female twin study. Pharmacol Biochem Behav 93:313–321

    Article  PubMed  CAS  Google Scholar 

  • Kuntsi J, Andreou P, Ma J et al (2005) Testing assumptions for endophenotype studies in ADHD: reliability and validity of tasks in a general population sample. BMC Psychiatry 5:40

    Article  PubMed  Google Scholar 

  • Lasky-Su J, Neale BM, Franke B et al (2008) Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations. Am J Med Genet Part B 147B:1345–1354

    Article  PubMed  CAS  Google Scholar 

  • Lodygensky GA, Seghier ML, Warfield SK et al (2008) Intrauterine growth restriction affects the preterm infant’s hippocampus. Pediatr Res 63:438–443

    Article  PubMed  Google Scholar 

  • Mai XM, Gäddin PO, Nilsson L et al (2003) Asthma, lung function and allergy in 12-year-old children with very low birth weight: a prospective study. Pediatr Allergy Immunol 14:184–192

    Article  PubMed  Google Scholar 

  • McClelland S, Korosi A, Cope J et al (2011) Emerging roles of epigenetic mechanisms in the enduring effects of early-life stress and experience on learning and memory. Neurobiol Learn Mem 96:79–88

    Article  PubMed  Google Scholar 

  • Mezzacappa E, Buckner JC, Earls F (2011) Prenatal cigarette exposure and infant learning stimulation as predictors of cognitive control in childhood. Dev Sci 14:881–891

    Article  PubMed  Google Scholar 

  • Mick E, Biederman J, Prince J et al (2002) Impact of low birth weight on attention-deficit hyperactivity disorder. J Dev Behav Pediatr 23:16–22

    Article  PubMed  Google Scholar 

  • Müller UC, Asherson P, Banaschewski T et al (2011) Behavioural patterns of ADHD in a large multicentre study. Part 1: Demographics, diagnoses, and symptoms in probands and selected siblings of the IMAGE project. BMC Psychiatry (in submission)

  • Myint AM, Kim YK, Verkerk R et al (2007) Kynurenine pathway in major depression: evidence of impaired neuroprotection. J Affect Disord 98:143–151

    Article  PubMed  CAS  Google Scholar 

  • Nagy Z, Lagercrantz H, Hutton C (2011) Effects of preterm birth on cortical thickness measured in adolescence. Cereb Cortex 21:300–306

    Article  PubMed  Google Scholar 

  • Niwa M, Matsumoto Y, Mouri A et al. (2011) Vulnerability in early life to changes in the rearing environment plays a crucial role in the aetiopathology of psychiatric disorders. Int J Neuropsychopharmacol. doi:10.1017/S1461145710001239

  • Noakes PS, Holt PG, Prescott SL (2003) Maternal smoking in pregnancy alters neonatal cytokine responses. Allergy 58:1053–1058

    Article  PubMed  CAS  Google Scholar 

  • Oades RD, Slusarek M, Velling S et al (2002) Serotonin platelet-transporter measures in childhood attention-deficit/hyperactivity disorder (ADHD): clinical versus experimental measures of impulsivity. World J Biol Psychiatry 3:96–100

    Article  PubMed  Google Scholar 

  • Oades RD, Dauvermann MR, Schwarz MJ et al (2009) Does glial function underlie ADHD variability? Evidence from measures of S100B, interleukins, tryptophan metabolism and the kynurenine metabolic pathway. Neurol Psychiat Brain Res Suppl 1:44

    Google Scholar 

  • Oades RD, Dauvermann MR, Schimmelmann BG et al (2010a) Attention-deficit hyperactivity disorder (ADHD) and glial integrity: S100B, cytokines and kynurenine metabolism—effects of medication. Behav Brain Funct 6:29

    Article  PubMed  Google Scholar 

  • Oades RD, Myint AM, Dauvermann MR et al (2010b) Attention-deficit hyperactivity disorder (ADHD) and glial integrity: an exploration of associations of cytokines and kynurenine metabolites with symptoms and attention. Behav Brain Funct 6:32

