Associations between Elemental Metabolic Dynamics and Default Mode Network Functional Connectivity Are Altered in Autism

Paul Curtin; Janina Neufeld; Austen Curtin; Christine Austin; Johan Isaksson; Karl Lundin Remnelius; Hjalmar Nobel Norrman; Manish Arora; Sven Bölte

doi:10.3390/jcm12031022

Associations between Elemental Metabolic Dynamics and Default Mode Network Functional Connectivity Are Altered in Autism

J Clin Med. 2023 Jan 28;12(3):1022. doi: 10.3390/jcm12031022.

Authors

Paul Curtin¹, Janina Neufeld^{2

3}, Austen Curtin^{1

4}, Christine Austin^{1

4}, Johan Isaksson^{2

5}, Karl Lundin Remnelius², Hjalmar Nobel Norrman², Manish Arora^{1

4}, Sven Bölte^{2

6

7}

Affiliations

¹ Linus Biotechnology Inc., New York, NY 10013, USA.
² Center of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research, Department of Women's and Children's Health, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, 11330 Stockholm, Sweden.
³ Swedish Collegium for Advanced Study, 75238 Uppsala, Sweden.
⁴ Environmental Medicine and Public Health, Mount Sinai School of Medicine, New York, NY 10029, USA.
⁵ Department of Medical Sciences, Child and Adolescent Psychiatry Unit, Uppsala University, 75185 Uppsala, Sweden.
⁶ Curtin Autism Research Group, Curtin School of Allied Health, Curtin University, Perth, WA 6102, Australia.
⁷ Child and Adolescent Psychiatry, Stockholm Health Care Services, Region Stockholm, 11861 Stockholm, Sweden.

Abstract

Autism is a neurodevelopmental condition associated with atypical social communication, cognitive, and sensory faculties. Recent advances in exposure biology suggest that biomarkers of elemental uptake and metabolism measured in hair samples can yield an effective signal predictive of autism diagnosis. Here, we investigated if elemental biomarkers in hair were associated with functional connectivity in regions of the default mode network (DMN) previously linked to autism. In a study sample which included twin pairs with concordant and discordant diagnoses for autism, our analysis of hair samples and neuroimaging data supported two general findings. First, independent of autism diagnosis, we found a broad pattern of association between elemental biomarkers and functional connectivity in the DMN, which primarily involved dynamics in zinc metabolism. Second, we found that associations between the DMN and elemental biomarkers, particularly involving phosphorus, calcium, manganese, and magnesium, differed significantly in autistic participants from control participants. In sum, these findings suggest that functional dynamics in elemental metabolism relate broadly to persistent patterns of functional connectivity in the DMN, and that these associations are altered in the emergence of autism.

Keywords: autism; default mode network; dynamical systems; environmental exposures; exposomics; metal exposures.

Grants and funding

This research was funded by the following: National Institute of Environmental Health Sciences (P30ES023515; M.A. and P.C.); National Institute of Environmental Health Sciences (R01ES026033; MA); National Institute of Environmental Health Sciences (U2CES030859; M.A. and P.C.); National Institute of Environmental Health Sciences (R35ES030435; M.A. and P.C.); National Institute of Environmental Health Sciences (R01ES02951; P.C.); National Institute of Mental Health (R01MH122447; P.C.); National Institute of Environmental Health Sciences (R01ES032294; P.C.); Swedish Research Council (S.B.); Knut and Alice Wallenberg Foundation (S.B.); Vinnova (S.B.); Formas (S.B.); FORTE (S.B.); Swedish Brain foundation (Hjärnfonden) (S.B.); Stockholm Brain Institute (S.B.); Autism and Asperger Association Stockholm (S.B.); Queen Silvia’s Jubilee Fund (S.B.); Solstickan Foundation (S.B.); PRIMA Child and Adult Psychiatry (S.B.); Pediatric Research Foundation at Astrid Lindgren Children’s Hospital (S.B.); Swedish Foundation for Strategic Research (S.B.); Jerring Foundation (S.B.); Swedish Order of Freemasons (S.B.); Kempe-Carlgrenska Foundation (S.B.); Sunnderdahls Handikappsfond (S.B.); Jeansson Foundation (S.B.) and EU-AIMS (European Autism Intervention) (S.B.); Innovative Medicines Initiative Joint Undertaking (grant No. 115300) (S.B.); Autism Speaks (S.B.); EU AIMS-2-TRIALS (S.B.).