There is well-established evidence of a P50 sensory gating deficit in patients of schizophrenia. This gating deficit refers broadly to an inability to prioritize environmental stimuli. More specifically, it refers to an inability to dampen the amplitude of the evoked P50 potential to the second of a pair of identical auditory stimuli presented 500 milliseconds apart. In one study sample, this deficit was observed in 91% of unrelated patients with schizophrenia vs 6% of appropriately matched controls.
Diminished sensory inhibition as measured by the P50 ratio serves as an endophenotype that reflects transmission of genetic risk for schizophrenia and is often detected in one of the two unaffected parents, or about half of the unaffected siblings, of a proband with schizophrenia. Moreover, the P50 sensory gating deficit is associated with a promoter variant of the gene encoding the ?7-nicotinic acetylcholine receptor (?7 nAChR) that results in its diminished expression. Diminished central inhibition may reflect genetic risk caused by a delay in the switch of GABA from an excitatory to inhibitory neurotransmitter in the fetal brain, which is dependent on expression of a specific membrane chloride transporter, termed KCC2. Expression of KCC2 and the switch of GABA from an excitatory to inhibitory neurotransmitter in the fetal brain are activated by stimulation of the ?7 nAChR. Thus, diminished fetal expression of ?7 nAChRs or deficient stimulation of these receptors could result in diminished central inhibitory tone during a critical period of fetal brain development, contributing to risk for schizophrenia that manifests decades later. A 4-year prospective study of infants with P50 sensory gating deficits revealed higher formal maternal reports of attentional problems than a group of control children with normal P50 suppression as infants, which suggests that there are long-term sequelae associated with deficits of sensory gating in infancy.1
Because cholinergic projections to ?7 nAChRs do not occur until the end of the third trimester in the developing fetal brain, much of the stimulation is provided by millimolar concentrations of free choline in the amniotic fluid; choline is a full agonist that mimics the actions of acetylcholine itself at the ?7 nAChR. Animal research has shown that adult offspring of animals with diminished expression of ?7 nAChRs show significant improvement of their central inhibition deficits when the mothers receive dietary choline supplementation from conception through weaning. This prompted a study of dietary supplementation of healthy pregnant women with phosphatidylcholine, a source of choline, from the second trimester until delivery, followed by supplementation of the infant through the third postnatal month.
A significant difference was observed in the ratios of P50 suppression at 33 days of age between infants randomized to receive phosphatidylcholine supplementation and those randomized to placebo. Seventy-six percent of the subjects treated as fetuses and infants with phosphatidylcholine showed intact cerebral inhibition, as reflected in a suppression ratio <0.5, whereas 43% of the placebo-treated infants showed intact cerebral inhibition. These provocative data support exploration of a population-wide dietary intervention (ie, choline supplementation of pregnant women and their newborn infants) for the possible prevention or reduction of risk for later onset of schizophrenia.