Amniotic fluid chemokines and autism spectrum disorders: An exploratory study utilizing a Danish Historic Birth Cohort Morsi W. Abdallah a,b,c,⇑ , Nanna Larsen b , Jakob Grove d , Bent Nørgaard-Pedersen b , Poul Thorsen e , Erik L. Mortensen c , David M. Hougaard b a Department of Epidemiology, Aarhus University School of Public Health, Aarhus, Denmark b Department of Clinical Biochemistry and Immunology, Statens Serum Institute, Copenhagen, Denmark c Institute of Public Health and Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark d Department of Biomedicine and Bioinformatics Research Centre (BiRC), Aarhus University Faculty of Health Sciences, Aarhus, Denmark e Department of Gynaecology and Obstetrics, Lillebaelt Hospital, Kolding, Denmark article info Article history: Received 1 June 2011 Received in revised form 17 August 2011 Accepted 2 September 2011 Available online 10 September 2011 Keywords: Autistic disorder Chemokine MCP-1 Amniotic fluid Population register abstract Introduction: Elevated levels of chemokines have been reported in plasma and brain tissue of individuals with Autism Spectrum Disorders (ASD). The aim of this study was to examine chemokine levels in amni- otic fluid (AF) samples of individuals diagnosed with ASD and their controls. Material and methods: A Danish Historic Birth Cohort (HBC) kept at Statens Serum Institute, Copenhagen was utilized. Using data from Danish nation-wide health registers, a case-control study design of 414 cases and 820 controls was adopted. Levels of MCP-1, MIP-1a and RANTES were analyzed using Luminex xMAP technology. Case-control differences were assessed as dichotomized at below the 10th percentile or above the 90th percentile cut-off points derived from the control biomarker distributions (logistic regression) or continuous measures (tobit regression). Results and conclusion: AF volume for 331 cases and 698 controls was sufficient for Luminex analysis. Including all individuals in the cohort yielded no significant differences in chemokine levels in cases ver- sus controls. Logistic regression analyses, performed on individuals diagnosed using ICD-10 only, showed increased risk for ASD with elevated MCP-1 (elevated 90th percentile adjusted OR: 2.32 [95% CI: 1.17– 4.61]) compared to controls. An increased risk for infantile autism with elevated MCP-1 was also found (adjusted OR: 2.28 [95% CI: 1.16–4.48]). Elevated levels of MCP-1 may decipher an etiologic immunologic dysfunction or play rather an indirect role in the pathophysiology of ASD. Further studies to confirm its role and to identify the potential pathways through which MCP-1 may contribute to the development of ASD are necessary. Ó 2011 Elsevier Inc. All rights reserved. 1. Introduction Since the term was first coined by the Swiss psychiatrist Eugen Bleuler a hundred years ago (Stotz-Ingenlath, 2000), autism has evolved from being an enigmatic disability to represent a challeng- ing public health issue with substantial cost of care (Ganz, 2006). By definition, Autism Spectrum Disorders (ASD) refers to a cluster of heterogeneous neurodevelopmental disorders characterized by a triad of qualitative impairments in social interaction, communi- cation and repetitive stereotypic behavior (Newschaffer et al., 2007). Despite the numerous research lines trying to disentangle the etiology of this group of disorders, no definitive biologic screening or diagnostic tools have been universally accepted, and the diagnostic standards are still based on behavioral criteria (American Psychiatric Association, 2000). Prevalence of autism has been escalating over time. Most recent estimates from the US indicate that ASD prevalence could be as high as 1% (Rice, 2007). In Denmark a parallel trend has been ob- served with the most recent estimates being around 0.74% (Parner et al., 2008). Chemokines represent a family of cytokines comprised of four subgroups based on their cysteine motif (C, CC, CXC, and CX3C) and have the capacity to control the attraction of leukocytes to dif- ferent tissue targets (Epstein and Luster, 1998). Recently, a crucial role of chemokines in neuroinflammation has been postulated 0889-1591/$ - see front matter Ó 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.bbi.2011.09.003 Abbreviations: DPCR, The Danish Psychiatric Central Register; DNHR, The Danish National Hospital Register; HBC, Historic Birth Cohort at Statens Serum Institute, Copenhagen, Denmark; MBR, The Danish Medical Birth Registry; MCP-1, monocyte chemotactic protein-1; MIP-1a, macrophage inflammatory protein-1a; NPC, no psychiatric comorbidity; OCPD, other childhood psychiatric disorders. ⇑ Corresponding author at: Unit of Medical Psychology, Institute of Public Health, University of Copenhagen, Oster Farimagsgade 5B, CSS 15.0.19, Postboks 2099, 1014 Copenhagen K, Denmark. Fax: +45 3532 7748. E-mail address: mab@soci.au.dk (M.W. Abdallah). Brain, Behavior, and Immunity 26 (2012) 170–176 Contents lists available at SciVerse ScienceDirect Brain, Behavior, and Immunity journal homepage: www.elsevier.com/locate/ybrbi