There is substantial evidence that early environmental insults increase risk for psychiatric disorders,

especially those with strong neurodevelopmental origins. Thus, there is a need to reliably identify these

environmental factors, as well as whether higher exposure level during critical periods for

neurodevelopment are related to greater risk for psychiatric disorders. Moreover, while environmental

toxins have been reliably associated with early neurodevelopment, similar investigations into longer term

and psychiatric outcomes are scarce.

Current approaches use indirect measures of fetal exposure, such as chemical concentrations in maternal

blood and urine, which may not accurately reflect fetal uptake for many toxins due to variable partitioning

across the placenta (Smith et al., 2007). Thus, a direct marker of early exposure is needed to aid our

understanding of the etiology of psychiatric disorders, as well as to aid prevention.

The current study proposes to use a unique and well-characterized birth cohort: the Avon Longitudinal

Study of Parents and Children (ALSPAC) and applying an extensively developed and piloted method to

determine multi-toxin early exposure (Arora et al., 2006, 2011; 2012; 2013; Hare et al., 2011; Austin et

al., 2013). Human deciduous teeth undergo systematic mineralization commencing prenatally and are

composed of a collagen-based, lipid-containing, calcium-rich apatite matrix, which accumulates bone

seeking elements and organic compounds. The methodology combines detailed histological analysis and

associated analytical tools to establish a comprehensive record of weekly to monthly exposure history of

multiple chemicals and metals and history of infections from the second trimester through early

childhood.

Aims

The overall goal of this project is to determine the association of early life environmental metal and

chemical toxin and infection exposures with multiple psychiatric and neurological outcomes: psychotic

like experiences, depression, mild cognitive impairment and autstic-like traits. A detailed history of

exposure during prenatal and early childhood development will be established to distinguish between two

important aspects of the exposure profile:

1) Exposure timing: We will construct weekly to monthly exposure history over the prenatal and early

childhood periods in order to identify the developmental period(s) most strongly associated with risk for

poor psychiatric and neurological outcomes.

2) Exposure intensity: Cumulative exposure may be more important than exposure during any single

developmental window and our biomarker allows measurement of cumulative exposure from the prenatal

period to the time of tooth shedding, which occurs between ages 6 to 12 years.