Perinatal Phosphatidylcholine Supplementation and Early Childhood Behavior Problems: Evidence for CHRNA7 Moderation

Abstract

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.

Preventive strategies for mental health

“…Recent studies suggest that dietary phosphatidylcholine supplementation during the second and third trimesters may prevent cerebral inhibition deficits associated with schizophrenia and attention deficit disorder. 53 There is also evidence suggesting that vitamin D supplementation during pregnancy may reduce rates of low birthweight and preterm delivery, 54 which have been associated with attention deficits and increased risk for childhood behavioural and emotional disorders. 55,56 .…”

Metabolic, Epigenetic, and Transgenerational Effects of Gut Bacterial Choline Consumption

“…During gestation, maternal choline deficiency reduces global DNA methylation in the fetal hippocampus and alters the development and function of cholinergic neurons that participate in learning, memory, and attention (Mellott et al, 2007; Zeisel, 2007). A recent study showed that perinatal phosphatidylcholine supplementation (above current standards) is associated with less social withdrawal and fewer attention-deficit problems in ~3 year-old children compared to an age-matched placebo group (Ross et al, 2016). Remarkably, it is estimated that 90–95% of pregnant women fail to meet the minimum recommended levels of choline intake (Brunst et al, 2014).…”

CA1 pyramidal neuron gene expression mosaics in the Ts65Dn murine model of Down syndrome and Alzheimer's disease following maternal choline supplementation

“…Further investigation of aging and MCS treatment shows an increase in ChAT intensity in 2N animals, but not in Ts65Dn mice when examined pre-BFCN degeneration (4-6 MO) and post-BFCN degeneration (14-18 MO), however this may be explained by the fact that unsupplemented Ts65Dn mice display septohippocampal degeneration during the aging process . MCS has also been shown to protect the cholinergic system in a mouse model of amyloid-beta precursor protein (APP) overexpression (Mellott et al, 2017) and behavioral and morphologic benefits in several models of neurodevelopmental disorders (Bearer, Wellmann, Tang, He, & Mooney, 2015;Ross et al, 2016;Scremin, Roch, Norman, Djazayeri, & Liu, 2015;Stevens et al, 2008;Ward, Agarwal, Wang, Berger-Sweeney, & Kolodny, 2008;Kolodny, Nag, & Berger-Sweeney, 2009), indicating that the effects are broadly neuroprotective across several disease entities.…”