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Transl Psychiatry. 2019 Oct 7;9(1):252. doi: 10.1038/s41398-019-0587-2.

Reduced neonatal brain-derived neurotrophic factor is associated with autism spectrum disorders.

Author information

1
Danish Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark. ksk@ssi.dk.
2
iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark. ksk@ssi.dk.
3
Danish Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
4
iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
5
Department of Biomedical Science, University of Copenhagen, Copenhagen, Denmark.
6
Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Copenhagen, Denmark.
7
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
8
Department of Biomedicine and iSEQ, Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark.
9
National Centre for Register-Based Research, Business and Social Sciences, Aarhus University, Aarhus, Denmark.
10
Center for Genomics and Personalized Medicine, Aarhus, Denmark.
11
Psychosis Research Unit, Aarhus University Hospital-Psychiatry, Aarhus, Denmark.
12
Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.
13
Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark.
14
Centre for Integrated Register-based Research, CIRRAU, Aarhus University, Aarhus, Denmark.

Abstract

Mental disorders have for the majority of cases an unknown etiology, but several studies indicate that neurodevelopmental changes happen in utero or early after birth. We performed a nested case-control study of the relation between blood levels of neuro-developmental (S100B, BDNF, and VEGF-A) and inflammatory (MCP-1, TARC, IL-8, IL-18, CRP, and IgA) biomarkers in newborns, and later development of autism spectrum disorders (ASD, N = 751), attention deficit hyperactivity disorders (ADHD, N = 801), schizophrenia (N = 1969), affective (N = 641) or bipolar disorders (N = 641). Samples and controls were obtained as part of the iPSYCH Danish Case-Cohort Study using dried blood spot samples collected between 1981 and 2004, and stored frozen at the Danish National Biobank. In newborns lower blood level of BDNF was significantly associated with increased odds (OR 1.15) of developing ASD (p = 0.001). This difference could not be explained by genetic variation in the BDNF coding gene region. A tendency of decreased levels of all the neurotrophic markers and increased levels of all inflammatory markers was noted. The low newborn blood levels of BDNF in children developing ASD is an important finding, suggesting that lower BDNF levels in newborns contributes to the etiology of ASD and indicates new directions for further research. It may also help identifying a long-sought marker for high-ASD risk in, e.g., younger siblings of ASD children.

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