Interaction of genes and nutritional factors in the etiology of autism and attention deficit/hyperactivity disorders: a case control study.

OBJECTIVE To compare risk factors of attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) to age/sex-matched controls with particular attention to family history, parental age and nutrition. METHOD 31 ASD and 81 ADHD patients were compared to 612 age/sex-matched controls by reviewing charts for parental age, sibling order, gestational age, and early feeding, and by parental interview for early feeding and family history of psychopathology on affected patients and 139 of those controls. FINDINGS Parental age affected ASD and ADHD females but not males. First-born males were at increased risk for both disorders even though their siblings had older parents and their parents were not more likely to stop having children. Breastfeeding in the absence of parental psychopathology reduced ADHD risk, but breastfeeding of first-born males by older mothers with psychopathology was a risk for ASD. Breastfeeding was only a risk for ADHD if the mother had psychopathology. Parent emigration from a place of high fish consumption was a significant ASD risk factor. RESULTING HYPOTHESES ADHD and ASD share risk factors due to shared genetic and nutritional interactions, likely revolving around deficiencies of omega-3 fatty acids (n3FAs) during brain development. Fatty acid metabolism genes are important in that process. The 4:1 male to female ratio for both disorders results from hormonally driven fat metabolism differences. Risk factors for both disorders including maternal smoking, prematurity, and gestational diabetes may also be attributed to their effect on n3FA supplies. Breastfeeding can be a risk factor when the mother's genes and/or age affect her milk quality. Parental age and gene defects may affect female more than male offspring. Childbirth with adequate spacing and breastfeeding can override maternal age and protect subsequent offspring. Genetic variations in fat metabolism can be influenced by cultural/geographic diet, causing deficiencies in offspring with migration-influenced diet changes. Interaction of n3FA deficient diets, delayed child-bearing, and breastfeeding by mothers with psychopathology may be important factors in the rising incidence of ASD and ADHD in recent decades. Partial prevention through diet and supplements may be possible.