    Google Scholar 

  • O’Callaghan MJ, Burns YR, Gray PH et al (1996) School performance of ELBW children: a controlled study. Dev Med Child Neurol 38:917–926

    Article  PubMed  Google Scholar 

  • O’Donnell K, O’Connor TG, Glover V (2009) Prenatal stress and neurodevelopment of the child: focus on the HPA axis and role of the placenta. Dev Neurosci 31:285–292

    Article  PubMed  Google Scholar 

  • Olsson SK, Samuelsson M, Saetre P et al (2010) Elevated levels of kynurenic acid in the cerebrospinal fluid of patients with bipolar disorder. J Psychiatry Neurosci 39:195–199

    Article  Google Scholar 

  • Polanczyk GV, Silva de Lima M, Horta BL et al (2007) The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry 164:942–948

    Article  PubMed  Google Scholar 

  • Ribeiro CAJ, Grando V, Filho CSD et al (2006) Evidence that quinolinic acid severely impairs energy metabolism through activation of NMDA receptors in striatum from developing rats. J Neurochem 99:1531–1542

    Article  PubMed  CAS  Google Scholar 

  • Rice F, Harold GT, Boivin J et al (2010) The links between prenatal stress and offspring development and psychopathology: disentangling environmental and inherited influences. Psychol Med 40:335–345

    Article  PubMed  CAS  Google Scholar 

  • Romanos M, Gerlach M, Warnke A et al (2010) Association of attention-deficit/hyperactivity disorder and atopic eczema modified by sleep disturbance in a large population-based sample. J Epidemiol Commun Health 64:269–273

    Article  Google Scholar 

  • Romero E, Ali C, Molina-Holgado E et al (2007) Neurobehavioral and immunological consequences of prenatal immune activation in rats. Influence of antipsychotics. Neuropsychopharmacol 32:1791–1804

    Article  CAS  Google Scholar 

  • Ronald A, Pennell CE, Whitehouse AJ (2011) Prenatal maternal stress associated with ADHD and autistic traits in early childhood. Front Psychol 1:223. doi:10.3389/fpsyg.2010.00223

    Article  Google Scholar 

  • Russell VA, Oades RD, Tannock R et al (2006) Response variability in attention-deficit/hyperactivity disorder: a neuronal and glial energetics hypothesis. Behav Brain Funct 2:30

    Article  PubMed  Google Scholar 

  • Sagvolden T, Johansen EB, Aase H et al (2005) A dynamic developmental theory of attention-deficit/hyperactivity disorder (ADHD) predominantly hyperactive/impulsive and combined subtypes. Behav Brain Sci 28:397–468

    Article  PubMed  Google Scholar 

  • Schlotz W, Phillips DW (2009) Fetal origins of mental health: evidence and mechanisms. Brain Behav Imm 23:905–916

    Article  Google Scholar 

  • Shaw P, Eckstrand K, Sharp W et al (2007) Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation. Proc Natl Acad Sci (USA) 104:19649–19654

    Article  CAS  Google Scholar 

  • Steiner J, Bernstein H-G, Bielau H et al (2007) Evidence for a wide extra-astrocytic distribution of S100B in human brain. BMC Neurosci 8:2

    Article  PubMed  Google Scholar 

  • Stöber G, Ben-Shachar D, Cardon M et al (2009) Schizophrenia: from the brain to peripheral markers. A consensus paper of the WFSBP task force on biological markers. World J Biol Psychiatry 10:127–155

    Article  PubMed  Google Scholar 

  • Suzuki K, Matsuzaki H, Iwata K et al (2011) Plasma cytokine profiles in subjects with high-functioning autism spectrum disorders. PLoS ONE 6:5

    Google Scholar 

  • Talge NM, Neal C, Glover V et al (2007) Antenatal maternal stress and long-term effects on child neurodevelopment: how and why? J Child Psychol Psychiatry 48:245–261

    Article  PubMed  Google Scholar 

  • Tappia PS, Troughton KL, Langley-Evans SC et al (1995) Cigarette smoking influences cytokine production and antioxidant defences. Clin Sci (Lond) 88:485–489

