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.
“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]
Perinatal phosphatidylcholine results in fewer attention problems and less social withdrawal.
“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]
Neurodevelopmental biomarkers have no available data on association with psychotic disorders.
“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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“However, an accompanying editorial by Rapoport (2016) suggested that clinical extrapolation of these findings might be premature, and instead encouraged a good diet and prevention of infection.”
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“5 years of age using the Child Behavior Checklist for age 11⁄2-5 years (87-88).”
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Lessons Learned from 50 Years of Violence Prevention Activities in the African American Community
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“While no study has specifically looked at HM choline levels and infant behavior, phosphatidylcholine supplementation during pregnancy has shown to result in fewer attention problems and less social withdrawal at infant age of 40 months by increasing activation of the α7-nicotinic acetylcholine receptor (68), and newbo…”
BackgroundPsychiatry and Obstetrics: An Imperative for Collaboration
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“Similarly, fetal programming of psychiatric disorders is an emerging domain of robust research (14, 16, 17).”
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“5 years of age; early cerebral inhibition was associated with fewer problems in attention and social behavior.(65) It is possible that the benefits of supplementation could last even longer because these problems in childhood are associated with later mental illnesses, including schizophrenia.”
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Cross-Cultural Perspectives on Parent–Infant Interactions
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Opportunities in precision psychiatry using PET neuroimaging in psychosis
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“Current trials vary widely in design, with some comparing 930 mg/day to 480 mg/day during the third trimester of pregnancy [7] and others providing 900 mg/day from week 16 of gestation through delivery, followed by 100 mg/day to infants [50,51].”
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A Role for Data Science in Precision Nutrition and Early Brain Development
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The Development of Infant Feeding
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“Alternatively, Hepsomali and Groeger (26) found that higher unprocessed red meat intake (but not processed meat) was associated with improved general cognitive ability, and Zhu et al .”
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Prenatal prevention of psychiatric illness and childhood development population‐wide
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- 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 · 2015: 1 · 2013: 1
- 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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