Early-life manganese exposure and substance use in adolescents: contribution of the neural circuitry supporting self-control


Manganese (Mn) is an essential nutrient that is neurotoxic at high levels of exposure.
Prenatal and childhood Mn exposure is associated with impaired self-control in
adolescents, including poor working memory. Little is known about the effects of early-life
exposure on substance use, a prevalent impulsive behavior in adolescents, and its
underlying neural mechanisms. The aim of the proposed study is to examine whether
early-life Mn exposure is associated with substance use, functional activity and
connectivity of self-control brain areas (e.g., prefrontal cortex, parietal cortex) in
adolescents. We will invite 120 adolescents (15-22 years) to participate in a functional
magnetic resonance imaging (fMRI) study that includes a working memory task and a
resting state scan (to assess intrinsic functional connectivity of the brain). Participants
will further report their recent smoking and alcohol use. Participants are living in three
different areas in Northern Italy, with either high, moderate or no Mn contamination. Mn
exposure during pregnancy and childhood will be determined using an innovative
biomarker of exposure, baby teeth, allowing us to identify windows of vulnerability. The
proposed host institute is the Icahn School of Medicine at Mount Sinai in New York.


Project number


Main applicant

Dr. E. de Water

Affiliated with

Icahn School of Medicine at Mount Sinai


01/06/2018 to 29/02/2020