Maternal Serotonin Deficiency During Pregnancy May Increase Children's ADHD Risk, 5-hydroxytryptophan
Medscape Today
October 12, 2010 — Researchers in Norway have found that decreased maternal serotonin synthesis during gestation may increase a child's risk for attention-deficit/hyperactivity disorder (ADHD) and related behavioral problems. The study focused on impaired serotonin production resulting from variants of TPH1 and TPH2 — genes that encode 2 enzymes that catalyze conversion of tryptophan to 5-hydroxytryptophan in serotonin biosynthesis.
"Our work was inspired from animal studies, where it has clearly been shown that maternal TPH1 has an effect on embryonic development and that this is related to levels of free serotonin," said senior author Jan Haavik, MD, PhD, from the Department of Biomedicine, University of Bergen, and Division of Psychiatry, Haukeland University Hospital, Bergen, Norway, via email to Medscape Medical News.
"However, this is more difficult to study in humans, where the role of local serotonin production in ovaries and other tissues is incompletely studied," Dr. Haavik explained.
TPH1 and TPH2 differ slightly in structure and function. TPH1 is present in the pineal gland, the striatum, and hippocampus, as well as in female reproductive tissues and other organs. TPH2 catalyzes most of the brain's production of serotonin.
The report notes that impaired serotonin function and TPH1 or TPH2 variants have been detected in a variety of psychiatric conditions — among them, anxiety, autism, depression, schizophrenia, and ADHD — but evidence for serotonin pathway abnormalities in ADHD has been inconclusive.
Dr. Haavik's motivation for the study grew from his frustration with the slow progress in psychiatric knowledge. As he observed: "Not a single 'candidate gene' for ADHD has been robustly replicated across studies, and virtually nothing is known about the function of the handful of genetic markers recently found to be associated with either schizophrenia, bipolar disorder, or autism."
The new study, published in the October issue of the Archives of General Psychiatry, enrolled adults diagnosed with ADHD, following Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. DNA was obtained from saliva or blood samples of participants; exons and intron-exon regions of TPH1 and TPH2 were sequenced in 457/459 adults with ADHD and 187/179 control individuals, respectively.
Patients found to have TPH1 mutations then recruited family members, with a guideline of 3 or more participants per family; the resulting TPH1 analyses assessed DNA samples from 86 members of 7 families.