    CAS  Google Scholar 

  • Taylor EA, Sandberg S, Thorley G et al (1991) The epidemiology of childhood hyperactivity. Oxford University Press, Oxford

    Google Scholar 

  • Thapar A, Rice F, Hay D et al (2009) Prenatal smoking might not cause attention-deficit/hyperactivity disorder: evidence from a novel design. Biol Psychiatry 66:722–727

    Article  PubMed  CAS  Google Scholar 

  • Tsunoda M, Litonjua AA, Kuniak MP et al (2003) Serum cytokine levels, cigarette smoking and airway responsiveness among pregnant women. Int Arch Allergy Immunol 130:158–164

    Article  PubMed  CAS  Google Scholar 

  • Uebel H, Albrecht B, Asherson P et al (2010) Performance variability, impulsivity errors and the impact of incentives as gender-independent endophenotypes for ADHD. J Child Psychol Psychiatry 51:210–218

    Article  PubMed  Google Scholar 

  • van de Kamp JL, Smolen A (1995) Response of kynurenine pathway enzymes to pregnancy and dietary level of vitamin B-6. Pharmacol Biochem Behav 51:753–758

    Article  PubMed  Google Scholar 

  • Van den Bergh BRH, Marcoen A (2004) High antenatal maternal anxiety is related to ADHD symptoms, externalizing problems, and anxiety in 8- and 9-year-olds. Child Dev 75:1085–1097

    Article  PubMed  Google Scholar 

  • Villarreal A, Aviles Reyes RX, Angelo MF et al (2011) S100B alters neuronal survival and dendrite extension via RAGE-mediated NF-κB signalling. J Neurochem 117:321–332

    Article  PubMed  CAS  Google Scholar 

  • Weiss RH (1996) CFT-20-R: Grundintelligenztest, revised edn. Hogrefe Verlag GmbH & Co KG, Göttingen

  • Whitaker AH, Van Rossem R, Feldman JF et al (1997) Psychiatric outcomes in low-birth-weight children at age 6 years: relation to neonatal cranial ultrasound abnormalities. Arch Gen Psychiatry 54:847–856

    PubMed  CAS  Google Scholar 

  • Winter C, Reutiman TJ, Folsom TD et al (2008) Dopamine and serotonin levels following prenatal viral infection in mouse-Implications for psychiatric disorders such as schizophrenia and autism. Eur Neuropsychopharmacol 18:712–716

    Article  PubMed  CAS  Google Scholar 

  • Zhang XY, Cao LY, Song C et al (2008) Lower serum cytokine levels in smokers than nonsmokers with chronic schizophrenia on long-term treatment with antipsychotics. Psychopharmacol 201:383–389

    Article  CAS  Google Scholar 

  • Zmarowski A, Wu H-Q, Brooks JM et al (2009) Astrocyte-derived kynurenic acid modulates basal and evoked cortical acetylcholine release. Eur J Neurosci 29:529–538

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

I am very grateful to Benno Schimmelmann, Maria Dauvermann, Victoria Kirchhoff, Adriana Banozic and Ellen Uslar for their help in running this study in Essen and to Aye-Mu Myint, Markus Schwarz and Johana Zach for their role in organising and running the biochemical analyses in Munich. We thank UCB Pharma GmbH for financial support.

Conflict of interest

RDO declares that he has no conflicting interests. Some of these data were communicated at the 10th Psychoimmunology Expert meeting at Ulm/Günzburg, 12–14th November 2009 (Oades et al. 2009).

Author information

Authors and Affiliations

  1. Clinic for Child and Adolescent Psychiatry and Psychotherapy, University of Duisburg-Essen, Virchowstr. 174, 45147, Essen, Germany

    Robert D. Oades

Authors
  1. Robert D. Oades
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert D. Oades.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oades, R.D. An exploration of the associations of pregnancy and perinatal features with cytokines and tryptophan/kynurenine metabolism in children with attention-deficit hyperactivity disorder (ADHD). ADHD Atten Def Hyp Disord 3, 301–318 (2011). https://doi.org/10.1007/s12402-011-0062-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12402-011-0062-2

Keywords

Search

Navigation