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Perinatal Phosphatidylcholine Supplementation and Early Childhood Behavior Problems: Evidence for CHRNA7 Moderation
Open accessAbstract
OBJECTIVE: α7-Nicotinic receptors are involved in the final maturation of GABA inhibitory synapses before birth. Choline at levels found in the amniotic fluid is an agonist at α7-nicotinic receptors. The authors conducted a double-blind placebo-controlled trial to assess whether high-dose oral phosphatidylcholine supplementation during pregnancy to increase maternal amniotic fluid choline levels would enhance fetal development of cerebral inhibition and, as a result, decrease childhood behavior problems associated with later mental illness. METHOD: The authors previously reported that newborns in the phosphatidylcholine treatment group have increased suppression of the cerebral evoked response to repeated auditory stimuli. In this follow-up, they report parental assessments of the children's behavior at 40 months of age, using the Child Behavior Checklist. RESULTS: At 40 months, parent ratings of children in the phosphatidylcholine group (N=23) indicated fewer attention problems and less social withdrawal compared with the placebo group (N=26). The improvement is comparable in magnitude to similar deficits at this age associated with later schizophrenia. The children's behavior is moderated by CHRNA7 variants associated with later mental illness and is related to their enhanced cerebral inhibition as newborns. CONCLUSIONS: CHRNA7, the α7-nicotinic acetylcholine receptor gene, has been associated with schizophrenia, autism, and attention deficit hyperactivity disorder. Maternal phosphatidylcholine treatment may, by increasing activation of the α7-nicotinic acetylcholine receptor, alter the development of behavior problems in early childhood that can presage later mental illness.
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“A subsequent study demonstrated that, at 40 months, phosphatidylcholine impacted neurocognitive biomarkers, leading to fewer attention problems and less social withdrawal compared with the placebo group, thus potentially altering the risk of later development of psychosis 165”
From Preventive psychiatry: a blueprint for improving the mental health of young people (2021) · cites this paper as [165]
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“Perinatal phosphatidylcholine (modulated biomarkers of neonatal brain development 164 *; fewer attention problems and less social withdrawal 165 *)”
From Preventive psychiatry: a blueprint for improving the mental health of young people (2021) · cites this paper as [165]
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“Neurodevelopmental biomarkers (data not available) 164,165,167 *”
From Preventive psychiatry: a blueprint for improving the mental health of young people (2021) · cites this paper as [165]
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Metadata
- Authors
- Ross, R. G., Hunter, S. K., Hoffman, M. C., McCarthy, L., Chambers, B. M., Law, A. J., Leonard, S., Zerbe, G. O., & Freedman, R.
- Affiliations
- Colorado School of Public Health (US)
- Corresponding author
- Ross, Randal G.
- Venue
- American Journal of Psychiatry
- Published
- 2016-05-01
- Volume
- 173
- Issue
- 5
- Pages
- 509-516
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC5892450
- OpenAlex
- W2191222387
- Cited by
- 123
- References
- 42
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 9 · 2023: 5 · 2022: 6 · 2021: 14 · 2020: 43 · 2019: 10 · 2018: 13 · 2017: 6 · 2016: 2
- FWCI
- 3.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Anschutz Foundation
- National Institutes of Health
- National Institute of Mental Health (P50MH086383, R01MH056539, R01MH101295)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Keywords
- alpha7 nicotinic acetylcholine receptor, CHRNA7, fetal brain development, early childhood behavior problems, attention deficits, social withdrawal, schizophrenia risk, autism spectrum disorder, attention deficit hyperactivity disorder, prenatal nutrition, Child Behavior Checklist
- MeSH terms
- Adult, Child Behavior, Child, Preschool, Double-Blind Method, Female, Genotype, Humans, Phosphatidylcholines, Pregnancy, Prenatal Exposure Delayed Effects, Young Adult, alpha7 Nicotinic Acetylcholine Receptor
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