Early-life metal exposure and schizophrenia: A proof-of-concept study using novel tooth-matrix biomarkers.
Despite evidence for the effects of metals on neurodevelopment, the long-term effects on mental health remain unclear due to methodological limitations. Our objective was to determine the feasibility of studying metal exposure during critical neurodevelopmental periods and to explore the association between early-life metal exposure and adult schizophrenia.



We analyzed childhood-shed teeth from nine individuals with schizophrenia and five healthy controls. We investigated the association between exposure to lead (Pb(2+)), manganese (Mn(2+)), cadmium (Cd(2+)), copper (Cu(2+)), magnesium (Mg(2+)), and zinc (Zn(2+)), and schizophrenia, psychotic experiences, and intelligence quotient (IQ). We reconstructed the dose and timing of early-life metal exposures using laser ablation inductively coupled plasma mass spectrometry.



We found higher early-life Pb(2+) exposure among patients with schizophrenia than controls. The differences in log Mn(2+) and log Cu(2+) changed relatively linearly over time to postnatal negative values. There was a positive correlation between early-life Pb(2+) levels and psychotic experiences in adulthood. Moreover, we found a negative correlation between Pb(2+) levels and adult IQ.



In our proof-of-concept study, using tooth-matrix biomarker that provides direct measurement of exposure in the fetus and newborn, we provide support for the role of metal exposure during critical neurodevelopmental periods in psychosis.
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, United States; Seaver Center for Autism Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, United States; Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, United States. Electronic address: Amirhossein.modabbernia@mssm.edu.
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Modabbernia
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, United States; Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
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Velthorst
Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, United States.
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Gennings
Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
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De Haan
Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, United States.
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Austin
Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
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Sutterland
Department of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, England, United Kingdom.
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Mollon
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, United States; Psychosis Research Program, Icahn School of Medicine at Mount Sinai, New York, United States.
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Frangou
Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, United States.
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Wright
Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, United States.
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Arora
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, United States; Seaver Center for Autism Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, United States; Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, United States; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, United States.
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Reichenberg
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D002104:Cadmium / Q000032:analysis; D016022:Case-Control Studies; D002648:Child; D003300:Copper / Q000032:analysis; D004781:Environmental Exposure / Q000009:adverse effects* / Q000032:analysis; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007361:Intelligence Tests; D007854:Lead / Q000032:analysis; D008297:Male; D019216:Metals, Heavy / Q000032:analysis*; D012559:Schizophrenia / Q000209:etiology*; D014070:Tooth; D015032:Zinc / Q000032:analysis
D015415:Biomarkers; D019216:Metals, Heavy; D002104:Cadmium; D007854:Lead; D003300:Copper; D015032:Zinc
Environmental exposure; Lead; Neurodevelopmental disorders; Psychosis; Tooth; Trace elements