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J Abnorm Child Psychol. 2003 Dec;31(6):565-74.

Developmental timing of exposure to elevated levels of phenylalanine is associated with ADHD symptom expression.

Author information

  • 1Children's Hospital-Boston, Division of Psychology, Department of Psychiatry, Harvard Medical School, Longwood Avenue, Boston, Massachusetts, USA. antshelk@upstate.edu


This study addresses attention deficit hyperactivity disorder (ADHD), with a focus on how the timing of a known biological insult affects ADHD symptom expression. The sample consists of children exposed to elevated levels of phenylalanine, either postnatally as in Phenylketonuria (PKU; n = 46) or prenatally as in Maternal PKU (MPKU; n = 15). Non-hyperphenylalaninemic siblings of children with PKU (n = 18) serve as controls. Results indicate that elevated levels of phenylalanine are associated with ADHD symptoms. The manifestations of the symptom expression are dependent on exposure timing: prenatal exposure is associated with a higher likelihood of expressing hyperactive/impulsive symptoms and postnatal exposure is associated with a higher likelihood of expressing inattentive symptoms. This toxicity is dose-dependent and higher levels of phenylalanine appear more detrimental.

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